User login
Iloprost
Endobronchial dysplasia significantly improved in former smokees who received oral iloprost during a phase II trial, says study investigator Dr. Robert Keith. Bob Finn of the Global Medical News Network (GMNN) reports from the World Conference on Lung Cancer in San Francisco.
Endobronchial dysplasia significantly improved in former smokees who received oral iloprost during a phase II trial, says study investigator Dr. Robert Keith. Bob Finn of the Global Medical News Network (GMNN) reports from the World Conference on Lung Cancer in San Francisco.
Endobronchial dysplasia significantly improved in former smokees who received oral iloprost during a phase II trial, says study investigator Dr. Robert Keith. Bob Finn of the Global Medical News Network (GMNN) reports from the World Conference on Lung Cancer in San Francisco.
Expert Perspective: Lung Cancer Meeting
Dr. Roy S. Herbst reflects on the most clinically relevant studies presented at the world conference of the International Association for the Study of Lung Cancer. Dr. Herbst is chief of Thoracic Head and Neck Medical Oncology at M. D. Anderson Cancer Center. He is also associate editor of the Oncology Report, an Elsevier publication. GMNN's Bob Finn reports.
Dr. Roy S. Herbst reflects on the most clinically relevant studies presented at the world conference of the International Association for the Study of Lung Cancer. Dr. Herbst is chief of Thoracic Head and Neck Medical Oncology at M. D. Anderson Cancer Center. He is also associate editor of the Oncology Report, an Elsevier publication. GMNN's Bob Finn reports.
Dr. Roy S. Herbst reflects on the most clinically relevant studies presented at the world conference of the International Association for the Study of Lung Cancer. Dr. Herbst is chief of Thoracic Head and Neck Medical Oncology at M. D. Anderson Cancer Center. He is also associate editor of the Oncology Report, an Elsevier publication. GMNN's Bob Finn reports.
Sputum Samples & Lung Cancer
An investigational device can discriminate normal cells from cancerous cells in sputum with 90% sensitivity and near 100% specificity, according to its manufacturer, VisionGate, Inc. Bob Finn of the Global Medical News Network (GMNN) reports from the World Conference on Lung Cancer in San Francisco.
An investigational device can discriminate normal cells from cancerous cells in sputum with 90% sensitivity and near 100% specificity, according to its manufacturer, VisionGate, Inc. Bob Finn of the Global Medical News Network (GMNN) reports from the World Conference on Lung Cancer in San Francisco.
An investigational device can discriminate normal cells from cancerous cells in sputum with 90% sensitivity and near 100% specificity, according to its manufacturer, VisionGate, Inc. Bob Finn of the Global Medical News Network (GMNN) reports from the World Conference on Lung Cancer in San Francisco.
A Shorter, Sweeter Stay
A hospitalist-orthopedic comanagement model at Loyola University Medical Center in Maywood, Ill., improves both patient care and satisfaction, according to a study published in the July issue of Orthopedics (2009;32:495).
The approach, which dedicates two hospitalists to work with the orthopedists, was the culmination of a joint effort that began in 2005 to address communication issues between the hospitalist consultation service and the orthopedic surgery team, says Edward Gurza, MD, associate professor of medicine and director of the Division of General Internal Medicine at Loyola's Stritch School of Medicine in Chicago. “The idea was to have the same group of people to take care of patients pre-operatively, peri-operatively, and post-operatively,” Dr. Gurza says. “That’s absolutely critical. With orthopedics, one of the big issues is lack of continuity in the coordination of care.”
The study reports that the length of hospital stays was 0.693 days for 86 high-risk, comanaged patients with multiple comorbidities compared with 0.862 days for 54 patients in the control group. The severity of illness and risk of mortality scores were higher in the study group. The analysis found little effect on costs of care, but patient satisfaction scores for the test groups rose by 5% and 14%, respectively, in the categories of “communication with doctors” and “doctors treated you with respect.”
Dr. Gurza says the program needed no new funding, just a commitment from HM group leaders to dedicate staff to the concept. Hospitalists breed familiarity that cements a bond between physician and patient. “It flows naturally,” he says. “You’re not going out to specifically charm a patient. Hopefully, if you’re doing your job as an internist delivering proper care, patients understand that.”
A hospitalist-orthopedic comanagement model at Loyola University Medical Center in Maywood, Ill., improves both patient care and satisfaction, according to a study published in the July issue of Orthopedics (2009;32:495).
The approach, which dedicates two hospitalists to work with the orthopedists, was the culmination of a joint effort that began in 2005 to address communication issues between the hospitalist consultation service and the orthopedic surgery team, says Edward Gurza, MD, associate professor of medicine and director of the Division of General Internal Medicine at Loyola's Stritch School of Medicine in Chicago. “The idea was to have the same group of people to take care of patients pre-operatively, peri-operatively, and post-operatively,” Dr. Gurza says. “That’s absolutely critical. With orthopedics, one of the big issues is lack of continuity in the coordination of care.”
The study reports that the length of hospital stays was 0.693 days for 86 high-risk, comanaged patients with multiple comorbidities compared with 0.862 days for 54 patients in the control group. The severity of illness and risk of mortality scores were higher in the study group. The analysis found little effect on costs of care, but patient satisfaction scores for the test groups rose by 5% and 14%, respectively, in the categories of “communication with doctors” and “doctors treated you with respect.”
Dr. Gurza says the program needed no new funding, just a commitment from HM group leaders to dedicate staff to the concept. Hospitalists breed familiarity that cements a bond between physician and patient. “It flows naturally,” he says. “You’re not going out to specifically charm a patient. Hopefully, if you’re doing your job as an internist delivering proper care, patients understand that.”
A hospitalist-orthopedic comanagement model at Loyola University Medical Center in Maywood, Ill., improves both patient care and satisfaction, according to a study published in the July issue of Orthopedics (2009;32:495).
The approach, which dedicates two hospitalists to work with the orthopedists, was the culmination of a joint effort that began in 2005 to address communication issues between the hospitalist consultation service and the orthopedic surgery team, says Edward Gurza, MD, associate professor of medicine and director of the Division of General Internal Medicine at Loyola's Stritch School of Medicine in Chicago. “The idea was to have the same group of people to take care of patients pre-operatively, peri-operatively, and post-operatively,” Dr. Gurza says. “That’s absolutely critical. With orthopedics, one of the big issues is lack of continuity in the coordination of care.”
The study reports that the length of hospital stays was 0.693 days for 86 high-risk, comanaged patients with multiple comorbidities compared with 0.862 days for 54 patients in the control group. The severity of illness and risk of mortality scores were higher in the study group. The analysis found little effect on costs of care, but patient satisfaction scores for the test groups rose by 5% and 14%, respectively, in the categories of “communication with doctors” and “doctors treated you with respect.”
Dr. Gurza says the program needed no new funding, just a commitment from HM group leaders to dedicate staff to the concept. Hospitalists breed familiarity that cements a bond between physician and patient. “It flows naturally,” he says. “You’re not going out to specifically charm a patient. Hopefully, if you’re doing your job as an internist delivering proper care, patients understand that.”
Summer Camp
Nurse practitioners (NPs) and physician assistants (PAs) are expected to help fill the HM ranks in the coming years, and more than 200 of them showed their dedication to the field by attending the first Adult Hospitalist Physician Assistant and Nurse Practitioner Boot Camp last week in Chantilly, Va.
Sponsored by SHM, the American Academy of Physician Assistants, and the American Academy of Nurse Practitioners, the soldout event provided intense training in such clinical areas as cardiac neurologic care, as well as infection control. Attendees also learned valuable practice management tips and learned how to report Physician Quality Reporting Initiative (PQRI) measures.
"The NPP bootcamp was a success; participants were happy with the content," says Jeanette Kalupa, MSN, ACNP-BC, APNP, an acute-care NP with Cogent Healthcare of Wisconsin in Milwaukee. "The faculty, who were a mix of MDs, NPs, and PAs, were terrific. The NPs and PAs who attended were a mix of experience levels and knowledge levels, in regards to hospital medicine."
Photo credit: Jay Westcott
Nurse practitioners (NPs) and physician assistants (PAs) are expected to help fill the HM ranks in the coming years, and more than 200 of them showed their dedication to the field by attending the first Adult Hospitalist Physician Assistant and Nurse Practitioner Boot Camp last week in Chantilly, Va.
Sponsored by SHM, the American Academy of Physician Assistants, and the American Academy of Nurse Practitioners, the soldout event provided intense training in such clinical areas as cardiac neurologic care, as well as infection control. Attendees also learned valuable practice management tips and learned how to report Physician Quality Reporting Initiative (PQRI) measures.
"The NPP bootcamp was a success; participants were happy with the content," says Jeanette Kalupa, MSN, ACNP-BC, APNP, an acute-care NP with Cogent Healthcare of Wisconsin in Milwaukee. "The faculty, who were a mix of MDs, NPs, and PAs, were terrific. The NPs and PAs who attended were a mix of experience levels and knowledge levels, in regards to hospital medicine."
Photo credit: Jay Westcott
Nurse practitioners (NPs) and physician assistants (PAs) are expected to help fill the HM ranks in the coming years, and more than 200 of them showed their dedication to the field by attending the first Adult Hospitalist Physician Assistant and Nurse Practitioner Boot Camp last week in Chantilly, Va.
Sponsored by SHM, the American Academy of Physician Assistants, and the American Academy of Nurse Practitioners, the soldout event provided intense training in such clinical areas as cardiac neurologic care, as well as infection control. Attendees also learned valuable practice management tips and learned how to report Physician Quality Reporting Initiative (PQRI) measures.
"The NPP bootcamp was a success; participants were happy with the content," says Jeanette Kalupa, MSN, ACNP-BC, APNP, an acute-care NP with Cogent Healthcare of Wisconsin in Milwaukee. "The faculty, who were a mix of MDs, NPs, and PAs, were terrific. The NPs and PAs who attended were a mix of experience levels and knowledge levels, in regards to hospital medicine."
Photo credit: Jay Westcott
Staging System
A revolutionary new staging system for lung cancer will unite clinicians from different specialties and nations in characterizing tumor characteristics, node involvement, and metastasis, says Dr. Peter Goldstraw. Betsy Bates of the Global Medical News Network (GMNN) reports from the World Conference on Lung Cancer in San Francisco.
A revolutionary new staging system for lung cancer will unite clinicians from different specialties and nations in characterizing tumor characteristics, node involvement, and metastasis, says Dr. Peter Goldstraw. Betsy Bates of the Global Medical News Network (GMNN) reports from the World Conference on Lung Cancer in San Francisco.
A revolutionary new staging system for lung cancer will unite clinicians from different specialties and nations in characterizing tumor characteristics, node involvement, and metastasis, says Dr. Peter Goldstraw. Betsy Bates of the Global Medical News Network (GMNN) reports from the World Conference on Lung Cancer in San Francisco.
Social Work
Editors’ note: “Alliances” is a new series written about the relationships that hospitalists have with members of the clinical care team—from the team members’ points of view. It’s our hope that each installment of “Alliances” will provide valuable, revealing feedback that hospitalists can use to continually improve their intrateam relationships and, ultimately, patient care.
Social workers are a natural fit with hospitalists and the hospitalist’s strongest allies and staunchest supporters, wrote Bradley Flansbaum, DO, MPH, in his Nov./Dec. 2003 article in The Hospitalist. What makes this collaboration such a positive one and what can members of these two professions learn from each other?
Dr. Flansbaum, a hospitalist and internist with the Division of Internal Medicine/Primary Care at Lenox Hill Hospital, Bronx, N.Y., and a former SHM board member, recently reiterated the benefits of the hospitalist-social worker relationship. In general, he believes that hospitalists provide a unique history-taking perspective that is useful to social workers in their work. Foremost, social workers bring a rich understanding of the available resources that patients need after discharge and a view of the patient’s nonmedical circumstances. Together, the two professionals’ daily interactions generate more effective discharge planning as a part of the multidisciplinary team.
ALWAYS THERE
Amy Lingg, MS, MPA, works on the general medicine unit at Greenwich Hospital (Conn). She says the role of the hospitalist is fairly new at Greenwich. In fact Sabitha Rajan, MD, MS, was the first one at Greenwich Hospital.
In Lingg’s view, nothing can replace the availability of the hospitalist to discuss patient cases, not only with the social worker but also as a team with the patient and family.
“[Attendings] are not there for the moment-by-moment events that happen on the unit, including availability when families are here,” says Lingg. “If I need to speak with a family and the physician’s input is important there, I can just page the hospitalist, she’s here. Whereas with an attending you have to make an appointment; you have to schedule around them. It can become difficult.”
Lingg, who works with hospitalist Dr. Rajan, director of hospitalist services at Greenwich Hospital, cites an example of the benefits of hospitalists’ 24/7 availability: “We had a fairly young woman in her mid-40s who was the divorced mother of a 17-year-old son. The father was not in the picture, and the woman was dying of alcoholic cirrhosis and liver failure. She was Dr. Rajan’s patient. One of the issues was the fact that there was no adult guardian for the son although he was going to be 18 in two months.
“So it involved a lot of talking with friends of the woman, who were sort of stepping in as surrogate guardians to him,” Lingg continues. “There were a lot of logistics [regarding] what would happen with him. We were trying to call the grandfather who was estranged. It was a very, very sensitive, very, very tricky case. It went on for days and days. … Dr. Rajan and I could work on this together on a dayto-day basis, [including] … the counseling, relaying medical knowledge to the family, what was going on clinically, trying to deal with that in a way where she was talking in one way to [the] adults and in a different, more appropriate [for the boy’s age] way to the 17-yearold son. And I can be there to help with that process.”
The situation was resolved to the satisfaction of the mother, the son, the friends, and the providers. “It was really pretty extraordinary,” she said. “I’ve talked about that a couple of times, including at a staff meetings when we were talking about getting new hospitalists. That is something I’ve described because, really, it was very special.”
TRUE TEAMWORK
Although everyone on a multidisciplinary team can bring something to the discussion that makes the team work better, social workers and hospitalists collaborate well in painting a more comprehensive picture of the patient’s lifestyle, living habits, and needs.
“In many hospitals … there’s a pattern that develops [whereby at] some time in the morning the hospitalist and social worker will get together and talk,” says Dr. Flansbaum “The hospitalist speaks the language of the social worker and knows what to tell them and how to direct them rather than just saying, ‘the patient’s homeless or the patient needs help at home.’”
After working regularly with social workers and recognizing what they need to know, he says, “the hospitalist is more likely to say, ‘the patient has Medicaid,’ or ‘the patient has this insurance,’ [or] ‘the patient has a home-health [caregiver] four hours a day and needs six or eight hours a day,’ or ‘the patient’s going to need a subacute nursing facility.’ … I think our insights are different from voluntary physicians and our face-time with social workers is more efficient.”
Sylvia Krafcik, MSSA, LISW, with MetroHealth Medical Center, Cleveland, says hospitalists are “great to work with because they’re very dedicated to the population they’re caring for, because this is their whole responsibility; they don’t have a private caseload.”
But in her view most hospitalists are focused on patients’ medical conditions and some of them are not as tuned in to all the other aspects of the patient, such as all the psychosocial dynamics.
“A lot of them are, but some aren’t,” Krafcik says. “Especially at MetroHealth, we’re a county hospital. So many of the patients that come here are poor. A lot of them are alcoholics or drug abusers. They’re homeless. They live on the streets. They don’t have a primary doctor. They’re usually not compliant with their medications.”
“Here at Metro we have a lot of patients who have extreme social circumstances that affect their medical issues so much,” says Sara Dunson, MSW, LSW, who also works as a social worker at Metro-Health. “I think the hospitalist has greater insight into the person’s environment and all the social structures that they have at home and that are going on in their life [than other physicians might].”
But there is always room for improvement.
“We had one patient who wasn’t able to read, and he never told anybody this,” says Dunson. “And as social workers, we have more of a way of finding that kind of stuff out from patients than the doctors might. And he kept coming in and coming in and was noncompliant with his medication. We eventually determined that this was why he was noncompliant and was causing all these medical issues. The doctors finally [understood] why this gentleman kept coming in with the same problems and he wasn’t taking care of himself. It wasn’t that he didn’t want to, it was just that he was having problems reading all the medications and all the discharge paperwork, and he was too ashamed to tell anybody. [Once the social workers questioned him and got this] out in the open, we were able to get him help with that.”
The doctors focused on what he was or wasn’t doing, but they hadn’t looked at why he wasn’t adherent, explains Dunson. If hospitalists do that more often, she thinks, they could save time and get better outcomes sooner.
COMMUNICATING WITH PATIENTS AND FAMILIES
“I think where hospitalists are coming from is a whole different mindset than a physician who has mainly an office practice,” said Lingg. “The office practice comes first [for them]. Some of our physicians have huge practices in town. And they’ll visit the hospital very early in the morning or in the evening. ... So if I need something in a case like that, if there was not a hospitalist involved, it would have been separate meetings for the family with the physician … and [with] me at another time.”
To hospitalists, a social worker can serve as an important adjunct in talking to the patient and family. “For example, if [social workers] are giving bad news, they warn the physician first,” says Dr. Rajan. “If they’re going to go in and tell the patient that they’re not going to qualify for any home services, they tell the physician as well so that [the hospitalist will not later be] meeting an angry patient.” In addition, she says, “for critically ill or long-term patients, social workers [can] help family members cope. Sometimes as physicians we don’t have the time or we don’t have the resources to do that.”
But this doesn’t let doctors off the hook in regard to addressing the whole person’s needs. Especially if someone has multiple medical problems, the social worker needs to know the availability and level of support for which the family can be counted.
“Social workers will ask questions such as: Are the families involved? or Is there any family?” says Krafcik. “Do they need to go in a nursing home or do they need 24-hour care at home? Is the family able to provide that? [E]very morning we meet to have team rounds. And the [team] go[es] over every patient on the floor, and then I will ask those questions if the doctor hasn’t given me that information.”
Social workers appreciate and would like hospitalists to do more listening to the patient and family for the aspects of the history and psychosocial status that the social worker will need to know.
TEACHING POINTS
In the course of their interactions, what do hospitalists and social workers teach each other that could lead to working a case more effectively and to the greater satisfaction of all involved?
Most of those we interviewed seem to think that the greatest service hospitalists provide is to teach the social worker the medical components that go along with what the social worker does every day.
“[Social workers] get a better understanding of [whether] someone comes in with heart failure or a fall or a stroke, just by repetition and also education; they get to understand after a while what’s needed for individual medical diagnoses,” says Dr. Flansbaum.
“When I know [better] what the medical condition is,” says Krafcik, “I have an idea of how much help [the patient] would need at home and their ability to function. And I would make sure that the patient gets physical therapy or occupational therapy referral or speech therapy.”
Again, perhaps the area where the social worker most teaches the hospitalist regards available resources to solve problems over and above the purely medical. “They know the social system and the needs of different forms and eligibility and what different patients are entitled to and what the system will provide,” says Dr. Flansbaum.
Dunson believes hospitalists are perceived as being more involved in a holistic way with the patient. “I always stress that it is so important to look at the whole person and not just the medical aspects,” she says. “It’s hard for the doctor sometimes to realize that this person might not be able to afford this medication and that’s why they’re noncompliant and all the other issues. So I think is important to open up to the other aspects of a person’s life and not just the medical aspects.”
CONCLUSION
Social workers’ knowledge of medical and nonmedical resources, both locally and nationally, offer hospitalists essential information that leads to designing more appropriate and effective post-discharge plans. Hospitalists can best team with social workers by consistently keeping in mind the patient’s overall circumstances and informing their colleagues of the medical information that can help social workers do their best work. TH
Writer Andrea Sattinger will write about the effect of poor communication skills in the November issue of The Hospitalist.
HOSPITALISTS AND SOCIAL WORKERS
Both sides of the clinical care team discuss the pros and cons of working together
In these … fractious healthcare times when resources are not plentiful and the expectations of patients might be higher, like getting 24-hour care at home, sometimes it might appear that the hospitalist or [another] physician is always the bringer of bad news. A good social worker can work well with the hospitalist in … letting the patient know the realistic expectations of what the system can provide [so that] we’re not in this alone. You know, ‘the world is a nail, the hospitalist is always the hammer’ kind of thing. Social workers can be very helpful in delivering information. … A good social worker can also add some “salve” to the wounds that the patient comes in with.
Some [patients] are borderline functioning or kind of on the precipice already. They come in with this problem and all of a sudden they can’t go back to the situation they were operating in prior. Social workers’ knowledge of the social safety net … is terrific, and they help us in directing what would be the best discharge plan for this patient, [including] knowing what the insurance status is, … what resources they have in place already, what else is available. … [I]t has a lot to do with discharge and recovery and functionality, and [to find out what’s the best place for the patient. They can help us with that.
Perhaps the greatest value social workers provide for all concerned is having the storehouse of knowledge of the available resources of the community. This is probably one of the most vital things to me; they can get a patient into services or programs that I didn’t even know exist. And the resources are very different in Connecticut than … in New York [where I practiced previously]. In New York there are many resources geared toward the Hispanic community, which I haven’t seen so far in Connecticut. But Connecticut has some other great resources; the local area clinic is a fantastic one.
Patients with end-of-life situations are dealt with differently in different states, too, and I wouldn’t have known about all this if it had not been for the social worker with whom I work. I also found out that there is a free program for alcohol rehabilitation in Connecticut; that does not exist in New York. We’ve sent a lot of our patients [to that]; you know they have to be the ones to initiate the call, but if they do, then that’s actually a resource for them. I wasn’t aware of that until I worked with the social workers here.
Editors’ note: “Alliances” is a new series written about the relationships that hospitalists have with members of the clinical care team—from the team members’ points of view. It’s our hope that each installment of “Alliances” will provide valuable, revealing feedback that hospitalists can use to continually improve their intrateam relationships and, ultimately, patient care.
Social workers are a natural fit with hospitalists and the hospitalist’s strongest allies and staunchest supporters, wrote Bradley Flansbaum, DO, MPH, in his Nov./Dec. 2003 article in The Hospitalist. What makes this collaboration such a positive one and what can members of these two professions learn from each other?
Dr. Flansbaum, a hospitalist and internist with the Division of Internal Medicine/Primary Care at Lenox Hill Hospital, Bronx, N.Y., and a former SHM board member, recently reiterated the benefits of the hospitalist-social worker relationship. In general, he believes that hospitalists provide a unique history-taking perspective that is useful to social workers in their work. Foremost, social workers bring a rich understanding of the available resources that patients need after discharge and a view of the patient’s nonmedical circumstances. Together, the two professionals’ daily interactions generate more effective discharge planning as a part of the multidisciplinary team.
ALWAYS THERE
Amy Lingg, MS, MPA, works on the general medicine unit at Greenwich Hospital (Conn). She says the role of the hospitalist is fairly new at Greenwich. In fact Sabitha Rajan, MD, MS, was the first one at Greenwich Hospital.
In Lingg’s view, nothing can replace the availability of the hospitalist to discuss patient cases, not only with the social worker but also as a team with the patient and family.
“[Attendings] are not there for the moment-by-moment events that happen on the unit, including availability when families are here,” says Lingg. “If I need to speak with a family and the physician’s input is important there, I can just page the hospitalist, she’s here. Whereas with an attending you have to make an appointment; you have to schedule around them. It can become difficult.”
Lingg, who works with hospitalist Dr. Rajan, director of hospitalist services at Greenwich Hospital, cites an example of the benefits of hospitalists’ 24/7 availability: “We had a fairly young woman in her mid-40s who was the divorced mother of a 17-year-old son. The father was not in the picture, and the woman was dying of alcoholic cirrhosis and liver failure. She was Dr. Rajan’s patient. One of the issues was the fact that there was no adult guardian for the son although he was going to be 18 in two months.
“So it involved a lot of talking with friends of the woman, who were sort of stepping in as surrogate guardians to him,” Lingg continues. “There were a lot of logistics [regarding] what would happen with him. We were trying to call the grandfather who was estranged. It was a very, very sensitive, very, very tricky case. It went on for days and days. … Dr. Rajan and I could work on this together on a dayto-day basis, [including] … the counseling, relaying medical knowledge to the family, what was going on clinically, trying to deal with that in a way where she was talking in one way to [the] adults and in a different, more appropriate [for the boy’s age] way to the 17-yearold son. And I can be there to help with that process.”
The situation was resolved to the satisfaction of the mother, the son, the friends, and the providers. “It was really pretty extraordinary,” she said. “I’ve talked about that a couple of times, including at a staff meetings when we were talking about getting new hospitalists. That is something I’ve described because, really, it was very special.”
TRUE TEAMWORK
Although everyone on a multidisciplinary team can bring something to the discussion that makes the team work better, social workers and hospitalists collaborate well in painting a more comprehensive picture of the patient’s lifestyle, living habits, and needs.
“In many hospitals … there’s a pattern that develops [whereby at] some time in the morning the hospitalist and social worker will get together and talk,” says Dr. Flansbaum “The hospitalist speaks the language of the social worker and knows what to tell them and how to direct them rather than just saying, ‘the patient’s homeless or the patient needs help at home.’”
After working regularly with social workers and recognizing what they need to know, he says, “the hospitalist is more likely to say, ‘the patient has Medicaid,’ or ‘the patient has this insurance,’ [or] ‘the patient has a home-health [caregiver] four hours a day and needs six or eight hours a day,’ or ‘the patient’s going to need a subacute nursing facility.’ … I think our insights are different from voluntary physicians and our face-time with social workers is more efficient.”
Sylvia Krafcik, MSSA, LISW, with MetroHealth Medical Center, Cleveland, says hospitalists are “great to work with because they’re very dedicated to the population they’re caring for, because this is their whole responsibility; they don’t have a private caseload.”
But in her view most hospitalists are focused on patients’ medical conditions and some of them are not as tuned in to all the other aspects of the patient, such as all the psychosocial dynamics.
“A lot of them are, but some aren’t,” Krafcik says. “Especially at MetroHealth, we’re a county hospital. So many of the patients that come here are poor. A lot of them are alcoholics or drug abusers. They’re homeless. They live on the streets. They don’t have a primary doctor. They’re usually not compliant with their medications.”
“Here at Metro we have a lot of patients who have extreme social circumstances that affect their medical issues so much,” says Sara Dunson, MSW, LSW, who also works as a social worker at Metro-Health. “I think the hospitalist has greater insight into the person’s environment and all the social structures that they have at home and that are going on in their life [than other physicians might].”
But there is always room for improvement.
“We had one patient who wasn’t able to read, and he never told anybody this,” says Dunson. “And as social workers, we have more of a way of finding that kind of stuff out from patients than the doctors might. And he kept coming in and coming in and was noncompliant with his medication. We eventually determined that this was why he was noncompliant and was causing all these medical issues. The doctors finally [understood] why this gentleman kept coming in with the same problems and he wasn’t taking care of himself. It wasn’t that he didn’t want to, it was just that he was having problems reading all the medications and all the discharge paperwork, and he was too ashamed to tell anybody. [Once the social workers questioned him and got this] out in the open, we were able to get him help with that.”
The doctors focused on what he was or wasn’t doing, but they hadn’t looked at why he wasn’t adherent, explains Dunson. If hospitalists do that more often, she thinks, they could save time and get better outcomes sooner.
COMMUNICATING WITH PATIENTS AND FAMILIES
“I think where hospitalists are coming from is a whole different mindset than a physician who has mainly an office practice,” said Lingg. “The office practice comes first [for them]. Some of our physicians have huge practices in town. And they’ll visit the hospital very early in the morning or in the evening. ... So if I need something in a case like that, if there was not a hospitalist involved, it would have been separate meetings for the family with the physician … and [with] me at another time.”
To hospitalists, a social worker can serve as an important adjunct in talking to the patient and family. “For example, if [social workers] are giving bad news, they warn the physician first,” says Dr. Rajan. “If they’re going to go in and tell the patient that they’re not going to qualify for any home services, they tell the physician as well so that [the hospitalist will not later be] meeting an angry patient.” In addition, she says, “for critically ill or long-term patients, social workers [can] help family members cope. Sometimes as physicians we don’t have the time or we don’t have the resources to do that.”
But this doesn’t let doctors off the hook in regard to addressing the whole person’s needs. Especially if someone has multiple medical problems, the social worker needs to know the availability and level of support for which the family can be counted.
“Social workers will ask questions such as: Are the families involved? or Is there any family?” says Krafcik. “Do they need to go in a nursing home or do they need 24-hour care at home? Is the family able to provide that? [E]very morning we meet to have team rounds. And the [team] go[es] over every patient on the floor, and then I will ask those questions if the doctor hasn’t given me that information.”
Social workers appreciate and would like hospitalists to do more listening to the patient and family for the aspects of the history and psychosocial status that the social worker will need to know.
TEACHING POINTS
In the course of their interactions, what do hospitalists and social workers teach each other that could lead to working a case more effectively and to the greater satisfaction of all involved?
Most of those we interviewed seem to think that the greatest service hospitalists provide is to teach the social worker the medical components that go along with what the social worker does every day.
“[Social workers] get a better understanding of [whether] someone comes in with heart failure or a fall or a stroke, just by repetition and also education; they get to understand after a while what’s needed for individual medical diagnoses,” says Dr. Flansbaum.
“When I know [better] what the medical condition is,” says Krafcik, “I have an idea of how much help [the patient] would need at home and their ability to function. And I would make sure that the patient gets physical therapy or occupational therapy referral or speech therapy.”
Again, perhaps the area where the social worker most teaches the hospitalist regards available resources to solve problems over and above the purely medical. “They know the social system and the needs of different forms and eligibility and what different patients are entitled to and what the system will provide,” says Dr. Flansbaum.
Dunson believes hospitalists are perceived as being more involved in a holistic way with the patient. “I always stress that it is so important to look at the whole person and not just the medical aspects,” she says. “It’s hard for the doctor sometimes to realize that this person might not be able to afford this medication and that’s why they’re noncompliant and all the other issues. So I think is important to open up to the other aspects of a person’s life and not just the medical aspects.”
CONCLUSION
Social workers’ knowledge of medical and nonmedical resources, both locally and nationally, offer hospitalists essential information that leads to designing more appropriate and effective post-discharge plans. Hospitalists can best team with social workers by consistently keeping in mind the patient’s overall circumstances and informing their colleagues of the medical information that can help social workers do their best work. TH
Writer Andrea Sattinger will write about the effect of poor communication skills in the November issue of The Hospitalist.
HOSPITALISTS AND SOCIAL WORKERS
Both sides of the clinical care team discuss the pros and cons of working together
In these … fractious healthcare times when resources are not plentiful and the expectations of patients might be higher, like getting 24-hour care at home, sometimes it might appear that the hospitalist or [another] physician is always the bringer of bad news. A good social worker can work well with the hospitalist in … letting the patient know the realistic expectations of what the system can provide [so that] we’re not in this alone. You know, ‘the world is a nail, the hospitalist is always the hammer’ kind of thing. Social workers can be very helpful in delivering information. … A good social worker can also add some “salve” to the wounds that the patient comes in with.
Some [patients] are borderline functioning or kind of on the precipice already. They come in with this problem and all of a sudden they can’t go back to the situation they were operating in prior. Social workers’ knowledge of the social safety net … is terrific, and they help us in directing what would be the best discharge plan for this patient, [including] knowing what the insurance status is, … what resources they have in place already, what else is available. … [I]t has a lot to do with discharge and recovery and functionality, and [to find out what’s the best place for the patient. They can help us with that.
Perhaps the greatest value social workers provide for all concerned is having the storehouse of knowledge of the available resources of the community. This is probably one of the most vital things to me; they can get a patient into services or programs that I didn’t even know exist. And the resources are very different in Connecticut than … in New York [where I practiced previously]. In New York there are many resources geared toward the Hispanic community, which I haven’t seen so far in Connecticut. But Connecticut has some other great resources; the local area clinic is a fantastic one.
Patients with end-of-life situations are dealt with differently in different states, too, and I wouldn’t have known about all this if it had not been for the social worker with whom I work. I also found out that there is a free program for alcohol rehabilitation in Connecticut; that does not exist in New York. We’ve sent a lot of our patients [to that]; you know they have to be the ones to initiate the call, but if they do, then that’s actually a resource for them. I wasn’t aware of that until I worked with the social workers here.
Editors’ note: “Alliances” is a new series written about the relationships that hospitalists have with members of the clinical care team—from the team members’ points of view. It’s our hope that each installment of “Alliances” will provide valuable, revealing feedback that hospitalists can use to continually improve their intrateam relationships and, ultimately, patient care.
Social workers are a natural fit with hospitalists and the hospitalist’s strongest allies and staunchest supporters, wrote Bradley Flansbaum, DO, MPH, in his Nov./Dec. 2003 article in The Hospitalist. What makes this collaboration such a positive one and what can members of these two professions learn from each other?
Dr. Flansbaum, a hospitalist and internist with the Division of Internal Medicine/Primary Care at Lenox Hill Hospital, Bronx, N.Y., and a former SHM board member, recently reiterated the benefits of the hospitalist-social worker relationship. In general, he believes that hospitalists provide a unique history-taking perspective that is useful to social workers in their work. Foremost, social workers bring a rich understanding of the available resources that patients need after discharge and a view of the patient’s nonmedical circumstances. Together, the two professionals’ daily interactions generate more effective discharge planning as a part of the multidisciplinary team.
ALWAYS THERE
Amy Lingg, MS, MPA, works on the general medicine unit at Greenwich Hospital (Conn). She says the role of the hospitalist is fairly new at Greenwich. In fact Sabitha Rajan, MD, MS, was the first one at Greenwich Hospital.
In Lingg’s view, nothing can replace the availability of the hospitalist to discuss patient cases, not only with the social worker but also as a team with the patient and family.
“[Attendings] are not there for the moment-by-moment events that happen on the unit, including availability when families are here,” says Lingg. “If I need to speak with a family and the physician’s input is important there, I can just page the hospitalist, she’s here. Whereas with an attending you have to make an appointment; you have to schedule around them. It can become difficult.”
Lingg, who works with hospitalist Dr. Rajan, director of hospitalist services at Greenwich Hospital, cites an example of the benefits of hospitalists’ 24/7 availability: “We had a fairly young woman in her mid-40s who was the divorced mother of a 17-year-old son. The father was not in the picture, and the woman was dying of alcoholic cirrhosis and liver failure. She was Dr. Rajan’s patient. One of the issues was the fact that there was no adult guardian for the son although he was going to be 18 in two months.
“So it involved a lot of talking with friends of the woman, who were sort of stepping in as surrogate guardians to him,” Lingg continues. “There were a lot of logistics [regarding] what would happen with him. We were trying to call the grandfather who was estranged. It was a very, very sensitive, very, very tricky case. It went on for days and days. … Dr. Rajan and I could work on this together on a dayto-day basis, [including] … the counseling, relaying medical knowledge to the family, what was going on clinically, trying to deal with that in a way where she was talking in one way to [the] adults and in a different, more appropriate [for the boy’s age] way to the 17-yearold son. And I can be there to help with that process.”
The situation was resolved to the satisfaction of the mother, the son, the friends, and the providers. “It was really pretty extraordinary,” she said. “I’ve talked about that a couple of times, including at a staff meetings when we were talking about getting new hospitalists. That is something I’ve described because, really, it was very special.”
TRUE TEAMWORK
Although everyone on a multidisciplinary team can bring something to the discussion that makes the team work better, social workers and hospitalists collaborate well in painting a more comprehensive picture of the patient’s lifestyle, living habits, and needs.
“In many hospitals … there’s a pattern that develops [whereby at] some time in the morning the hospitalist and social worker will get together and talk,” says Dr. Flansbaum “The hospitalist speaks the language of the social worker and knows what to tell them and how to direct them rather than just saying, ‘the patient’s homeless or the patient needs help at home.’”
After working regularly with social workers and recognizing what they need to know, he says, “the hospitalist is more likely to say, ‘the patient has Medicaid,’ or ‘the patient has this insurance,’ [or] ‘the patient has a home-health [caregiver] four hours a day and needs six or eight hours a day,’ or ‘the patient’s going to need a subacute nursing facility.’ … I think our insights are different from voluntary physicians and our face-time with social workers is more efficient.”
Sylvia Krafcik, MSSA, LISW, with MetroHealth Medical Center, Cleveland, says hospitalists are “great to work with because they’re very dedicated to the population they’re caring for, because this is their whole responsibility; they don’t have a private caseload.”
But in her view most hospitalists are focused on patients’ medical conditions and some of them are not as tuned in to all the other aspects of the patient, such as all the psychosocial dynamics.
“A lot of them are, but some aren’t,” Krafcik says. “Especially at MetroHealth, we’re a county hospital. So many of the patients that come here are poor. A lot of them are alcoholics or drug abusers. They’re homeless. They live on the streets. They don’t have a primary doctor. They’re usually not compliant with their medications.”
“Here at Metro we have a lot of patients who have extreme social circumstances that affect their medical issues so much,” says Sara Dunson, MSW, LSW, who also works as a social worker at Metro-Health. “I think the hospitalist has greater insight into the person’s environment and all the social structures that they have at home and that are going on in their life [than other physicians might].”
But there is always room for improvement.
“We had one patient who wasn’t able to read, and he never told anybody this,” says Dunson. “And as social workers, we have more of a way of finding that kind of stuff out from patients than the doctors might. And he kept coming in and coming in and was noncompliant with his medication. We eventually determined that this was why he was noncompliant and was causing all these medical issues. The doctors finally [understood] why this gentleman kept coming in with the same problems and he wasn’t taking care of himself. It wasn’t that he didn’t want to, it was just that he was having problems reading all the medications and all the discharge paperwork, and he was too ashamed to tell anybody. [Once the social workers questioned him and got this] out in the open, we were able to get him help with that.”
The doctors focused on what he was or wasn’t doing, but they hadn’t looked at why he wasn’t adherent, explains Dunson. If hospitalists do that more often, she thinks, they could save time and get better outcomes sooner.
COMMUNICATING WITH PATIENTS AND FAMILIES
“I think where hospitalists are coming from is a whole different mindset than a physician who has mainly an office practice,” said Lingg. “The office practice comes first [for them]. Some of our physicians have huge practices in town. And they’ll visit the hospital very early in the morning or in the evening. ... So if I need something in a case like that, if there was not a hospitalist involved, it would have been separate meetings for the family with the physician … and [with] me at another time.”
To hospitalists, a social worker can serve as an important adjunct in talking to the patient and family. “For example, if [social workers] are giving bad news, they warn the physician first,” says Dr. Rajan. “If they’re going to go in and tell the patient that they’re not going to qualify for any home services, they tell the physician as well so that [the hospitalist will not later be] meeting an angry patient.” In addition, she says, “for critically ill or long-term patients, social workers [can] help family members cope. Sometimes as physicians we don’t have the time or we don’t have the resources to do that.”
But this doesn’t let doctors off the hook in regard to addressing the whole person’s needs. Especially if someone has multiple medical problems, the social worker needs to know the availability and level of support for which the family can be counted.
“Social workers will ask questions such as: Are the families involved? or Is there any family?” says Krafcik. “Do they need to go in a nursing home or do they need 24-hour care at home? Is the family able to provide that? [E]very morning we meet to have team rounds. And the [team] go[es] over every patient on the floor, and then I will ask those questions if the doctor hasn’t given me that information.”
Social workers appreciate and would like hospitalists to do more listening to the patient and family for the aspects of the history and psychosocial status that the social worker will need to know.
TEACHING POINTS
In the course of their interactions, what do hospitalists and social workers teach each other that could lead to working a case more effectively and to the greater satisfaction of all involved?
Most of those we interviewed seem to think that the greatest service hospitalists provide is to teach the social worker the medical components that go along with what the social worker does every day.
“[Social workers] get a better understanding of [whether] someone comes in with heart failure or a fall or a stroke, just by repetition and also education; they get to understand after a while what’s needed for individual medical diagnoses,” says Dr. Flansbaum.
“When I know [better] what the medical condition is,” says Krafcik, “I have an idea of how much help [the patient] would need at home and their ability to function. And I would make sure that the patient gets physical therapy or occupational therapy referral or speech therapy.”
Again, perhaps the area where the social worker most teaches the hospitalist regards available resources to solve problems over and above the purely medical. “They know the social system and the needs of different forms and eligibility and what different patients are entitled to and what the system will provide,” says Dr. Flansbaum.
Dunson believes hospitalists are perceived as being more involved in a holistic way with the patient. “I always stress that it is so important to look at the whole person and not just the medical aspects,” she says. “It’s hard for the doctor sometimes to realize that this person might not be able to afford this medication and that’s why they’re noncompliant and all the other issues. So I think is important to open up to the other aspects of a person’s life and not just the medical aspects.”
CONCLUSION
Social workers’ knowledge of medical and nonmedical resources, both locally and nationally, offer hospitalists essential information that leads to designing more appropriate and effective post-discharge plans. Hospitalists can best team with social workers by consistently keeping in mind the patient’s overall circumstances and informing their colleagues of the medical information that can help social workers do their best work. TH
Writer Andrea Sattinger will write about the effect of poor communication skills in the November issue of The Hospitalist.
HOSPITALISTS AND SOCIAL WORKERS
Both sides of the clinical care team discuss the pros and cons of working together
In these … fractious healthcare times when resources are not plentiful and the expectations of patients might be higher, like getting 24-hour care at home, sometimes it might appear that the hospitalist or [another] physician is always the bringer of bad news. A good social worker can work well with the hospitalist in … letting the patient know the realistic expectations of what the system can provide [so that] we’re not in this alone. You know, ‘the world is a nail, the hospitalist is always the hammer’ kind of thing. Social workers can be very helpful in delivering information. … A good social worker can also add some “salve” to the wounds that the patient comes in with.
Some [patients] are borderline functioning or kind of on the precipice already. They come in with this problem and all of a sudden they can’t go back to the situation they were operating in prior. Social workers’ knowledge of the social safety net … is terrific, and they help us in directing what would be the best discharge plan for this patient, [including] knowing what the insurance status is, … what resources they have in place already, what else is available. … [I]t has a lot to do with discharge and recovery and functionality, and [to find out what’s the best place for the patient. They can help us with that.
Perhaps the greatest value social workers provide for all concerned is having the storehouse of knowledge of the available resources of the community. This is probably one of the most vital things to me; they can get a patient into services or programs that I didn’t even know exist. And the resources are very different in Connecticut than … in New York [where I practiced previously]. In New York there are many resources geared toward the Hispanic community, which I haven’t seen so far in Connecticut. But Connecticut has some other great resources; the local area clinic is a fantastic one.
Patients with end-of-life situations are dealt with differently in different states, too, and I wouldn’t have known about all this if it had not been for the social worker with whom I work. I also found out that there is a free program for alcohol rehabilitation in Connecticut; that does not exist in New York. We’ve sent a lot of our patients [to that]; you know they have to be the ones to initiate the call, but if they do, then that’s actually a resource for them. I wasn’t aware of that until I worked with the social workers here.
Leadership Lessons
In more than 30 years as a healthcare industry consultant, Jack Silversin, DMD, DrPH, has watched as hospitals have evolved into complex organizations that emphasize efficiency, teamwork, and cost-effectiveness—three things absent from most medical training programs, he says.
“Doctors have been trained to be autonomous, but the new organizational structure is to be collective,” says Dr. Silversin, CEO of the Boston-based consulting firm Amicus Inc.
The changes doctors and HM groups are being asked to make are challenging their way of life and their work, Dr. Silversin says, and leading a group of independent-thinking hospitalists is no easy task.
“It’s a very challenging thing to be a leader. … It’s having the confidence and mind-set to engage people and make decisions,” says Dr. Silversin, who plans to address such issues during his daylong seminar at SHM’s Leadership Academy Sept. 14-17 in Miami.
Part of an expert faculty that teaches skills and concepts on beginner and advanced tracks, Dr. Silversin says Leadership Academy attendees learn how to define their roles and how to present their expectations to their groups.
“You go back to your hospital and see things in a different light,” he says. “You need to have the answers, but you need to balance that with relationships.”
The next Leadership Academy is Jan. 25-28 in Scottsdale, Ariz. For complete faculty bios and more information on participating, visit SHM’s events Web site.
In more than 30 years as a healthcare industry consultant, Jack Silversin, DMD, DrPH, has watched as hospitals have evolved into complex organizations that emphasize efficiency, teamwork, and cost-effectiveness—three things absent from most medical training programs, he says.
“Doctors have been trained to be autonomous, but the new organizational structure is to be collective,” says Dr. Silversin, CEO of the Boston-based consulting firm Amicus Inc.
The changes doctors and HM groups are being asked to make are challenging their way of life and their work, Dr. Silversin says, and leading a group of independent-thinking hospitalists is no easy task.
“It’s a very challenging thing to be a leader. … It’s having the confidence and mind-set to engage people and make decisions,” says Dr. Silversin, who plans to address such issues during his daylong seminar at SHM’s Leadership Academy Sept. 14-17 in Miami.
Part of an expert faculty that teaches skills and concepts on beginner and advanced tracks, Dr. Silversin says Leadership Academy attendees learn how to define their roles and how to present their expectations to their groups.
“You go back to your hospital and see things in a different light,” he says. “You need to have the answers, but you need to balance that with relationships.”
The next Leadership Academy is Jan. 25-28 in Scottsdale, Ariz. For complete faculty bios and more information on participating, visit SHM’s events Web site.
In more than 30 years as a healthcare industry consultant, Jack Silversin, DMD, DrPH, has watched as hospitals have evolved into complex organizations that emphasize efficiency, teamwork, and cost-effectiveness—three things absent from most medical training programs, he says.
“Doctors have been trained to be autonomous, but the new organizational structure is to be collective,” says Dr. Silversin, CEO of the Boston-based consulting firm Amicus Inc.
The changes doctors and HM groups are being asked to make are challenging their way of life and their work, Dr. Silversin says, and leading a group of independent-thinking hospitalists is no easy task.
“It’s a very challenging thing to be a leader. … It’s having the confidence and mind-set to engage people and make decisions,” says Dr. Silversin, who plans to address such issues during his daylong seminar at SHM’s Leadership Academy Sept. 14-17 in Miami.
Part of an expert faculty that teaches skills and concepts on beginner and advanced tracks, Dr. Silversin says Leadership Academy attendees learn how to define their roles and how to present their expectations to their groups.
“You go back to your hospital and see things in a different light,” he says. “You need to have the answers, but you need to balance that with relationships.”
The next Leadership Academy is Jan. 25-28 in Scottsdale, Ariz. For complete faculty bios and more information on participating, visit SHM’s events Web site.
The Happiness Factor
HM groups are built—in part—on the theory of work-life balance. But what about work-work balance?
A study published this spring found that faculty physicians at academic medical centers might be more satisfied if they spend at least one day per week on the part of their job that is most meaningful to them (Arch Intern Med, 2009;169(10):990-995).
“The notion of ‘job fit’ is clearly important,” says Noah Harris, MD, FHM, a hospitalist at Presbyterian Hospital in Albuquerque, N.M., and a member of SHM’s Career Satisfaction Task Force. “Since most physicians are drawn to medicine for the notion of patient care, the other activities may be troublesome for many of us.”
To improve employees’ job satisfaction, Dr. Harris and Chad Whelan, MD, FHM, chair of SHM’s career task force, suggest HM leaders do the following:
- Understand what your group has to offer. Let physicians explore parts of the practice unfamiliar to them—and if they find something they have a passion for, encourage it.
- Identify hospitalists who are at risk for burnout and guide them to potential opportunities. Be proactive before dissatisfaction sets in.
- Don’t push people into leadership roles they don’t want. Some people want clinical posts, while others want to be medical directors who meet with administration daily.
- Recognize the importance of flexibility. As HM groups evolve, there are chances to offer new schedules or build in new clinical and nonclinical initiatives.
- Support staff members via mentoring and professional development to make them feel as if they’re doing work they want to do.
“A common mistake, though, is to simply pay people a stipend for doing more,” says Dr. Whelan, associate professor of medicine and director of the division of hospital medicine at Loyola University Chicago Stritch School of Medicine. “If their professional time is already fully taken with other activities, a stipend will not provide time to appropriately pursue those meaningful activities.”
HM groups are built—in part—on the theory of work-life balance. But what about work-work balance?
A study published this spring found that faculty physicians at academic medical centers might be more satisfied if they spend at least one day per week on the part of their job that is most meaningful to them (Arch Intern Med, 2009;169(10):990-995).
“The notion of ‘job fit’ is clearly important,” says Noah Harris, MD, FHM, a hospitalist at Presbyterian Hospital in Albuquerque, N.M., and a member of SHM’s Career Satisfaction Task Force. “Since most physicians are drawn to medicine for the notion of patient care, the other activities may be troublesome for many of us.”
To improve employees’ job satisfaction, Dr. Harris and Chad Whelan, MD, FHM, chair of SHM’s career task force, suggest HM leaders do the following:
- Understand what your group has to offer. Let physicians explore parts of the practice unfamiliar to them—and if they find something they have a passion for, encourage it.
- Identify hospitalists who are at risk for burnout and guide them to potential opportunities. Be proactive before dissatisfaction sets in.
- Don’t push people into leadership roles they don’t want. Some people want clinical posts, while others want to be medical directors who meet with administration daily.
- Recognize the importance of flexibility. As HM groups evolve, there are chances to offer new schedules or build in new clinical and nonclinical initiatives.
- Support staff members via mentoring and professional development to make them feel as if they’re doing work they want to do.
“A common mistake, though, is to simply pay people a stipend for doing more,” says Dr. Whelan, associate professor of medicine and director of the division of hospital medicine at Loyola University Chicago Stritch School of Medicine. “If their professional time is already fully taken with other activities, a stipend will not provide time to appropriately pursue those meaningful activities.”
HM groups are built—in part—on the theory of work-life balance. But what about work-work balance?
A study published this spring found that faculty physicians at academic medical centers might be more satisfied if they spend at least one day per week on the part of their job that is most meaningful to them (Arch Intern Med, 2009;169(10):990-995).
“The notion of ‘job fit’ is clearly important,” says Noah Harris, MD, FHM, a hospitalist at Presbyterian Hospital in Albuquerque, N.M., and a member of SHM’s Career Satisfaction Task Force. “Since most physicians are drawn to medicine for the notion of patient care, the other activities may be troublesome for many of us.”
To improve employees’ job satisfaction, Dr. Harris and Chad Whelan, MD, FHM, chair of SHM’s career task force, suggest HM leaders do the following:
- Understand what your group has to offer. Let physicians explore parts of the practice unfamiliar to them—and if they find something they have a passion for, encourage it.
- Identify hospitalists who are at risk for burnout and guide them to potential opportunities. Be proactive before dissatisfaction sets in.
- Don’t push people into leadership roles they don’t want. Some people want clinical posts, while others want to be medical directors who meet with administration daily.
- Recognize the importance of flexibility. As HM groups evolve, there are chances to offer new schedules or build in new clinical and nonclinical initiatives.
- Support staff members via mentoring and professional development to make them feel as if they’re doing work they want to do.
“A common mistake, though, is to simply pay people a stipend for doing more,” says Dr. Whelan, associate professor of medicine and director of the division of hospital medicine at Loyola University Chicago Stritch School of Medicine. “If their professional time is already fully taken with other activities, a stipend will not provide time to appropriately pursue those meaningful activities.”
Antibiotics for MDR Pathogens
Case 1
A 53‐year‐old woman with a history of hemodialysis‐dependent end‐stage renal disease presents with left lower extremity pain and redness for the past 3 days. On physical examination, her temperature is 102.3F. Erythema, induration, and warmth are noted over her left lower leg and foot. Her history is remarkable for a line‐related bloodstream infection due to methicillin‐resistant Staphylococcus aureus (MRSA) 4 weeks ago. The infected line was removed and replaced with a right‐sided subclavian catheter. You note that the new line site is clean, not erythematous, and not tender. In the emergency department, the patient receives a dose of vancomycin for presumed MRSA cellulitis. Your patient wants to know if there are alternative agents for her infection so she does not require hospitalization.
Unfortunately, MRSA has become commonplace to the hospital setting. Among intensive care units in 2003, 64.4% of healthcare‐associated Staphylococcus aureus infections were caused by MRSA, compared with only 35.9% in 1992; a 3.1% increase per year.1, 2 Increased MRSA rates are not without consequence; a recent review suggests that MRSA infections kill nearly 19,000 hospitalized American patients annually.3 Of note, MRSA infection rates have also increased among previously healthy individuals. These community‐associated isolates (CA‐MRSA) often manifest as pyogenic skin and soft‐tissue infections (SSTIs). In a recent multicenter study, CA‐MRSA accounted for 59% of SSTIs among patients presenting to emergency rooms in the United States.4 In cases of SSTI, oral agents such as clindamycin, doxycycline, and trimethoprim‐sulfamethoxazole have proven successful. For invasive MRSA, vancomycin is still considered the standard treatment; however, several alternatives have emerged in recent years. The advantages and disadvantages of linezolid, daptomycin, tigecycline, and dalbavancin in the treatment of MRSA are described below.
Linezolid
Linezolid (Zyvox), an oxazolidinone approved in 2000, has been touted for its oral bioavailability, twice‐daily dosing, gram‐positive coverage, and unique mechanism of action. Like several other antimicrobials, linezolid inhibits bacterial protein synthesis. The drug binds to the 50S ribosomal subunit near its site of interaction with the 30S subunit, preventing formation of the 70S initiation complex.5 This site of action on the 50S subunit is unique to linezolid; as a result, cross‐resistance between linezolid and other antimicrobials that act at the 50S subunit (eg, chloramphenicol, macrolides, aminoglycosides, and tetracycline) does not occur.6
The oxazolidinones have excellent bacteriostatic activity against all pathogenic gram‐positive bacteria. The U.S. Food and Drug Administration (FDA) approved linezolid for the treatment of serious infections due to vancomycin‐resistant enterococci (VRE), including bacteremia, complicated skin and soft‐tissue infections (cSSTIs) due to Staphylococcus aureus (including MRSA), and nosocomial pneumonia due to Staphylococcus aureus (including MRSA) or penicillin‐susceptible Streptococcus pneumoniae (Table 1).
| Activity | Agent | FDA‐Approved Indications | Limitations in Use | Side Effects |
|---|---|---|---|---|
| ||||
| Gram‐positive | Daptomycin | cSSTIs; MSSA/MRSA bacteremia; MSSA/MRSA endocarditis | Not indicated for pneumonia (inhibited by pulmonary surfactant) | Reversible myopathy may be exacerbated by use with other medications |
| Quinupristin‐dalfopristin | Vancomycin‐resistant E. faecium; group A streptococci or MSSA cSSTIs | Myalgias and arthralgias; infusion site reaction;* thrombophlebitis;* liver enzyme elevation; inhibition of cytochrome p450 34a | ||
| Linezolid | Serious infections due to VRE; MSSA/MRSA cSSTIs; MSSA/MRSA nosocomial pneumonia; pneumonia due to penicillin‐sensitive S. pneumoniae | Not indicated for catheter‐related bloodstream infections or catheter site infections | Myelosuppression; serotonin syndrome; tyramine reaction; peripheral neuropathy; optic neuropathy | |
| Dalbavancin | Approval pending for cSSTIs | Not indicated for pneumonia bone and joint infection | Unknown | |
| Gram‐negative | Colistin | Gram‐negative bacteria that have demonstrated sensitivity to the drug | Not indicated for Proteus spp, Providencia spp, or Serratia spp | Acute tubular necrosis; neurotoxicity∥; bronchospasm |
| Gram‐positive and Gram‐negative | Ertapenem | Complicated intraabdominal infections#; cSSTIs; acute pelvic infections; complicated UTIs; community‐acquired pneumonia; prophylaxis of SSI following colorectal surgery in adult patients | Not indicated for Pseudomonas, Acinetobacter, S. maltophilia | Cross‐reactivity with penicillin; cross‐reactivity with cephalosporins; caution use if history of seizures |
| Doripenem | Complicated intraabdominal infections# and complicated UTIs, including pyelonephritis | Cross‐reactivity with penicillin; cross‐reactivity with cephalosporins; caution use if history of seizures | ||
| Tigecycline | cSSTIs (including those due to MRSA) complicated intraabdominal infections# | Nausea and vomiting; tooth discoloration in children | ||
In retrospective analyses of SSTIs due to MRSA, linezolid was as effective as vancomycin, resulting in higher clinical cure rates and shorter hospitalizations.7 As a result, linezolid has established a role in the treatment of community‐acquired MRSA SSTIs. Evidence limited to case reports and case series suggest that linezolid may also have a role in the treatment of bone and joint infections. In these cases, linezolid was often used because treatment with other agents had failed, the administration of other antibiotics was not indicated due to resistance patterns, the patient refused intravenous therapy, or the patient did not tolerate vancomycin. When such conditions exist, linezolid may be a consideration in cases of osteomyelitis or prosthetic joint infection.8
Potential side effects of linezolid may limit its use, especially for patients who require prolonged therapy (Table 1). Of note, as a reversible, relatively weak nonselective inhibitor of monoamine oxidase, linezolid may interact with adrenergic and serotonergic agents. Concomitant of a serotonin agent such as a selective serotonin‐reuptake inhibitor (SSRI) and linezolid should be approached with caution. Subsequent serotonin syndrome is characterized by autonomic dysfunction (eg, diaphoresis, tachycardia, hypertension) and neuromuscular hyperactivity (eg, muscle rigidity, clonus, hyperreflexia). Though infrequent, cases of reversible myelosuppression have been reported with linezolid use.9 Patients who will receive this drug for more than 2 weeks should be monitored for myelosuppression with a weekly complete blood count. Isolated reports suggest that the prolonged administration of linezolid (>28 days) may be associated with peripheral neuropathy and optic neuropathy. While prompt discontinuation of the drug often results in resolution of symptoms, peripheral or optic nerve injury can be permanent. The mechanism of injury is unclear, though mitochondrial toxicity is suspected.10
Daptomycin
Daptomycin (Cubicin), a cyclic lipopeptide, was discovered in the early 1980s, but skeletal muscle toxicity led to the discontinuation of early clinical trials. When a change from twice‐daily to once‐daily dosing in 2003 resulted in fewer adverse events, the FDA approved daptomycin to treat complicated skin and skin‐structure infections.11 Daptomycin binds to the cell membrane via a calcium‐dependent process, eventually disrupting the cell membrane potential. The bactericidal effect is limited to gram‐positive organisms.12
Daptomycin is effective against almost all gram‐positive organisms including methicillin‐susceptible Staphylococcus aureus (MSSA), MRSA, and VRE.12 As a result, it has FDA approval for the treatment of cSSTIs. While beta‐lactams remain the standard of care for MSSA bacteremia, daptomycin has FDA approval for bloodstream infections and right‐sided endocarditis due to MSSA or MRSA (Table 1).13 Daptomycin has poor penetration into alveolar fluid14 and is inhibited by pulmonary surfactants; as a consequence, it is not indicated for patients with pneumonia.15
Of note, daptomycin is mainly excreted via the kidneys and should be dose‐adjusted for patients with a creatinine clearance 30 mL/minute. A reversible myopathy may occur with daptomycin, requiring intermittent monitoring of creatinine kinase if prolonged use is anticipated. Caution should be used with the coadministration of medications that can also cause a myopathy, such as statins.
Tigecycline
Tigecycline (Tygacil) was approved for use by the FDA in 2005. The first in a class of new tetracycline analogs, the glycylcyclines, tigecycline is notable for its activity against several multidrug‐resistant (MDR) organisms, including MRSA, VRE, and Enterobacteriaceae carrying extended‐spectrum beta‐lactamases (ESBL). Tigecycline impairs bacterial protein synthesis by binding to the 30S ribosomal subunit. Due to steric hindrance from an N‐alkyl‐glycylamido group at position 9, tigecycline cannot be removed by most bacterial efflux mechanisms.16
Tigecycline has been approved for the therapy of cSSTIs, including those due to MSSA and MRSA. In a pooled analysis of 2 international, multicenter, phase III randomized, double‐blind trials, tigecycline was not inferior to vancomycin plus aztreonam in the treatment of cSSTIs. Of note, MRSA eradication rates were similar between patients treated with tigecycline and vancomycin plus aztreonam (78.1% and 75.8%, respectively).17
Dalbavancin
Dalbavancin (Zeven), a new, semisynthetic lipoglycopeptide, was approved by the FDA in late 2007; however, it has not been cleared for marketing. Though dalbavancin is derived from teicoplanin, its lipophilic anchor to the bacterial cell membrane makes the drug more potent than its predecessor. Dalbavancin interferes with bacterial cell wall synthesis by binding to the C‐terminal D‐alanyl‐D alanine of the growing peptidoglycan chains.18 Enhanced pharmacokinetic properties of dalbavancin (half‐life 149‐250 hours) allow it to be dosed once‐weekly, a novel concept in antimicrobial use.19
Like other glycopeptides, dalbavancin maintains in vitro activity against most gram‐positive aerobic organisms, including MRSA and penicillin‐susceptible and penicillin‐resistant strains of Streptococcus pneumoniae. Notably, when compared to vancomycin in vitro, the agent is more active against Enterococcus faecium and Enterococcus faecalis isolates. In a recent phase III double‐blind trial, dalbavancin was compared to linezolid for the treatment of cSSTIs. Dalbavancin was not inferior to linezolid (clinical success rate 90% vs. 92%). Of note, 51% of study patients with SSTI had infection due to MRSA. Microbiological response to dalbavancin paralleled the clinical success rate; MRSA eradication rates after dalbavancin and linezolid were 91% and 89%, respectively.20
Given its once‐weekly dosing, dalbavancin may be an attractive agent in the outpatient treatment of gram‐positive bacteremia. In a phase II study, dalbavancin administered as a single 1‐g dose, followed by a 500‐mg dose 1 week later, was comparable to 14 days of vancomycin for the treatment of catheter‐related bloodstream infections (CRBSI) due to coagulase‐negative staphylococci or S. aureus (including MRSA).21 Phase III studies are underway. At present, there is no evidence to support the use of dalbavancin for the treatment of pneumonia or bone and joint infections.
Despite the administration of vancomycin, the patient continues to experience fever and chills. Blood cultures drawn in the emergency department are now growing Enterococcus species. You review the patient's medical record and notice that she was colonized with VRE on a prior admission. You consider the antibiotic options for serious infections due to VRE.
Though rates of VRE have remained fairly stable in recent years,22 the pathogen continues to present a challenge to hospital epidemiologists. A national survey in 2004 suggested that nearly 30% of enterococci in U.S. intensive care units display vancomycin resistance.1 Additional U.S. surveillance data reveals that VRE accounts for 10% to 26% of enterococci hospital‐wide.23, 24 In 2005, a meta‐analysis noted that bloodstream infections due to VRE resulted in higher mortality rates than those due to vancomycin‐susceptible enterococci.25 This discrepancy is most evident among neutropenia patients.26 Unfortunately, the options for the treatment of serious infections due to VRE are limited. The advantages and disadvantages of linezolid, quinupristin‐dalfopristin, tigecycline, and daptomycin in the treatment for VRE are discussed below.
Linezolid
Currently, linezolid is the only oral drug that is FDA‐approved for the treatment of infections due to VRE, including bacteremia. Notably, linezolid therapy resulted in the cure of 77% of 22 cases of vancomycin‐resistant enterococcal endocarditis.27 Current guidelines by the Infectious Disease Society of America (IDSA) support the use of linezolid in cases of endocarditis due to ampicillin‐resistant and vancomycin‐resistant Enterococcus faecium.28 Unfortunately, recent reports highlight the emergence of linezolid‐resistant VRE,29 suggesting use of this drug should be limited to circumstances in which other alternatives do not exist.
Quinupristin‐Dalfopristin
Quinupristin‐dalfopristin (Synercid) was approved by the FDA in 1999. It is used in the treatment of infections caused by gram‐positive organisms and is a combination of 2 semisynthetic pristinamycin derivatives. They diffuse into bacteria and bind to different areas on the 50S ribosomal subunit, thereby inhibiting protein synthesis. Individually, quinupristin and dalfopristin are bacteriostatic but together they are bactericidal.30
Quinupristin‐dalfopristin has activity against Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, gram‐positive anaerobes, and vancomycin‐sensitive and resistant Enterococcus faecium. It has little activity against Enterococcus faecalis.31 FDA‐approved uses of quinupristin‐dalfopristin are limited, but include the treatment of serious infections caused by vancomycin‐resistant E. faecium (VREF).32 In a study of 396 patients with VREF the clinical success rate of quinupristin‐dalfopristin was 73.6%.33 The drug also has FDA approval for the use in cSSTIs due to group A streptococci or MSSA.32 The use of this agent is limited due to its toxicity profile. In cases of serious VRE‐related infection, quinupristin‐dalfopristin is often only utilized if linezolid cannot be tolerated.
Daptomycin
In vitro studies suggest that daptomycin is active against enterococci, including vancomycin‐resistant isolates.34 However, clinical data on the use of this agent in the treatment of infections due to VRE are lacking. FDA approval for the use of daptomycin in cSSTI included the treatment of 45 patients infected with Enterococcus faecalis.13 In addition, several reports have detailed the successful treatment of VRE bloodstream infections with daptomycin,35, 36 including a case series of VRE endocarditis.37 To determine the role of this agent in the treatment of invasive infections due to VRE, further study is needed.
You decide to discontinue vancomycin and administer linezolid. The patient's vascular catheter is removed; catheter‐tip cultures grow >1000 colonies of VRE. Blood cultures the following day are negative and a new catheter is placed. You ask the patient to continue oral linezolid to complete a 2‐week course. A review of her medication list reveals that she is not taking SSRIs or monoamine oxidase inhibitors (MAOIs).
While linezolid has retained its FDA indication for VRE bacteremia, empiric use in suspected cases of CRBSI or catheter site infection is not advised. In an open‐label trial among seriously ill patients with intravascular catheter‐related infections, linezolid use was associated with a higher mortality when compared to vancomycin/oxacillin. Interestingly, mortality among linezolid‐treated patients included those with CRBSI due to gram‐negative pathogens, due to both gram‐negative and gram‐positive pathogens, or due to an identifiable pathogen; mortality rates did not differ among patients with gram‐positive infections only.38
Case 2
A 27‐year‐old male with a history of T10 paraplegia following a motor vehicle accident presents with abdominal pain, fever, and chills. He notes that he experiences these symptoms when he has a urinary tract infection (UTI), a frequent complication of his chronic indwelling suprapubic catheter. You review his medical record and notice that he has had prior UTIs with multiple gram‐negative rods over the past 2 years, including MDR Pseudomonas and Acinetobacter. When his urine culture grows >100,000 colonies of gram‐negative rods, you initiate meropenem and consider the options for treatment of these MDR pathogens.
According to national U.S. surveillance in 2001, 22% of Pseudomonas aeruginosa were resistant to imipenem, an increase of 32% from 1997.39 More alarming is the recent development of MDR P. aeruginosa, a pathogen resistant not only to the beta‐lactams (including the carbapenems) but to the fluoroquinolones and aminoglycosides as well.40 MDR P. aeruginosa is virulent, and has been associated with higher rates of mortality, longer hospital stays, and greater cost.41
Already equipped with intrinsic resistance to the aminopenicillins and first‐generation and second‐generation cephalosporins, A. baumannii has gained recent notoriety with acquired resistance to beta‐lactams, aminoglycosides, fluoroquinolones, and tetracyclines. Most notably, carbapenem‐resistant A. baumannii has emerged due to enzymes capable of hydrolyzing imipenem. Like MDR P. aeruginosa, MDR A. baumannii infection has led to longer hospital stays42 and increased patient mortality43 when compared to infections with more susceptible strains.
Therapeutic options for these MDR gram‐negative pathogens remain limited, but the advent of doripenem and the return of colistin may play a role in treatment. The use of these 2 agents and tigecycline in the treatment of MDR P. aeruginosa and/or A. baumannii are described below.
Doripenem
In October 2007, the FDA approved the use of doripenem (Doribax), a much‐anticipated carbapenem. In structure, doripenem resembles meropenem and does not require a renal dehydropeptidase I inhibitor (eg, cilastatin).44 Similar to other beta‐lactams, doripenem binds to penicillin‐binding proteins (PBPs), inhibiting PBP‐directed cell wall synthesis.
Like imipenem and meropenem, doripenem has broad‐spectrum antimicrobial activity. It demonstrates in vitro activity against most gram‐positive pathogens including MSSA and ampicillin‐sensitive enterococci. Doripenem also has in vitro activity against most gram‐negative pathogens (including ESBL‐producing Enterobacteriaceae) and most anaerobes, including Bacteriodes fragilis. Most notably, when compared to other carbapenems, doripenem has demonstrated better in vitro activity against Pseudomonas aeruginosa.45 However, clinical implications of this in vitro activity are unclear.
When compared to meropenem or levofloxacin for the treatment of complicated UTIs, doripenem is an effective alternative. Clinical response rates among affected patients were 95% to 96% with doripenem, 89% with meropenem, and 90% with levofloxacin.46, 47 Doripenem was not inferior to meropenem in patients with serious lower respiratory tract infections, and comparable to imipenem‐cilastin and pipercillin‐tazobactam for the treatment of nosocomial or ventilator‐associated pneumonia (VAP).48, 49 Finally, for the treatment of complicated intraabdominal infections, doripenem was not inferior to meropenem; both drugs achieved microbiologic cure rates of >84%.50
Currently, doripenem is FDA‐approved for the treatment of complicated intraabdominal infections (eg, appendicitis, pancreatitis, cholecystitis, peritonitis) and complicated lower UTIs or pyelonephritis (Table 1). Given its expanded spectrum of activity, use of doripenem should be limited to circumstances in which a MDR pathogen is highly suspected or confirmed.
Colistin
Colistin (Coly‐Mycin M) falls within the family of polymyxin antibiotics, which were discovered in 1947. Colistin has been available for almost 50 years for the treatment of infections caused by gram‐negative bacteria, including Pseudomonas spp. However, early use of colistin was associated with significant nephrotoxicity. Its use decreased markedly with the advent of new antibiotics that had the same antimicrobial spectrum and a better side effect profile. With the emergence of MDR gram‐negative bacteria, colistin has returned to limited clinical use.51 As a polymyxin, colistin is a cell membrane detergent. It disrupts the cell membrane, causing leakage of bacterial cell content and ultimately cell death.52
Colistin has bactericidal activity against most gram‐negative bacteria including Acinetobacter spp, and members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs.53 Colistin is not active against several predominant gram‐negative pathogens including Proteus spp, Providencia spp, or Serratia spp (Table 1).
In 2007, several studies suggested that colistin monotherapy was effective for patients with VAP due to MDR P. aeruginosa or A. baumannii isolate.54, 55 A third trial that year suggested that colistin may have a role in the treatment of MDR P. aeruginosa among neutropenic patients. In that study, infected patients receiving colistin monotherapy experienced higher rates of clinical and microbiologic response than those receiving other antipseudomonal agents (eg, beta‐lactams or fluoroquinolones if active against the isolate).56 While uncontrolled studies suggest that the use of colistin in combination with other antimicrobials (including carbapenems, ampicillin‐sulbactam, aminoglycosides, and rifampin) may have some success in the treatment of VAP due to MDR A. baumannii,57, 58 further trials are needed.
Currently, colistin has FDA approval only for the treatment of acute infections due to gram‐negative bacteria that have demonstrated susceptibility to the drug and is therefore administered on a case by case basis. Although it has been used via the inhalation route to treat infections in cystic fibrosis patients, colistin does not have FDA approval for this indication.
Tigecycline
Tigecycline is approved for the treatment of complicated intraabdominal infections based on the results of 2 international, multicenter, phase III, randomized, double‐blind trials. In this pooled analysis, tigecycline was as effective and as safe as imipenem/cilastatin. Notably, study patients were not severely ill (baseline APACHE II score of 6.0).59 FDA approval suggests tigecycline use be focused on intraabdominal infections due to members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs, vancomycin‐sensitive enterococci, and/or MSSA. Notably, tigecycline lacks significant in vitro activity against Pseudomonas spp, Proteus spp, or Providencia spp. It has demonstrated in vitro activity against MDR strains of Acinetobacter spp (Table 1).
Given its bacteriostatic activity, tigecycline's effectiveness in the treatment bacteremia is unclear.
In addition, as no published studies have addressed its activity among seriously ill patients, tigecycline is considered a second‐line or third‐line agent for SSTI and complicated intraabdominal infections. Evidence for use of tigecycline for the treatment of UTIs is lacking and, as a rule, its use should be limited to scenarios in which alternatives for the proven or suspected pathogens do not exist.
The urine isolate is identified as Escherichia coli. You review the susceptibility profile and determine that this isolate is an ESBL‐producing strain. In addition, the patient's isolate demonstrates resistance to the fluoroquinolones and trimethoprim‐sulfamethoxazole. You consider other options for treatment of this ESBL‐producing E. coli.
According to national surveillance data, more than 20% of Klebsiella isolates in U.S. intensive care units produced ESBLs in 2003, a 47% increase when compared to 1998.39 Bloodstream infections due to ESBL‐producing isolates have led to increased length of hospital stay,60, 61 increased hospital costs,4 improper antibiotic use,5 and, most notably, increased mortality.61‐63 Of concern, ESBLs have been demonstrated within community Enterobacteriaceae isolates, most notably due to CTX‐M beta‐lactamase production among E. coli. In addition to ESBL production, these community E. coli isolates tend to express fluoroquinolone and trimethoprim‐sulfamethoxazole resistance.64 Carbapenems remain the mainstay of therapy for serious infections due to ESBL‐producing organisms. The once‐daily dosing of ertapenem makes this agent an attractive alternative for outpatient management.
Ertapenem
Ertapenem (Invanz) obtained FDA approval for use in the United States in 2001 and in the European Union in 2002.65 Similar to doripenem, ertapenem blocks cell wall synthesis by binding to specific penicillin‐binding proteins (PBPs).
Ertapenem has activity against numerous gram‐positive and gram‐negative bacteria as well as some anaerobic microorganisms. The FDA‐approved indications include complicated intraabdominal infections, cSSTIs, acute pelvic infections, complicated UTIs, and community‐acquired pneumonias (Table 1).66 Of note, in contrast to other carabapenems, ertapenem does not have activity against Pseudomonas aeruginosa or Acinetobacter spp.67
Ertapenem is approved as a single daily dose of 1 g and can be administered intravenously or intramuscularly. Changes in dosing must also be considered for critically ill patients. When administered to patients with VAP, ertapenem achieved a lower maximum concentration and area under the curve.68 In such patients, it is recommended that the dosage interval be decreased or that a continuous infusion of ertapenem be administered.
The patient's symptoms improve on meropenem. A peripherally‐inserted central catheter is placed for the administration of intravenous antibiotics at home. You prescribe ertapenem (1 g/day) for the remainder of a 14‐day course.
Conclusions
MDR bacteria continue to present a clinical challenge to hospitalists. Proper treatment of patients infected with these organisms is necessary, as inappropriate antibiotic use for MDR bacterial infections has been associated with longer hospital stays, greater cost, and, in some cases, increased mortality. Unfortunately, antibiotic production and development has declined steadily in the past 25 years. To minimize the rate of antimicrobial resistance, physicians must take care to prescribe antibiotics appropriately. While these promising new agents for resistant gram‐positive and gram‐negative infections may aid in battling MDR infections, these antibiotics must be used judiciously to maintain their clinical utility. Hospitalists will continue to play an important role in ensuring that hospitalized patients receive the most effective antimicrobial therapy to both treat the infection and prevent the development of resistance.
- National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004.Am J Infect Control.2004;32:470–485.
- ,,,,,.Changes in the epidemiology of methicillin‐resistant Staphylococcus aureus in intensive care units in US hospitals, 1992‐2003.Clin Infect Dis.2006;42:389–391.
- ,,, et al.Invasive methicillin‐resistant Staphylococcus aureus infections in the United States.JAMA.2007;298:1763–1771.
- ,,,,,.Emergence of community‐acquired methicillin‐resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft tissue infections.Ann Intern Med.2006;144:309–317.
- ,,,.The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria.Antimicrob Agents Chemother.1998;42:3251–3255.
- ,.Activity of linezolid against gram‐positive cocci possessing genes conferring resistance to protein synthesis inhibitors.J Antimicrob Chemother.2000;45:797–802.
- ,,.Clinical and economic outcomes of oral linezolid versus intravenous vancomycin in the treatment of MRSA‐complicated, lower‐extremity skin and soft‐tissue infections caused by methicillin‐resistant Staphylococcus aureus.Am J Surg.2005;189:425–428.
- ,,,.Linezolid for the treatment of adults with bone and joint infections.Intern J Antimicrob Agents.2007;29:233–239.
- .Efficacy and safety of linezolid in the treatment of skin and soft tissue infections.Eur J Clin Microbiol Infect Dis.2002;21:491–498.
- ,,.Linezolid‐associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome.Pharmacotherapy.2007;27(8):1189–1197.
- ,.Development of daptomycin for gram‐positive infections.J Antimicrob Chemother.2000;46(4):523–526.
- .Daptomycin and tigecycline: a review of clinical efficacy in the antimicrobial era.Expert Opin Pharmacother.2007;8(14):2279–2292.
- ,,, et al.Daptomycin verses standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.N Engl J Med.2006:355(7):653–665.
- .Lipopeptides, focusing on daptomycin, for the treatment of gram‐positive infections.Expert Opin Invest Drugs.2004;13:1159–1169.
- .Alternatives to vancomycin for the treatment of methicillin‐resistant Staphylococcus aureus infections.Clin Infect Dis.2007;45(suppl 3):S184–S190.
- .Tigecycline: a new glycylcycline for treatment of serious infections.Clin Infect Dis.2005;41(suppl 5):S303–S314.
- ,,, et al.The efficacy and safety of tigecycline in the treatment of skin and skin‐structure infections: results of 2 double‐blind phase 3 comparison studies with vancomycin‐aztreonam.Clin Infect Dis.2005;41(suppl 5):S341–S353.
- ,.Origin, structure, and activity in vitro and in vivo of dalbavancin.J Antimicrob Chemother2005;55(suppl S2):ii15–ii20.
- ,.Dalbavancin: a novel lipoglycopeptide antibacterial.Pharmacotherapy2006;26:908–918.
- ,,, et al.Randomized, double‐blind comparison of a once‐weekly dalbavancin versus twice‐daily linezolid therapy for the treatment of complicated skin and skin structure infections.Clin Infect Dis.2005;41:1407–1415.
- ,,, et al.Efficacy and safety of weekly dalbavancin therapy for catheter‐related bloodstream infection caused by gram‐positive pathogens.Clin Infect Dis.2005;40:374–380.
- ,.Vancomycin‐resistant staphylococci and enterococci: epidemiology and control.Curr Opin Infect Dis.2005;18:300–305.
- National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992‐June 2001, issued August 2001.Am J Infect Control.2001;29:404–421.
- ,,,,, et al.Antimicrobial resistance trends and outbreak frequency in United States hospitals.Clin Infect Dis.2004;38:78–85.
- ,,,.Comparison of mortality associated with vancomycin‐resistant and vancomycin‐susceptible enterococcal bloodstream infections: a meta‐analysis.Clin Infect Dis.2005;41:327–333.
- ,.Impact of vancomycin resistance on mortality among patients with neutropenia and enterococcal bloodstream infection.J Infect Dis.2005;191(4):588–595.
- ,,,,,.Linezolid for the treatment of multidrug‐resistant gram positive infections: experience from a compassionate‐use program.Clin Infect Dis.2003;36:159–168.
- ,,, et al.Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America.Circulation.2005;111(23):e394–e434.
- ,,.Nosocomial spread of linezolid‐resistant, vancomycin‐resistant Enterococcus faecium.N Engl J Med.2002;346:867–869.
- ,.Novel antibacterial agents for skin and skin structure infections.J Am Acad Dermatol.2004;50(3):331–340.
- ,,.New antimicrobial agents as therapy for resistant gram‐positive cocci.Eur J Clin Microbiol Infect Dis.2008;27(1):3–15.
- .Quinupristin‐dalfopristin and linezolid: evidence and opinion.Clin Infect Dis.2003;36(4):473–481.
- ,,,,,.The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin‐resistant Enterococcus faecium. Synercid Emergency‐Use Study Group.J Antimicrob Chemother.1999:44(2):251–261.
- ,,.Evaluation of the in vitro activity of daptomycin against 19615 clinical isolates of gram‐positive cocci collected in North American hospitals (2002‐2005).Diagn Microbiol Infect Dis.2007;57(4):459–465.
- ,,,,.Daptomycin in the treatment of vancomycin‐resistant Enterococcus faecium bacteremia in neutropenic patients.J Infect.2007;54(6):567–571.
- ,,,,.Daptomycin for the treatment of vancomycin resistant Enterococcus faecium bacteremia.Scand J Infect Dis.2006;38:290–292.
- ,,.Daptomycin for the treatment of gram‐positive bacteremia and infective endocarditis: a retrospective case series of 31 patients.Pharmacotherapy.2006;26(3):347–352.
- Pfizer Pharmacia and Upjohn Company. United States Pharmacopeia. Zyvox. Available at: http://media.pfizer.com/files/products/uspi_zyvox.pdf. Accessed April 2009.
- NNIS System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2003, issued August 2003.Am J Infect Control.2003;31(8):481–498.
- .Resistance in nonfermenting gram‐negative bacteria: multidrug resistance to the maximum.Am J Med.2006;119:S29–S36.
- ,,, et al.Emergence of antibiotic‐resistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents.Antimicrob Agents Chemother.1999;43(6):1379–1382.
- ,,, et al.Multidrug‐resistant Acinetobacter infection mortality rate and length of hospitalization.Emerg Infect Dis.2007;13:97–103.
- ,,, et al.Bloodstream infections due to Acinetobacter spp: epidemiology, risk factors, and impact of multi‐drug resistance.Eur J Clin Microbiol Infect Dis.2008;27(7):607–612.
- ,,,,.Doripenem (S‐4661), a novel carbapenem: comparative activity against contemporary pathogens including bactericidal action and preliminary in vitro methods evaluation.J Antimicrob Chemother.2004;54:144–154.
- ,,.Antimicrobial activity of doripenem (S‐4661): a global surveillance report.Clin Microbiol Infect.2005;11:974–984.
- ,,, et al.Intravenous therapy with. doripenem versus levofloxacin with an option for oral step‐down therapy in the treatment of complicated urinary tract infections and pyelonephritis. 17th European Congress of Clinical Microbiology and Infectious Diseases and the 25th International Congress of Chemotherapy. Munich, Germany. March 31‐April 3, 2007. Abstract no. 833 plus poster.
- .New uses for older antibiotics: nitrofurantoin, amikacin, colistin, polymyxin B, doxycyline, and minocycline revisited.Med Clin North Am.2006;90(6):1089–1107.
- ,,, et al.Efficacy and safety of doripenem versus piperacillin/tazobactam in nosocomial pneumonia: a randomized, open‐label, multicenter study.Curr Med Res Opin.2008;24(7):2113–2126.
- ,,, et al.Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator‐associated pneumonia: a multicenter, randomized study.Crit Care Med.2008;36(4):1089–1096.
- ,,, et al.Efficacy and tolerability of IV doripenem versus meropenem in adults with complicated intra‐abdominal infection: a phase III, prospective, multicenter, randomized, double‐blind, noninferiority study.Clin Ther.2008;30(5):868–883.
- ,,,,.Evaluation of colistin as an agent against multi‐resistant Gram‐negative bacteria.Int J Antimicrob Agents.2005;25(1):11–25.
- .New uses for older antibiotics: nitrofurantoin, amikacin, colistin, polymyxin B, doxycycline, and minocycline revisited.Med Clin North Am.2006;90(6):1089–1107.
- ,.Colistin: the revival of polymyxins for the management of multidrug‐resistant gram‐negative bacterial infections.Clin Infect Dis.2005;40(9):1333–1341.
- ,,, et al.Ventilator‐associated pneumonia (VAP) due to susceptible only to colistin microorganisms.Eur Respir J.2007;30(2):307–313.
- ,,, et al.Safety and efficacy of colistin compared with imipenem in the treatment of ventilator‐associated pneumonia: a matched case‐control study.Intensive Care Med.2007;33(7):1162–1167.
- ,,, et al.Colistin is effective in treatment of infections caused by multidrug‐resistant Pseudomonas aeruginosa in cancer patients.Antimicrob Agents Chemother.2007;51(6):1905–1911.
- ,,,,,.Combination therapy with intravenous colistin for management of infections due to multidrug‐resistant gram‐negative bacteria in patients without cystic fibrosis.Antimicrob Agents Chemother.2005;49:3136–3146.
- ,,, et al.Combined colistin and rifampicin therapy for carbapenem‐resistant Acinetobacter baumannii infections: clinical outcome and adverse events.Clin Microbiol Infect.2005;11:682–683.
- ,,, et al.The efficacy and safety of tigecycline for the treatment of complicated intra‐abdominal infections: analysis of pooled clinical trial data.Clin Infect Dis.2005;41(suppl 5):S354–S367.
- ,,,,.Clinical implications of extended‐spectrum beta‐lactamase‐producing Klebsiella pneumoniae bacteraemia.J Hosp Infect.2002;52:99–106.
- ,,,,,.Clinical and economic impact of bacteremia with extended spectrum beta‐lactamase–producing Enterobacteriaceae.Antimicrob Agents Chemother.2006;50:1257–1262.
- ,,, et al.Ceftazidime‐resistant Klebsiella pneumoniae bloodstream infection in children with febrile neutropenia.Int J Infect Dis.2000;4:21–25.
- ,,, et al.Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended‐ spectrum beta‐lactamases.Clin Infect Dis.2004;39:31–37.
- ,.Extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae: an emerging public‐health concern.Lancet Infect Dis.2008;8(3):159–166.
- ,.Ertapenem, the first of a new group of carbapenems.J Antimicrob Chemother.2003;52(4):538–542.
- Merck 2006.
- ,,.Ertapenem: the new carbapenem 5 years after first FDA licensing for clinical practice.Expert Opin Pharmacother.2007;8(2):237–256.
- ,,, et al.Ertapenem in critically ill patients with early‐onset ventilator‐associated pneumonia: pharmacokinetics with special consideration of free‐drug concentration.J Antimicrob Chemother.2007;59(2):277–284.
- ,.Quinupristin/dalfopristin: a therapeutic review.Clin Ther.2001;23(1):24–44.
Case 1
A 53‐year‐old woman with a history of hemodialysis‐dependent end‐stage renal disease presents with left lower extremity pain and redness for the past 3 days. On physical examination, her temperature is 102.3F. Erythema, induration, and warmth are noted over her left lower leg and foot. Her history is remarkable for a line‐related bloodstream infection due to methicillin‐resistant Staphylococcus aureus (MRSA) 4 weeks ago. The infected line was removed and replaced with a right‐sided subclavian catheter. You note that the new line site is clean, not erythematous, and not tender. In the emergency department, the patient receives a dose of vancomycin for presumed MRSA cellulitis. Your patient wants to know if there are alternative agents for her infection so she does not require hospitalization.
Unfortunately, MRSA has become commonplace to the hospital setting. Among intensive care units in 2003, 64.4% of healthcare‐associated Staphylococcus aureus infections were caused by MRSA, compared with only 35.9% in 1992; a 3.1% increase per year.1, 2 Increased MRSA rates are not without consequence; a recent review suggests that MRSA infections kill nearly 19,000 hospitalized American patients annually.3 Of note, MRSA infection rates have also increased among previously healthy individuals. These community‐associated isolates (CA‐MRSA) often manifest as pyogenic skin and soft‐tissue infections (SSTIs). In a recent multicenter study, CA‐MRSA accounted for 59% of SSTIs among patients presenting to emergency rooms in the United States.4 In cases of SSTI, oral agents such as clindamycin, doxycycline, and trimethoprim‐sulfamethoxazole have proven successful. For invasive MRSA, vancomycin is still considered the standard treatment; however, several alternatives have emerged in recent years. The advantages and disadvantages of linezolid, daptomycin, tigecycline, and dalbavancin in the treatment of MRSA are described below.
Linezolid
Linezolid (Zyvox), an oxazolidinone approved in 2000, has been touted for its oral bioavailability, twice‐daily dosing, gram‐positive coverage, and unique mechanism of action. Like several other antimicrobials, linezolid inhibits bacterial protein synthesis. The drug binds to the 50S ribosomal subunit near its site of interaction with the 30S subunit, preventing formation of the 70S initiation complex.5 This site of action on the 50S subunit is unique to linezolid; as a result, cross‐resistance between linezolid and other antimicrobials that act at the 50S subunit (eg, chloramphenicol, macrolides, aminoglycosides, and tetracycline) does not occur.6
The oxazolidinones have excellent bacteriostatic activity against all pathogenic gram‐positive bacteria. The U.S. Food and Drug Administration (FDA) approved linezolid for the treatment of serious infections due to vancomycin‐resistant enterococci (VRE), including bacteremia, complicated skin and soft‐tissue infections (cSSTIs) due to Staphylococcus aureus (including MRSA), and nosocomial pneumonia due to Staphylococcus aureus (including MRSA) or penicillin‐susceptible Streptococcus pneumoniae (Table 1).
| Activity | Agent | FDA‐Approved Indications | Limitations in Use | Side Effects |
|---|---|---|---|---|
| ||||
| Gram‐positive | Daptomycin | cSSTIs; MSSA/MRSA bacteremia; MSSA/MRSA endocarditis | Not indicated for pneumonia (inhibited by pulmonary surfactant) | Reversible myopathy may be exacerbated by use with other medications |
| Quinupristin‐dalfopristin | Vancomycin‐resistant E. faecium; group A streptococci or MSSA cSSTIs | Myalgias and arthralgias; infusion site reaction;* thrombophlebitis;* liver enzyme elevation; inhibition of cytochrome p450 34a | ||
| Linezolid | Serious infections due to VRE; MSSA/MRSA cSSTIs; MSSA/MRSA nosocomial pneumonia; pneumonia due to penicillin‐sensitive S. pneumoniae | Not indicated for catheter‐related bloodstream infections or catheter site infections | Myelosuppression; serotonin syndrome; tyramine reaction; peripheral neuropathy; optic neuropathy | |
| Dalbavancin | Approval pending for cSSTIs | Not indicated for pneumonia bone and joint infection | Unknown | |
| Gram‐negative | Colistin | Gram‐negative bacteria that have demonstrated sensitivity to the drug | Not indicated for Proteus spp, Providencia spp, or Serratia spp | Acute tubular necrosis; neurotoxicity∥; bronchospasm |
| Gram‐positive and Gram‐negative | Ertapenem | Complicated intraabdominal infections#; cSSTIs; acute pelvic infections; complicated UTIs; community‐acquired pneumonia; prophylaxis of SSI following colorectal surgery in adult patients | Not indicated for Pseudomonas, Acinetobacter, S. maltophilia | Cross‐reactivity with penicillin; cross‐reactivity with cephalosporins; caution use if history of seizures |
| Doripenem | Complicated intraabdominal infections# and complicated UTIs, including pyelonephritis | Cross‐reactivity with penicillin; cross‐reactivity with cephalosporins; caution use if history of seizures | ||
| Tigecycline | cSSTIs (including those due to MRSA) complicated intraabdominal infections# | Nausea and vomiting; tooth discoloration in children | ||
In retrospective analyses of SSTIs due to MRSA, linezolid was as effective as vancomycin, resulting in higher clinical cure rates and shorter hospitalizations.7 As a result, linezolid has established a role in the treatment of community‐acquired MRSA SSTIs. Evidence limited to case reports and case series suggest that linezolid may also have a role in the treatment of bone and joint infections. In these cases, linezolid was often used because treatment with other agents had failed, the administration of other antibiotics was not indicated due to resistance patterns, the patient refused intravenous therapy, or the patient did not tolerate vancomycin. When such conditions exist, linezolid may be a consideration in cases of osteomyelitis or prosthetic joint infection.8
Potential side effects of linezolid may limit its use, especially for patients who require prolonged therapy (Table 1). Of note, as a reversible, relatively weak nonselective inhibitor of monoamine oxidase, linezolid may interact with adrenergic and serotonergic agents. Concomitant of a serotonin agent such as a selective serotonin‐reuptake inhibitor (SSRI) and linezolid should be approached with caution. Subsequent serotonin syndrome is characterized by autonomic dysfunction (eg, diaphoresis, tachycardia, hypertension) and neuromuscular hyperactivity (eg, muscle rigidity, clonus, hyperreflexia). Though infrequent, cases of reversible myelosuppression have been reported with linezolid use.9 Patients who will receive this drug for more than 2 weeks should be monitored for myelosuppression with a weekly complete blood count. Isolated reports suggest that the prolonged administration of linezolid (>28 days) may be associated with peripheral neuropathy and optic neuropathy. While prompt discontinuation of the drug often results in resolution of symptoms, peripheral or optic nerve injury can be permanent. The mechanism of injury is unclear, though mitochondrial toxicity is suspected.10
Daptomycin
Daptomycin (Cubicin), a cyclic lipopeptide, was discovered in the early 1980s, but skeletal muscle toxicity led to the discontinuation of early clinical trials. When a change from twice‐daily to once‐daily dosing in 2003 resulted in fewer adverse events, the FDA approved daptomycin to treat complicated skin and skin‐structure infections.11 Daptomycin binds to the cell membrane via a calcium‐dependent process, eventually disrupting the cell membrane potential. The bactericidal effect is limited to gram‐positive organisms.12
Daptomycin is effective against almost all gram‐positive organisms including methicillin‐susceptible Staphylococcus aureus (MSSA), MRSA, and VRE.12 As a result, it has FDA approval for the treatment of cSSTIs. While beta‐lactams remain the standard of care for MSSA bacteremia, daptomycin has FDA approval for bloodstream infections and right‐sided endocarditis due to MSSA or MRSA (Table 1).13 Daptomycin has poor penetration into alveolar fluid14 and is inhibited by pulmonary surfactants; as a consequence, it is not indicated for patients with pneumonia.15
Of note, daptomycin is mainly excreted via the kidneys and should be dose‐adjusted for patients with a creatinine clearance 30 mL/minute. A reversible myopathy may occur with daptomycin, requiring intermittent monitoring of creatinine kinase if prolonged use is anticipated. Caution should be used with the coadministration of medications that can also cause a myopathy, such as statins.
Tigecycline
Tigecycline (Tygacil) was approved for use by the FDA in 2005. The first in a class of new tetracycline analogs, the glycylcyclines, tigecycline is notable for its activity against several multidrug‐resistant (MDR) organisms, including MRSA, VRE, and Enterobacteriaceae carrying extended‐spectrum beta‐lactamases (ESBL). Tigecycline impairs bacterial protein synthesis by binding to the 30S ribosomal subunit. Due to steric hindrance from an N‐alkyl‐glycylamido group at position 9, tigecycline cannot be removed by most bacterial efflux mechanisms.16
Tigecycline has been approved for the therapy of cSSTIs, including those due to MSSA and MRSA. In a pooled analysis of 2 international, multicenter, phase III randomized, double‐blind trials, tigecycline was not inferior to vancomycin plus aztreonam in the treatment of cSSTIs. Of note, MRSA eradication rates were similar between patients treated with tigecycline and vancomycin plus aztreonam (78.1% and 75.8%, respectively).17
Dalbavancin
Dalbavancin (Zeven), a new, semisynthetic lipoglycopeptide, was approved by the FDA in late 2007; however, it has not been cleared for marketing. Though dalbavancin is derived from teicoplanin, its lipophilic anchor to the bacterial cell membrane makes the drug more potent than its predecessor. Dalbavancin interferes with bacterial cell wall synthesis by binding to the C‐terminal D‐alanyl‐D alanine of the growing peptidoglycan chains.18 Enhanced pharmacokinetic properties of dalbavancin (half‐life 149‐250 hours) allow it to be dosed once‐weekly, a novel concept in antimicrobial use.19
Like other glycopeptides, dalbavancin maintains in vitro activity against most gram‐positive aerobic organisms, including MRSA and penicillin‐susceptible and penicillin‐resistant strains of Streptococcus pneumoniae. Notably, when compared to vancomycin in vitro, the agent is more active against Enterococcus faecium and Enterococcus faecalis isolates. In a recent phase III double‐blind trial, dalbavancin was compared to linezolid for the treatment of cSSTIs. Dalbavancin was not inferior to linezolid (clinical success rate 90% vs. 92%). Of note, 51% of study patients with SSTI had infection due to MRSA. Microbiological response to dalbavancin paralleled the clinical success rate; MRSA eradication rates after dalbavancin and linezolid were 91% and 89%, respectively.20
Given its once‐weekly dosing, dalbavancin may be an attractive agent in the outpatient treatment of gram‐positive bacteremia. In a phase II study, dalbavancin administered as a single 1‐g dose, followed by a 500‐mg dose 1 week later, was comparable to 14 days of vancomycin for the treatment of catheter‐related bloodstream infections (CRBSI) due to coagulase‐negative staphylococci or S. aureus (including MRSA).21 Phase III studies are underway. At present, there is no evidence to support the use of dalbavancin for the treatment of pneumonia or bone and joint infections.
Despite the administration of vancomycin, the patient continues to experience fever and chills. Blood cultures drawn in the emergency department are now growing Enterococcus species. You review the patient's medical record and notice that she was colonized with VRE on a prior admission. You consider the antibiotic options for serious infections due to VRE.
Though rates of VRE have remained fairly stable in recent years,22 the pathogen continues to present a challenge to hospital epidemiologists. A national survey in 2004 suggested that nearly 30% of enterococci in U.S. intensive care units display vancomycin resistance.1 Additional U.S. surveillance data reveals that VRE accounts for 10% to 26% of enterococci hospital‐wide.23, 24 In 2005, a meta‐analysis noted that bloodstream infections due to VRE resulted in higher mortality rates than those due to vancomycin‐susceptible enterococci.25 This discrepancy is most evident among neutropenia patients.26 Unfortunately, the options for the treatment of serious infections due to VRE are limited. The advantages and disadvantages of linezolid, quinupristin‐dalfopristin, tigecycline, and daptomycin in the treatment for VRE are discussed below.
Linezolid
Currently, linezolid is the only oral drug that is FDA‐approved for the treatment of infections due to VRE, including bacteremia. Notably, linezolid therapy resulted in the cure of 77% of 22 cases of vancomycin‐resistant enterococcal endocarditis.27 Current guidelines by the Infectious Disease Society of America (IDSA) support the use of linezolid in cases of endocarditis due to ampicillin‐resistant and vancomycin‐resistant Enterococcus faecium.28 Unfortunately, recent reports highlight the emergence of linezolid‐resistant VRE,29 suggesting use of this drug should be limited to circumstances in which other alternatives do not exist.
Quinupristin‐Dalfopristin
Quinupristin‐dalfopristin (Synercid) was approved by the FDA in 1999. It is used in the treatment of infections caused by gram‐positive organisms and is a combination of 2 semisynthetic pristinamycin derivatives. They diffuse into bacteria and bind to different areas on the 50S ribosomal subunit, thereby inhibiting protein synthesis. Individually, quinupristin and dalfopristin are bacteriostatic but together they are bactericidal.30
Quinupristin‐dalfopristin has activity against Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, gram‐positive anaerobes, and vancomycin‐sensitive and resistant Enterococcus faecium. It has little activity against Enterococcus faecalis.31 FDA‐approved uses of quinupristin‐dalfopristin are limited, but include the treatment of serious infections caused by vancomycin‐resistant E. faecium (VREF).32 In a study of 396 patients with VREF the clinical success rate of quinupristin‐dalfopristin was 73.6%.33 The drug also has FDA approval for the use in cSSTIs due to group A streptococci or MSSA.32 The use of this agent is limited due to its toxicity profile. In cases of serious VRE‐related infection, quinupristin‐dalfopristin is often only utilized if linezolid cannot be tolerated.
Daptomycin
In vitro studies suggest that daptomycin is active against enterococci, including vancomycin‐resistant isolates.34 However, clinical data on the use of this agent in the treatment of infections due to VRE are lacking. FDA approval for the use of daptomycin in cSSTI included the treatment of 45 patients infected with Enterococcus faecalis.13 In addition, several reports have detailed the successful treatment of VRE bloodstream infections with daptomycin,35, 36 including a case series of VRE endocarditis.37 To determine the role of this agent in the treatment of invasive infections due to VRE, further study is needed.
You decide to discontinue vancomycin and administer linezolid. The patient's vascular catheter is removed; catheter‐tip cultures grow >1000 colonies of VRE. Blood cultures the following day are negative and a new catheter is placed. You ask the patient to continue oral linezolid to complete a 2‐week course. A review of her medication list reveals that she is not taking SSRIs or monoamine oxidase inhibitors (MAOIs).
While linezolid has retained its FDA indication for VRE bacteremia, empiric use in suspected cases of CRBSI or catheter site infection is not advised. In an open‐label trial among seriously ill patients with intravascular catheter‐related infections, linezolid use was associated with a higher mortality when compared to vancomycin/oxacillin. Interestingly, mortality among linezolid‐treated patients included those with CRBSI due to gram‐negative pathogens, due to both gram‐negative and gram‐positive pathogens, or due to an identifiable pathogen; mortality rates did not differ among patients with gram‐positive infections only.38
Case 2
A 27‐year‐old male with a history of T10 paraplegia following a motor vehicle accident presents with abdominal pain, fever, and chills. He notes that he experiences these symptoms when he has a urinary tract infection (UTI), a frequent complication of his chronic indwelling suprapubic catheter. You review his medical record and notice that he has had prior UTIs with multiple gram‐negative rods over the past 2 years, including MDR Pseudomonas and Acinetobacter. When his urine culture grows >100,000 colonies of gram‐negative rods, you initiate meropenem and consider the options for treatment of these MDR pathogens.
According to national U.S. surveillance in 2001, 22% of Pseudomonas aeruginosa were resistant to imipenem, an increase of 32% from 1997.39 More alarming is the recent development of MDR P. aeruginosa, a pathogen resistant not only to the beta‐lactams (including the carbapenems) but to the fluoroquinolones and aminoglycosides as well.40 MDR P. aeruginosa is virulent, and has been associated with higher rates of mortality, longer hospital stays, and greater cost.41
Already equipped with intrinsic resistance to the aminopenicillins and first‐generation and second‐generation cephalosporins, A. baumannii has gained recent notoriety with acquired resistance to beta‐lactams, aminoglycosides, fluoroquinolones, and tetracyclines. Most notably, carbapenem‐resistant A. baumannii has emerged due to enzymes capable of hydrolyzing imipenem. Like MDR P. aeruginosa, MDR A. baumannii infection has led to longer hospital stays42 and increased patient mortality43 when compared to infections with more susceptible strains.
Therapeutic options for these MDR gram‐negative pathogens remain limited, but the advent of doripenem and the return of colistin may play a role in treatment. The use of these 2 agents and tigecycline in the treatment of MDR P. aeruginosa and/or A. baumannii are described below.
Doripenem
In October 2007, the FDA approved the use of doripenem (Doribax), a much‐anticipated carbapenem. In structure, doripenem resembles meropenem and does not require a renal dehydropeptidase I inhibitor (eg, cilastatin).44 Similar to other beta‐lactams, doripenem binds to penicillin‐binding proteins (PBPs), inhibiting PBP‐directed cell wall synthesis.
Like imipenem and meropenem, doripenem has broad‐spectrum antimicrobial activity. It demonstrates in vitro activity against most gram‐positive pathogens including MSSA and ampicillin‐sensitive enterococci. Doripenem also has in vitro activity against most gram‐negative pathogens (including ESBL‐producing Enterobacteriaceae) and most anaerobes, including Bacteriodes fragilis. Most notably, when compared to other carbapenems, doripenem has demonstrated better in vitro activity against Pseudomonas aeruginosa.45 However, clinical implications of this in vitro activity are unclear.
When compared to meropenem or levofloxacin for the treatment of complicated UTIs, doripenem is an effective alternative. Clinical response rates among affected patients were 95% to 96% with doripenem, 89% with meropenem, and 90% with levofloxacin.46, 47 Doripenem was not inferior to meropenem in patients with serious lower respiratory tract infections, and comparable to imipenem‐cilastin and pipercillin‐tazobactam for the treatment of nosocomial or ventilator‐associated pneumonia (VAP).48, 49 Finally, for the treatment of complicated intraabdominal infections, doripenem was not inferior to meropenem; both drugs achieved microbiologic cure rates of >84%.50
Currently, doripenem is FDA‐approved for the treatment of complicated intraabdominal infections (eg, appendicitis, pancreatitis, cholecystitis, peritonitis) and complicated lower UTIs or pyelonephritis (Table 1). Given its expanded spectrum of activity, use of doripenem should be limited to circumstances in which a MDR pathogen is highly suspected or confirmed.
Colistin
Colistin (Coly‐Mycin M) falls within the family of polymyxin antibiotics, which were discovered in 1947. Colistin has been available for almost 50 years for the treatment of infections caused by gram‐negative bacteria, including Pseudomonas spp. However, early use of colistin was associated with significant nephrotoxicity. Its use decreased markedly with the advent of new antibiotics that had the same antimicrobial spectrum and a better side effect profile. With the emergence of MDR gram‐negative bacteria, colistin has returned to limited clinical use.51 As a polymyxin, colistin is a cell membrane detergent. It disrupts the cell membrane, causing leakage of bacterial cell content and ultimately cell death.52
Colistin has bactericidal activity against most gram‐negative bacteria including Acinetobacter spp, and members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs.53 Colistin is not active against several predominant gram‐negative pathogens including Proteus spp, Providencia spp, or Serratia spp (Table 1).
In 2007, several studies suggested that colistin monotherapy was effective for patients with VAP due to MDR P. aeruginosa or A. baumannii isolate.54, 55 A third trial that year suggested that colistin may have a role in the treatment of MDR P. aeruginosa among neutropenic patients. In that study, infected patients receiving colistin monotherapy experienced higher rates of clinical and microbiologic response than those receiving other antipseudomonal agents (eg, beta‐lactams or fluoroquinolones if active against the isolate).56 While uncontrolled studies suggest that the use of colistin in combination with other antimicrobials (including carbapenems, ampicillin‐sulbactam, aminoglycosides, and rifampin) may have some success in the treatment of VAP due to MDR A. baumannii,57, 58 further trials are needed.
Currently, colistin has FDA approval only for the treatment of acute infections due to gram‐negative bacteria that have demonstrated susceptibility to the drug and is therefore administered on a case by case basis. Although it has been used via the inhalation route to treat infections in cystic fibrosis patients, colistin does not have FDA approval for this indication.
Tigecycline
Tigecycline is approved for the treatment of complicated intraabdominal infections based on the results of 2 international, multicenter, phase III, randomized, double‐blind trials. In this pooled analysis, tigecycline was as effective and as safe as imipenem/cilastatin. Notably, study patients were not severely ill (baseline APACHE II score of 6.0).59 FDA approval suggests tigecycline use be focused on intraabdominal infections due to members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs, vancomycin‐sensitive enterococci, and/or MSSA. Notably, tigecycline lacks significant in vitro activity against Pseudomonas spp, Proteus spp, or Providencia spp. It has demonstrated in vitro activity against MDR strains of Acinetobacter spp (Table 1).
Given its bacteriostatic activity, tigecycline's effectiveness in the treatment bacteremia is unclear.
In addition, as no published studies have addressed its activity among seriously ill patients, tigecycline is considered a second‐line or third‐line agent for SSTI and complicated intraabdominal infections. Evidence for use of tigecycline for the treatment of UTIs is lacking and, as a rule, its use should be limited to scenarios in which alternatives for the proven or suspected pathogens do not exist.
The urine isolate is identified as Escherichia coli. You review the susceptibility profile and determine that this isolate is an ESBL‐producing strain. In addition, the patient's isolate demonstrates resistance to the fluoroquinolones and trimethoprim‐sulfamethoxazole. You consider other options for treatment of this ESBL‐producing E. coli.
According to national surveillance data, more than 20% of Klebsiella isolates in U.S. intensive care units produced ESBLs in 2003, a 47% increase when compared to 1998.39 Bloodstream infections due to ESBL‐producing isolates have led to increased length of hospital stay,60, 61 increased hospital costs,4 improper antibiotic use,5 and, most notably, increased mortality.61‐63 Of concern, ESBLs have been demonstrated within community Enterobacteriaceae isolates, most notably due to CTX‐M beta‐lactamase production among E. coli. In addition to ESBL production, these community E. coli isolates tend to express fluoroquinolone and trimethoprim‐sulfamethoxazole resistance.64 Carbapenems remain the mainstay of therapy for serious infections due to ESBL‐producing organisms. The once‐daily dosing of ertapenem makes this agent an attractive alternative for outpatient management.
Ertapenem
Ertapenem (Invanz) obtained FDA approval for use in the United States in 2001 and in the European Union in 2002.65 Similar to doripenem, ertapenem blocks cell wall synthesis by binding to specific penicillin‐binding proteins (PBPs).
Ertapenem has activity against numerous gram‐positive and gram‐negative bacteria as well as some anaerobic microorganisms. The FDA‐approved indications include complicated intraabdominal infections, cSSTIs, acute pelvic infections, complicated UTIs, and community‐acquired pneumonias (Table 1).66 Of note, in contrast to other carabapenems, ertapenem does not have activity against Pseudomonas aeruginosa or Acinetobacter spp.67
Ertapenem is approved as a single daily dose of 1 g and can be administered intravenously or intramuscularly. Changes in dosing must also be considered for critically ill patients. When administered to patients with VAP, ertapenem achieved a lower maximum concentration and area under the curve.68 In such patients, it is recommended that the dosage interval be decreased or that a continuous infusion of ertapenem be administered.
The patient's symptoms improve on meropenem. A peripherally‐inserted central catheter is placed for the administration of intravenous antibiotics at home. You prescribe ertapenem (1 g/day) for the remainder of a 14‐day course.
Conclusions
MDR bacteria continue to present a clinical challenge to hospitalists. Proper treatment of patients infected with these organisms is necessary, as inappropriate antibiotic use for MDR bacterial infections has been associated with longer hospital stays, greater cost, and, in some cases, increased mortality. Unfortunately, antibiotic production and development has declined steadily in the past 25 years. To minimize the rate of antimicrobial resistance, physicians must take care to prescribe antibiotics appropriately. While these promising new agents for resistant gram‐positive and gram‐negative infections may aid in battling MDR infections, these antibiotics must be used judiciously to maintain their clinical utility. Hospitalists will continue to play an important role in ensuring that hospitalized patients receive the most effective antimicrobial therapy to both treat the infection and prevent the development of resistance.
Case 1
A 53‐year‐old woman with a history of hemodialysis‐dependent end‐stage renal disease presents with left lower extremity pain and redness for the past 3 days. On physical examination, her temperature is 102.3F. Erythema, induration, and warmth are noted over her left lower leg and foot. Her history is remarkable for a line‐related bloodstream infection due to methicillin‐resistant Staphylococcus aureus (MRSA) 4 weeks ago. The infected line was removed and replaced with a right‐sided subclavian catheter. You note that the new line site is clean, not erythematous, and not tender. In the emergency department, the patient receives a dose of vancomycin for presumed MRSA cellulitis. Your patient wants to know if there are alternative agents for her infection so she does not require hospitalization.
Unfortunately, MRSA has become commonplace to the hospital setting. Among intensive care units in 2003, 64.4% of healthcare‐associated Staphylococcus aureus infections were caused by MRSA, compared with only 35.9% in 1992; a 3.1% increase per year.1, 2 Increased MRSA rates are not without consequence; a recent review suggests that MRSA infections kill nearly 19,000 hospitalized American patients annually.3 Of note, MRSA infection rates have also increased among previously healthy individuals. These community‐associated isolates (CA‐MRSA) often manifest as pyogenic skin and soft‐tissue infections (SSTIs). In a recent multicenter study, CA‐MRSA accounted for 59% of SSTIs among patients presenting to emergency rooms in the United States.4 In cases of SSTI, oral agents such as clindamycin, doxycycline, and trimethoprim‐sulfamethoxazole have proven successful. For invasive MRSA, vancomycin is still considered the standard treatment; however, several alternatives have emerged in recent years. The advantages and disadvantages of linezolid, daptomycin, tigecycline, and dalbavancin in the treatment of MRSA are described below.
Linezolid
Linezolid (Zyvox), an oxazolidinone approved in 2000, has been touted for its oral bioavailability, twice‐daily dosing, gram‐positive coverage, and unique mechanism of action. Like several other antimicrobials, linezolid inhibits bacterial protein synthesis. The drug binds to the 50S ribosomal subunit near its site of interaction with the 30S subunit, preventing formation of the 70S initiation complex.5 This site of action on the 50S subunit is unique to linezolid; as a result, cross‐resistance between linezolid and other antimicrobials that act at the 50S subunit (eg, chloramphenicol, macrolides, aminoglycosides, and tetracycline) does not occur.6
The oxazolidinones have excellent bacteriostatic activity against all pathogenic gram‐positive bacteria. The U.S. Food and Drug Administration (FDA) approved linezolid for the treatment of serious infections due to vancomycin‐resistant enterococci (VRE), including bacteremia, complicated skin and soft‐tissue infections (cSSTIs) due to Staphylococcus aureus (including MRSA), and nosocomial pneumonia due to Staphylococcus aureus (including MRSA) or penicillin‐susceptible Streptococcus pneumoniae (Table 1).
| Activity | Agent | FDA‐Approved Indications | Limitations in Use | Side Effects |
|---|---|---|---|---|
| ||||
| Gram‐positive | Daptomycin | cSSTIs; MSSA/MRSA bacteremia; MSSA/MRSA endocarditis | Not indicated for pneumonia (inhibited by pulmonary surfactant) | Reversible myopathy may be exacerbated by use with other medications |
| Quinupristin‐dalfopristin | Vancomycin‐resistant E. faecium; group A streptococci or MSSA cSSTIs | Myalgias and arthralgias; infusion site reaction;* thrombophlebitis;* liver enzyme elevation; inhibition of cytochrome p450 34a | ||
| Linezolid | Serious infections due to VRE; MSSA/MRSA cSSTIs; MSSA/MRSA nosocomial pneumonia; pneumonia due to penicillin‐sensitive S. pneumoniae | Not indicated for catheter‐related bloodstream infections or catheter site infections | Myelosuppression; serotonin syndrome; tyramine reaction; peripheral neuropathy; optic neuropathy | |
| Dalbavancin | Approval pending for cSSTIs | Not indicated for pneumonia bone and joint infection | Unknown | |
| Gram‐negative | Colistin | Gram‐negative bacteria that have demonstrated sensitivity to the drug | Not indicated for Proteus spp, Providencia spp, or Serratia spp | Acute tubular necrosis; neurotoxicity∥; bronchospasm |
| Gram‐positive and Gram‐negative | Ertapenem | Complicated intraabdominal infections#; cSSTIs; acute pelvic infections; complicated UTIs; community‐acquired pneumonia; prophylaxis of SSI following colorectal surgery in adult patients | Not indicated for Pseudomonas, Acinetobacter, S. maltophilia | Cross‐reactivity with penicillin; cross‐reactivity with cephalosporins; caution use if history of seizures |
| Doripenem | Complicated intraabdominal infections# and complicated UTIs, including pyelonephritis | Cross‐reactivity with penicillin; cross‐reactivity with cephalosporins; caution use if history of seizures | ||
| Tigecycline | cSSTIs (including those due to MRSA) complicated intraabdominal infections# | Nausea and vomiting; tooth discoloration in children | ||
In retrospective analyses of SSTIs due to MRSA, linezolid was as effective as vancomycin, resulting in higher clinical cure rates and shorter hospitalizations.7 As a result, linezolid has established a role in the treatment of community‐acquired MRSA SSTIs. Evidence limited to case reports and case series suggest that linezolid may also have a role in the treatment of bone and joint infections. In these cases, linezolid was often used because treatment with other agents had failed, the administration of other antibiotics was not indicated due to resistance patterns, the patient refused intravenous therapy, or the patient did not tolerate vancomycin. When such conditions exist, linezolid may be a consideration in cases of osteomyelitis or prosthetic joint infection.8
Potential side effects of linezolid may limit its use, especially for patients who require prolonged therapy (Table 1). Of note, as a reversible, relatively weak nonselective inhibitor of monoamine oxidase, linezolid may interact with adrenergic and serotonergic agents. Concomitant of a serotonin agent such as a selective serotonin‐reuptake inhibitor (SSRI) and linezolid should be approached with caution. Subsequent serotonin syndrome is characterized by autonomic dysfunction (eg, diaphoresis, tachycardia, hypertension) and neuromuscular hyperactivity (eg, muscle rigidity, clonus, hyperreflexia). Though infrequent, cases of reversible myelosuppression have been reported with linezolid use.9 Patients who will receive this drug for more than 2 weeks should be monitored for myelosuppression with a weekly complete blood count. Isolated reports suggest that the prolonged administration of linezolid (>28 days) may be associated with peripheral neuropathy and optic neuropathy. While prompt discontinuation of the drug often results in resolution of symptoms, peripheral or optic nerve injury can be permanent. The mechanism of injury is unclear, though mitochondrial toxicity is suspected.10
Daptomycin
Daptomycin (Cubicin), a cyclic lipopeptide, was discovered in the early 1980s, but skeletal muscle toxicity led to the discontinuation of early clinical trials. When a change from twice‐daily to once‐daily dosing in 2003 resulted in fewer adverse events, the FDA approved daptomycin to treat complicated skin and skin‐structure infections.11 Daptomycin binds to the cell membrane via a calcium‐dependent process, eventually disrupting the cell membrane potential. The bactericidal effect is limited to gram‐positive organisms.12
Daptomycin is effective against almost all gram‐positive organisms including methicillin‐susceptible Staphylococcus aureus (MSSA), MRSA, and VRE.12 As a result, it has FDA approval for the treatment of cSSTIs. While beta‐lactams remain the standard of care for MSSA bacteremia, daptomycin has FDA approval for bloodstream infections and right‐sided endocarditis due to MSSA or MRSA (Table 1).13 Daptomycin has poor penetration into alveolar fluid14 and is inhibited by pulmonary surfactants; as a consequence, it is not indicated for patients with pneumonia.15
Of note, daptomycin is mainly excreted via the kidneys and should be dose‐adjusted for patients with a creatinine clearance 30 mL/minute. A reversible myopathy may occur with daptomycin, requiring intermittent monitoring of creatinine kinase if prolonged use is anticipated. Caution should be used with the coadministration of medications that can also cause a myopathy, such as statins.
Tigecycline
Tigecycline (Tygacil) was approved for use by the FDA in 2005. The first in a class of new tetracycline analogs, the glycylcyclines, tigecycline is notable for its activity against several multidrug‐resistant (MDR) organisms, including MRSA, VRE, and Enterobacteriaceae carrying extended‐spectrum beta‐lactamases (ESBL). Tigecycline impairs bacterial protein synthesis by binding to the 30S ribosomal subunit. Due to steric hindrance from an N‐alkyl‐glycylamido group at position 9, tigecycline cannot be removed by most bacterial efflux mechanisms.16
Tigecycline has been approved for the therapy of cSSTIs, including those due to MSSA and MRSA. In a pooled analysis of 2 international, multicenter, phase III randomized, double‐blind trials, tigecycline was not inferior to vancomycin plus aztreonam in the treatment of cSSTIs. Of note, MRSA eradication rates were similar between patients treated with tigecycline and vancomycin plus aztreonam (78.1% and 75.8%, respectively).17
Dalbavancin
Dalbavancin (Zeven), a new, semisynthetic lipoglycopeptide, was approved by the FDA in late 2007; however, it has not been cleared for marketing. Though dalbavancin is derived from teicoplanin, its lipophilic anchor to the bacterial cell membrane makes the drug more potent than its predecessor. Dalbavancin interferes with bacterial cell wall synthesis by binding to the C‐terminal D‐alanyl‐D alanine of the growing peptidoglycan chains.18 Enhanced pharmacokinetic properties of dalbavancin (half‐life 149‐250 hours) allow it to be dosed once‐weekly, a novel concept in antimicrobial use.19
Like other glycopeptides, dalbavancin maintains in vitro activity against most gram‐positive aerobic organisms, including MRSA and penicillin‐susceptible and penicillin‐resistant strains of Streptococcus pneumoniae. Notably, when compared to vancomycin in vitro, the agent is more active against Enterococcus faecium and Enterococcus faecalis isolates. In a recent phase III double‐blind trial, dalbavancin was compared to linezolid for the treatment of cSSTIs. Dalbavancin was not inferior to linezolid (clinical success rate 90% vs. 92%). Of note, 51% of study patients with SSTI had infection due to MRSA. Microbiological response to dalbavancin paralleled the clinical success rate; MRSA eradication rates after dalbavancin and linezolid were 91% and 89%, respectively.20
Given its once‐weekly dosing, dalbavancin may be an attractive agent in the outpatient treatment of gram‐positive bacteremia. In a phase II study, dalbavancin administered as a single 1‐g dose, followed by a 500‐mg dose 1 week later, was comparable to 14 days of vancomycin for the treatment of catheter‐related bloodstream infections (CRBSI) due to coagulase‐negative staphylococci or S. aureus (including MRSA).21 Phase III studies are underway. At present, there is no evidence to support the use of dalbavancin for the treatment of pneumonia or bone and joint infections.
Despite the administration of vancomycin, the patient continues to experience fever and chills. Blood cultures drawn in the emergency department are now growing Enterococcus species. You review the patient's medical record and notice that she was colonized with VRE on a prior admission. You consider the antibiotic options for serious infections due to VRE.
Though rates of VRE have remained fairly stable in recent years,22 the pathogen continues to present a challenge to hospital epidemiologists. A national survey in 2004 suggested that nearly 30% of enterococci in U.S. intensive care units display vancomycin resistance.1 Additional U.S. surveillance data reveals that VRE accounts for 10% to 26% of enterococci hospital‐wide.23, 24 In 2005, a meta‐analysis noted that bloodstream infections due to VRE resulted in higher mortality rates than those due to vancomycin‐susceptible enterococci.25 This discrepancy is most evident among neutropenia patients.26 Unfortunately, the options for the treatment of serious infections due to VRE are limited. The advantages and disadvantages of linezolid, quinupristin‐dalfopristin, tigecycline, and daptomycin in the treatment for VRE are discussed below.
Linezolid
Currently, linezolid is the only oral drug that is FDA‐approved for the treatment of infections due to VRE, including bacteremia. Notably, linezolid therapy resulted in the cure of 77% of 22 cases of vancomycin‐resistant enterococcal endocarditis.27 Current guidelines by the Infectious Disease Society of America (IDSA) support the use of linezolid in cases of endocarditis due to ampicillin‐resistant and vancomycin‐resistant Enterococcus faecium.28 Unfortunately, recent reports highlight the emergence of linezolid‐resistant VRE,29 suggesting use of this drug should be limited to circumstances in which other alternatives do not exist.
Quinupristin‐Dalfopristin
Quinupristin‐dalfopristin (Synercid) was approved by the FDA in 1999. It is used in the treatment of infections caused by gram‐positive organisms and is a combination of 2 semisynthetic pristinamycin derivatives. They diffuse into bacteria and bind to different areas on the 50S ribosomal subunit, thereby inhibiting protein synthesis. Individually, quinupristin and dalfopristin are bacteriostatic but together they are bactericidal.30
Quinupristin‐dalfopristin has activity against Staphylococcus aureus (including MRSA), Streptococcus pneumoniae, gram‐positive anaerobes, and vancomycin‐sensitive and resistant Enterococcus faecium. It has little activity against Enterococcus faecalis.31 FDA‐approved uses of quinupristin‐dalfopristin are limited, but include the treatment of serious infections caused by vancomycin‐resistant E. faecium (VREF).32 In a study of 396 patients with VREF the clinical success rate of quinupristin‐dalfopristin was 73.6%.33 The drug also has FDA approval for the use in cSSTIs due to group A streptococci or MSSA.32 The use of this agent is limited due to its toxicity profile. In cases of serious VRE‐related infection, quinupristin‐dalfopristin is often only utilized if linezolid cannot be tolerated.
Daptomycin
In vitro studies suggest that daptomycin is active against enterococci, including vancomycin‐resistant isolates.34 However, clinical data on the use of this agent in the treatment of infections due to VRE are lacking. FDA approval for the use of daptomycin in cSSTI included the treatment of 45 patients infected with Enterococcus faecalis.13 In addition, several reports have detailed the successful treatment of VRE bloodstream infections with daptomycin,35, 36 including a case series of VRE endocarditis.37 To determine the role of this agent in the treatment of invasive infections due to VRE, further study is needed.
You decide to discontinue vancomycin and administer linezolid. The patient's vascular catheter is removed; catheter‐tip cultures grow >1000 colonies of VRE. Blood cultures the following day are negative and a new catheter is placed. You ask the patient to continue oral linezolid to complete a 2‐week course. A review of her medication list reveals that she is not taking SSRIs or monoamine oxidase inhibitors (MAOIs).
While linezolid has retained its FDA indication for VRE bacteremia, empiric use in suspected cases of CRBSI or catheter site infection is not advised. In an open‐label trial among seriously ill patients with intravascular catheter‐related infections, linezolid use was associated with a higher mortality when compared to vancomycin/oxacillin. Interestingly, mortality among linezolid‐treated patients included those with CRBSI due to gram‐negative pathogens, due to both gram‐negative and gram‐positive pathogens, or due to an identifiable pathogen; mortality rates did not differ among patients with gram‐positive infections only.38
Case 2
A 27‐year‐old male with a history of T10 paraplegia following a motor vehicle accident presents with abdominal pain, fever, and chills. He notes that he experiences these symptoms when he has a urinary tract infection (UTI), a frequent complication of his chronic indwelling suprapubic catheter. You review his medical record and notice that he has had prior UTIs with multiple gram‐negative rods over the past 2 years, including MDR Pseudomonas and Acinetobacter. When his urine culture grows >100,000 colonies of gram‐negative rods, you initiate meropenem and consider the options for treatment of these MDR pathogens.
According to national U.S. surveillance in 2001, 22% of Pseudomonas aeruginosa were resistant to imipenem, an increase of 32% from 1997.39 More alarming is the recent development of MDR P. aeruginosa, a pathogen resistant not only to the beta‐lactams (including the carbapenems) but to the fluoroquinolones and aminoglycosides as well.40 MDR P. aeruginosa is virulent, and has been associated with higher rates of mortality, longer hospital stays, and greater cost.41
Already equipped with intrinsic resistance to the aminopenicillins and first‐generation and second‐generation cephalosporins, A. baumannii has gained recent notoriety with acquired resistance to beta‐lactams, aminoglycosides, fluoroquinolones, and tetracyclines. Most notably, carbapenem‐resistant A. baumannii has emerged due to enzymes capable of hydrolyzing imipenem. Like MDR P. aeruginosa, MDR A. baumannii infection has led to longer hospital stays42 and increased patient mortality43 when compared to infections with more susceptible strains.
Therapeutic options for these MDR gram‐negative pathogens remain limited, but the advent of doripenem and the return of colistin may play a role in treatment. The use of these 2 agents and tigecycline in the treatment of MDR P. aeruginosa and/or A. baumannii are described below.
Doripenem
In October 2007, the FDA approved the use of doripenem (Doribax), a much‐anticipated carbapenem. In structure, doripenem resembles meropenem and does not require a renal dehydropeptidase I inhibitor (eg, cilastatin).44 Similar to other beta‐lactams, doripenem binds to penicillin‐binding proteins (PBPs), inhibiting PBP‐directed cell wall synthesis.
Like imipenem and meropenem, doripenem has broad‐spectrum antimicrobial activity. It demonstrates in vitro activity against most gram‐positive pathogens including MSSA and ampicillin‐sensitive enterococci. Doripenem also has in vitro activity against most gram‐negative pathogens (including ESBL‐producing Enterobacteriaceae) and most anaerobes, including Bacteriodes fragilis. Most notably, when compared to other carbapenems, doripenem has demonstrated better in vitro activity against Pseudomonas aeruginosa.45 However, clinical implications of this in vitro activity are unclear.
When compared to meropenem or levofloxacin for the treatment of complicated UTIs, doripenem is an effective alternative. Clinical response rates among affected patients were 95% to 96% with doripenem, 89% with meropenem, and 90% with levofloxacin.46, 47 Doripenem was not inferior to meropenem in patients with serious lower respiratory tract infections, and comparable to imipenem‐cilastin and pipercillin‐tazobactam for the treatment of nosocomial or ventilator‐associated pneumonia (VAP).48, 49 Finally, for the treatment of complicated intraabdominal infections, doripenem was not inferior to meropenem; both drugs achieved microbiologic cure rates of >84%.50
Currently, doripenem is FDA‐approved for the treatment of complicated intraabdominal infections (eg, appendicitis, pancreatitis, cholecystitis, peritonitis) and complicated lower UTIs or pyelonephritis (Table 1). Given its expanded spectrum of activity, use of doripenem should be limited to circumstances in which a MDR pathogen is highly suspected or confirmed.
Colistin
Colistin (Coly‐Mycin M) falls within the family of polymyxin antibiotics, which were discovered in 1947. Colistin has been available for almost 50 years for the treatment of infections caused by gram‐negative bacteria, including Pseudomonas spp. However, early use of colistin was associated with significant nephrotoxicity. Its use decreased markedly with the advent of new antibiotics that had the same antimicrobial spectrum and a better side effect profile. With the emergence of MDR gram‐negative bacteria, colistin has returned to limited clinical use.51 As a polymyxin, colistin is a cell membrane detergent. It disrupts the cell membrane, causing leakage of bacterial cell content and ultimately cell death.52
Colistin has bactericidal activity against most gram‐negative bacteria including Acinetobacter spp, and members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs.53 Colistin is not active against several predominant gram‐negative pathogens including Proteus spp, Providencia spp, or Serratia spp (Table 1).
In 2007, several studies suggested that colistin monotherapy was effective for patients with VAP due to MDR P. aeruginosa or A. baumannii isolate.54, 55 A third trial that year suggested that colistin may have a role in the treatment of MDR P. aeruginosa among neutropenic patients. In that study, infected patients receiving colistin monotherapy experienced higher rates of clinical and microbiologic response than those receiving other antipseudomonal agents (eg, beta‐lactams or fluoroquinolones if active against the isolate).56 While uncontrolled studies suggest that the use of colistin in combination with other antimicrobials (including carbapenems, ampicillin‐sulbactam, aminoglycosides, and rifampin) may have some success in the treatment of VAP due to MDR A. baumannii,57, 58 further trials are needed.
Currently, colistin has FDA approval only for the treatment of acute infections due to gram‐negative bacteria that have demonstrated susceptibility to the drug and is therefore administered on a case by case basis. Although it has been used via the inhalation route to treat infections in cystic fibrosis patients, colistin does not have FDA approval for this indication.
Tigecycline
Tigecycline is approved for the treatment of complicated intraabdominal infections based on the results of 2 international, multicenter, phase III, randomized, double‐blind trials. In this pooled analysis, tigecycline was as effective and as safe as imipenem/cilastatin. Notably, study patients were not severely ill (baseline APACHE II score of 6.0).59 FDA approval suggests tigecycline use be focused on intraabdominal infections due to members of the family Enterobacteriaceae (eg, Klebsiella spp, Escherichia coli, Enterobacter spp), including those producing ESBLs, vancomycin‐sensitive enterococci, and/or MSSA. Notably, tigecycline lacks significant in vitro activity against Pseudomonas spp, Proteus spp, or Providencia spp. It has demonstrated in vitro activity against MDR strains of Acinetobacter spp (Table 1).
Given its bacteriostatic activity, tigecycline's effectiveness in the treatment bacteremia is unclear.
In addition, as no published studies have addressed its activity among seriously ill patients, tigecycline is considered a second‐line or third‐line agent for SSTI and complicated intraabdominal infections. Evidence for use of tigecycline for the treatment of UTIs is lacking and, as a rule, its use should be limited to scenarios in which alternatives for the proven or suspected pathogens do not exist.
The urine isolate is identified as Escherichia coli. You review the susceptibility profile and determine that this isolate is an ESBL‐producing strain. In addition, the patient's isolate demonstrates resistance to the fluoroquinolones and trimethoprim‐sulfamethoxazole. You consider other options for treatment of this ESBL‐producing E. coli.
According to national surveillance data, more than 20% of Klebsiella isolates in U.S. intensive care units produced ESBLs in 2003, a 47% increase when compared to 1998.39 Bloodstream infections due to ESBL‐producing isolates have led to increased length of hospital stay,60, 61 increased hospital costs,4 improper antibiotic use,5 and, most notably, increased mortality.61‐63 Of concern, ESBLs have been demonstrated within community Enterobacteriaceae isolates, most notably due to CTX‐M beta‐lactamase production among E. coli. In addition to ESBL production, these community E. coli isolates tend to express fluoroquinolone and trimethoprim‐sulfamethoxazole resistance.64 Carbapenems remain the mainstay of therapy for serious infections due to ESBL‐producing organisms. The once‐daily dosing of ertapenem makes this agent an attractive alternative for outpatient management.
Ertapenem
Ertapenem (Invanz) obtained FDA approval for use in the United States in 2001 and in the European Union in 2002.65 Similar to doripenem, ertapenem blocks cell wall synthesis by binding to specific penicillin‐binding proteins (PBPs).
Ertapenem has activity against numerous gram‐positive and gram‐negative bacteria as well as some anaerobic microorganisms. The FDA‐approved indications include complicated intraabdominal infections, cSSTIs, acute pelvic infections, complicated UTIs, and community‐acquired pneumonias (Table 1).66 Of note, in contrast to other carabapenems, ertapenem does not have activity against Pseudomonas aeruginosa or Acinetobacter spp.67
Ertapenem is approved as a single daily dose of 1 g and can be administered intravenously or intramuscularly. Changes in dosing must also be considered for critically ill patients. When administered to patients with VAP, ertapenem achieved a lower maximum concentration and area under the curve.68 In such patients, it is recommended that the dosage interval be decreased or that a continuous infusion of ertapenem be administered.
The patient's symptoms improve on meropenem. A peripherally‐inserted central catheter is placed for the administration of intravenous antibiotics at home. You prescribe ertapenem (1 g/day) for the remainder of a 14‐day course.
Conclusions
MDR bacteria continue to present a clinical challenge to hospitalists. Proper treatment of patients infected with these organisms is necessary, as inappropriate antibiotic use for MDR bacterial infections has been associated with longer hospital stays, greater cost, and, in some cases, increased mortality. Unfortunately, antibiotic production and development has declined steadily in the past 25 years. To minimize the rate of antimicrobial resistance, physicians must take care to prescribe antibiotics appropriately. While these promising new agents for resistant gram‐positive and gram‐negative infections may aid in battling MDR infections, these antibiotics must be used judiciously to maintain their clinical utility. Hospitalists will continue to play an important role in ensuring that hospitalized patients receive the most effective antimicrobial therapy to both treat the infection and prevent the development of resistance.
- National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004.Am J Infect Control.2004;32:470–485.
- ,,,,,.Changes in the epidemiology of methicillin‐resistant Staphylococcus aureus in intensive care units in US hospitals, 1992‐2003.Clin Infect Dis.2006;42:389–391.
- ,,, et al.Invasive methicillin‐resistant Staphylococcus aureus infections in the United States.JAMA.2007;298:1763–1771.
- ,,,,,.Emergence of community‐acquired methicillin‐resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft tissue infections.Ann Intern Med.2006;144:309–317.
- ,,,.The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria.Antimicrob Agents Chemother.1998;42:3251–3255.
- ,.Activity of linezolid against gram‐positive cocci possessing genes conferring resistance to protein synthesis inhibitors.J Antimicrob Chemother.2000;45:797–802.
- ,,.Clinical and economic outcomes of oral linezolid versus intravenous vancomycin in the treatment of MRSA‐complicated, lower‐extremity skin and soft‐tissue infections caused by methicillin‐resistant Staphylococcus aureus.Am J Surg.2005;189:425–428.
- ,,,.Linezolid for the treatment of adults with bone and joint infections.Intern J Antimicrob Agents.2007;29:233–239.
- .Efficacy and safety of linezolid in the treatment of skin and soft tissue infections.Eur J Clin Microbiol Infect Dis.2002;21:491–498.
- ,,.Linezolid‐associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome.Pharmacotherapy.2007;27(8):1189–1197.
- ,.Development of daptomycin for gram‐positive infections.J Antimicrob Chemother.2000;46(4):523–526.
- .Daptomycin and tigecycline: a review of clinical efficacy in the antimicrobial era.Expert Opin Pharmacother.2007;8(14):2279–2292.
- ,,, et al.Daptomycin verses standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.N Engl J Med.2006:355(7):653–665.
- .Lipopeptides, focusing on daptomycin, for the treatment of gram‐positive infections.Expert Opin Invest Drugs.2004;13:1159–1169.
- .Alternatives to vancomycin for the treatment of methicillin‐resistant Staphylococcus aureus infections.Clin Infect Dis.2007;45(suppl 3):S184–S190.
- .Tigecycline: a new glycylcycline for treatment of serious infections.Clin Infect Dis.2005;41(suppl 5):S303–S314.
- ,,, et al.The efficacy and safety of tigecycline in the treatment of skin and skin‐structure infections: results of 2 double‐blind phase 3 comparison studies with vancomycin‐aztreonam.Clin Infect Dis.2005;41(suppl 5):S341–S353.
- ,.Origin, structure, and activity in vitro and in vivo of dalbavancin.J Antimicrob Chemother2005;55(suppl S2):ii15–ii20.
- ,.Dalbavancin: a novel lipoglycopeptide antibacterial.Pharmacotherapy2006;26:908–918.
- ,,, et al.Randomized, double‐blind comparison of a once‐weekly dalbavancin versus twice‐daily linezolid therapy for the treatment of complicated skin and skin structure infections.Clin Infect Dis.2005;41:1407–1415.
- ,,, et al.Efficacy and safety of weekly dalbavancin therapy for catheter‐related bloodstream infection caused by gram‐positive pathogens.Clin Infect Dis.2005;40:374–380.
- ,.Vancomycin‐resistant staphylococci and enterococci: epidemiology and control.Curr Opin Infect Dis.2005;18:300–305.
- National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992‐June 2001, issued August 2001.Am J Infect Control.2001;29:404–421.
- ,,,,, et al.Antimicrobial resistance trends and outbreak frequency in United States hospitals.Clin Infect Dis.2004;38:78–85.
- ,,,.Comparison of mortality associated with vancomycin‐resistant and vancomycin‐susceptible enterococcal bloodstream infections: a meta‐analysis.Clin Infect Dis.2005;41:327–333.
- ,.Impact of vancomycin resistance on mortality among patients with neutropenia and enterococcal bloodstream infection.J Infect Dis.2005;191(4):588–595.
- ,,,,,.Linezolid for the treatment of multidrug‐resistant gram positive infections: experience from a compassionate‐use program.Clin Infect Dis.2003;36:159–168.
- ,,, et al.Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America.Circulation.2005;111(23):e394–e434.
- ,,.Nosocomial spread of linezolid‐resistant, vancomycin‐resistant Enterococcus faecium.N Engl J Med.2002;346:867–869.
- ,.Novel antibacterial agents for skin and skin structure infections.J Am Acad Dermatol.2004;50(3):331–340.
- ,,.New antimicrobial agents as therapy for resistant gram‐positive cocci.Eur J Clin Microbiol Infect Dis.2008;27(1):3–15.
- .Quinupristin‐dalfopristin and linezolid: evidence and opinion.Clin Infect Dis.2003;36(4):473–481.
- ,,,,,.The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin‐resistant Enterococcus faecium. Synercid Emergency‐Use Study Group.J Antimicrob Chemother.1999:44(2):251–261.
- ,,.Evaluation of the in vitro activity of daptomycin against 19615 clinical isolates of gram‐positive cocci collected in North American hospitals (2002‐2005).Diagn Microbiol Infect Dis.2007;57(4):459–465.
- ,,,,.Daptomycin in the treatment of vancomycin‐resistant Enterococcus faecium bacteremia in neutropenic patients.J Infect.2007;54(6):567–571.
- ,,,,.Daptomycin for the treatment of vancomycin resistant Enterococcus faecium bacteremia.Scand J Infect Dis.2006;38:290–292.
- ,,.Daptomycin for the treatment of gram‐positive bacteremia and infective endocarditis: a retrospective case series of 31 patients.Pharmacotherapy.2006;26(3):347–352.
- Pfizer Pharmacia and Upjohn Company. United States Pharmacopeia. Zyvox. Available at: http://media.pfizer.com/files/products/uspi_zyvox.pdf. Accessed April 2009.
- NNIS System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2003, issued August 2003.Am J Infect Control.2003;31(8):481–498.
- .Resistance in nonfermenting gram‐negative bacteria: multidrug resistance to the maximum.Am J Med.2006;119:S29–S36.
- ,,, et al.Emergence of antibiotic‐resistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents.Antimicrob Agents Chemother.1999;43(6):1379–1382.
- ,,, et al.Multidrug‐resistant Acinetobacter infection mortality rate and length of hospitalization.Emerg Infect Dis.2007;13:97–103.
- ,,, et al.Bloodstream infections due to Acinetobacter spp: epidemiology, risk factors, and impact of multi‐drug resistance.Eur J Clin Microbiol Infect Dis.2008;27(7):607–612.
- ,,,,.Doripenem (S‐4661), a novel carbapenem: comparative activity against contemporary pathogens including bactericidal action and preliminary in vitro methods evaluation.J Antimicrob Chemother.2004;54:144–154.
- ,,.Antimicrobial activity of doripenem (S‐4661): a global surveillance report.Clin Microbiol Infect.2005;11:974–984.
- ,,, et al.Intravenous therapy with. doripenem versus levofloxacin with an option for oral step‐down therapy in the treatment of complicated urinary tract infections and pyelonephritis. 17th European Congress of Clinical Microbiology and Infectious Diseases and the 25th International Congress of Chemotherapy. Munich, Germany. March 31‐April 3, 2007. Abstract no. 833 plus poster.
- .New uses for older antibiotics: nitrofurantoin, amikacin, colistin, polymyxin B, doxycyline, and minocycline revisited.Med Clin North Am.2006;90(6):1089–1107.
- ,,, et al.Efficacy and safety of doripenem versus piperacillin/tazobactam in nosocomial pneumonia: a randomized, open‐label, multicenter study.Curr Med Res Opin.2008;24(7):2113–2126.
- ,,, et al.Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator‐associated pneumonia: a multicenter, randomized study.Crit Care Med.2008;36(4):1089–1096.
- ,,, et al.Efficacy and tolerability of IV doripenem versus meropenem in adults with complicated intra‐abdominal infection: a phase III, prospective, multicenter, randomized, double‐blind, noninferiority study.Clin Ther.2008;30(5):868–883.
- ,,,,.Evaluation of colistin as an agent against multi‐resistant Gram‐negative bacteria.Int J Antimicrob Agents.2005;25(1):11–25.
- .New uses for older antibiotics: nitrofurantoin, amikacin, colistin, polymyxin B, doxycycline, and minocycline revisited.Med Clin North Am.2006;90(6):1089–1107.
- ,.Colistin: the revival of polymyxins for the management of multidrug‐resistant gram‐negative bacterial infections.Clin Infect Dis.2005;40(9):1333–1341.
- ,,, et al.Ventilator‐associated pneumonia (VAP) due to susceptible only to colistin microorganisms.Eur Respir J.2007;30(2):307–313.
- ,,, et al.Safety and efficacy of colistin compared with imipenem in the treatment of ventilator‐associated pneumonia: a matched case‐control study.Intensive Care Med.2007;33(7):1162–1167.
- ,,, et al.Colistin is effective in treatment of infections caused by multidrug‐resistant Pseudomonas aeruginosa in cancer patients.Antimicrob Agents Chemother.2007;51(6):1905–1911.
- ,,,,,.Combination therapy with intravenous colistin for management of infections due to multidrug‐resistant gram‐negative bacteria in patients without cystic fibrosis.Antimicrob Agents Chemother.2005;49:3136–3146.
- ,,, et al.Combined colistin and rifampicin therapy for carbapenem‐resistant Acinetobacter baumannii infections: clinical outcome and adverse events.Clin Microbiol Infect.2005;11:682–683.
- ,,, et al.The efficacy and safety of tigecycline for the treatment of complicated intra‐abdominal infections: analysis of pooled clinical trial data.Clin Infect Dis.2005;41(suppl 5):S354–S367.
- ,,,,.Clinical implications of extended‐spectrum beta‐lactamase‐producing Klebsiella pneumoniae bacteraemia.J Hosp Infect.2002;52:99–106.
- ,,,,,.Clinical and economic impact of bacteremia with extended spectrum beta‐lactamase–producing Enterobacteriaceae.Antimicrob Agents Chemother.2006;50:1257–1262.
- ,,, et al.Ceftazidime‐resistant Klebsiella pneumoniae bloodstream infection in children with febrile neutropenia.Int J Infect Dis.2000;4:21–25.
- ,,, et al.Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended‐ spectrum beta‐lactamases.Clin Infect Dis.2004;39:31–37.
- ,.Extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae: an emerging public‐health concern.Lancet Infect Dis.2008;8(3):159–166.
- ,.Ertapenem, the first of a new group of carbapenems.J Antimicrob Chemother.2003;52(4):538–542.
- Merck 2006.
- ,,.Ertapenem: the new carbapenem 5 years after first FDA licensing for clinical practice.Expert Opin Pharmacother.2007;8(2):237–256.
- ,,, et al.Ertapenem in critically ill patients with early‐onset ventilator‐associated pneumonia: pharmacokinetics with special consideration of free‐drug concentration.J Antimicrob Chemother.2007;59(2):277–284.
- ,.Quinupristin/dalfopristin: a therapeutic review.Clin Ther.2001;23(1):24–44.
- National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004.Am J Infect Control.2004;32:470–485.
- ,,,,,.Changes in the epidemiology of methicillin‐resistant Staphylococcus aureus in intensive care units in US hospitals, 1992‐2003.Clin Infect Dis.2006;42:389–391.
- ,,, et al.Invasive methicillin‐resistant Staphylococcus aureus infections in the United States.JAMA.2007;298:1763–1771.
- ,,,,,.Emergence of community‐acquired methicillin‐resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft tissue infections.Ann Intern Med.2006;144:309–317.
- ,,,.The oxazolidinone linezolid inhibits initiation of protein synthesis in bacteria.Antimicrob Agents Chemother.1998;42:3251–3255.
- ,.Activity of linezolid against gram‐positive cocci possessing genes conferring resistance to protein synthesis inhibitors.J Antimicrob Chemother.2000;45:797–802.
- ,,.Clinical and economic outcomes of oral linezolid versus intravenous vancomycin in the treatment of MRSA‐complicated, lower‐extremity skin and soft‐tissue infections caused by methicillin‐resistant Staphylococcus aureus.Am J Surg.2005;189:425–428.
- ,,,.Linezolid for the treatment of adults with bone and joint infections.Intern J Antimicrob Agents.2007;29:233–239.
- .Efficacy and safety of linezolid in the treatment of skin and soft tissue infections.Eur J Clin Microbiol Infect Dis.2002;21:491–498.
- ,,.Linezolid‐associated peripheral and optic neuropathy, lactic acidosis, and serotonin syndrome.Pharmacotherapy.2007;27(8):1189–1197.
- ,.Development of daptomycin for gram‐positive infections.J Antimicrob Chemother.2000;46(4):523–526.
- .Daptomycin and tigecycline: a review of clinical efficacy in the antimicrobial era.Expert Opin Pharmacother.2007;8(14):2279–2292.
- ,,, et al.Daptomycin verses standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus.N Engl J Med.2006:355(7):653–665.
- .Lipopeptides, focusing on daptomycin, for the treatment of gram‐positive infections.Expert Opin Invest Drugs.2004;13:1159–1169.
- .Alternatives to vancomycin for the treatment of methicillin‐resistant Staphylococcus aureus infections.Clin Infect Dis.2007;45(suppl 3):S184–S190.
- .Tigecycline: a new glycylcycline for treatment of serious infections.Clin Infect Dis.2005;41(suppl 5):S303–S314.
- ,,, et al.The efficacy and safety of tigecycline in the treatment of skin and skin‐structure infections: results of 2 double‐blind phase 3 comparison studies with vancomycin‐aztreonam.Clin Infect Dis.2005;41(suppl 5):S341–S353.
- ,.Origin, structure, and activity in vitro and in vivo of dalbavancin.J Antimicrob Chemother2005;55(suppl S2):ii15–ii20.
- ,.Dalbavancin: a novel lipoglycopeptide antibacterial.Pharmacotherapy2006;26:908–918.
- ,,, et al.Randomized, double‐blind comparison of a once‐weekly dalbavancin versus twice‐daily linezolid therapy for the treatment of complicated skin and skin structure infections.Clin Infect Dis.2005;41:1407–1415.
- ,,, et al.Efficacy and safety of weekly dalbavancin therapy for catheter‐related bloodstream infection caused by gram‐positive pathogens.Clin Infect Dis.2005;40:374–380.
- ,.Vancomycin‐resistant staphylococci and enterococci: epidemiology and control.Curr Opin Infect Dis.2005;18:300–305.
- National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992‐June 2001, issued August 2001.Am J Infect Control.2001;29:404–421.
- ,,,,, et al.Antimicrobial resistance trends and outbreak frequency in United States hospitals.Clin Infect Dis.2004;38:78–85.
- ,,,.Comparison of mortality associated with vancomycin‐resistant and vancomycin‐susceptible enterococcal bloodstream infections: a meta‐analysis.Clin Infect Dis.2005;41:327–333.
- ,.Impact of vancomycin resistance on mortality among patients with neutropenia and enterococcal bloodstream infection.J Infect Dis.2005;191(4):588–595.
- ,,,,,.Linezolid for the treatment of multidrug‐resistant gram positive infections: experience from a compassionate‐use program.Clin Infect Dis.2003;36:159–168.
- ,,, et al.Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America.Circulation.2005;111(23):e394–e434.
- ,,.Nosocomial spread of linezolid‐resistant, vancomycin‐resistant Enterococcus faecium.N Engl J Med.2002;346:867–869.
- ,.Novel antibacterial agents for skin and skin structure infections.J Am Acad Dermatol.2004;50(3):331–340.
- ,,.New antimicrobial agents as therapy for resistant gram‐positive cocci.Eur J Clin Microbiol Infect Dis.2008;27(1):3–15.
- .Quinupristin‐dalfopristin and linezolid: evidence and opinion.Clin Infect Dis.2003;36(4):473–481.
- ,,,,,.The efficacy and safety of quinupristin/dalfopristin for the treatment of infections caused by vancomycin‐resistant Enterococcus faecium. Synercid Emergency‐Use Study Group.J Antimicrob Chemother.1999:44(2):251–261.
- ,,.Evaluation of the in vitro activity of daptomycin against 19615 clinical isolates of gram‐positive cocci collected in North American hospitals (2002‐2005).Diagn Microbiol Infect Dis.2007;57(4):459–465.
- ,,,,.Daptomycin in the treatment of vancomycin‐resistant Enterococcus faecium bacteremia in neutropenic patients.J Infect.2007;54(6):567–571.
- ,,,,.Daptomycin for the treatment of vancomycin resistant Enterococcus faecium bacteremia.Scand J Infect Dis.2006;38:290–292.
- ,,.Daptomycin for the treatment of gram‐positive bacteremia and infective endocarditis: a retrospective case series of 31 patients.Pharmacotherapy.2006;26(3):347–352.
- Pfizer Pharmacia and Upjohn Company. United States Pharmacopeia. Zyvox. Available at: http://media.pfizer.com/files/products/uspi_zyvox.pdf. Accessed April 2009.
- NNIS System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2003, issued August 2003.Am J Infect Control.2003;31(8):481–498.
- .Resistance in nonfermenting gram‐negative bacteria: multidrug resistance to the maximum.Am J Med.2006;119:S29–S36.
- ,,, et al.Emergence of antibiotic‐resistant Pseudomonas aeruginosa: comparison of risks associated with different antipseudomonal agents.Antimicrob Agents Chemother.1999;43(6):1379–1382.
- ,,, et al.Multidrug‐resistant Acinetobacter infection mortality rate and length of hospitalization.Emerg Infect Dis.2007;13:97–103.
- ,,, et al.Bloodstream infections due to Acinetobacter spp: epidemiology, risk factors, and impact of multi‐drug resistance.Eur J Clin Microbiol Infect Dis.2008;27(7):607–612.
- ,,,,.Doripenem (S‐4661), a novel carbapenem: comparative activity against contemporary pathogens including bactericidal action and preliminary in vitro methods evaluation.J Antimicrob Chemother.2004;54:144–154.
- ,,.Antimicrobial activity of doripenem (S‐4661): a global surveillance report.Clin Microbiol Infect.2005;11:974–984.
- ,,, et al.Intravenous therapy with. doripenem versus levofloxacin with an option for oral step‐down therapy in the treatment of complicated urinary tract infections and pyelonephritis. 17th European Congress of Clinical Microbiology and Infectious Diseases and the 25th International Congress of Chemotherapy. Munich, Germany. March 31‐April 3, 2007. Abstract no. 833 plus poster.
- .New uses for older antibiotics: nitrofurantoin, amikacin, colistin, polymyxin B, doxycyline, and minocycline revisited.Med Clin North Am.2006;90(6):1089–1107.
- ,,, et al.Efficacy and safety of doripenem versus piperacillin/tazobactam in nosocomial pneumonia: a randomized, open‐label, multicenter study.Curr Med Res Opin.2008;24(7):2113–2126.
- ,,, et al.Efficacy and safety of intravenous infusion of doripenem versus imipenem in ventilator‐associated pneumonia: a multicenter, randomized study.Crit Care Med.2008;36(4):1089–1096.
- ,,, et al.Efficacy and tolerability of IV doripenem versus meropenem in adults with complicated intra‐abdominal infection: a phase III, prospective, multicenter, randomized, double‐blind, noninferiority study.Clin Ther.2008;30(5):868–883.
- ,,,,.Evaluation of colistin as an agent against multi‐resistant Gram‐negative bacteria.Int J Antimicrob Agents.2005;25(1):11–25.
- .New uses for older antibiotics: nitrofurantoin, amikacin, colistin, polymyxin B, doxycycline, and minocycline revisited.Med Clin North Am.2006;90(6):1089–1107.
- ,.Colistin: the revival of polymyxins for the management of multidrug‐resistant gram‐negative bacterial infections.Clin Infect Dis.2005;40(9):1333–1341.
- ,,, et al.Ventilator‐associated pneumonia (VAP) due to susceptible only to colistin microorganisms.Eur Respir J.2007;30(2):307–313.
- ,,, et al.Safety and efficacy of colistin compared with imipenem in the treatment of ventilator‐associated pneumonia: a matched case‐control study.Intensive Care Med.2007;33(7):1162–1167.
- ,,, et al.Colistin is effective in treatment of infections caused by multidrug‐resistant Pseudomonas aeruginosa in cancer patients.Antimicrob Agents Chemother.2007;51(6):1905–1911.
- ,,,,,.Combination therapy with intravenous colistin for management of infections due to multidrug‐resistant gram‐negative bacteria in patients without cystic fibrosis.Antimicrob Agents Chemother.2005;49:3136–3146.
- ,,, et al.Combined colistin and rifampicin therapy for carbapenem‐resistant Acinetobacter baumannii infections: clinical outcome and adverse events.Clin Microbiol Infect.2005;11:682–683.
- ,,, et al.The efficacy and safety of tigecycline for the treatment of complicated intra‐abdominal infections: analysis of pooled clinical trial data.Clin Infect Dis.2005;41(suppl 5):S354–S367.
- ,,,,.Clinical implications of extended‐spectrum beta‐lactamase‐producing Klebsiella pneumoniae bacteraemia.J Hosp Infect.2002;52:99–106.
- ,,,,,.Clinical and economic impact of bacteremia with extended spectrum beta‐lactamase–producing Enterobacteriaceae.Antimicrob Agents Chemother.2006;50:1257–1262.
- ,,, et al.Ceftazidime‐resistant Klebsiella pneumoniae bloodstream infection in children with febrile neutropenia.Int J Infect Dis.2000;4:21–25.
- ,,, et al.Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended‐ spectrum beta‐lactamases.Clin Infect Dis.2004;39:31–37.
- ,.Extended‐spectrum beta‐lactamase‐producing Enterobacteriaceae: an emerging public‐health concern.Lancet Infect Dis.2008;8(3):159–166.
- ,.Ertapenem, the first of a new group of carbapenems.J Antimicrob Chemother.2003;52(4):538–542.
- Merck 2006.
- ,,.Ertapenem: the new carbapenem 5 years after first FDA licensing for clinical practice.Expert Opin Pharmacother.2007;8(2):237–256.
- ,,, et al.Ertapenem in critically ill patients with early‐onset ventilator‐associated pneumonia: pharmacokinetics with special consideration of free‐drug concentration.J Antimicrob Chemother.2007;59(2):277–284.
- ,.Quinupristin/dalfopristin: a therapeutic review.Clin Ther.2001;23(1):24–44.