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Sharon Worcester is an award-winning medical journalist for MDedge News. She has been with the company since 1996, first as the Southeast Bureau Chief (1996-2009) when the company was known as International Medical News Group, then as a freelance writer (2010-2015) before returning as a reporter in 2015. She previously worked as a daily newspaper reporter covering health and local government. Sharon currently reports primarily on oncology and hematology. She has a BA from Eckerd College and an MA in Mass Communication/Print Journalism from the University of Florida. Connect with her via LinkedIn and follow her on twitter @SW_MedReporter.
Continue DMARDs, biologics in RA surgery patients
WASHINGTON – The perioperative use of disease-modifying antirheumatic drug monotherapy or combined therapy with methotrexate and a tumor necrosis factor (TNF) inhibitor is not associated with increased rates of postoperative infectious complications or wound infections in patients with rheumatoid arthritis, according to findings from a retrospective review of more than 9,000 surgeries.
With respect to monotherapy, treatment was continued in 1,951 of 2,601 surgeries among patients receiving methotrexate, in 1,496 of 2,012 surgeries among patients receiving hydroxychloroquine, and in 508 of 652 surgeries among patient receiving leflunomide. The odds ratios for postoperative infection (including urinary tract, pneumonia, or sepsis) and postoperative wound infection, respectively, were 0.79 and 0.77 with methotrexate continuation, 0.93 and 0.86 with hydroxychloroquine continuation, and 0.78 and 0.87 with leflunomide continuation, Hsin-Hsuan Juo, MD, reported at the annual meeting of the American College of Rheumatology.
Data for this study were derived from the U.S. Department of Veterans Affairs administrative database and surgical quality registry. Rheumatoid arthritis patients who underwent a surgical procedure and who were on at least one disease-modifying antirheumatic drug (DMARD) or one biologic agent in the perioperative period during the study period of Oct. 1, 1999, through Sept. 30, 2009, were included. Subjects had a mean age of 67 years, and 91% were men.
The finding that the continuation of DMARD monotherapy or the combination of methotrexate and TNF inhibitor therapy for RA in the perioperative setting was not associated with increased rates of overall postoperative infectious complications and wound infections is important, because many patients are advised to stop taking these drugs prior to surgery because of concerns about increased susceptibility to infection. Discontinuing RA medication can increase the risk of disease flares requiring treatment with prednisone, which can further increase the risk of postsurgical complications, Dr. Juo said.
Clear, consistent guidance on the continuation of treatment among RA patients undergoing surgery has been lacking, she said, noting that guidelines over the years from the ACR, the British Society for Rheumatology, and the Canadian Rheumatology Association have differed in their recommendations.
A new draft guideline reported the morning of Dr. Juo’s presentation at the ACR annual meeting recommended continuing DMARDs but discontinuing biologics prior to surgery, but that guideline is limited to orthopedic surgery among patients with various rheumatic diseases.
“With literature review, the results are conflicting as well; some recommend continuing medication, and others recommend discontinuing medications prior to surgery,” she said.
The current findings, though limited by the study’s observational design and generally older, male population, suggest that continuing antirheumatic medications during the perioperative period is not associated with increased rates of postoperative complications.
“Our study results suggest that discontinuing DMARDs and biologic agents prior to surgery may not be necessary. Therefore, being on DMARDs or biologic agents should not preclude patients from receiving urgent surgeries,” Dr. Juo concluded.
Dr. Juo reported having no disclosures.
WASHINGTON – The perioperative use of disease-modifying antirheumatic drug monotherapy or combined therapy with methotrexate and a tumor necrosis factor (TNF) inhibitor is not associated with increased rates of postoperative infectious complications or wound infections in patients with rheumatoid arthritis, according to findings from a retrospective review of more than 9,000 surgeries.
With respect to monotherapy, treatment was continued in 1,951 of 2,601 surgeries among patients receiving methotrexate, in 1,496 of 2,012 surgeries among patients receiving hydroxychloroquine, and in 508 of 652 surgeries among patient receiving leflunomide. The odds ratios for postoperative infection (including urinary tract, pneumonia, or sepsis) and postoperative wound infection, respectively, were 0.79 and 0.77 with methotrexate continuation, 0.93 and 0.86 with hydroxychloroquine continuation, and 0.78 and 0.87 with leflunomide continuation, Hsin-Hsuan Juo, MD, reported at the annual meeting of the American College of Rheumatology.
Data for this study were derived from the U.S. Department of Veterans Affairs administrative database and surgical quality registry. Rheumatoid arthritis patients who underwent a surgical procedure and who were on at least one disease-modifying antirheumatic drug (DMARD) or one biologic agent in the perioperative period during the study period of Oct. 1, 1999, through Sept. 30, 2009, were included. Subjects had a mean age of 67 years, and 91% were men.
The finding that the continuation of DMARD monotherapy or the combination of methotrexate and TNF inhibitor therapy for RA in the perioperative setting was not associated with increased rates of overall postoperative infectious complications and wound infections is important, because many patients are advised to stop taking these drugs prior to surgery because of concerns about increased susceptibility to infection. Discontinuing RA medication can increase the risk of disease flares requiring treatment with prednisone, which can further increase the risk of postsurgical complications, Dr. Juo said.
Clear, consistent guidance on the continuation of treatment among RA patients undergoing surgery has been lacking, she said, noting that guidelines over the years from the ACR, the British Society for Rheumatology, and the Canadian Rheumatology Association have differed in their recommendations.
A new draft guideline reported the morning of Dr. Juo’s presentation at the ACR annual meeting recommended continuing DMARDs but discontinuing biologics prior to surgery, but that guideline is limited to orthopedic surgery among patients with various rheumatic diseases.
“With literature review, the results are conflicting as well; some recommend continuing medication, and others recommend discontinuing medications prior to surgery,” she said.
The current findings, though limited by the study’s observational design and generally older, male population, suggest that continuing antirheumatic medications during the perioperative period is not associated with increased rates of postoperative complications.
“Our study results suggest that discontinuing DMARDs and biologic agents prior to surgery may not be necessary. Therefore, being on DMARDs or biologic agents should not preclude patients from receiving urgent surgeries,” Dr. Juo concluded.
Dr. Juo reported having no disclosures.
WASHINGTON – The perioperative use of disease-modifying antirheumatic drug monotherapy or combined therapy with methotrexate and a tumor necrosis factor (TNF) inhibitor is not associated with increased rates of postoperative infectious complications or wound infections in patients with rheumatoid arthritis, according to findings from a retrospective review of more than 9,000 surgeries.
With respect to monotherapy, treatment was continued in 1,951 of 2,601 surgeries among patients receiving methotrexate, in 1,496 of 2,012 surgeries among patients receiving hydroxychloroquine, and in 508 of 652 surgeries among patient receiving leflunomide. The odds ratios for postoperative infection (including urinary tract, pneumonia, or sepsis) and postoperative wound infection, respectively, were 0.79 and 0.77 with methotrexate continuation, 0.93 and 0.86 with hydroxychloroquine continuation, and 0.78 and 0.87 with leflunomide continuation, Hsin-Hsuan Juo, MD, reported at the annual meeting of the American College of Rheumatology.
Data for this study were derived from the U.S. Department of Veterans Affairs administrative database and surgical quality registry. Rheumatoid arthritis patients who underwent a surgical procedure and who were on at least one disease-modifying antirheumatic drug (DMARD) or one biologic agent in the perioperative period during the study period of Oct. 1, 1999, through Sept. 30, 2009, were included. Subjects had a mean age of 67 years, and 91% were men.
The finding that the continuation of DMARD monotherapy or the combination of methotrexate and TNF inhibitor therapy for RA in the perioperative setting was not associated with increased rates of overall postoperative infectious complications and wound infections is important, because many patients are advised to stop taking these drugs prior to surgery because of concerns about increased susceptibility to infection. Discontinuing RA medication can increase the risk of disease flares requiring treatment with prednisone, which can further increase the risk of postsurgical complications, Dr. Juo said.
Clear, consistent guidance on the continuation of treatment among RA patients undergoing surgery has been lacking, she said, noting that guidelines over the years from the ACR, the British Society for Rheumatology, and the Canadian Rheumatology Association have differed in their recommendations.
A new draft guideline reported the morning of Dr. Juo’s presentation at the ACR annual meeting recommended continuing DMARDs but discontinuing biologics prior to surgery, but that guideline is limited to orthopedic surgery among patients with various rheumatic diseases.
“With literature review, the results are conflicting as well; some recommend continuing medication, and others recommend discontinuing medications prior to surgery,” she said.
The current findings, though limited by the study’s observational design and generally older, male population, suggest that continuing antirheumatic medications during the perioperative period is not associated with increased rates of postoperative complications.
“Our study results suggest that discontinuing DMARDs and biologic agents prior to surgery may not be necessary. Therefore, being on DMARDs or biologic agents should not preclude patients from receiving urgent surgeries,” Dr. Juo concluded.
Dr. Juo reported having no disclosures.
AT THE ACR ANNUAL MEETING
Key clinical point:
Major finding: Odds ratios for postoperative infection and postoperative wound infection, respectively, were 0.79 and 0.77 with methotrexate continuation, 0.93 and 0.86 with hydroxychloroquine continuation, 0.78 and 0.87 with leflunomide continuation, and 0.35 and 0.38 with combined methotrexate/TNF inhibitor continuation.
Data source: A retrospective review of more than 9,000 surgeries.
Disclosures: Dr. Juo reported having no disclosures.
Inpatient telemedicine could bridge infectious disease specialist gap
NEW ORLEANS – Telemedicine inpatient consultations are a relatively new component in health care, but they could help address the problem of infectious disease physician shortages, particularly in rural communities, according to Lewis McCurdy, MD.
Dr. McCurdy of Carolinas HealthCare System in Charlotte, N.C., shared his experience providing virtual consultations for inpatients at a rural community hospital, noting that the approach was well received by patients, and that uptake by providers doubled during the first year.
Further, the virtual consultations appeared to have important clinical benefits, because very few patients had to be transferred to higher-level acuity facilities. The consultations seemed to help providers with challenging situations that they might not have felt comfortable managing otherwise, such as bloodstream infections, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
In a video interview, Dr. McCurdy discussed the development of the process for using telemedicine for inpatient consultations, outcomes after about 18 months at one facility, and challenges of providing telemedicine services.
The approach could be very helpful for smaller communities without an infectious disease provider, Dr. McCurdy said.
“This allows us to sort of expand our expertise into those communities on a more efficiently scaled basis,” he explained. “So, it does provide one solution to trying to meet the demand in the community for ID expertise.”
Dr. McCurdy reported having no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NEW ORLEANS – Telemedicine inpatient consultations are a relatively new component in health care, but they could help address the problem of infectious disease physician shortages, particularly in rural communities, according to Lewis McCurdy, MD.
Dr. McCurdy of Carolinas HealthCare System in Charlotte, N.C., shared his experience providing virtual consultations for inpatients at a rural community hospital, noting that the approach was well received by patients, and that uptake by providers doubled during the first year.
Further, the virtual consultations appeared to have important clinical benefits, because very few patients had to be transferred to higher-level acuity facilities. The consultations seemed to help providers with challenging situations that they might not have felt comfortable managing otherwise, such as bloodstream infections, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
In a video interview, Dr. McCurdy discussed the development of the process for using telemedicine for inpatient consultations, outcomes after about 18 months at one facility, and challenges of providing telemedicine services.
The approach could be very helpful for smaller communities without an infectious disease provider, Dr. McCurdy said.
“This allows us to sort of expand our expertise into those communities on a more efficiently scaled basis,” he explained. “So, it does provide one solution to trying to meet the demand in the community for ID expertise.”
Dr. McCurdy reported having no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NEW ORLEANS – Telemedicine inpatient consultations are a relatively new component in health care, but they could help address the problem of infectious disease physician shortages, particularly in rural communities, according to Lewis McCurdy, MD.
Dr. McCurdy of Carolinas HealthCare System in Charlotte, N.C., shared his experience providing virtual consultations for inpatients at a rural community hospital, noting that the approach was well received by patients, and that uptake by providers doubled during the first year.
Further, the virtual consultations appeared to have important clinical benefits, because very few patients had to be transferred to higher-level acuity facilities. The consultations seemed to help providers with challenging situations that they might not have felt comfortable managing otherwise, such as bloodstream infections, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
In a video interview, Dr. McCurdy discussed the development of the process for using telemedicine for inpatient consultations, outcomes after about 18 months at one facility, and challenges of providing telemedicine services.
The approach could be very helpful for smaller communities without an infectious disease provider, Dr. McCurdy said.
“This allows us to sort of expand our expertise into those communities on a more efficiently scaled basis,” he explained. “So, it does provide one solution to trying to meet the demand in the community for ID expertise.”
Dr. McCurdy reported having no disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Infectious disease physicians: Antibiotic shortages are the new norm
NEW ORLEANS – Antibiotic shortages reported by the Emerging Infections Network (EIN) in 2011 persist in 2016, according to a web-based follow-up survey of infectious disease physicians.
Of 701 network members who responded to the EIN survey in early 2016, 70% reported needing to modify their antimicrobial choice because of a shortage in the past 2 years. They did so by using broader-spectrum agents (75% of respondents), more costly agents (58%), less effective second-line agents (45%), and more toxic agents (37%), Adi Gundlapalli, MD, PhD, reported at an annual scientific meeting on infectious diseases.
In addition, 73% of respondents reported that the shortages affected patient care or outcomes, reported Dr. Gundlapalli of the University of Utah, Salt Lake City.
The percentage of respondents reporting adverse patient outcomes related to shortages increased from 2011 to 2016 (51% vs.73%), he noted at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The top 10 antimicrobials they reported as being in short supply were piperacillin-tazobactam, ampicillin-sulbactam, meropenem, cefotaxime, cefepime, trimethoprim-sulfamethoxazole (TMP-SMX), doxycycline, imipenem, acyclovir, and amikacin. TMP-SMX and acyclovir were in short supply at both time points.
The most common ways respondents reported learning about drug shortages were from hospital notification (76%), from a colleague (56%), from a pharmacy that contacted them regarding a prescription for the agent (53%), or from the Food and Drug Administration website or another website on shortages (23%). The most common ways of learning about a shortage changed – from notification after trying to prescribe a drug in 2011, to proactive hospital/system (local) notification in 2016; 71% of respondents said that communications in 2016 were sufficient.
Most respondents (83%) reported that guidelines for dealing with shortages had been developed by an antimicrobial stewardship program (ASP) at their institution.
“This, I think, is one of the highlight results,” said Dr. Gundlapalli, who is also a staff physician at the VA Salt Lake City Health System. “In 2011, we had no specific question or comments received about [ASPs], and here in 2016, 83% of respondents’ institutions had developed guidelines related to drug shortages.”
Respondents also had the opportunity to submit free-text responses, and among the themes that emerged was concern regarding toxicity and adverse outcomes associated with increased use of aminoglycosides because of the shortage of piperacillin-tazobactam. Another – described as a blessing in disguise – was the shortage of meropenem, which led one ASP to “institute restrictions on its use, which have continued,” he said.
“Another theme was ‘simpler agents seem more likely to be in shortage,’ ” Dr. Gundlapalli said, noting ampicillin-sulbactam in 2016 and Pen-G as examples.
“And then, of course, the other theme across the board ... was our new asset,” he said, explaining that some respondents commented on the value of ASP pharmacists and programs to help with drug shortage issues.
The overall theme of this follow-up survey, in the context of prior surveys in 2001 and 2011, is that antibiotic shortages are the “new normal – a way of life,” Dr. Gundlapalli said.
“The concerns do persist, and we feel there is further work to be done here,” he said. He specifically noted that there is a need to inform and educate fellows and colleagues in hospitals, increase awareness generally, improve communication strategies, and conduct detailed studies on adverse effects and outcomes.
“And now, since ASPs are very pervasive ... maybe it’s time to formalize and delineate the role of ASPs in antimicrobial shortages,” he said.
The problem of antibiotic shortages “harkens back to the day when penicillin was recycled in the urine [of soldiers in World War II] to save this very scarce resource ... but that’s a very extreme measure to take,” noted Donald Graham, MD, of the Springfield (Ill.) Clinic, one of the study’s coauthors. “It seems like it’s time for the other federal arm – namely, the Food and Drug Administration – to do something about this.”
Dr. Graham said he believes the problem is in part because of economics, and in part because of “the higher standards that the FDA imposes upon these manufacturing concerns.” These drugs often are low-profit items, and it isn’t always in the financial best interest of a pharmaceutical company to upgrade their facilities.
“But they really have to recognize the importance of having availability of these simple agents,” he said, pleading with any FDA representatives in the audience to “maybe think about some of these very high standards.”
Dr. Gundlapalli reported having no disclosures. Dr. Graham disclosed relationships with Astellas and Theravance Biopharma.
NEW ORLEANS – Antibiotic shortages reported by the Emerging Infections Network (EIN) in 2011 persist in 2016, according to a web-based follow-up survey of infectious disease physicians.
Of 701 network members who responded to the EIN survey in early 2016, 70% reported needing to modify their antimicrobial choice because of a shortage in the past 2 years. They did so by using broader-spectrum agents (75% of respondents), more costly agents (58%), less effective second-line agents (45%), and more toxic agents (37%), Adi Gundlapalli, MD, PhD, reported at an annual scientific meeting on infectious diseases.
In addition, 73% of respondents reported that the shortages affected patient care or outcomes, reported Dr. Gundlapalli of the University of Utah, Salt Lake City.
The percentage of respondents reporting adverse patient outcomes related to shortages increased from 2011 to 2016 (51% vs.73%), he noted at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The top 10 antimicrobials they reported as being in short supply were piperacillin-tazobactam, ampicillin-sulbactam, meropenem, cefotaxime, cefepime, trimethoprim-sulfamethoxazole (TMP-SMX), doxycycline, imipenem, acyclovir, and amikacin. TMP-SMX and acyclovir were in short supply at both time points.
The most common ways respondents reported learning about drug shortages were from hospital notification (76%), from a colleague (56%), from a pharmacy that contacted them regarding a prescription for the agent (53%), or from the Food and Drug Administration website or another website on shortages (23%). The most common ways of learning about a shortage changed – from notification after trying to prescribe a drug in 2011, to proactive hospital/system (local) notification in 2016; 71% of respondents said that communications in 2016 were sufficient.
Most respondents (83%) reported that guidelines for dealing with shortages had been developed by an antimicrobial stewardship program (ASP) at their institution.
“This, I think, is one of the highlight results,” said Dr. Gundlapalli, who is also a staff physician at the VA Salt Lake City Health System. “In 2011, we had no specific question or comments received about [ASPs], and here in 2016, 83% of respondents’ institutions had developed guidelines related to drug shortages.”
Respondents also had the opportunity to submit free-text responses, and among the themes that emerged was concern regarding toxicity and adverse outcomes associated with increased use of aminoglycosides because of the shortage of piperacillin-tazobactam. Another – described as a blessing in disguise – was the shortage of meropenem, which led one ASP to “institute restrictions on its use, which have continued,” he said.
“Another theme was ‘simpler agents seem more likely to be in shortage,’ ” Dr. Gundlapalli said, noting ampicillin-sulbactam in 2016 and Pen-G as examples.
“And then, of course, the other theme across the board ... was our new asset,” he said, explaining that some respondents commented on the value of ASP pharmacists and programs to help with drug shortage issues.
The overall theme of this follow-up survey, in the context of prior surveys in 2001 and 2011, is that antibiotic shortages are the “new normal – a way of life,” Dr. Gundlapalli said.
“The concerns do persist, and we feel there is further work to be done here,” he said. He specifically noted that there is a need to inform and educate fellows and colleagues in hospitals, increase awareness generally, improve communication strategies, and conduct detailed studies on adverse effects and outcomes.
“And now, since ASPs are very pervasive ... maybe it’s time to formalize and delineate the role of ASPs in antimicrobial shortages,” he said.
The problem of antibiotic shortages “harkens back to the day when penicillin was recycled in the urine [of soldiers in World War II] to save this very scarce resource ... but that’s a very extreme measure to take,” noted Donald Graham, MD, of the Springfield (Ill.) Clinic, one of the study’s coauthors. “It seems like it’s time for the other federal arm – namely, the Food and Drug Administration – to do something about this.”
Dr. Graham said he believes the problem is in part because of economics, and in part because of “the higher standards that the FDA imposes upon these manufacturing concerns.” These drugs often are low-profit items, and it isn’t always in the financial best interest of a pharmaceutical company to upgrade their facilities.
“But they really have to recognize the importance of having availability of these simple agents,” he said, pleading with any FDA representatives in the audience to “maybe think about some of these very high standards.”
Dr. Gundlapalli reported having no disclosures. Dr. Graham disclosed relationships with Astellas and Theravance Biopharma.
NEW ORLEANS – Antibiotic shortages reported by the Emerging Infections Network (EIN) in 2011 persist in 2016, according to a web-based follow-up survey of infectious disease physicians.
Of 701 network members who responded to the EIN survey in early 2016, 70% reported needing to modify their antimicrobial choice because of a shortage in the past 2 years. They did so by using broader-spectrum agents (75% of respondents), more costly agents (58%), less effective second-line agents (45%), and more toxic agents (37%), Adi Gundlapalli, MD, PhD, reported at an annual scientific meeting on infectious diseases.
In addition, 73% of respondents reported that the shortages affected patient care or outcomes, reported Dr. Gundlapalli of the University of Utah, Salt Lake City.
The percentage of respondents reporting adverse patient outcomes related to shortages increased from 2011 to 2016 (51% vs.73%), he noted at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The top 10 antimicrobials they reported as being in short supply were piperacillin-tazobactam, ampicillin-sulbactam, meropenem, cefotaxime, cefepime, trimethoprim-sulfamethoxazole (TMP-SMX), doxycycline, imipenem, acyclovir, and amikacin. TMP-SMX and acyclovir were in short supply at both time points.
The most common ways respondents reported learning about drug shortages were from hospital notification (76%), from a colleague (56%), from a pharmacy that contacted them regarding a prescription for the agent (53%), or from the Food and Drug Administration website or another website on shortages (23%). The most common ways of learning about a shortage changed – from notification after trying to prescribe a drug in 2011, to proactive hospital/system (local) notification in 2016; 71% of respondents said that communications in 2016 were sufficient.
Most respondents (83%) reported that guidelines for dealing with shortages had been developed by an antimicrobial stewardship program (ASP) at their institution.
“This, I think, is one of the highlight results,” said Dr. Gundlapalli, who is also a staff physician at the VA Salt Lake City Health System. “In 2011, we had no specific question or comments received about [ASPs], and here in 2016, 83% of respondents’ institutions had developed guidelines related to drug shortages.”
Respondents also had the opportunity to submit free-text responses, and among the themes that emerged was concern regarding toxicity and adverse outcomes associated with increased use of aminoglycosides because of the shortage of piperacillin-tazobactam. Another – described as a blessing in disguise – was the shortage of meropenem, which led one ASP to “institute restrictions on its use, which have continued,” he said.
“Another theme was ‘simpler agents seem more likely to be in shortage,’ ” Dr. Gundlapalli said, noting ampicillin-sulbactam in 2016 and Pen-G as examples.
“And then, of course, the other theme across the board ... was our new asset,” he said, explaining that some respondents commented on the value of ASP pharmacists and programs to help with drug shortage issues.
The overall theme of this follow-up survey, in the context of prior surveys in 2001 and 2011, is that antibiotic shortages are the “new normal – a way of life,” Dr. Gundlapalli said.
“The concerns do persist, and we feel there is further work to be done here,” he said. He specifically noted that there is a need to inform and educate fellows and colleagues in hospitals, increase awareness generally, improve communication strategies, and conduct detailed studies on adverse effects and outcomes.
“And now, since ASPs are very pervasive ... maybe it’s time to formalize and delineate the role of ASPs in antimicrobial shortages,” he said.
The problem of antibiotic shortages “harkens back to the day when penicillin was recycled in the urine [of soldiers in World War II] to save this very scarce resource ... but that’s a very extreme measure to take,” noted Donald Graham, MD, of the Springfield (Ill.) Clinic, one of the study’s coauthors. “It seems like it’s time for the other federal arm – namely, the Food and Drug Administration – to do something about this.”
Dr. Graham said he believes the problem is in part because of economics, and in part because of “the higher standards that the FDA imposes upon these manufacturing concerns.” These drugs often are low-profit items, and it isn’t always in the financial best interest of a pharmaceutical company to upgrade their facilities.
“But they really have to recognize the importance of having availability of these simple agents,” he said, pleading with any FDA representatives in the audience to “maybe think about some of these very high standards.”
Dr. Gundlapalli reported having no disclosures. Dr. Graham disclosed relationships with Astellas and Theravance Biopharma.
AT IDWEEK 2016
Key clinical point:
Major finding: 70% of respondents reported needing to modify their antimicrobial choice because of a shortage in the past 2 years, and 73% said shortages affected patient care or outcomes.
Data source: A follow-up survey of 701 physicians.
Disclosures: Dr. Gundlapalli reported having no disclosures. Dr. Graham disclosed relationships with Astellas and Theravance Biopharma.
Phase II data suggest IV zanamivir safe for severe flu in kids
NEW ORLEANS – The investigational intravenous formulation of the neuraminidase inhibitor zanamivir appears to be a safe influenza treatment for hospitalized children and adolescents at high risk of complications who can’t tolerate enteral therapy, according to findings from an open-label, multicenter, phase II study.
In 71 such patients with laboratory-confirmed flu, who presented within 7 days of illness onset and who received intravenous zanamivir (IVZ) for 5-10 days, 72% experienced adverse events (AEs), 21% experienced serious adverse events, and 5 deaths occurred, but none were considered by the investigators to be attributable to IVZ, Jeffrey Blumer, MD, reported at IDWeek, an annual scientific meeting on infectious diseases.
Rather, the adverse events were “fairly diverse. ... the kinds of things normally seen in critically ill pediatric populations,” he said.
The patients, who had a mean age of 7 years, were treated with IVZ doses selected to provide exposures comparable to 600 mg in adults – a dosage shown in prior studies to be safe and well-tolerated in adults. Patients aged 6 months to under age 6 years received twice-daily doses of 14 mg/kg, and those aged 6 years to less than 18 years received twice-daily doses of 12 mg/kg, not to exceed 600 mg. Doses were adjusted for renal function.
Patients were enrolled from five countries, and most (69%) had received prior treatment with oseltamivir. More than half (56%) had chronic medical conditions.
The median time from symptom onset to IVZ treatment was 4 days, Dr. Blumer of the University of Toledo (Ohio) said at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
Infiltrate on chest x-ray was seen in 59% of patients, mechanical ventilation was required in 34% of patients, and extracorporeal membrane oxygenation was required in 6% of patients. Treatment in the intensive care unit was required in 65% of patients, and cumulative mortality was 4% at 14 days, and 7% at 28 days.
“Overall, the [IVZ] exposure and then the elimination profiles were consistent across the entire age cohort – unusual for most drugs, but it seemed to hold true, which makes zanamivir a lot easier for us to work with in pediatrics,” Dr. Blumer said.
While the numbers are small, exposure and response delineation didn’t seem to be impacted by mechanical ventilation, by extracorporeal membrane oxygenation, or by continuous renal replacement therapy, which is a good sign, he noted.
“So we generally had good, consistent experience here. ... Overall, 64 of the 71 patients survived, got better, left the ICU, and left the hospital,” Dr. Blumer said.
Of note, a treatment-emergent resistance substitution, E119G, was detected in a day 5 H1N1 isolate from an immunocompetent patient who improved clinically while on IVZ, he said, adding that no phenotype data were available as the sample could not be cultured.
The findings are important, because while zanamivir is currently labeled for patients older than 7 years, and the intravenous formulation currently in development has been shown to be safe for adults, there is a critical unmet need for an effective parenteral treatment for severe flu in children at high risk of complications who cannot tolerate enteral therapy.
“We need a drug that is available for the critically ill. We need a drug available for kids who are unable to take oral therapy, and for treatment of oseltamivir-resistant strains,” he said, adding that the current findings suggest that IVZ – with dose selection based on age, weight, and renal function – is a suitable treatment option for such patients.
“In conclusion, what we saw in this open-label trial was that the dose selection that we utilized gave us the kind of exposure we’d expect, and it seems it was an appropriate way to approach pediatric patients,” he said. “There wasn’t any safety signal attributable to the drug, and the overall pattern was more that of serious influenza, rather than of drug exposure.”
Dr. Blumer reported receiving research support from GlaxoSmithKline, which sponsored the study.
NEW ORLEANS – The investigational intravenous formulation of the neuraminidase inhibitor zanamivir appears to be a safe influenza treatment for hospitalized children and adolescents at high risk of complications who can’t tolerate enteral therapy, according to findings from an open-label, multicenter, phase II study.
In 71 such patients with laboratory-confirmed flu, who presented within 7 days of illness onset and who received intravenous zanamivir (IVZ) for 5-10 days, 72% experienced adverse events (AEs), 21% experienced serious adverse events, and 5 deaths occurred, but none were considered by the investigators to be attributable to IVZ, Jeffrey Blumer, MD, reported at IDWeek, an annual scientific meeting on infectious diseases.
Rather, the adverse events were “fairly diverse. ... the kinds of things normally seen in critically ill pediatric populations,” he said.
The patients, who had a mean age of 7 years, were treated with IVZ doses selected to provide exposures comparable to 600 mg in adults – a dosage shown in prior studies to be safe and well-tolerated in adults. Patients aged 6 months to under age 6 years received twice-daily doses of 14 mg/kg, and those aged 6 years to less than 18 years received twice-daily doses of 12 mg/kg, not to exceed 600 mg. Doses were adjusted for renal function.
Patients were enrolled from five countries, and most (69%) had received prior treatment with oseltamivir. More than half (56%) had chronic medical conditions.
The median time from symptom onset to IVZ treatment was 4 days, Dr. Blumer of the University of Toledo (Ohio) said at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
Infiltrate on chest x-ray was seen in 59% of patients, mechanical ventilation was required in 34% of patients, and extracorporeal membrane oxygenation was required in 6% of patients. Treatment in the intensive care unit was required in 65% of patients, and cumulative mortality was 4% at 14 days, and 7% at 28 days.
“Overall, the [IVZ] exposure and then the elimination profiles were consistent across the entire age cohort – unusual for most drugs, but it seemed to hold true, which makes zanamivir a lot easier for us to work with in pediatrics,” Dr. Blumer said.
While the numbers are small, exposure and response delineation didn’t seem to be impacted by mechanical ventilation, by extracorporeal membrane oxygenation, or by continuous renal replacement therapy, which is a good sign, he noted.
“So we generally had good, consistent experience here. ... Overall, 64 of the 71 patients survived, got better, left the ICU, and left the hospital,” Dr. Blumer said.
Of note, a treatment-emergent resistance substitution, E119G, was detected in a day 5 H1N1 isolate from an immunocompetent patient who improved clinically while on IVZ, he said, adding that no phenotype data were available as the sample could not be cultured.
The findings are important, because while zanamivir is currently labeled for patients older than 7 years, and the intravenous formulation currently in development has been shown to be safe for adults, there is a critical unmet need for an effective parenteral treatment for severe flu in children at high risk of complications who cannot tolerate enteral therapy.
“We need a drug that is available for the critically ill. We need a drug available for kids who are unable to take oral therapy, and for treatment of oseltamivir-resistant strains,” he said, adding that the current findings suggest that IVZ – with dose selection based on age, weight, and renal function – is a suitable treatment option for such patients.
“In conclusion, what we saw in this open-label trial was that the dose selection that we utilized gave us the kind of exposure we’d expect, and it seems it was an appropriate way to approach pediatric patients,” he said. “There wasn’t any safety signal attributable to the drug, and the overall pattern was more that of serious influenza, rather than of drug exposure.”
Dr. Blumer reported receiving research support from GlaxoSmithKline, which sponsored the study.
NEW ORLEANS – The investigational intravenous formulation of the neuraminidase inhibitor zanamivir appears to be a safe influenza treatment for hospitalized children and adolescents at high risk of complications who can’t tolerate enteral therapy, according to findings from an open-label, multicenter, phase II study.
In 71 such patients with laboratory-confirmed flu, who presented within 7 days of illness onset and who received intravenous zanamivir (IVZ) for 5-10 days, 72% experienced adverse events (AEs), 21% experienced serious adverse events, and 5 deaths occurred, but none were considered by the investigators to be attributable to IVZ, Jeffrey Blumer, MD, reported at IDWeek, an annual scientific meeting on infectious diseases.
Rather, the adverse events were “fairly diverse. ... the kinds of things normally seen in critically ill pediatric populations,” he said.
The patients, who had a mean age of 7 years, were treated with IVZ doses selected to provide exposures comparable to 600 mg in adults – a dosage shown in prior studies to be safe and well-tolerated in adults. Patients aged 6 months to under age 6 years received twice-daily doses of 14 mg/kg, and those aged 6 years to less than 18 years received twice-daily doses of 12 mg/kg, not to exceed 600 mg. Doses were adjusted for renal function.
Patients were enrolled from five countries, and most (69%) had received prior treatment with oseltamivir. More than half (56%) had chronic medical conditions.
The median time from symptom onset to IVZ treatment was 4 days, Dr. Blumer of the University of Toledo (Ohio) said at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
Infiltrate on chest x-ray was seen in 59% of patients, mechanical ventilation was required in 34% of patients, and extracorporeal membrane oxygenation was required in 6% of patients. Treatment in the intensive care unit was required in 65% of patients, and cumulative mortality was 4% at 14 days, and 7% at 28 days.
“Overall, the [IVZ] exposure and then the elimination profiles were consistent across the entire age cohort – unusual for most drugs, but it seemed to hold true, which makes zanamivir a lot easier for us to work with in pediatrics,” Dr. Blumer said.
While the numbers are small, exposure and response delineation didn’t seem to be impacted by mechanical ventilation, by extracorporeal membrane oxygenation, or by continuous renal replacement therapy, which is a good sign, he noted.
“So we generally had good, consistent experience here. ... Overall, 64 of the 71 patients survived, got better, left the ICU, and left the hospital,” Dr. Blumer said.
Of note, a treatment-emergent resistance substitution, E119G, was detected in a day 5 H1N1 isolate from an immunocompetent patient who improved clinically while on IVZ, he said, adding that no phenotype data were available as the sample could not be cultured.
The findings are important, because while zanamivir is currently labeled for patients older than 7 years, and the intravenous formulation currently in development has been shown to be safe for adults, there is a critical unmet need for an effective parenteral treatment for severe flu in children at high risk of complications who cannot tolerate enteral therapy.
“We need a drug that is available for the critically ill. We need a drug available for kids who are unable to take oral therapy, and for treatment of oseltamivir-resistant strains,” he said, adding that the current findings suggest that IVZ – with dose selection based on age, weight, and renal function – is a suitable treatment option for such patients.
“In conclusion, what we saw in this open-label trial was that the dose selection that we utilized gave us the kind of exposure we’d expect, and it seems it was an appropriate way to approach pediatric patients,” he said. “There wasn’t any safety signal attributable to the drug, and the overall pattern was more that of serious influenza, rather than of drug exposure.”
Dr. Blumer reported receiving research support from GlaxoSmithKline, which sponsored the study.
AT ID WEEK 2016
Key clinical point:
Major finding: A total of 72% of patients experienced adverse events and 21% experienced serious adverse events, but none were considered by the investigators to be attributable to intravenous zanamivir.
Data source: An open-label, multicenter, phase II study of 71 children with laboratory-confirmed influenza.
Disclosures: Dr. Blumer reported receiving research support from GlaxoSmithKline, which sponsored the study.
Behavioral interventions durably reduced inappropriate antibiotic prescribing
NEW ORLEANS – The benefits of an 18-month behavioral intervention to reduce inappropriate antibiotic prescribing in the primary care setting were maintained 18 months after the intervention ended, according to follow-up data from a cluster randomized clinical trial.
During the 18-month intervention period, physicians at 47 adult and pediatric practices that participated in the trial, which compared three behavioral interventions and intervention combinations, significantly reduced their inappropriate prescribing.
After 18 months, the results were durable – and particularly so in the groups that received interventions that used “social motivation,” Jeffrey Linder, MD, of Brigham & Women’s Hospital and Harvard Medical School, Boston, reported at an annual scientific meeting on infectious diseases.
A total of 16,959 antibiotic-inappropriate visits (visits for nonspecific upper respiratory tract infections, acute bronchitis, and influenza) were made to 248 clinicians during the 18-month intervention period, and 3,192 such visits were made to 224 clinicians during the postintervention period (JAMA. 2016 Feb 9;315[6]:562-70).
The interventions included “suggested alternatives,” which was an electronic health record-based approach that prompted the prescriber to answer whether a prescription was for an acute respiratory infection. A “yes” answer resulted in the prescriber receiving information about appropriate prescribing, along with a list of “easy nonantibiotic alternatives,” Dr. Linder explained, noting that the interventions involved “trying to make it easy to do the right thing.”
An “accountable justification” intervention used a similar process, but rather than suggesting alternative options, the program asked the prescriber to input a “tweet-length justification” of the prescription. The justification was then entered into the patient’s chart.
The third intervention involved “peer comparison.” Prescribers received monthly e-mail feedback regarding how their prescribing stacked up to that of their peers – specifically noting whether they were or were not “top performers.”
Some of the groups in the trial received combinations of these interventions, but the follow-up analysis showed that the latter two approaches, which involved “social motivation,” had the most durable effects.
For example, the inappropriate antibiotic prescribing rate for those in the “accountable justification” group decreased from 23.2% to 5.2% at the end of the 18-month intervention period (absolute difference, -18.1%) and increased to 9% at the end of follow-up.
The inappropriate prescribing rate decreased from about 20% to about 4% in the “peer comparison” group at the end of the intervention period (absolute difference of -16.3%), then increased to 5% at the end of follow-up, Dr. Linder said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
“The statistically best player here – the peer comparison group – went from 20% to 4% to 5%, so it only went back up 1% even after we turned the intervention off for 18 months,” he said.
Antibiotics often are inappropriately prescribed for acute respiratory infections in primary care. Such infections – including colds, sinusitis, strep throat, nonstrep pharyngitis, acute bronchitis, and influenza – make up only 10% of all ambulatory visits in the United States, but they account for 44% of all antibiotic prescribing, Dr. Linder said.
An estimated 50% of antibiotic prescriptions for acute respiratory infections are inappropriate, he added, noting that little success has been achieved with prior antibiotic stewardship efforts that focused largely on clinician education.
“So, we tried to tackle it a bit differently,” he said. “We saw a persistent significant change in antibiotic prescribing in the peer comparison intervention group. ... I would say that interventions that take advantage of social motivation appear to be effective or persistent.”
Dr. Linder reported having no relevant disclosures.
NEW ORLEANS – The benefits of an 18-month behavioral intervention to reduce inappropriate antibiotic prescribing in the primary care setting were maintained 18 months after the intervention ended, according to follow-up data from a cluster randomized clinical trial.
During the 18-month intervention period, physicians at 47 adult and pediatric practices that participated in the trial, which compared three behavioral interventions and intervention combinations, significantly reduced their inappropriate prescribing.
After 18 months, the results were durable – and particularly so in the groups that received interventions that used “social motivation,” Jeffrey Linder, MD, of Brigham & Women’s Hospital and Harvard Medical School, Boston, reported at an annual scientific meeting on infectious diseases.
A total of 16,959 antibiotic-inappropriate visits (visits for nonspecific upper respiratory tract infections, acute bronchitis, and influenza) were made to 248 clinicians during the 18-month intervention period, and 3,192 such visits were made to 224 clinicians during the postintervention period (JAMA. 2016 Feb 9;315[6]:562-70).
The interventions included “suggested alternatives,” which was an electronic health record-based approach that prompted the prescriber to answer whether a prescription was for an acute respiratory infection. A “yes” answer resulted in the prescriber receiving information about appropriate prescribing, along with a list of “easy nonantibiotic alternatives,” Dr. Linder explained, noting that the interventions involved “trying to make it easy to do the right thing.”
An “accountable justification” intervention used a similar process, but rather than suggesting alternative options, the program asked the prescriber to input a “tweet-length justification” of the prescription. The justification was then entered into the patient’s chart.
The third intervention involved “peer comparison.” Prescribers received monthly e-mail feedback regarding how their prescribing stacked up to that of their peers – specifically noting whether they were or were not “top performers.”
Some of the groups in the trial received combinations of these interventions, but the follow-up analysis showed that the latter two approaches, which involved “social motivation,” had the most durable effects.
For example, the inappropriate antibiotic prescribing rate for those in the “accountable justification” group decreased from 23.2% to 5.2% at the end of the 18-month intervention period (absolute difference, -18.1%) and increased to 9% at the end of follow-up.
The inappropriate prescribing rate decreased from about 20% to about 4% in the “peer comparison” group at the end of the intervention period (absolute difference of -16.3%), then increased to 5% at the end of follow-up, Dr. Linder said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
“The statistically best player here – the peer comparison group – went from 20% to 4% to 5%, so it only went back up 1% even after we turned the intervention off for 18 months,” he said.
Antibiotics often are inappropriately prescribed for acute respiratory infections in primary care. Such infections – including colds, sinusitis, strep throat, nonstrep pharyngitis, acute bronchitis, and influenza – make up only 10% of all ambulatory visits in the United States, but they account for 44% of all antibiotic prescribing, Dr. Linder said.
An estimated 50% of antibiotic prescriptions for acute respiratory infections are inappropriate, he added, noting that little success has been achieved with prior antibiotic stewardship efforts that focused largely on clinician education.
“So, we tried to tackle it a bit differently,” he said. “We saw a persistent significant change in antibiotic prescribing in the peer comparison intervention group. ... I would say that interventions that take advantage of social motivation appear to be effective or persistent.”
Dr. Linder reported having no relevant disclosures.
NEW ORLEANS – The benefits of an 18-month behavioral intervention to reduce inappropriate antibiotic prescribing in the primary care setting were maintained 18 months after the intervention ended, according to follow-up data from a cluster randomized clinical trial.
During the 18-month intervention period, physicians at 47 adult and pediatric practices that participated in the trial, which compared three behavioral interventions and intervention combinations, significantly reduced their inappropriate prescribing.
After 18 months, the results were durable – and particularly so in the groups that received interventions that used “social motivation,” Jeffrey Linder, MD, of Brigham & Women’s Hospital and Harvard Medical School, Boston, reported at an annual scientific meeting on infectious diseases.
A total of 16,959 antibiotic-inappropriate visits (visits for nonspecific upper respiratory tract infections, acute bronchitis, and influenza) were made to 248 clinicians during the 18-month intervention period, and 3,192 such visits were made to 224 clinicians during the postintervention period (JAMA. 2016 Feb 9;315[6]:562-70).
The interventions included “suggested alternatives,” which was an electronic health record-based approach that prompted the prescriber to answer whether a prescription was for an acute respiratory infection. A “yes” answer resulted in the prescriber receiving information about appropriate prescribing, along with a list of “easy nonantibiotic alternatives,” Dr. Linder explained, noting that the interventions involved “trying to make it easy to do the right thing.”
An “accountable justification” intervention used a similar process, but rather than suggesting alternative options, the program asked the prescriber to input a “tweet-length justification” of the prescription. The justification was then entered into the patient’s chart.
The third intervention involved “peer comparison.” Prescribers received monthly e-mail feedback regarding how their prescribing stacked up to that of their peers – specifically noting whether they were or were not “top performers.”
Some of the groups in the trial received combinations of these interventions, but the follow-up analysis showed that the latter two approaches, which involved “social motivation,” had the most durable effects.
For example, the inappropriate antibiotic prescribing rate for those in the “accountable justification” group decreased from 23.2% to 5.2% at the end of the 18-month intervention period (absolute difference, -18.1%) and increased to 9% at the end of follow-up.
The inappropriate prescribing rate decreased from about 20% to about 4% in the “peer comparison” group at the end of the intervention period (absolute difference of -16.3%), then increased to 5% at the end of follow-up, Dr. Linder said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
“The statistically best player here – the peer comparison group – went from 20% to 4% to 5%, so it only went back up 1% even after we turned the intervention off for 18 months,” he said.
Antibiotics often are inappropriately prescribed for acute respiratory infections in primary care. Such infections – including colds, sinusitis, strep throat, nonstrep pharyngitis, acute bronchitis, and influenza – make up only 10% of all ambulatory visits in the United States, but they account for 44% of all antibiotic prescribing, Dr. Linder said.
An estimated 50% of antibiotic prescriptions for acute respiratory infections are inappropriate, he added, noting that little success has been achieved with prior antibiotic stewardship efforts that focused largely on clinician education.
“So, we tried to tackle it a bit differently,” he said. “We saw a persistent significant change in antibiotic prescribing in the peer comparison intervention group. ... I would say that interventions that take advantage of social motivation appear to be effective or persistent.”
Dr. Linder reported having no relevant disclosures.
Key clinical point: The benefits of an 18-month behavioral intervention to reduce inappropriate antibiotic prescribing in the primary care setting were maintained 18 months after the intervention ended, according to follow-up data from a cluster randomized clinical trial.
Major finding: Inappropriate antibiotic prescribing increased only slightly, from 4% to 5%, during 18 months of follow-up in the “peer comparison” group.
Data source: Follow-up of a cluster randomized, controlled clinical trial involving nearly 3,200 patient visits with 224 clinicians.
Disclosures: Dr. Linder reported having no disclosures.
Clindamycin, TMP-SMX both of benefit for small abscesses
NEW ORLEANS – Both clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) were superior to placebo when used after incision and drainage for the treatment of small, uncomplicated abscesses in children and adults in a prospective, randomized, placebo-controlled study.
Further, the cure rates were similar with both antibiotics, except in subjects with a clindamycin-resistant Staphylococcus aureus isolate, in whom the cure rate was lower, Robert S. Daum, MD, of the University of Chicago reported at an annual scientific meeting on infectious diseases.
Small, uncomplicated skin abscesses are common in ambulatory settings, but the optimal treatment strategy in the era of community-acquired methicillin-resistant S. aureus has been unclear. A prior study showed that clindamycin and TMP-SMX are both of benefit in the setting of large skin abscesses. The current findings further demonstrate that they also are of benefit when used in conjunction with incision and drainage for the treatment of small abscesses.
In 786 outpatient subjects, including 505 adults and 281 children who were randomized to receive 10 days of treatment with either clindamycin, TMP-SMX, or placebo following incision and drainage, mean cure rates at the 10-day posttherapy test of cure visit were 83% in the clindamycin group, 82% in the TMP-SMX group, and 69% in the placebo group, he said, noting that the differences were statistically significant for both treatments vs. placebo.
Study participants had a single skin abscess of 5 cm or less in diameter. Those with significant comorbidity, such as diabetes, were excluded.
S. aureus was isolated from 527 subjects (67%), and methicillin-resistant S. aureus was isolated from 388 (49%).
In clindamycin-treated subjects with an S. aureus lesion, 54% with a clindamycin-resistant isolate were cured, compared with 85% with a clindamycin-susceptible isolate.
Of note, subjects without S. aureus did not do better with antibiotics vs. placebo, Dr. Daum said.
“Staph aureus matters,” he said. People who did not grow Staph aureus did not do better with placebo than with antibiotic ... incision and drainage was basically all that was needed [in those patients],” he said.
Adverse events were more common in the clindamycin group (22% vs. 11% with TMP-SMX and 12.5% with placebo), but all events were mild and resolved without sequelae, and among those who were cured initially, fewer new skin infections were noted at a 1-month follow-up visit among clindamycin recipients, compared with those who received TMP-SMX or placebo, he noted at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
No cases of Clostridium difficile-associated diarrhea were reported among study subjects.
Dr. Daum reported having no disclosures.
NEW ORLEANS – Both clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) were superior to placebo when used after incision and drainage for the treatment of small, uncomplicated abscesses in children and adults in a prospective, randomized, placebo-controlled study.
Further, the cure rates were similar with both antibiotics, except in subjects with a clindamycin-resistant Staphylococcus aureus isolate, in whom the cure rate was lower, Robert S. Daum, MD, of the University of Chicago reported at an annual scientific meeting on infectious diseases.
Small, uncomplicated skin abscesses are common in ambulatory settings, but the optimal treatment strategy in the era of community-acquired methicillin-resistant S. aureus has been unclear. A prior study showed that clindamycin and TMP-SMX are both of benefit in the setting of large skin abscesses. The current findings further demonstrate that they also are of benefit when used in conjunction with incision and drainage for the treatment of small abscesses.
In 786 outpatient subjects, including 505 adults and 281 children who were randomized to receive 10 days of treatment with either clindamycin, TMP-SMX, or placebo following incision and drainage, mean cure rates at the 10-day posttherapy test of cure visit were 83% in the clindamycin group, 82% in the TMP-SMX group, and 69% in the placebo group, he said, noting that the differences were statistically significant for both treatments vs. placebo.
Study participants had a single skin abscess of 5 cm or less in diameter. Those with significant comorbidity, such as diabetes, were excluded.
S. aureus was isolated from 527 subjects (67%), and methicillin-resistant S. aureus was isolated from 388 (49%).
In clindamycin-treated subjects with an S. aureus lesion, 54% with a clindamycin-resistant isolate were cured, compared with 85% with a clindamycin-susceptible isolate.
Of note, subjects without S. aureus did not do better with antibiotics vs. placebo, Dr. Daum said.
“Staph aureus matters,” he said. People who did not grow Staph aureus did not do better with placebo than with antibiotic ... incision and drainage was basically all that was needed [in those patients],” he said.
Adverse events were more common in the clindamycin group (22% vs. 11% with TMP-SMX and 12.5% with placebo), but all events were mild and resolved without sequelae, and among those who were cured initially, fewer new skin infections were noted at a 1-month follow-up visit among clindamycin recipients, compared with those who received TMP-SMX or placebo, he noted at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
No cases of Clostridium difficile-associated diarrhea were reported among study subjects.
Dr. Daum reported having no disclosures.
NEW ORLEANS – Both clindamycin and trimethoprim-sulfamethoxazole (TMP-SMX) were superior to placebo when used after incision and drainage for the treatment of small, uncomplicated abscesses in children and adults in a prospective, randomized, placebo-controlled study.
Further, the cure rates were similar with both antibiotics, except in subjects with a clindamycin-resistant Staphylococcus aureus isolate, in whom the cure rate was lower, Robert S. Daum, MD, of the University of Chicago reported at an annual scientific meeting on infectious diseases.
Small, uncomplicated skin abscesses are common in ambulatory settings, but the optimal treatment strategy in the era of community-acquired methicillin-resistant S. aureus has been unclear. A prior study showed that clindamycin and TMP-SMX are both of benefit in the setting of large skin abscesses. The current findings further demonstrate that they also are of benefit when used in conjunction with incision and drainage for the treatment of small abscesses.
In 786 outpatient subjects, including 505 adults and 281 children who were randomized to receive 10 days of treatment with either clindamycin, TMP-SMX, or placebo following incision and drainage, mean cure rates at the 10-day posttherapy test of cure visit were 83% in the clindamycin group, 82% in the TMP-SMX group, and 69% in the placebo group, he said, noting that the differences were statistically significant for both treatments vs. placebo.
Study participants had a single skin abscess of 5 cm or less in diameter. Those with significant comorbidity, such as diabetes, were excluded.
S. aureus was isolated from 527 subjects (67%), and methicillin-resistant S. aureus was isolated from 388 (49%).
In clindamycin-treated subjects with an S. aureus lesion, 54% with a clindamycin-resistant isolate were cured, compared with 85% with a clindamycin-susceptible isolate.
Of note, subjects without S. aureus did not do better with antibiotics vs. placebo, Dr. Daum said.
“Staph aureus matters,” he said. People who did not grow Staph aureus did not do better with placebo than with antibiotic ... incision and drainage was basically all that was needed [in those patients],” he said.
Adverse events were more common in the clindamycin group (22% vs. 11% with TMP-SMX and 12.5% with placebo), but all events were mild and resolved without sequelae, and among those who were cured initially, fewer new skin infections were noted at a 1-month follow-up visit among clindamycin recipients, compared with those who received TMP-SMX or placebo, he noted at the combined annual meetings of the Infectious Diseases Society of America, the Society of Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
No cases of Clostridium difficile-associated diarrhea were reported among study subjects.
Dr. Daum reported having no disclosures.
AT IDWEEK 2016
Key clinical point:
Major finding: Mean cure rates were 83%, 82%, and 69% with clindamycin, TMP-SMX, and placebo, respectively.
Data source: A randomized, placebo-controlled, multicenter study of 786 subjects.
Disclosures: Dr. Daum reported having no disclosures.
Secondary reference panel expands access for CML monitoring
A cell-based BCR-ABL1 secondary reference panel traceable to the World Health Organization BCR-ABL1 International Genetic Reference Panel – with an additional MR4.5 level – provides easier access to International Scale calibration and can act as a tool for assay optimization, validation, and quality assurance for molecular monitoring in chronic myeloid leukemia patients.
Such monitoring is important to disease management, especially for decision making with respect to treatment cessation. The new secondary reference panel would allow laboratories to circumvent the oft-used and time-consuming sample exchange process with reference laboratories for International Scale (IS) calibration, Nicholas C. P. Cross, PhD, of the University of Southampton (England) and colleagues wrote in an article published in Leukemia (2016 Jun 3;30:1844-52).
“The development of BCR-ABL1 tyrosine kinase inhibitors ... has enabled progressively deeper molecular responses in CML patients undergoing tyrosine kinase inhibitor therapy,” the authors wrote, noting that deeper molecular responses are “important milestones for patients considering treatment cessation,” and that “other landmarks on the IS also represent different treatment decision thresholds and prognostic outcomes.”
For this reason, regular molecular monitoring using real-time reverse-transcription quantitative PCR (RqPCR) is recommended for optimal disease management, they said.
“As treatment decisions are directly impacted by test results, accuracy and precision of BCR-ABL1 assays across the entire measurement range is crucial for patient management, especially in patients with deep molecular responses when considering possible treatment cessation,” they wrote.
Access to the material for the WHO BCR-ABL1 reference panel (MR1-MR4), which was developed in 2010 as a primary standard for BCR-ABL1 assay IS calibration, is limited, particularly for smaller laboratories, the authors said.
The secondary reference panel they developed, however, is “traceable to and faithfully replicates the WHO panel in both raw materials (lyopholized.K562 and HL-60 cell mixes) and manufacturing process, with the addition of a MR4.5 level.” The secondary panel was calibrated to IS using digital PCR against ABL1, BCR, and GUSB as reference genes, and was successfully evaluated by 45 different BCR-ABL1 assays at 44 different clinical laboratories in a multinational evaluation study.
The MR4.5 level was added to allow for more accurate IS calibration “as CML patients reaching this deep molecular response are increasingly being considered for treatment cessation,” the authors noted.
“Quality-control assessments indicated that the secondary panel had minimal residual moisture, excellent vial-to-vial homogeneity and greater than 2.5 years of real-time stability,” they said.
Further, the panel was successfully processed by all of the laboratories, indicating that it is compatible with many different BCR-ABL1 test configurations, they added.
Of note, the number of assays that achieved good precision and sensitivity exceeded the number that achieved good IS accuracy, suggesting an unmet need for “a simple and broadly available calibration mechanism, such as this secondary panel, to ensure IS accuracy is maintained in laboratories over time,” they wrote, concluding that such a panel “can provide easier access to IS calibration, as well as act as a tool for assay optimization, validation and quality assurance.”
In a letter to the editor in regard to the findings by Cross et al., Maria Sol Ruiz of Instituto Alexander Fleming in Buenos Aires, and colleagues wrote about their own development and validation of “secondary reference materials calibrated to the IS through the WHO primary standards in order to facilitate standardization of molecular monitoring in Latin America,” (Leukemia. 2016 Aug 19. doi: 10.1038/leu.2016.197).
In their study, the letter’s authors demonstrated that secondary reference biological calibrators anchored to the WHO primary standards can decrease inter-laboratory variability.
“Our results, together with those recently reported by Cross et al., substantiate the objective initially set during the establishment of the WHO primary standards, that is, to facilitate worldwide diffusion of the IS. For the first time in Latin America, this study provides a platform on which to assess the performance of distinct clinical BCR-ABL1 tests and confirm the utility of secondary reference materials to further improve IS accuracy and inter-laboratory precision,” they wrote, noting that their efforts will continue through provision of secondary reference material to centers involved in their project, as well as to potential new participants.
“Moreover, due to its higher precision and absolute quantification capability, we are evaluating the possibility of including digital PCR as the calibration method for the future,” they said.
The study discussed in the letter to the editor was supported by a grant from Novartis to one of the authors. Novartis also paid speaking fees to some of the authors. The study by Dr. Cross et al. was also funded by Novartis and some authors are employed by Novartis. The remaining authors, including Dr. Cross, reported having no disclosures.
Harmonizing BCR-ABL1 real time quantitative PCR (RqPCR) is extremely important for precisely interpreting therapeutic response in CML patients and for being able to compare results from various laboratories.
Levels of BCR-ABL1 RNA transcripts are expected to progressively decline with successful response to tyrosine kinase inhibitor therapy. A rise in those levels indicates a loss of response to therapy and typically prompts dose modification or a change in therapy.
Initially, only a qualitative test was available and it measured only the presence or absence of the transcript. The International Standard (IS) allowed the development of a quantitative test. The test is identical to that used in the International Randomized Study of Interferons and STI571 (IRIS), which has a standard baseline of 100% of BCR-ABL1 and major molecular response is defined as a 3 log reduction relative to standard baseline or 0.1% of BCR-ABL1 IS.
However, access became limited – especially for smaller laboratories – to the material for the WHO BCR-ABL1 reference panel (MR1-MR4), a primary standard for BCR-ABL1 assay IS calibration. Calibrated, accredited, primary reference reagents for BCR-ABL1 RqPCR were often too expensive for emergent economies. In response, some laboratories developed conversion factors – a laborious process – and other alternative methods.
By using locally produced secondary cellular calibrators anchored to the WHO primary standards, the elegant work of Cross et al. and Ruiz et al. provided standardization. With this type of initiative, more regional laboratories can assess the performance of their tests and improve their accuracy. Indeed, it is of utmost importance that the exchange of reference standards and quality control samples becomes a common practice in such regions to maximize the reliability of this test. The authors of these studies have started down that path, but there is still a long way to go to achieve higher sensitivity that would permit the detection of even deeper responses and the introduction of digitalized PCR testing.
Maria de Lourdes Chauffaille, MD, and Daniella Kerbauy, MD, are with Fleury Medicina Diagnostica, Sao Paulo, Brazil. Both reported having no disclosures.
Harmonizing BCR-ABL1 real time quantitative PCR (RqPCR) is extremely important for precisely interpreting therapeutic response in CML patients and for being able to compare results from various laboratories.
Levels of BCR-ABL1 RNA transcripts are expected to progressively decline with successful response to tyrosine kinase inhibitor therapy. A rise in those levels indicates a loss of response to therapy and typically prompts dose modification or a change in therapy.
Initially, only a qualitative test was available and it measured only the presence or absence of the transcript. The International Standard (IS) allowed the development of a quantitative test. The test is identical to that used in the International Randomized Study of Interferons and STI571 (IRIS), which has a standard baseline of 100% of BCR-ABL1 and major molecular response is defined as a 3 log reduction relative to standard baseline or 0.1% of BCR-ABL1 IS.
However, access became limited – especially for smaller laboratories – to the material for the WHO BCR-ABL1 reference panel (MR1-MR4), a primary standard for BCR-ABL1 assay IS calibration. Calibrated, accredited, primary reference reagents for BCR-ABL1 RqPCR were often too expensive for emergent economies. In response, some laboratories developed conversion factors – a laborious process – and other alternative methods.
By using locally produced secondary cellular calibrators anchored to the WHO primary standards, the elegant work of Cross et al. and Ruiz et al. provided standardization. With this type of initiative, more regional laboratories can assess the performance of their tests and improve their accuracy. Indeed, it is of utmost importance that the exchange of reference standards and quality control samples becomes a common practice in such regions to maximize the reliability of this test. The authors of these studies have started down that path, but there is still a long way to go to achieve higher sensitivity that would permit the detection of even deeper responses and the introduction of digitalized PCR testing.
Maria de Lourdes Chauffaille, MD, and Daniella Kerbauy, MD, are with Fleury Medicina Diagnostica, Sao Paulo, Brazil. Both reported having no disclosures.
Harmonizing BCR-ABL1 real time quantitative PCR (RqPCR) is extremely important for precisely interpreting therapeutic response in CML patients and for being able to compare results from various laboratories.
Levels of BCR-ABL1 RNA transcripts are expected to progressively decline with successful response to tyrosine kinase inhibitor therapy. A rise in those levels indicates a loss of response to therapy and typically prompts dose modification or a change in therapy.
Initially, only a qualitative test was available and it measured only the presence or absence of the transcript. The International Standard (IS) allowed the development of a quantitative test. The test is identical to that used in the International Randomized Study of Interferons and STI571 (IRIS), which has a standard baseline of 100% of BCR-ABL1 and major molecular response is defined as a 3 log reduction relative to standard baseline or 0.1% of BCR-ABL1 IS.
However, access became limited – especially for smaller laboratories – to the material for the WHO BCR-ABL1 reference panel (MR1-MR4), a primary standard for BCR-ABL1 assay IS calibration. Calibrated, accredited, primary reference reagents for BCR-ABL1 RqPCR were often too expensive for emergent economies. In response, some laboratories developed conversion factors – a laborious process – and other alternative methods.
By using locally produced secondary cellular calibrators anchored to the WHO primary standards, the elegant work of Cross et al. and Ruiz et al. provided standardization. With this type of initiative, more regional laboratories can assess the performance of their tests and improve their accuracy. Indeed, it is of utmost importance that the exchange of reference standards and quality control samples becomes a common practice in such regions to maximize the reliability of this test. The authors of these studies have started down that path, but there is still a long way to go to achieve higher sensitivity that would permit the detection of even deeper responses and the introduction of digitalized PCR testing.
Maria de Lourdes Chauffaille, MD, and Daniella Kerbauy, MD, are with Fleury Medicina Diagnostica, Sao Paulo, Brazil. Both reported having no disclosures.
A cell-based BCR-ABL1 secondary reference panel traceable to the World Health Organization BCR-ABL1 International Genetic Reference Panel – with an additional MR4.5 level – provides easier access to International Scale calibration and can act as a tool for assay optimization, validation, and quality assurance for molecular monitoring in chronic myeloid leukemia patients.
Such monitoring is important to disease management, especially for decision making with respect to treatment cessation. The new secondary reference panel would allow laboratories to circumvent the oft-used and time-consuming sample exchange process with reference laboratories for International Scale (IS) calibration, Nicholas C. P. Cross, PhD, of the University of Southampton (England) and colleagues wrote in an article published in Leukemia (2016 Jun 3;30:1844-52).
“The development of BCR-ABL1 tyrosine kinase inhibitors ... has enabled progressively deeper molecular responses in CML patients undergoing tyrosine kinase inhibitor therapy,” the authors wrote, noting that deeper molecular responses are “important milestones for patients considering treatment cessation,” and that “other landmarks on the IS also represent different treatment decision thresholds and prognostic outcomes.”
For this reason, regular molecular monitoring using real-time reverse-transcription quantitative PCR (RqPCR) is recommended for optimal disease management, they said.
“As treatment decisions are directly impacted by test results, accuracy and precision of BCR-ABL1 assays across the entire measurement range is crucial for patient management, especially in patients with deep molecular responses when considering possible treatment cessation,” they wrote.
Access to the material for the WHO BCR-ABL1 reference panel (MR1-MR4), which was developed in 2010 as a primary standard for BCR-ABL1 assay IS calibration, is limited, particularly for smaller laboratories, the authors said.
The secondary reference panel they developed, however, is “traceable to and faithfully replicates the WHO panel in both raw materials (lyopholized.K562 and HL-60 cell mixes) and manufacturing process, with the addition of a MR4.5 level.” The secondary panel was calibrated to IS using digital PCR against ABL1, BCR, and GUSB as reference genes, and was successfully evaluated by 45 different BCR-ABL1 assays at 44 different clinical laboratories in a multinational evaluation study.
The MR4.5 level was added to allow for more accurate IS calibration “as CML patients reaching this deep molecular response are increasingly being considered for treatment cessation,” the authors noted.
“Quality-control assessments indicated that the secondary panel had minimal residual moisture, excellent vial-to-vial homogeneity and greater than 2.5 years of real-time stability,” they said.
Further, the panel was successfully processed by all of the laboratories, indicating that it is compatible with many different BCR-ABL1 test configurations, they added.
Of note, the number of assays that achieved good precision and sensitivity exceeded the number that achieved good IS accuracy, suggesting an unmet need for “a simple and broadly available calibration mechanism, such as this secondary panel, to ensure IS accuracy is maintained in laboratories over time,” they wrote, concluding that such a panel “can provide easier access to IS calibration, as well as act as a tool for assay optimization, validation and quality assurance.”
In a letter to the editor in regard to the findings by Cross et al., Maria Sol Ruiz of Instituto Alexander Fleming in Buenos Aires, and colleagues wrote about their own development and validation of “secondary reference materials calibrated to the IS through the WHO primary standards in order to facilitate standardization of molecular monitoring in Latin America,” (Leukemia. 2016 Aug 19. doi: 10.1038/leu.2016.197).
In their study, the letter’s authors demonstrated that secondary reference biological calibrators anchored to the WHO primary standards can decrease inter-laboratory variability.
“Our results, together with those recently reported by Cross et al., substantiate the objective initially set during the establishment of the WHO primary standards, that is, to facilitate worldwide diffusion of the IS. For the first time in Latin America, this study provides a platform on which to assess the performance of distinct clinical BCR-ABL1 tests and confirm the utility of secondary reference materials to further improve IS accuracy and inter-laboratory precision,” they wrote, noting that their efforts will continue through provision of secondary reference material to centers involved in their project, as well as to potential new participants.
“Moreover, due to its higher precision and absolute quantification capability, we are evaluating the possibility of including digital PCR as the calibration method for the future,” they said.
The study discussed in the letter to the editor was supported by a grant from Novartis to one of the authors. Novartis also paid speaking fees to some of the authors. The study by Dr. Cross et al. was also funded by Novartis and some authors are employed by Novartis. The remaining authors, including Dr. Cross, reported having no disclosures.
A cell-based BCR-ABL1 secondary reference panel traceable to the World Health Organization BCR-ABL1 International Genetic Reference Panel – with an additional MR4.5 level – provides easier access to International Scale calibration and can act as a tool for assay optimization, validation, and quality assurance for molecular monitoring in chronic myeloid leukemia patients.
Such monitoring is important to disease management, especially for decision making with respect to treatment cessation. The new secondary reference panel would allow laboratories to circumvent the oft-used and time-consuming sample exchange process with reference laboratories for International Scale (IS) calibration, Nicholas C. P. Cross, PhD, of the University of Southampton (England) and colleagues wrote in an article published in Leukemia (2016 Jun 3;30:1844-52).
“The development of BCR-ABL1 tyrosine kinase inhibitors ... has enabled progressively deeper molecular responses in CML patients undergoing tyrosine kinase inhibitor therapy,” the authors wrote, noting that deeper molecular responses are “important milestones for patients considering treatment cessation,” and that “other landmarks on the IS also represent different treatment decision thresholds and prognostic outcomes.”
For this reason, regular molecular monitoring using real-time reverse-transcription quantitative PCR (RqPCR) is recommended for optimal disease management, they said.
“As treatment decisions are directly impacted by test results, accuracy and precision of BCR-ABL1 assays across the entire measurement range is crucial for patient management, especially in patients with deep molecular responses when considering possible treatment cessation,” they wrote.
Access to the material for the WHO BCR-ABL1 reference panel (MR1-MR4), which was developed in 2010 as a primary standard for BCR-ABL1 assay IS calibration, is limited, particularly for smaller laboratories, the authors said.
The secondary reference panel they developed, however, is “traceable to and faithfully replicates the WHO panel in both raw materials (lyopholized.K562 and HL-60 cell mixes) and manufacturing process, with the addition of a MR4.5 level.” The secondary panel was calibrated to IS using digital PCR against ABL1, BCR, and GUSB as reference genes, and was successfully evaluated by 45 different BCR-ABL1 assays at 44 different clinical laboratories in a multinational evaluation study.
The MR4.5 level was added to allow for more accurate IS calibration “as CML patients reaching this deep molecular response are increasingly being considered for treatment cessation,” the authors noted.
“Quality-control assessments indicated that the secondary panel had minimal residual moisture, excellent vial-to-vial homogeneity and greater than 2.5 years of real-time stability,” they said.
Further, the panel was successfully processed by all of the laboratories, indicating that it is compatible with many different BCR-ABL1 test configurations, they added.
Of note, the number of assays that achieved good precision and sensitivity exceeded the number that achieved good IS accuracy, suggesting an unmet need for “a simple and broadly available calibration mechanism, such as this secondary panel, to ensure IS accuracy is maintained in laboratories over time,” they wrote, concluding that such a panel “can provide easier access to IS calibration, as well as act as a tool for assay optimization, validation and quality assurance.”
In a letter to the editor in regard to the findings by Cross et al., Maria Sol Ruiz of Instituto Alexander Fleming in Buenos Aires, and colleagues wrote about their own development and validation of “secondary reference materials calibrated to the IS through the WHO primary standards in order to facilitate standardization of molecular monitoring in Latin America,” (Leukemia. 2016 Aug 19. doi: 10.1038/leu.2016.197).
In their study, the letter’s authors demonstrated that secondary reference biological calibrators anchored to the WHO primary standards can decrease inter-laboratory variability.
“Our results, together with those recently reported by Cross et al., substantiate the objective initially set during the establishment of the WHO primary standards, that is, to facilitate worldwide diffusion of the IS. For the first time in Latin America, this study provides a platform on which to assess the performance of distinct clinical BCR-ABL1 tests and confirm the utility of secondary reference materials to further improve IS accuracy and inter-laboratory precision,” they wrote, noting that their efforts will continue through provision of secondary reference material to centers involved in their project, as well as to potential new participants.
“Moreover, due to its higher precision and absolute quantification capability, we are evaluating the possibility of including digital PCR as the calibration method for the future,” they said.
The study discussed in the letter to the editor was supported by a grant from Novartis to one of the authors. Novartis also paid speaking fees to some of the authors. The study by Dr. Cross et al. was also funded by Novartis and some authors are employed by Novartis. The remaining authors, including Dr. Cross, reported having no disclosures.
FROM LEUKEMIA
Key clinical point:
Major finding: The secondary panel was calibrated to IS using digital PCR against ABL1, BCR, and GUSB as reference genes, and was successfully evaluated by 45 different BCR-ABL1 assays at 44 different clinical laboratories.
Data source: A multicenter evaluation study of a secondary reference panel for BCR-ABL1 quantification on the IS.
Disclosures: The study discussed in the letter to the editor was supported by a grant from Novartis to one of the authors. Novartis also paid speaking fees to some of the authors. The study by Dr. Cross et al. was also funded by Novartis and some authors are employed by Novartis. The remaining authors, including Dr. Cross, reported having no disclosures.
VIDEO: No effect of donor on FMT outcomes in C. difficile patients
NEW ORLEANS – Fecal microbiota transplantation, or FMT, is a highly effective treatment for Clostridium difficile infection (CDI) and other digestive and autoimmune disorders, but little is known about the role of donor characteristics with respect to outcomes in patients with recurrent CDI.
A study of nearly 1,999 patients with an 83.9% cure rate showed no significant difference between 28 donors in terms of clinical outcomes at 8 weeks, according to Majdi Osman, MD, of OpenBiome, a not-for-profit stool bank in the Boston area.
Studies in inflammatory bowel diseases have suggested that donors do matter, but that does not appear to be the case when it comes to recurrent CDI, Dr. Osman said at an annual scientific meeting on infectious diseases.
“Broadly speaking, it seems like the efficacy rate is the same amongst all of our donors,” he said in a video interview at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Potential donors are subject to a rigorous screening process, and less than 3% are accepted, but given that donors were shown in previous studies to play a role in effectiveness in some other conditions, Dr. Osman said it was worth checking to see if outcomes in CDI could be further improved through donor selection.
In fact, it appears that “the donor doesn’t matter,” he said, noting that it may be that “we are selecting for a fairly narrow spectrum of the population, and actually the stool that we’re selecting is fairly similar in composition.”
Efforts are underway to look more closely at that possibility, and Dr. Osman said he hopes to see more standardized clinical trials and clinical follow-up. He also said he is excited about an FMT registry – a joint project of the American Gastroenterology Association and the Infectious Diseases Society of America – that will follow 4,000 patients for 10 years.
“We will be working closely with them to provide material and get some really good robust clinical data going forward,” he said.
Dr. Osman reported having no disclosures.
NEW ORLEANS – Fecal microbiota transplantation, or FMT, is a highly effective treatment for Clostridium difficile infection (CDI) and other digestive and autoimmune disorders, but little is known about the role of donor characteristics with respect to outcomes in patients with recurrent CDI.
A study of nearly 1,999 patients with an 83.9% cure rate showed no significant difference between 28 donors in terms of clinical outcomes at 8 weeks, according to Majdi Osman, MD, of OpenBiome, a not-for-profit stool bank in the Boston area.
Studies in inflammatory bowel diseases have suggested that donors do matter, but that does not appear to be the case when it comes to recurrent CDI, Dr. Osman said at an annual scientific meeting on infectious diseases.
“Broadly speaking, it seems like the efficacy rate is the same amongst all of our donors,” he said in a video interview at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Potential donors are subject to a rigorous screening process, and less than 3% are accepted, but given that donors were shown in previous studies to play a role in effectiveness in some other conditions, Dr. Osman said it was worth checking to see if outcomes in CDI could be further improved through donor selection.
In fact, it appears that “the donor doesn’t matter,” he said, noting that it may be that “we are selecting for a fairly narrow spectrum of the population, and actually the stool that we’re selecting is fairly similar in composition.”
Efforts are underway to look more closely at that possibility, and Dr. Osman said he hopes to see more standardized clinical trials and clinical follow-up. He also said he is excited about an FMT registry – a joint project of the American Gastroenterology Association and the Infectious Diseases Society of America – that will follow 4,000 patients for 10 years.
“We will be working closely with them to provide material and get some really good robust clinical data going forward,” he said.
Dr. Osman reported having no disclosures.
NEW ORLEANS – Fecal microbiota transplantation, or FMT, is a highly effective treatment for Clostridium difficile infection (CDI) and other digestive and autoimmune disorders, but little is known about the role of donor characteristics with respect to outcomes in patients with recurrent CDI.
A study of nearly 1,999 patients with an 83.9% cure rate showed no significant difference between 28 donors in terms of clinical outcomes at 8 weeks, according to Majdi Osman, MD, of OpenBiome, a not-for-profit stool bank in the Boston area.
Studies in inflammatory bowel diseases have suggested that donors do matter, but that does not appear to be the case when it comes to recurrent CDI, Dr. Osman said at an annual scientific meeting on infectious diseases.
“Broadly speaking, it seems like the efficacy rate is the same amongst all of our donors,” he said in a video interview at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Potential donors are subject to a rigorous screening process, and less than 3% are accepted, but given that donors were shown in previous studies to play a role in effectiveness in some other conditions, Dr. Osman said it was worth checking to see if outcomes in CDI could be further improved through donor selection.
In fact, it appears that “the donor doesn’t matter,” he said, noting that it may be that “we are selecting for a fairly narrow spectrum of the population, and actually the stool that we’re selecting is fairly similar in composition.”
Efforts are underway to look more closely at that possibility, and Dr. Osman said he hopes to see more standardized clinical trials and clinical follow-up. He also said he is excited about an FMT registry – a joint project of the American Gastroenterology Association and the Infectious Diseases Society of America – that will follow 4,000 patients for 10 years.
“We will be working closely with them to provide material and get some really good robust clinical data going forward,” he said.
Dr. Osman reported having no disclosures.
Bezlotoxumab reduces CDI recurrence across antibiotic subgroups
NEW ORLEANS – The monoclonal antibody bezlotoxumab significantly reduces the risk of Clostridium difficile infection (CDI) recurrence in adults receiving standard of care antibiotic treatment, regardless of whether that treatment is with metronidazole, vancomycin, or fidaxomicin, according to an analysis of data from the MODIFY I and II trials.
The global, randomized, double-blind, placebo-controlled trials demonstrated that bezlotoxumab was safe and effective for preventing CDI recurrence, and the current prespecified analysis further showed that choice of standard of care antibiotic therapy did not affect the outcomes, Erik R. Dubberke, MD, of Washington University in St. Louis, reported at IDWeek, an annual scientific meeting on infectious diseases.
Consistent with the overall study results, clinical cure rates were similar with bezlotoxumab and placebo, regardless of the standard of care antibiotic received (80% vs. 80.3%, respectively, overall; 81% vs. 81.3% in the metronidazole group; 78.5% vs. 79.6% in the vancomycin group; and 86.7% vs. 76.9% in the fidaxomicin group), he said.
However, CDI recurrence rates were lower among those who received bezlotoxumab, compared with those who received placebo in all three standard of care subgroups, with 10%, 15%, and 12% fewer bezlotoxumab vs. placebo patients experiencing recurrence in the metronidazole, vancomycin, and fidaxomicin groups, respectively, and 12% fewer experiencing recurrence overall.
The primary endpoint of CDI recurrence was defined in the studies as a new episode of diarrhea (at least three unformed stools in 24 hours) and a positive stool test for toxigenic C. difficile after clinical cure of the baseline CDI episode. Clinical cure was defined as standard of care antibiotics given for 14 days or less and no diarrhea for 2 consecutive days after completing standard of care treatment.
Of note, the patients in the vancomycin group were older and sicker, and had more risk factors for CDI, he said, noting, for example, that 57% of vancomycin patients were aged at least 65 years and 33% were aged at least 75 years, vs. 46% and 26% for metronidazole, respectively, and 46% and 18% for fidaxomicin; 72% of vancomycin patients were inpatients, compared with 65% and 50% of metronidazole and fidaxomicin patients.
Further, 19% of vancomycin patients, vs. 13% and 14% of metronidazole and fidaxomicin patients met criteria for severe CDI.
The findings of the current analysis are important, because the incidence of CDI recurrence is about 25%, and the risk increases with each subsequent recurrence, Dr. Dubberke said, concluding that this novel, nonantibiotic approach to prevention of CDI recurrence using bezlotoxumab, which recently received Food and Drug Administration approval for this indication, is of benefit for reducing that risk, regardless of the antibiotic used as part of standard of care therapy for CDI.
Dr. Dubberke reported serving as an investigator, adviser and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.
NEW ORLEANS – The monoclonal antibody bezlotoxumab significantly reduces the risk of Clostridium difficile infection (CDI) recurrence in adults receiving standard of care antibiotic treatment, regardless of whether that treatment is with metronidazole, vancomycin, or fidaxomicin, according to an analysis of data from the MODIFY I and II trials.
The global, randomized, double-blind, placebo-controlled trials demonstrated that bezlotoxumab was safe and effective for preventing CDI recurrence, and the current prespecified analysis further showed that choice of standard of care antibiotic therapy did not affect the outcomes, Erik R. Dubberke, MD, of Washington University in St. Louis, reported at IDWeek, an annual scientific meeting on infectious diseases.
Consistent with the overall study results, clinical cure rates were similar with bezlotoxumab and placebo, regardless of the standard of care antibiotic received (80% vs. 80.3%, respectively, overall; 81% vs. 81.3% in the metronidazole group; 78.5% vs. 79.6% in the vancomycin group; and 86.7% vs. 76.9% in the fidaxomicin group), he said.
However, CDI recurrence rates were lower among those who received bezlotoxumab, compared with those who received placebo in all three standard of care subgroups, with 10%, 15%, and 12% fewer bezlotoxumab vs. placebo patients experiencing recurrence in the metronidazole, vancomycin, and fidaxomicin groups, respectively, and 12% fewer experiencing recurrence overall.
The primary endpoint of CDI recurrence was defined in the studies as a new episode of diarrhea (at least three unformed stools in 24 hours) and a positive stool test for toxigenic C. difficile after clinical cure of the baseline CDI episode. Clinical cure was defined as standard of care antibiotics given for 14 days or less and no diarrhea for 2 consecutive days after completing standard of care treatment.
Of note, the patients in the vancomycin group were older and sicker, and had more risk factors for CDI, he said, noting, for example, that 57% of vancomycin patients were aged at least 65 years and 33% were aged at least 75 years, vs. 46% and 26% for metronidazole, respectively, and 46% and 18% for fidaxomicin; 72% of vancomycin patients were inpatients, compared with 65% and 50% of metronidazole and fidaxomicin patients.
Further, 19% of vancomycin patients, vs. 13% and 14% of metronidazole and fidaxomicin patients met criteria for severe CDI.
The findings of the current analysis are important, because the incidence of CDI recurrence is about 25%, and the risk increases with each subsequent recurrence, Dr. Dubberke said, concluding that this novel, nonantibiotic approach to prevention of CDI recurrence using bezlotoxumab, which recently received Food and Drug Administration approval for this indication, is of benefit for reducing that risk, regardless of the antibiotic used as part of standard of care therapy for CDI.
Dr. Dubberke reported serving as an investigator, adviser and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.
NEW ORLEANS – The monoclonal antibody bezlotoxumab significantly reduces the risk of Clostridium difficile infection (CDI) recurrence in adults receiving standard of care antibiotic treatment, regardless of whether that treatment is with metronidazole, vancomycin, or fidaxomicin, according to an analysis of data from the MODIFY I and II trials.
The global, randomized, double-blind, placebo-controlled trials demonstrated that bezlotoxumab was safe and effective for preventing CDI recurrence, and the current prespecified analysis further showed that choice of standard of care antibiotic therapy did not affect the outcomes, Erik R. Dubberke, MD, of Washington University in St. Louis, reported at IDWeek, an annual scientific meeting on infectious diseases.
Consistent with the overall study results, clinical cure rates were similar with bezlotoxumab and placebo, regardless of the standard of care antibiotic received (80% vs. 80.3%, respectively, overall; 81% vs. 81.3% in the metronidazole group; 78.5% vs. 79.6% in the vancomycin group; and 86.7% vs. 76.9% in the fidaxomicin group), he said.
However, CDI recurrence rates were lower among those who received bezlotoxumab, compared with those who received placebo in all three standard of care subgroups, with 10%, 15%, and 12% fewer bezlotoxumab vs. placebo patients experiencing recurrence in the metronidazole, vancomycin, and fidaxomicin groups, respectively, and 12% fewer experiencing recurrence overall.
The primary endpoint of CDI recurrence was defined in the studies as a new episode of diarrhea (at least three unformed stools in 24 hours) and a positive stool test for toxigenic C. difficile after clinical cure of the baseline CDI episode. Clinical cure was defined as standard of care antibiotics given for 14 days or less and no diarrhea for 2 consecutive days after completing standard of care treatment.
Of note, the patients in the vancomycin group were older and sicker, and had more risk factors for CDI, he said, noting, for example, that 57% of vancomycin patients were aged at least 65 years and 33% were aged at least 75 years, vs. 46% and 26% for metronidazole, respectively, and 46% and 18% for fidaxomicin; 72% of vancomycin patients were inpatients, compared with 65% and 50% of metronidazole and fidaxomicin patients.
Further, 19% of vancomycin patients, vs. 13% and 14% of metronidazole and fidaxomicin patients met criteria for severe CDI.
The findings of the current analysis are important, because the incidence of CDI recurrence is about 25%, and the risk increases with each subsequent recurrence, Dr. Dubberke said, concluding that this novel, nonantibiotic approach to prevention of CDI recurrence using bezlotoxumab, which recently received Food and Drug Administration approval for this indication, is of benefit for reducing that risk, regardless of the antibiotic used as part of standard of care therapy for CDI.
Dr. Dubberke reported serving as an investigator, adviser and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.
AT IDWEEK 2016
Key clinical point:
Major finding: 12% fewer bezlotoxumab vs. placebo patients experienced CDI recurrence.
Data source: A prespecified analysis of data from 1,554 subjects from the MODIFY I and II trials.
Disclosures: Dr. Dubberke reported serving as an investigator, adviser, and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.
Fatal measles complication occurs more often than realized
NEW ORLEANS – A fatal complication of measles known as subacute sclerosing panencephalitis (SSPE) can develop years after measles infection and appears to occur much more often than published reports suggest, according to a review of cases in California from 1998 to 2015.
The findings underscore the vital importance of herd immunity by vaccination, Kristen Wendorf, MD, reported at an annual scientific meeting on infectious diseases.
The incidence of postmeasles SSPE was previously thought be about 1 in 100,000, according to an IDWeek press release.
“There is no cure for SSPE, and the only way to prevent it is to vaccinate everyone against measles,” the release stated.
The cases in the current study were among children with a clinically compatible illness, and either measles IgG antibody detected in cerebrospinal fluid, a characteristic pattern on electroencephalography, typical histologic findings on brain biopsy, or medical record documentation of SSPE-related complications. They were identified based on death certificates, reports from the Centers for Diseases Control and Prevention, or through investigations for undiagnosed neurologic disease. Twelve of the 17 affected children had a clinical history of a febrile rash illness compatible with measles, and all 12 of those experienced illness before age 15 months and before measles vaccination.
Most (67%) were living in the United States when they had measles, Dr. Wendorf said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The median age at diagnosis of SSPE was 12 years, although the range was 3-35 years, and the mean latency period was 9.5 years. In many cases, long-standing cognitive or motor problems were experienced prior to diagnosis, she noted.
The findings suggest that SSPE is more common than previously recognized in unvaccinated children with measles during infancy, Dr. Wendorf said.
Protection of infants younger than 12-15 months of age – before the time when measles vaccine is routinely administered – and in those who can’t be vaccinated because of immune system disorders requires avoidance of travel to endemic areas. Parents also may consider early vaccination prior to such travel.
Further, clinicians should be aware of the risk of SSPE in patients with symptoms suggestive of the disease. This is true even among older patients in whom no specific history of measles infection is known, she said.
In the press release, coauthor James D. Cherry, MD, professor of pediatrics at the University of California, Los Angeles, further stressed the importance of protecting unvaccinated infants.
“Parents of infants who have not yet been vaccinated should avoid putting their children at risk. For example, they should postpone trips overseas – including to Europe – where measles is endemic and epidemic until after their baby has been vaccinated with two doses,” he said. “It’s just not worth the risk.”
The authors reported having no disclosures.
NEW ORLEANS – A fatal complication of measles known as subacute sclerosing panencephalitis (SSPE) can develop years after measles infection and appears to occur much more often than published reports suggest, according to a review of cases in California from 1998 to 2015.
The findings underscore the vital importance of herd immunity by vaccination, Kristen Wendorf, MD, reported at an annual scientific meeting on infectious diseases.
The incidence of postmeasles SSPE was previously thought be about 1 in 100,000, according to an IDWeek press release.
“There is no cure for SSPE, and the only way to prevent it is to vaccinate everyone against measles,” the release stated.
The cases in the current study were among children with a clinically compatible illness, and either measles IgG antibody detected in cerebrospinal fluid, a characteristic pattern on electroencephalography, typical histologic findings on brain biopsy, or medical record documentation of SSPE-related complications. They were identified based on death certificates, reports from the Centers for Diseases Control and Prevention, or through investigations for undiagnosed neurologic disease. Twelve of the 17 affected children had a clinical history of a febrile rash illness compatible with measles, and all 12 of those experienced illness before age 15 months and before measles vaccination.
Most (67%) were living in the United States when they had measles, Dr. Wendorf said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The median age at diagnosis of SSPE was 12 years, although the range was 3-35 years, and the mean latency period was 9.5 years. In many cases, long-standing cognitive or motor problems were experienced prior to diagnosis, she noted.
The findings suggest that SSPE is more common than previously recognized in unvaccinated children with measles during infancy, Dr. Wendorf said.
Protection of infants younger than 12-15 months of age – before the time when measles vaccine is routinely administered – and in those who can’t be vaccinated because of immune system disorders requires avoidance of travel to endemic areas. Parents also may consider early vaccination prior to such travel.
Further, clinicians should be aware of the risk of SSPE in patients with symptoms suggestive of the disease. This is true even among older patients in whom no specific history of measles infection is known, she said.
In the press release, coauthor James D. Cherry, MD, professor of pediatrics at the University of California, Los Angeles, further stressed the importance of protecting unvaccinated infants.
“Parents of infants who have not yet been vaccinated should avoid putting their children at risk. For example, they should postpone trips overseas – including to Europe – where measles is endemic and epidemic until after their baby has been vaccinated with two doses,” he said. “It’s just not worth the risk.”
The authors reported having no disclosures.
NEW ORLEANS – A fatal complication of measles known as subacute sclerosing panencephalitis (SSPE) can develop years after measles infection and appears to occur much more often than published reports suggest, according to a review of cases in California from 1998 to 2015.
The findings underscore the vital importance of herd immunity by vaccination, Kristen Wendorf, MD, reported at an annual scientific meeting on infectious diseases.
The incidence of postmeasles SSPE was previously thought be about 1 in 100,000, according to an IDWeek press release.
“There is no cure for SSPE, and the only way to prevent it is to vaccinate everyone against measles,” the release stated.
The cases in the current study were among children with a clinically compatible illness, and either measles IgG antibody detected in cerebrospinal fluid, a characteristic pattern on electroencephalography, typical histologic findings on brain biopsy, or medical record documentation of SSPE-related complications. They were identified based on death certificates, reports from the Centers for Diseases Control and Prevention, or through investigations for undiagnosed neurologic disease. Twelve of the 17 affected children had a clinical history of a febrile rash illness compatible with measles, and all 12 of those experienced illness before age 15 months and before measles vaccination.
Most (67%) were living in the United States when they had measles, Dr. Wendorf said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.
The median age at diagnosis of SSPE was 12 years, although the range was 3-35 years, and the mean latency period was 9.5 years. In many cases, long-standing cognitive or motor problems were experienced prior to diagnosis, she noted.
The findings suggest that SSPE is more common than previously recognized in unvaccinated children with measles during infancy, Dr. Wendorf said.
Protection of infants younger than 12-15 months of age – before the time when measles vaccine is routinely administered – and in those who can’t be vaccinated because of immune system disorders requires avoidance of travel to endemic areas. Parents also may consider early vaccination prior to such travel.
Further, clinicians should be aware of the risk of SSPE in patients with symptoms suggestive of the disease. This is true even among older patients in whom no specific history of measles infection is known, she said.
In the press release, coauthor James D. Cherry, MD, professor of pediatrics at the University of California, Los Angeles, further stressed the importance of protecting unvaccinated infants.
“Parents of infants who have not yet been vaccinated should avoid putting their children at risk. For example, they should postpone trips overseas – including to Europe – where measles is endemic and epidemic until after their baby has been vaccinated with two doses,” he said. “It’s just not worth the risk.”
The authors reported having no disclosures.
AT IDWEEK 2016
Key clinical point:
Major finding: The incidence of SSPE among measles cases was 1 in 1,367 children under age 5 years and 1 in 609 children under age 12 months at the time of measles disease.
Data source: A review of records and 17 cases of SSPE.
Disclosures: The authors reported having no disclosures.