Mary Ann Moon

A simple bedside technique – gently probing the loosely closed surgical incision to clean it – dramatically reduced infections of contaminated abdominal surgical wounds without increasing pain, according to a report in the April issue of Archives of Surgery.

Use of this wound-probing technique for surgical incisions "will reduce surgical site infection and decrease hospital stay, both of which may result in improved rates of long-term outcomes such as fascial dehiscence and incisional hernias, reduced labor for wound care by nursing staff and physicians, improved cosmetic outcome with primary closure, and possibly reduced overall cost," said Dr. Shirin Towfigh of Cedars-Sinai Medical Center, Los Angeles, and her associates.

"We recommend that wound probing be practiced in the first-line management of incisions after open surgery, such as bowel resection, in the face of contamination," they noted.

Until now, no local wound therapy – including topical antibiotics, subcutaneous drain placement, or delayed primary closure – has been proved to decrease surgical site infection in a rigorous clinical trial. "There is no standard wound management for contaminated wounds, [and] the topic has not been aggressively pursued for decades," the investigators said.

According to surveillance of nosocomial infections in the United States, the infection rate for contaminated surgical wounds is 7% overall, and can rise as high as 50% in certain subgroups of patients.

Some surgeons, including Dr. Towfigh, routinely use this probing technique and report good results anecdotally. In what they described as the first prospective clinical trial of the technique, Dr. Towfigh and her colleagues assessed surgical site infections in 76 adults who underwent appendectomy for perforated appendicitis at a single academic medical center over a 3-year period.

Half of the patients were randomly assigned to have standard primary skin closure with staples (control group), and the other half had loose primary skin closure with staples placed at 2-cm intervals. Postoperatively, the control group had daily swabbing of their closed incision with povidone iodine.

The intervention group had this standard postoperative care followed by wound probing in which dry, sterile, cotton-tip applicators were used to penetrate the skin and soft tissue between the staples, reaching down to the external oblique fascia. Any fluid that was extruded was blotted dry, and the wound was covered with a dry dressing. This process was repeated once daily until the wound was dry and no longer penetrable in this fashion, which usually took 3 days.

The two study groups were similar in terms of demographic characteristics as well as comorbidities that might affect wound healing, such as the presence of diabetes, larger abdominal girth, and higher body mass index. Both groups had similar incisional lengths (approximately 8 cm).

Study subjects were assessed throughout hospitalization, as well as at 2 weeks and 3 months following hospital discharge; 64% of subjects completed the 3-month follow-up. The primary outcome measure was the rate of surgical site infections, defined by both subjective daily evaluation by a surgical team blinded to treatment assignment and objective scores on the ASEPSIS (Additional Treatment, Presence of Serous Discharge, Erythema, Purulent Exudate, and Separation of the Deep Tissues, Isolation of Bacteria, and Duration of Inpatient Stay) instrument.

Only one patient (3%) in the intervention group developed surgical site infection, compared with seven patients (19%) in the control group (P = .03). Moreover, patients in the intervention group did not report greater pain than did those in the control group, either immediately after surgery or at follow-up, Dr. Towfigh and her associates said (Arch. Surg. 2011;146:448-52).

By reducing surgical site infections, the intervention also significantly decreased length of stay, compared with the control group (5 days vs. 7 days, respectively; P = .049), as well as the amount of time that caregivers spent on wound care.

"When primary closure fails or is deemed inappropriate, the wound is opened and allowed to close by secondary intention [that is, packing an open wound multiple times a day]. Closure by secondary intention can be painful to the patient, can be labor intensive, and has a poor cosmetic outcome. Nevertheless it is the most widely used closure technique in adults with contaminated wounds," the researchers said.

"We recommend that wound probing be practiced for contaminated wounds due to open appendectomy for perforated appendicitis. We believe that our results can also be extrapolated to other contaminated abdominal wounds regardless of their incisional length," they added.

The exact mechanism by which this technique prevents surgical site infection is not yet clear, but the investigators surmised that it "allows for drainage of contaminated fluid within the soft tissue, thus reducing the bacterial count while maintaining a moist wound for improved healing.

"We are currently analyzing the bacteriology data gathered from this study to gain insight into the process," Dr. Towfigh and her associates added.

This study was supported in part by a James H. Zumberge Faculty Research and Innovation grant from the University of Southern California, Los Angeles. No financial conflicts of interest were reported.

A simple bedside technique – gently probing the loosely closed surgical incision to clean it – dramatically reduced infections of contaminated abdominal surgical wounds without increasing pain, according to a report in the April issue of Archives of Surgery.

Use of this wound-probing technique for surgical incisions "will reduce surgical site infection and decrease hospital stay, both of which may result in improved rates of long-term outcomes such as fascial dehiscence and incisional hernias, reduced labor for wound care by nursing staff and physicians, improved cosmetic outcome with primary closure, and possibly reduced overall cost," said Dr. Shirin Towfigh of Cedars-Sinai Medical Center, Los Angeles, and her associates.

"We recommend that wound probing be practiced in the first-line management of incisions after open surgery, such as bowel resection, in the face of contamination," they noted.

Until now, no local wound therapy – including topical antibiotics, subcutaneous drain placement, or delayed primary closure – has been proved to decrease surgical site infection in a rigorous clinical trial. "There is no standard wound management for contaminated wounds, [and] the topic has not been aggressively pursued for decades," the investigators said.

According to surveillance of nosocomial infections in the United States, the infection rate for contaminated surgical wounds is 7% overall, and can rise as high as 50% in certain subgroups of patients.

Some surgeons, including Dr. Towfigh, routinely use this probing technique and report good results anecdotally. In what they described as the first prospective clinical trial of the technique, Dr. Towfigh and her colleagues assessed surgical site infections in 76 adults who underwent appendectomy for perforated appendicitis at a single academic medical center over a 3-year period.

Half of the patients were randomly assigned to have standard primary skin closure with staples (control group), and the other half had loose primary skin closure with staples placed at 2-cm intervals. Postoperatively, the control group had daily swabbing of their closed incision with povidone iodine.

The intervention group had this standard postoperative care followed by wound probing in which dry, sterile, cotton-tip applicators were used to penetrate the skin and soft tissue between the staples, reaching down to the external oblique fascia. Any fluid that was extruded was blotted dry, and the wound was covered with a dry dressing. This process was repeated once daily until the wound was dry and no longer penetrable in this fashion, which usually took 3 days.

The two study groups were similar in terms of demographic characteristics as well as comorbidities that might affect wound healing, such as the presence of diabetes, larger abdominal girth, and higher body mass index. Both groups had similar incisional lengths (approximately 8 cm).

Study subjects were assessed throughout hospitalization, as well as at 2 weeks and 3 months following hospital discharge; 64% of subjects completed the 3-month follow-up. The primary outcome measure was the rate of surgical site infections, defined by both subjective daily evaluation by a surgical team blinded to treatment assignment and objective scores on the ASEPSIS (Additional Treatment, Presence of Serous Discharge, Erythema, Purulent Exudate, and Separation of the Deep Tissues, Isolation of Bacteria, and Duration of Inpatient Stay) instrument.

Only one patient (3%) in the intervention group developed surgical site infection, compared with seven patients (19%) in the control group (P = .03). Moreover, patients in the intervention group did not report greater pain than did those in the control group, either immediately after surgery or at follow-up, Dr. Towfigh and her associates said (Arch. Surg. 2011;146:448-52).

By reducing surgical site infections, the intervention also significantly decreased length of stay, compared with the control group (5 days vs. 7 days, respectively; P = .049), as well as the amount of time that caregivers spent on wound care.

"When primary closure fails or is deemed inappropriate, the wound is opened and allowed to close by secondary intention [that is, packing an open wound multiple times a day]. Closure by secondary intention can be painful to the patient, can be labor intensive, and has a poor cosmetic outcome. Nevertheless it is the most widely used closure technique in adults with contaminated wounds," the researchers said.

"We recommend that wound probing be practiced for contaminated wounds due to open appendectomy for perforated appendicitis. We believe that our results can also be extrapolated to other contaminated abdominal wounds regardless of their incisional length," they added.

The exact mechanism by which this technique prevents surgical site infection is not yet clear, but the investigators surmised that it "allows for drainage of contaminated fluid within the soft tissue, thus reducing the bacterial count while maintaining a moist wound for improved healing.

"We are currently analyzing the bacteriology data gathered from this study to gain insight into the process," Dr. Towfigh and her associates added.

This study was supported in part by a James H. Zumberge Faculty Research and Innovation grant from the University of Southern California, Los Angeles. No financial conflicts of interest were reported.

A simple bedside technique – gently probing the loosely closed surgical incision to clean it – dramatically reduced infections of contaminated abdominal surgical wounds without increasing pain, according to a report in the April issue of Archives of Surgery.

Use of this wound-probing technique for surgical incisions "will reduce surgical site infection and decrease hospital stay, both of which may result in improved rates of long-term outcomes such as fascial dehiscence and incisional hernias, reduced labor for wound care by nursing staff and physicians, improved cosmetic outcome with primary closure, and possibly reduced overall cost," said Dr. Shirin Towfigh of Cedars-Sinai Medical Center, Los Angeles, and her associates.

"We recommend that wound probing be practiced in the first-line management of incisions after open surgery, such as bowel resection, in the face of contamination," they noted.

Until now, no local wound therapy – including topical antibiotics, subcutaneous drain placement, or delayed primary closure – has been proved to decrease surgical site infection in a rigorous clinical trial. "There is no standard wound management for contaminated wounds, [and] the topic has not been aggressively pursued for decades," the investigators said.

According to surveillance of nosocomial infections in the United States, the infection rate for contaminated surgical wounds is 7% overall, and can rise as high as 50% in certain subgroups of patients.

Some surgeons, including Dr. Towfigh, routinely use this probing technique and report good results anecdotally. In what they described as the first prospective clinical trial of the technique, Dr. Towfigh and her colleagues assessed surgical site infections in 76 adults who underwent appendectomy for perforated appendicitis at a single academic medical center over a 3-year period.

Half of the patients were randomly assigned to have standard primary skin closure with staples (control group), and the other half had loose primary skin closure with staples placed at 2-cm intervals. Postoperatively, the control group had daily swabbing of their closed incision with povidone iodine.

The intervention group had this standard postoperative care followed by wound probing in which dry, sterile, cotton-tip applicators were used to penetrate the skin and soft tissue between the staples, reaching down to the external oblique fascia. Any fluid that was extruded was blotted dry, and the wound was covered with a dry dressing. This process was repeated once daily until the wound was dry and no longer penetrable in this fashion, which usually took 3 days.

The two study groups were similar in terms of demographic characteristics as well as comorbidities that might affect wound healing, such as the presence of diabetes, larger abdominal girth, and higher body mass index. Both groups had similar incisional lengths (approximately 8 cm).

Study subjects were assessed throughout hospitalization, as well as at 2 weeks and 3 months following hospital discharge; 64% of subjects completed the 3-month follow-up. The primary outcome measure was the rate of surgical site infections, defined by both subjective daily evaluation by a surgical team blinded to treatment assignment and objective scores on the ASEPSIS (Additional Treatment, Presence of Serous Discharge, Erythema, Purulent Exudate, and Separation of the Deep Tissues, Isolation of Bacteria, and Duration of Inpatient Stay) instrument.

Only one patient (3%) in the intervention group developed surgical site infection, compared with seven patients (19%) in the control group (P = .03). Moreover, patients in the intervention group did not report greater pain than did those in the control group, either immediately after surgery or at follow-up, Dr. Towfigh and her associates said (Arch. Surg. 2011;146:448-52).

By reducing surgical site infections, the intervention also significantly decreased length of stay, compared with the control group (5 days vs. 7 days, respectively; P = .049), as well as the amount of time that caregivers spent on wound care.

"When primary closure fails or is deemed inappropriate, the wound is opened and allowed to close by secondary intention [that is, packing an open wound multiple times a day]. Closure by secondary intention can be painful to the patient, can be labor intensive, and has a poor cosmetic outcome. Nevertheless it is the most widely used closure technique in adults with contaminated wounds," the researchers said.

"We recommend that wound probing be practiced for contaminated wounds due to open appendectomy for perforated appendicitis. We believe that our results can also be extrapolated to other contaminated abdominal wounds regardless of their incisional length," they added.

The exact mechanism by which this technique prevents surgical site infection is not yet clear, but the investigators surmised that it "allows for drainage of contaminated fluid within the soft tissue, thus reducing the bacterial count while maintaining a moist wound for improved healing.

"We are currently analyzing the bacteriology data gathered from this study to gain insight into the process," Dr. Towfigh and her associates added.

This study was supported in part by a James H. Zumberge Faculty Research and Innovation grant from the University of Southern California, Los Angeles. No financial conflicts of interest were reported.

Two similar interventions to prevent hospital-associated methicillin-resistant Staphylococcus aureus infections produced opposite results: One yielded dramatic reductions in overall, bloodstream, device-associated, and non–device-associated MRSA, whereas the other showed no effect, according to separate reports in the April 14 issue of the New England Journal of Medicine.

Both interventions centered on culture-based active surveillance for resistant organisms, the expanded use of barrier precautions, attention to hand hygiene, and substantial "culture change" among health care providers to take action against resistant infections. And both interventions substantially improved in-hospital safety practices.

Photo credit: Janice Haney Carr/CDC

But only one intervention actually decreased MRSA transmission, leaving the issue of how to reduce hospital-associated resistant infections as unclear as ever.

In one study, researchers in the STAR*ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial compared an infection-control intervention vs. existing, standard safety procedures in 19 adult medical and surgical ICUs during a 6-month period. They analyzed outcomes for 1,356 patients in the intervention group (10 ICUs) and 2,132 patients in the control group (9 ICUs).

The intervention called for obtaining nasal swabs for MRSA cultures and stool or perianal swabs for vancomycin-resistant enterococcus (VRE) cultures within 2 days of admission to the ICU and weekly thereafter, to actively identify patients who carried or were infected with these organisms. Patients who were found to be colonized or infected – along with patients known to have been colonized or infected during the previous year – were assigned to care with contact precautions, which continued for the duration of their ICU stay. All other patients were assigned to care with universal gloving until surveillance cultures were found to be negative, at which time standard ICU practices resumed.

In control ICUs, swabs were taken in an identical manner, but the culture results were not communicated to ICU staff. Standard existing procedures were used to identify patients who were colonized or infected with MRSA or VRE, and they were then treated using contact precautions, said Dr. W. Charles Huskins of the Mayo Clinic, Rochester, Minn., and his associates.

In addition, "intervention ICUs received training in the intervention, door signs describing each category of precautions, and an aggregate report on the providers’ use of universal gloving during the first month of the intervention period."

In all the ICUs, monitors recorded contacts between providers and patients at random times on random dates, and providers’ use of hand hygiene, clean gloves, and gowns was noted.

Patients who carried or were infected with MRSA or VRE were more often identified in the intervention ICUs than in the control ICUs, and thus were more often assigned to expanded barrier precautions (mean, 51% of all patient-days), universal gloving (43%), and either one or the other (92%). In contrast, patients in the control ICUs were assigned to expanded barrier precautions on only 38% of all patient-days, and universal gloving was not used.

A composite measure of caregivers’ hand hygiene and use of clean gloves was nearly twice as high in the intervention ICUs (47% of contacts) as in the control ICUs (25%). In intervention ICUs, clean gloves were used for 82% of contacts, gowns were used in 77%, and hygiene after contact in 69%. In contrast, these proportions were 72%, 59%, and 59%, respectively, in control ICUs.

Nevertheless the primary outcome (ICU-level incidence of new colonization or infection with MRSA or VRE per 1,000 patient-days at risk) was not significantly different between the intervention and control groups, at 40% and 36%, respectively.

This lack of effectiveness was "surprising, given that surveillance cultures identified a sizable subgroup of colonized patients who were not otherwise recognized, and that colonized or infected patients were assigned to either contact precautions or universal gloving for nearly all their ICU patient-days," Dr. Huskins and his colleagues said (N. Engl. J. Med. 2011;364:1407-18).

It is unclear why the intervention failed to reduce the infection rate, but there are several possibilities.

First, the prolonged lag time (an average of 5 days) between admission to the ICU and reporting of the culture results allowed for transmission before the expanded precautions were undertaken. Second, the providers’ use of proper safety measures was greater but still not optimal in the intervention ICUs.

Third, body sites other than those that were cultured – such as the pharynx, open wounds, the skin, respiratory secretions, or the rectum – may have been harboring MRSA or VRE. Fourth, a different route of transmission that wasn’t addressed by this intervention – such as contaminated instruments or colonized care providers – may have been at fault.

And finally, the intervention period may not have been long enough to demonstrate an effect. "Previous studies have observed that a reduction in the incidence of MRSA infection may not be evident until a year or more after initiation of an intervention," the investigators said.

They concluded that "merely improving the identification of colonized patients and expanding the use of barrier precautions ... are measures that are not likely to be broadly effective." Additional interventions that "reduce the density of colonization of body sites or contamination of the environment may be necessary."

In the other study, Dr. Rajiv Jain of the Veterans Health Administration and his associates assessed outcomes after implementation of a nationwide initiative to decrease health care–associated MRSA infections in acute care hospitals. The prevalence of MRSA carriage at hospital admission is much higher among VA patients (approximately 14%) than among patients at non-VA hospitals (6.3%) and in the general population (1.5%), they noted.

The intervention called for surveillance of nasal MRSA colonization for all patients who were admitted to the hospital, transferred from one unit to another within the hospital, or discharged from the hospital, followed by contact precautions for all patients who were found to be either colonized or infected with MRSA. As with the intervention in Dr. Huskins’ study, the VA intervention emphasized hand hygiene and "change in the institutional culture" so that all caregivers were held responsible for infection control.

Outcomes were assessed for 1,934,598 admissions, transfers, or discharges at all the medical, coronary care, or surgical ICUs and all the medical, surgical, rehabilitation medicine, and spinal-cord injury units at 150 VA hospitals across the country in 2007-2010.

After the intervention was implemented in 2007, the rate of hospital-associated MRSA infections in ICUs dropped 62% (from 1.64 per 1,000 patient-days to 0.62). The rate of bloodstream MRSA infections not related to a device declined 79% (from 0.14 per 1,000 patient-days to 0.03). The rate of bloodstream MRSA infections related to a device decreased 62% (from 0.16 to 0.06 per 1,000 patient-days), said Dr. Jain, also of the VA Pittsburgh Healthcare System and the University of Pittsburgh, and his colleagues.

In particular, the rate of ventilator-associated MRSA pneumonia in ICUs decreased 72% (from 1.17 to 0.33 per 1,000 device-days), and that of bloodstream MRSA associated with central venous catheters in ICUs dropped 33% (from 0.46 to 0.31 per 1,000 device-days), Dr. Jain and his associates said (N. Engl. J. Med. 2011;364:1419-30).

The rates of other, non-MRSA ICU infections also decreased significantly. The rate of pneumonia not related to a device declined 37% (from 0.35 to 0.22 per 1,000 patient-days), and that of pneumonia related to a device dropped 75% (from 0.32 to 0.08 per 1,000 patient-days). The rate of urinary tract infections also decreased 75% (from 0.16 to 0.04 per 1,000 patient-day), as did that of skin and soft-tissue infections (from 0.16 to 0.04 per 1,000 patient-days).

The results were similar in non-ICU units, where overall hospital-related MRSA infections declined 45%. Bloodstream infection decreased 58%, pneumonia dropped 38%, UTIs declined 44%, and skin and soft-tissue infections dropped 53%.

Contrary to the findings by Dr. Huskins and colleagues, these results "suggest that proactive efforts to prevent the transmission of MRSA are associated with a reduction in [health care–associated] MRSA infections," and that patients in other, non-VA acute care hospitals might benefit from a similar intervention, the investigators said.

Dr. Huskins’ study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, Merck, Elan Pharmaceuticals, Roche Diagnostics, and Kimberly Clark. Dr. Huskins and his associates reported ties to Roche, GlaxoSmithKline, Medegen, and BioNeutral Group. Dr. Jain’s study was supported by the Veterans Health Administration, and no financial conflicts of interest were reported.

Two similar interventions to prevent hospital-associated methicillin-resistant Staphylococcus aureus infections produced opposite results: One yielded dramatic reductions in overall, bloodstream, device-associated, and non–device-associated MRSA, whereas the other showed no effect, according to separate reports in the April 14 issue of the New England Journal of Medicine.

Both interventions centered on culture-based active surveillance for resistant organisms, the expanded use of barrier precautions, attention to hand hygiene, and substantial "culture change" among health care providers to take action against resistant infections. And both interventions substantially improved in-hospital safety practices.

Photo credit: Janice Haney Carr/CDC

But only one intervention actually decreased MRSA transmission, leaving the issue of how to reduce hospital-associated resistant infections as unclear as ever.

In one study, researchers in the STAR*ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial compared an infection-control intervention vs. existing, standard safety procedures in 19 adult medical and surgical ICUs during a 6-month period. They analyzed outcomes for 1,356 patients in the intervention group (10 ICUs) and 2,132 patients in the control group (9 ICUs).

The intervention called for obtaining nasal swabs for MRSA cultures and stool or perianal swabs for vancomycin-resistant enterococcus (VRE) cultures within 2 days of admission to the ICU and weekly thereafter, to actively identify patients who carried or were infected with these organisms. Patients who were found to be colonized or infected – along with patients known to have been colonized or infected during the previous year – were assigned to care with contact precautions, which continued for the duration of their ICU stay. All other patients were assigned to care with universal gloving until surveillance cultures were found to be negative, at which time standard ICU practices resumed.

In control ICUs, swabs were taken in an identical manner, but the culture results were not communicated to ICU staff. Standard existing procedures were used to identify patients who were colonized or infected with MRSA or VRE, and they were then treated using contact precautions, said Dr. W. Charles Huskins of the Mayo Clinic, Rochester, Minn., and his associates.

In addition, "intervention ICUs received training in the intervention, door signs describing each category of precautions, and an aggregate report on the providers’ use of universal gloving during the first month of the intervention period."

In all the ICUs, monitors recorded contacts between providers and patients at random times on random dates, and providers’ use of hand hygiene, clean gloves, and gowns was noted.

Patients who carried or were infected with MRSA or VRE were more often identified in the intervention ICUs than in the control ICUs, and thus were more often assigned to expanded barrier precautions (mean, 51% of all patient-days), universal gloving (43%), and either one or the other (92%). In contrast, patients in the control ICUs were assigned to expanded barrier precautions on only 38% of all patient-days, and universal gloving was not used.

A composite measure of caregivers’ hand hygiene and use of clean gloves was nearly twice as high in the intervention ICUs (47% of contacts) as in the control ICUs (25%). In intervention ICUs, clean gloves were used for 82% of contacts, gowns were used in 77%, and hygiene after contact in 69%. In contrast, these proportions were 72%, 59%, and 59%, respectively, in control ICUs.

Nevertheless the primary outcome (ICU-level incidence of new colonization or infection with MRSA or VRE per 1,000 patient-days at risk) was not significantly different between the intervention and control groups, at 40% and 36%, respectively.

This lack of effectiveness was "surprising, given that surveillance cultures identified a sizable subgroup of colonized patients who were not otherwise recognized, and that colonized or infected patients were assigned to either contact precautions or universal gloving for nearly all their ICU patient-days," Dr. Huskins and his colleagues said (N. Engl. J. Med. 2011;364:1407-18).

It is unclear why the intervention failed to reduce the infection rate, but there are several possibilities.

First, the prolonged lag time (an average of 5 days) between admission to the ICU and reporting of the culture results allowed for transmission before the expanded precautions were undertaken. Second, the providers’ use of proper safety measures was greater but still not optimal in the intervention ICUs.

Third, body sites other than those that were cultured – such as the pharynx, open wounds, the skin, respiratory secretions, or the rectum – may have been harboring MRSA or VRE. Fourth, a different route of transmission that wasn’t addressed by this intervention – such as contaminated instruments or colonized care providers – may have been at fault.

And finally, the intervention period may not have been long enough to demonstrate an effect. "Previous studies have observed that a reduction in the incidence of MRSA infection may not be evident until a year or more after initiation of an intervention," the investigators said.

They concluded that "merely improving the identification of colonized patients and expanding the use of barrier precautions ... are measures that are not likely to be broadly effective." Additional interventions that "reduce the density of colonization of body sites or contamination of the environment may be necessary."

In the other study, Dr. Rajiv Jain of the Veterans Health Administration and his associates assessed outcomes after implementation of a nationwide initiative to decrease health care–associated MRSA infections in acute care hospitals. The prevalence of MRSA carriage at hospital admission is much higher among VA patients (approximately 14%) than among patients at non-VA hospitals (6.3%) and in the general population (1.5%), they noted.

The intervention called for surveillance of nasal MRSA colonization for all patients who were admitted to the hospital, transferred from one unit to another within the hospital, or discharged from the hospital, followed by contact precautions for all patients who were found to be either colonized or infected with MRSA. As with the intervention in Dr. Huskins’ study, the VA intervention emphasized hand hygiene and "change in the institutional culture" so that all caregivers were held responsible for infection control.

Outcomes were assessed for 1,934,598 admissions, transfers, or discharges at all the medical, coronary care, or surgical ICUs and all the medical, surgical, rehabilitation medicine, and spinal-cord injury units at 150 VA hospitals across the country in 2007-2010.

After the intervention was implemented in 2007, the rate of hospital-associated MRSA infections in ICUs dropped 62% (from 1.64 per 1,000 patient-days to 0.62). The rate of bloodstream MRSA infections not related to a device declined 79% (from 0.14 per 1,000 patient-days to 0.03). The rate of bloodstream MRSA infections related to a device decreased 62% (from 0.16 to 0.06 per 1,000 patient-days), said Dr. Jain, also of the VA Pittsburgh Healthcare System and the University of Pittsburgh, and his colleagues.

In particular, the rate of ventilator-associated MRSA pneumonia in ICUs decreased 72% (from 1.17 to 0.33 per 1,000 device-days), and that of bloodstream MRSA associated with central venous catheters in ICUs dropped 33% (from 0.46 to 0.31 per 1,000 device-days), Dr. Jain and his associates said (N. Engl. J. Med. 2011;364:1419-30).

The rates of other, non-MRSA ICU infections also decreased significantly. The rate of pneumonia not related to a device declined 37% (from 0.35 to 0.22 per 1,000 patient-days), and that of pneumonia related to a device dropped 75% (from 0.32 to 0.08 per 1,000 patient-days). The rate of urinary tract infections also decreased 75% (from 0.16 to 0.04 per 1,000 patient-day), as did that of skin and soft-tissue infections (from 0.16 to 0.04 per 1,000 patient-days).

The results were similar in non-ICU units, where overall hospital-related MRSA infections declined 45%. Bloodstream infection decreased 58%, pneumonia dropped 38%, UTIs declined 44%, and skin and soft-tissue infections dropped 53%.

Contrary to the findings by Dr. Huskins and colleagues, these results "suggest that proactive efforts to prevent the transmission of MRSA are associated with a reduction in [health care–associated] MRSA infections," and that patients in other, non-VA acute care hospitals might benefit from a similar intervention, the investigators said.

Dr. Huskins’ study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, Merck, Elan Pharmaceuticals, Roche Diagnostics, and Kimberly Clark. Dr. Huskins and his associates reported ties to Roche, GlaxoSmithKline, Medegen, and BioNeutral Group. Dr. Jain’s study was supported by the Veterans Health Administration, and no financial conflicts of interest were reported.

Two similar interventions to prevent hospital-associated methicillin-resistant Staphylococcus aureus infections produced opposite results: One yielded dramatic reductions in overall, bloodstream, device-associated, and non–device-associated MRSA, whereas the other showed no effect, according to separate reports in the April 14 issue of the New England Journal of Medicine.

Both interventions centered on culture-based active surveillance for resistant organisms, the expanded use of barrier precautions, attention to hand hygiene, and substantial "culture change" among health care providers to take action against resistant infections. And both interventions substantially improved in-hospital safety practices.

Photo credit: Janice Haney Carr/CDC

But only one intervention actually decreased MRSA transmission, leaving the issue of how to reduce hospital-associated resistant infections as unclear as ever.

In one study, researchers in the STAR*ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial compared an infection-control intervention vs. existing, standard safety procedures in 19 adult medical and surgical ICUs during a 6-month period. They analyzed outcomes for 1,356 patients in the intervention group (10 ICUs) and 2,132 patients in the control group (9 ICUs).

The intervention called for obtaining nasal swabs for MRSA cultures and stool or perianal swabs for vancomycin-resistant enterococcus (VRE) cultures within 2 days of admission to the ICU and weekly thereafter, to actively identify patients who carried or were infected with these organisms. Patients who were found to be colonized or infected – along with patients known to have been colonized or infected during the previous year – were assigned to care with contact precautions, which continued for the duration of their ICU stay. All other patients were assigned to care with universal gloving until surveillance cultures were found to be negative, at which time standard ICU practices resumed.

In control ICUs, swabs were taken in an identical manner, but the culture results were not communicated to ICU staff. Standard existing procedures were used to identify patients who were colonized or infected with MRSA or VRE, and they were then treated using contact precautions, said Dr. W. Charles Huskins of the Mayo Clinic, Rochester, Minn., and his associates.

In addition, "intervention ICUs received training in the intervention, door signs describing each category of precautions, and an aggregate report on the providers’ use of universal gloving during the first month of the intervention period."

In all the ICUs, monitors recorded contacts between providers and patients at random times on random dates, and providers’ use of hand hygiene, clean gloves, and gowns was noted.

Patients who carried or were infected with MRSA or VRE were more often identified in the intervention ICUs than in the control ICUs, and thus were more often assigned to expanded barrier precautions (mean, 51% of all patient-days), universal gloving (43%), and either one or the other (92%). In contrast, patients in the control ICUs were assigned to expanded barrier precautions on only 38% of all patient-days, and universal gloving was not used.

A composite measure of caregivers’ hand hygiene and use of clean gloves was nearly twice as high in the intervention ICUs (47% of contacts) as in the control ICUs (25%). In intervention ICUs, clean gloves were used for 82% of contacts, gowns were used in 77%, and hygiene after contact in 69%. In contrast, these proportions were 72%, 59%, and 59%, respectively, in control ICUs.

Nevertheless the primary outcome (ICU-level incidence of new colonization or infection with MRSA or VRE per 1,000 patient-days at risk) was not significantly different between the intervention and control groups, at 40% and 36%, respectively.

This lack of effectiveness was "surprising, given that surveillance cultures identified a sizable subgroup of colonized patients who were not otherwise recognized, and that colonized or infected patients were assigned to either contact precautions or universal gloving for nearly all their ICU patient-days," Dr. Huskins and his colleagues said (N. Engl. J. Med. 2011;364:1407-18).

It is unclear why the intervention failed to reduce the infection rate, but there are several possibilities.

First, the prolonged lag time (an average of 5 days) between admission to the ICU and reporting of the culture results allowed for transmission before the expanded precautions were undertaken. Second, the providers’ use of proper safety measures was greater but still not optimal in the intervention ICUs.

Third, body sites other than those that were cultured – such as the pharynx, open wounds, the skin, respiratory secretions, or the rectum – may have been harboring MRSA or VRE. Fourth, a different route of transmission that wasn’t addressed by this intervention – such as contaminated instruments or colonized care providers – may have been at fault.

And finally, the intervention period may not have been long enough to demonstrate an effect. "Previous studies have observed that a reduction in the incidence of MRSA infection may not be evident until a year or more after initiation of an intervention," the investigators said.

They concluded that "merely improving the identification of colonized patients and expanding the use of barrier precautions ... are measures that are not likely to be broadly effective." Additional interventions that "reduce the density of colonization of body sites or contamination of the environment may be necessary."

In the other study, Dr. Rajiv Jain of the Veterans Health Administration and his associates assessed outcomes after implementation of a nationwide initiative to decrease health care–associated MRSA infections in acute care hospitals. The prevalence of MRSA carriage at hospital admission is much higher among VA patients (approximately 14%) than among patients at non-VA hospitals (6.3%) and in the general population (1.5%), they noted.

The intervention called for surveillance of nasal MRSA colonization for all patients who were admitted to the hospital, transferred from one unit to another within the hospital, or discharged from the hospital, followed by contact precautions for all patients who were found to be either colonized or infected with MRSA. As with the intervention in Dr. Huskins’ study, the VA intervention emphasized hand hygiene and "change in the institutional culture" so that all caregivers were held responsible for infection control.

Outcomes were assessed for 1,934,598 admissions, transfers, or discharges at all the medical, coronary care, or surgical ICUs and all the medical, surgical, rehabilitation medicine, and spinal-cord injury units at 150 VA hospitals across the country in 2007-2010.

After the intervention was implemented in 2007, the rate of hospital-associated MRSA infections in ICUs dropped 62% (from 1.64 per 1,000 patient-days to 0.62). The rate of bloodstream MRSA infections not related to a device declined 79% (from 0.14 per 1,000 patient-days to 0.03). The rate of bloodstream MRSA infections related to a device decreased 62% (from 0.16 to 0.06 per 1,000 patient-days), said Dr. Jain, also of the VA Pittsburgh Healthcare System and the University of Pittsburgh, and his colleagues.

In particular, the rate of ventilator-associated MRSA pneumonia in ICUs decreased 72% (from 1.17 to 0.33 per 1,000 device-days), and that of bloodstream MRSA associated with central venous catheters in ICUs dropped 33% (from 0.46 to 0.31 per 1,000 device-days), Dr. Jain and his associates said (N. Engl. J. Med. 2011;364:1419-30).

The rates of other, non-MRSA ICU infections also decreased significantly. The rate of pneumonia not related to a device declined 37% (from 0.35 to 0.22 per 1,000 patient-days), and that of pneumonia related to a device dropped 75% (from 0.32 to 0.08 per 1,000 patient-days). The rate of urinary tract infections also decreased 75% (from 0.16 to 0.04 per 1,000 patient-day), as did that of skin and soft-tissue infections (from 0.16 to 0.04 per 1,000 patient-days).

The results were similar in non-ICU units, where overall hospital-related MRSA infections declined 45%. Bloodstream infection decreased 58%, pneumonia dropped 38%, UTIs declined 44%, and skin and soft-tissue infections dropped 53%.

Contrary to the findings by Dr. Huskins and colleagues, these results "suggest that proactive efforts to prevent the transmission of MRSA are associated with a reduction in [health care–associated] MRSA infections," and that patients in other, non-VA acute care hospitals might benefit from a similar intervention, the investigators said.

Dr. Huskins’ study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, Merck, Elan Pharmaceuticals, Roche Diagnostics, and Kimberly Clark. Dr. Huskins and his associates reported ties to Roche, GlaxoSmithKline, Medegen, and BioNeutral Group. Dr. Jain’s study was supported by the Veterans Health Administration, and no financial conflicts of interest were reported.

Two similar interventions to prevent hospital-associated methicillin-resistant Staphylococcus aureus infections produced opposite results: One yielded dramatic reductions in overall, bloodstream, device-associated, and non–device-associated MRSA, whereas the other showed no effect, according to separate reports in the April 14 issue of the New England Journal of Medicine.

Both interventions centered on culture-based active surveillance for resistant organisms, the expanded use of barrier precautions, attention to hand hygiene, and substantial "culture change" among health care providers to take action against resistant infections. And both interventions substantially improved in-hospital safety practices.

Photo credit: Janice Haney Carr/CDC

But only one intervention actually decreased MRSA transmission, leaving the issue of how to reduce hospital-associated resistant infections as unclear as ever.

In one study, researchers in the STAR*ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial compared an infection-control intervention vs. existing, standard safety procedures in 19 adult medical and surgical ICUs during a 6-month period. They analyzed outcomes for 1,356 patients in the intervention group (10 ICUs) and 2,132 patients in the control group (9 ICUs).

The intervention called for obtaining nasal swabs for MRSA cultures and stool or perianal swabs for vancomycin-resistant enterococcus (VRE) cultures within 2 days of admission to the ICU and weekly thereafter, to actively identify patients who carried or were infected with these organisms. Patients who were found to be colonized or infected – along with patients known to have been colonized or infected during the previous year – were assigned to care with contact precautions, which continued for the duration of their ICU stay. All other patients were assigned to care with universal gloving until surveillance cultures were found to be negative, at which time standard ICU practices resumed.

In control ICUs, swabs were taken in an identical manner, but the culture results were not communicated to ICU staff. Standard existing procedures were used to identify patients who were colonized or infected with MRSA or VRE, and they were then treated using contact precautions, said Dr. W. Charles Huskins of the Mayo Clinic, Rochester, Minn., and his associates.

In addition, "intervention ICUs received training in the intervention, door signs describing each category of precautions, and an aggregate report on the providers’ use of universal gloving during the first month of the intervention period."

In all the ICUs, monitors recorded contacts between providers and patients at random times on random dates, and providers’ use of hand hygiene, clean gloves, and gowns was noted.

Patients who carried or were infected with MRSA or VRE were more often identified in the intervention ICUs than in the control ICUs, and thus were more often assigned to expanded barrier precautions (mean, 51% of all patient-days), universal gloving (43%), and either one or the other (92%). In contrast, patients in the control ICUs were assigned to expanded barrier precautions on only 38% of all patient-days, and universal gloving was not used.

A composite measure of caregivers’ hand hygiene and use of clean gloves was nearly twice as high in the intervention ICUs (47% of contacts) as in the control ICUs (25%). In intervention ICUs, clean gloves were used for 82% of contacts, gowns were used in 77%, and hygiene after contact in 69%. In contrast, these proportions were 72%, 59%, and 59%, respectively, in control ICUs.

Nevertheless the primary outcome (ICU-level incidence of new colonization or infection with MRSA or VRE per 1,000 patient-days at risk) was not significantly different between the intervention and control groups, at 40% and 36%, respectively.

This lack of effectiveness was "surprising, given that surveillance cultures identified a sizable subgroup of colonized patients who were not otherwise recognized, and that colonized or infected patients were assigned to either contact precautions or universal gloving for nearly all their ICU patient-days," Dr. Huskins and his colleagues said (N. Engl. J. Med. 2011;364:1407-18).

It is unclear why the intervention failed to reduce the infection rate, but there are several possibilities.

First, the prolonged lag time (an average of 5 days) between admission to the ICU and reporting of the culture results allowed for transmission before the expanded precautions were undertaken. Second, the providers’ use of proper safety measures was greater but still not optimal in the intervention ICUs.

Third, body sites other than those that were cultured – such as the pharynx, open wounds, the skin, respiratory secretions, or the rectum – may have been harboring MRSA or VRE. Fourth, a different route of transmission that wasn’t addressed by this intervention – such as contaminated instruments or colonized care providers – may have been at fault.

And finally, the intervention period may not have been long enough to demonstrate an effect. "Previous studies have observed that a reduction in the incidence of MRSA infection may not be evident until a year or more after initiation of an intervention," the investigators said.

They concluded that "merely improving the identification of colonized patients and expanding the use of barrier precautions ... are measures that are not likely to be broadly effective." Additional interventions that "reduce the density of colonization of body sites or contamination of the environment may be necessary."

In the other study, Dr. Rajiv Jain of the Veterans Health Administration and his associates assessed outcomes after implementation of a nationwide initiative to decrease health care–associated MRSA infections in acute care hospitals. The prevalence of MRSA carriage at hospital admission is much higher among VA patients (approximately 14%) than among patients at non-VA hospitals (6.3%) and in the general population (1.5%), they noted.

The intervention called for surveillance of nasal MRSA colonization for all patients who were admitted to the hospital, transferred from one unit to another within the hospital, or discharged from the hospital, followed by contact precautions for all patients who were found to be either colonized or infected with MRSA. As with the intervention in Dr. Huskins’ study, the VA intervention emphasized hand hygiene and "change in the institutional culture" so that all caregivers were held responsible for infection control.

Outcomes were assessed for 1,934,598 admissions, transfers, or discharges at all the medical, coronary care, or surgical ICUs and all the medical, surgical, rehabilitation medicine, and spinal-cord injury units at 150 VA hospitals across the country in 2007-2010.

After the intervention was implemented in 2007, the rate of hospital-associated MRSA infections in ICUs dropped 62% (from 1.64 per 1,000 patient-days to 0.62). The rate of bloodstream MRSA infections not related to a device declined 79% (from 0.14 per 1,000 patient-days to 0.03). The rate of bloodstream MRSA infections related to a device decreased 62% (from 0.16 to 0.06 per 1,000 patient-days), said Dr. Jain, also of the VA Pittsburgh Healthcare System and the University of Pittsburgh, and his colleagues.

In particular, the rate of ventilator-associated MRSA pneumonia in ICUs decreased 72% (from 1.17 to 0.33 per 1,000 device-days), and that of bloodstream MRSA associated with central venous catheters in ICUs dropped 33% (from 0.46 to 0.31 per 1,000 device-days), Dr. Jain and his associates said (N. Engl. J. Med. 2011;364:1419-30).

The rates of other, non-MRSA ICU infections also decreased significantly. The rate of pneumonia not related to a device declined 37% (from 0.35 to 0.22 per 1,000 patient-days), and that of pneumonia related to a device dropped 75% (from 0.32 to 0.08 per 1,000 patient-days). The rate of urinary tract infections also decreased 75% (from 0.16 to 0.04 per 1,000 patient-day), as did that of skin and soft-tissue infections (from 0.16 to 0.04 per 1,000 patient-days).

The results were similar in non-ICU units, where overall hospital-related MRSA infections declined 45%. Bloodstream infection decreased 58%, pneumonia dropped 38%, UTIs declined 44%, and skin and soft-tissue infections dropped 53%.

Contrary to the findings by Dr. Huskins and colleagues, these results "suggest that proactive efforts to prevent the transmission of MRSA are associated with a reduction in [health care–associated] MRSA infections," and that patients in other, non-VA acute care hospitals might benefit from a similar intervention, the investigators said.

Dr. Huskins’ study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, Merck, Elan Pharmaceuticals, Roche Diagnostics, and Kimberly Clark. Dr. Huskins and his associates reported ties to Roche, GlaxoSmithKline, Medegen, and BioNeutral Group. Dr. Jain’s study was supported by the Veterans Health Administration, and no financial conflicts of interest were reported.

Two similar interventions to prevent hospital-associated methicillin-resistant Staphylococcus aureus infections produced opposite results: One yielded dramatic reductions in overall, bloodstream, device-associated, and non–device-associated MRSA, whereas the other showed no effect, according to separate reports in the April 14 issue of the New England Journal of Medicine.

Both interventions centered on culture-based active surveillance for resistant organisms, the expanded use of barrier precautions, attention to hand hygiene, and substantial "culture change" among health care providers to take action against resistant infections. And both interventions substantially improved in-hospital safety practices.

Photo credit: Janice Haney Carr/CDC

But only one intervention actually decreased MRSA transmission, leaving the issue of how to reduce hospital-associated resistant infections as unclear as ever.

In one study, researchers in the STAR*ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial compared an infection-control intervention vs. existing, standard safety procedures in 19 adult medical and surgical ICUs during a 6-month period. They analyzed outcomes for 1,356 patients in the intervention group (10 ICUs) and 2,132 patients in the control group (9 ICUs).

The intervention called for obtaining nasal swabs for MRSA cultures and stool or perianal swabs for vancomycin-resistant enterococcus (VRE) cultures within 2 days of admission to the ICU and weekly thereafter, to actively identify patients who carried or were infected with these organisms. Patients who were found to be colonized or infected – along with patients known to have been colonized or infected during the previous year – were assigned to care with contact precautions, which continued for the duration of their ICU stay. All other patients were assigned to care with universal gloving until surveillance cultures were found to be negative, at which time standard ICU practices resumed.

In control ICUs, swabs were taken in an identical manner, but the culture results were not communicated to ICU staff. Standard existing procedures were used to identify patients who were colonized or infected with MRSA or VRE, and they were then treated using contact precautions, said Dr. W. Charles Huskins of the Mayo Clinic, Rochester, Minn., and his associates.

In addition, "intervention ICUs received training in the intervention, door signs describing each category of precautions, and an aggregate report on the providers’ use of universal gloving during the first month of the intervention period."

In all the ICUs, monitors recorded contacts between providers and patients at random times on random dates, and providers’ use of hand hygiene, clean gloves, and gowns was noted.

Patients who carried or were infected with MRSA or VRE were more often identified in the intervention ICUs than in the control ICUs, and thus were more often assigned to expanded barrier precautions (mean, 51% of all patient-days), universal gloving (43%), and either one or the other (92%). In contrast, patients in the control ICUs were assigned to expanded barrier precautions on only 38% of all patient-days, and universal gloving was not used.

A composite measure of caregivers’ hand hygiene and use of clean gloves was nearly twice as high in the intervention ICUs (47% of contacts) as in the control ICUs (25%). In intervention ICUs, clean gloves were used for 82% of contacts, gowns were used in 77%, and hygiene after contact in 69%. In contrast, these proportions were 72%, 59%, and 59%, respectively, in control ICUs.

Nevertheless the primary outcome (ICU-level incidence of new colonization or infection with MRSA or VRE per 1,000 patient-days at risk) was not significantly different between the intervention and control groups, at 40% and 36%, respectively.

This lack of effectiveness was "surprising, given that surveillance cultures identified a sizable subgroup of colonized patients who were not otherwise recognized, and that colonized or infected patients were assigned to either contact precautions or universal gloving for nearly all their ICU patient-days," Dr. Huskins and his colleagues said (N. Engl. J. Med. 2011;364:1407-18).

It is unclear why the intervention failed to reduce the infection rate, but there are several possibilities.

First, the prolonged lag time (an average of 5 days) between admission to the ICU and reporting of the culture results allowed for transmission before the expanded precautions were undertaken. Second, the providers’ use of proper safety measures was greater but still not optimal in the intervention ICUs.

Third, body sites other than those that were cultured – such as the pharynx, open wounds, the skin, respiratory secretions, or the rectum – may have been harboring MRSA or VRE. Fourth, a different route of transmission that wasn’t addressed by this intervention – such as contaminated instruments or colonized care providers – may have been at fault.

And finally, the intervention period may not have been long enough to demonstrate an effect. "Previous studies have observed that a reduction in the incidence of MRSA infection may not be evident until a year or more after initiation of an intervention," the investigators said.

They concluded that "merely improving the identification of colonized patients and expanding the use of barrier precautions ... are measures that are not likely to be broadly effective." Additional interventions that "reduce the density of colonization of body sites or contamination of the environment may be necessary."

In the other study, Dr. Rajiv Jain of the Veterans Health Administration and his associates assessed outcomes after implementation of a nationwide initiative to decrease health care–associated MRSA infections in acute care hospitals. The prevalence of MRSA carriage at hospital admission is much higher among VA patients (approximately 14%) than among patients at non-VA hospitals (6.3%) and in the general population (1.5%), they noted.

The intervention called for surveillance of nasal MRSA colonization for all patients who were admitted to the hospital, transferred from one unit to another within the hospital, or discharged from the hospital, followed by contact precautions for all patients who were found to be either colonized or infected with MRSA. As with the intervention in Dr. Huskins’ study, the VA intervention emphasized hand hygiene and "change in the institutional culture" so that all caregivers were held responsible for infection control.

Outcomes were assessed for 1,934,598 admissions, transfers, or discharges at all the medical, coronary care, or surgical ICUs and all the medical, surgical, rehabilitation medicine, and spinal-cord injury units at 150 VA hospitals across the country in 2007-2010.

After the intervention was implemented in 2007, the rate of hospital-associated MRSA infections in ICUs dropped 62% (from 1.64 per 1,000 patient-days to 0.62). The rate of bloodstream MRSA infections not related to a device declined 79% (from 0.14 per 1,000 patient-days to 0.03). The rate of bloodstream MRSA infections related to a device decreased 62% (from 0.16 to 0.06 per 1,000 patient-days), said Dr. Jain, also of the VA Pittsburgh Healthcare System and the University of Pittsburgh, and his colleagues.

In particular, the rate of ventilator-associated MRSA pneumonia in ICUs decreased 72% (from 1.17 to 0.33 per 1,000 device-days), and that of bloodstream MRSA associated with central venous catheters in ICUs dropped 33% (from 0.46 to 0.31 per 1,000 device-days), Dr. Jain and his associates said (N. Engl. J. Med. 2011;364:1419-30).

The rates of other, non-MRSA ICU infections also decreased significantly. The rate of pneumonia not related to a device declined 37% (from 0.35 to 0.22 per 1,000 patient-days), and that of pneumonia related to a device dropped 75% (from 0.32 to 0.08 per 1,000 patient-days). The rate of urinary tract infections also decreased 75% (from 0.16 to 0.04 per 1,000 patient-day), as did that of skin and soft-tissue infections (from 0.16 to 0.04 per 1,000 patient-days).

The results were similar in non-ICU units, where overall hospital-related MRSA infections declined 45%. Bloodstream infection decreased 58%, pneumonia dropped 38%, UTIs declined 44%, and skin and soft-tissue infections dropped 53%.

Contrary to the findings by Dr. Huskins and colleagues, these results "suggest that proactive efforts to prevent the transmission of MRSA are associated with a reduction in [health care–associated] MRSA infections," and that patients in other, non-VA acute care hospitals might benefit from a similar intervention, the investigators said.

Dr. Huskins’ study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, Merck, Elan Pharmaceuticals, Roche Diagnostics, and Kimberly Clark. Dr. Huskins and his associates reported ties to Roche, GlaxoSmithKline, Medegen, and BioNeutral Group. Dr. Jain’s study was supported by the Veterans Health Administration, and no financial conflicts of interest were reported.

Two similar interventions to prevent hospital-associated methicillin-resistant Staphylococcus aureus infections produced opposite results: One yielded dramatic reductions in overall, bloodstream, device-associated, and non–device-associated MRSA, whereas the other showed no effect, according to separate reports in the April 14 issue of the New England Journal of Medicine.

Both interventions centered on culture-based active surveillance for resistant organisms, the expanded use of barrier precautions, attention to hand hygiene, and substantial "culture change" among health care providers to take action against resistant infections. And both interventions substantially improved in-hospital safety practices.

Photo credit: Janice Haney Carr/CDC

But only one intervention actually decreased MRSA transmission, leaving the issue of how to reduce hospital-associated resistant infections as unclear as ever.

In one study, researchers in the STAR*ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial compared an infection-control intervention vs. existing, standard safety procedures in 19 adult medical and surgical ICUs during a 6-month period. They analyzed outcomes for 1,356 patients in the intervention group (10 ICUs) and 2,132 patients in the control group (9 ICUs).

The intervention called for obtaining nasal swabs for MRSA cultures and stool or perianal swabs for vancomycin-resistant enterococcus (VRE) cultures within 2 days of admission to the ICU and weekly thereafter, to actively identify patients who carried or were infected with these organisms. Patients who were found to be colonized or infected – along with patients known to have been colonized or infected during the previous year – were assigned to care with contact precautions, which continued for the duration of their ICU stay. All other patients were assigned to care with universal gloving until surveillance cultures were found to be negative, at which time standard ICU practices resumed.

In control ICUs, swabs were taken in an identical manner, but the culture results were not communicated to ICU staff. Standard existing procedures were used to identify patients who were colonized or infected with MRSA or VRE, and they were then treated using contact precautions, said Dr. W. Charles Huskins of the Mayo Clinic, Rochester, Minn., and his associates.

In addition, "intervention ICUs received training in the intervention, door signs describing each category of precautions, and an aggregate report on the providers’ use of universal gloving during the first month of the intervention period."

In all the ICUs, monitors recorded contacts between providers and patients at random times on random dates, and providers’ use of hand hygiene, clean gloves, and gowns was noted.

Patients who carried or were infected with MRSA or VRE were more often identified in the intervention ICUs than in the control ICUs, and thus were more often assigned to expanded barrier precautions (mean, 51% of all patient-days), universal gloving (43%), and either one or the other (92%). In contrast, patients in the control ICUs were assigned to expanded barrier precautions on only 38% of all patient-days, and universal gloving was not used.

A composite measure of caregivers’ hand hygiene and use of clean gloves was nearly twice as high in the intervention ICUs (47% of contacts) as in the control ICUs (25%). In intervention ICUs, clean gloves were used for 82% of contacts, gowns were used in 77%, and hygiene after contact in 69%. In contrast, these proportions were 72%, 59%, and 59%, respectively, in control ICUs.

Nevertheless the primary outcome (ICU-level incidence of new colonization or infection with MRSA or VRE per 1,000 patient-days at risk) was not significantly different between the intervention and control groups, at 40% and 36%, respectively.

This lack of effectiveness was "surprising, given that surveillance cultures identified a sizable subgroup of colonized patients who were not otherwise recognized, and that colonized or infected patients were assigned to either contact precautions or universal gloving for nearly all their ICU patient-days," Dr. Huskins and his colleagues said (N. Engl. J. Med. 2011;364:1407-18).

It is unclear why the intervention failed to reduce the infection rate, but there are several possibilities.

First, the prolonged lag time (an average of 5 days) between admission to the ICU and reporting of the culture results allowed for transmission before the expanded precautions were undertaken. Second, the providers’ use of proper safety measures was greater but still not optimal in the intervention ICUs.

Third, body sites other than those that were cultured – such as the pharynx, open wounds, the skin, respiratory secretions, or the rectum – may have been harboring MRSA or VRE. Fourth, a different route of transmission that wasn’t addressed by this intervention – such as contaminated instruments or colonized care providers – may have been at fault.

And finally, the intervention period may not have been long enough to demonstrate an effect. "Previous studies have observed that a reduction in the incidence of MRSA infection may not be evident until a year or more after initiation of an intervention," the investigators said.

They concluded that "merely improving the identification of colonized patients and expanding the use of barrier precautions ... are measures that are not likely to be broadly effective." Additional interventions that "reduce the density of colonization of body sites or contamination of the environment may be necessary."

In the other study, Dr. Rajiv Jain of the Veterans Health Administration and his associates assessed outcomes after implementation of a nationwide initiative to decrease health care–associated MRSA infections in acute care hospitals. The prevalence of MRSA carriage at hospital admission is much higher among VA patients (approximately 14%) than among patients at non-VA hospitals (6.3%) and in the general population (1.5%), they noted.

The intervention called for surveillance of nasal MRSA colonization for all patients who were admitted to the hospital, transferred from one unit to another within the hospital, or discharged from the hospital, followed by contact precautions for all patients who were found to be either colonized or infected with MRSA. As with the intervention in Dr. Huskins’ study, the VA intervention emphasized hand hygiene and "change in the institutional culture" so that all caregivers were held responsible for infection control.

Outcomes were assessed for 1,934,598 admissions, transfers, or discharges at all the medical, coronary care, or surgical ICUs and all the medical, surgical, rehabilitation medicine, and spinal-cord injury units at 150 VA hospitals across the country in 2007-2010.

After the intervention was implemented in 2007, the rate of hospital-associated MRSA infections in ICUs dropped 62% (from 1.64 per 1,000 patient-days to 0.62). The rate of bloodstream MRSA infections not related to a device declined 79% (from 0.14 per 1,000 patient-days to 0.03). The rate of bloodstream MRSA infections related to a device decreased 62% (from 0.16 to 0.06 per 1,000 patient-days), said Dr. Jain, also of the VA Pittsburgh Healthcare System and the University of Pittsburgh, and his colleagues.

In particular, the rate of ventilator-associated MRSA pneumonia in ICUs decreased 72% (from 1.17 to 0.33 per 1,000 device-days), and that of bloodstream MRSA associated with central venous catheters in ICUs dropped 33% (from 0.46 to 0.31 per 1,000 device-days), Dr. Jain and his associates said (N. Engl. J. Med. 2011;364:1419-30).

The rates of other, non-MRSA ICU infections also decreased significantly. The rate of pneumonia not related to a device declined 37% (from 0.35 to 0.22 per 1,000 patient-days), and that of pneumonia related to a device dropped 75% (from 0.32 to 0.08 per 1,000 patient-days). The rate of urinary tract infections also decreased 75% (from 0.16 to 0.04 per 1,000 patient-day), as did that of skin and soft-tissue infections (from 0.16 to 0.04 per 1,000 patient-days).

The results were similar in non-ICU units, where overall hospital-related MRSA infections declined 45%. Bloodstream infection decreased 58%, pneumonia dropped 38%, UTIs declined 44%, and skin and soft-tissue infections dropped 53%.

Contrary to the findings by Dr. Huskins and colleagues, these results "suggest that proactive efforts to prevent the transmission of MRSA are associated with a reduction in [health care–associated] MRSA infections," and that patients in other, non-VA acute care hospitals might benefit from a similar intervention, the investigators said.

Dr. Huskins’ study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, Merck, Elan Pharmaceuticals, Roche Diagnostics, and Kimberly Clark. Dr. Huskins and his associates reported ties to Roche, GlaxoSmithKline, Medegen, and BioNeutral Group. Dr. Jain’s study was supported by the Veterans Health Administration, and no financial conflicts of interest were reported.

Two similar interventions to prevent hospital-associated methicillin-resistant Staphylococcus aureus infections produced opposite results: One yielded dramatic reductions in overall, bloodstream, device-associated, and non–device-associated MRSA, whereas the other showed no effect, according to separate reports in the April 14 issue of the New England Journal of Medicine.

Photo credit: Janice Haney Carr/CDC

Both interventions centered on culture-based active surveillance for resistant organisms, the expanded use of barrier precautions, attention to hand hygiene, and substantial "culture change" among health care providers to take action against resistant infections. And both interventions substantially improved in-hospital safety practices.

But only one intervention actually decreased MRSA transmission, leaving the issue of how to reduce hospital-associated resistant infections as unclear as ever.

In one study, researchers in the STAR*ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial compared an infection-control intervention vs. existing, standard safety procedures in 19 adult medical and surgical ICUs during a 6-month period. They analyzed outcomes for 1,356 patients in the intervention group (10 ICUs) and 2,132 patients in the control group (9 ICUs).

The intervention called for obtaining nasal swabs for MRSA cultures and stool or perianal swabs for vancomycin-resistant enterococcus (VRE) cultures within 2 days of admission to the ICU and weekly thereafter, to actively identify patients who carried or were infected with these organisms. Patients who were found to be colonized or infected – along with patients known to have been colonized or infected during the previous year – were assigned to care with contact precautions, which continued for the duration of their ICU stay. All other patients were assigned to care with universal gloving until surveillance cultures were found to be negative, at which time standard ICU practices resumed.

In control ICUs, swabs were taken in an identical manner, but the culture results were not communicated to ICU staff. Standard existing procedures were used to identify patients who were colonized or infected with MRSA or VRE, and they were then treated using contact precautions, said Dr. W. Charles Huskins of the Mayo Clinic, Rochester, Minn., and his associates.

In addition, "intervention ICUs received training in the intervention, door signs describing each category of precautions, and an aggregate report on the providers’ use of universal gloving during the first month of the intervention period."

In all the ICUs, monitors recorded contacts between providers and patients at random times on random dates, and providers’ use of hand hygiene, clean gloves, and gowns was noted.

Patients who carried or were infected with MRSA or VRE were more often identified in the intervention ICUs than in the control ICUs, and thus were more often assigned to expanded barrier precautions (mean, 51% of all patient-days), universal gloving (43%), and either one or the other (92%). In contrast, patients in the control ICUs were assigned to expanded barrier precautions on only 38% of all patient-days, and universal gloving was not used.

A composite measure of caregivers’ hand hygiene and use of clean gloves was nearly twice as high in the intervention ICUs (47% of contacts) as in the control ICUs (25%). In intervention ICUs, clean gloves were used for 82% of contacts, gowns were used in 77%, and hygiene after contact in 69%. In contrast, these proportions were 72%, 59%, and 59%, respectively, in control ICUs.

Nevertheless the primary outcome (ICU-level incidence of new colonization or infection with MRSA or VRE per 1,000 patient-days at risk) was not significantly different between the intervention and control groups, at 40% and 36%, respectively.

This lack of effectiveness was "surprising, given that surveillance cultures identified a sizable subgroup of colonized patients who were not otherwise recognized, and that colonized or infected patients were assigned to either contact precautions or universal gloving for nearly all their ICU patient-days," Dr. Huskins and his colleagues said (N. Engl. J. Med. 2011;364:1407-18).

It is unclear why the intervention failed to reduce the infection rate, but there are several possibilities.

First, the prolonged lag time (an average of 5 days) between admission to the ICU and reporting of the culture results allowed for transmission before the expanded precautions were undertaken. Second, the providers’ use of proper safety measures was greater but still not optimal in the intervention ICUs.

Third, body sites other than those that were cultured – such as the pharynx, open wounds, the skin, respiratory secretions, or the rectum – may have been harboring MRSA or VRE. Fourth, a different route of transmission that wasn’t addressed by this intervention – such as contaminated instruments or colonized care providers – may have been at fault.

And finally, the intervention period may not have been long enough to demonstrate an effect. "Previous studies have observed that a reduction in the incidence of MRSA infection may not be evident until a year or more after initiation of an intervention," the investigators said.

They concluded that "merely improving the identification of colonized patients and expanding the use of barrier precautions ... are measures that are not likely to be broadly effective." Additional interventions that "reduce the density of colonization of body sites or contamination of the environment may be necessary."

In the other study, Dr. Rajiv Jain of the Veterans Health Administration and his associates assessed outcomes after implementation of a nationwide initiative to decrease health care–associated MRSA infections in acute care hospitals. The prevalence of MRSA carriage at hospital admission is much higher among VA patients (approximately 14%) than among patients at non-VA hospitals (6.3%) and in the general population (1.5%), they noted.

The intervention called for surveillance of nasal MRSA colonization for all patients who were admitted to the hospital, transferred from one unit to another within the hospital, or discharged from the hospital, followed by contact precautions for all patients who were found to be either colonized or infected with MRSA. As with the intervention in Dr. Huskins’ study, the VA intervention emphasized hand hygiene and "change in the institutional culture" so that all caregivers were held responsible for infection control.

Outcomes were assessed for 1,934,598 admissions, transfers, or discharges at all the medical, coronary care, or surgical ICUs and all the medical, surgical, rehabilitation medicine, and spinal-cord injury units at 150 VA hospitals across the country in 2007-2010.

After the intervention was implemented in 2007, the rate of hospital-associated MRSA infections in ICUs dropped 62% (from 1.64 per 1,000 patient-days to 0.62). The rate of bloodstream MRSA infections not related to a device declined 79% (from 0.14 per 1,000 patient-days to 0.03). The rate of bloodstream MRSA infections related to a device decreased 62% (from 0.16 to 0.06 per 1,000 patient-days), said Dr. Jain, also of the VA Pittsburgh Healthcare System and the University of Pittsburgh, and his colleagues.

In particular, the rate of ventilator-associated MRSA pneumonia in ICUs decreased 72% (from 1.17 to 0.33 per 1,000 device-days), and that of bloodstream MRSA associated with central venous catheters in ICUs dropped 33% (from 0.46 to 0.31 per 1,000 device-days), Dr. Jain and his associates said (N. Engl. J. Med. 2011;364:1419-30).

The rates of other, non-MRSA ICU infections also decreased significantly. The rate of pneumonia not related to a device declined 37% (from 0.35 to 0.22 per 1,000 patient-days), and that of pneumonia related to a device dropped 75% (from 0.32 to 0.08 per 1,000 patient-days). The rate of urinary tract infections also decreased 75% (from 0.16 to 0.04 per 1,000 patient-day), as did that of skin and soft-tissue infections (from 0.16 to 0.04 per 1,000 patient-days).

The results were similar in non-ICU units, where overall hospital-related MRSA infections declined 45%. Bloodstream infection decreased 58%, pneumonia dropped 38%, UTIs declined 44%, and skin and soft-tissue infections dropped 53%.

Contrary to the findings by Dr. Huskins and colleagues, these results "suggest that proactive efforts to prevent the transmission of MRSA are associated with a reduction in [health care–associated] MRSA infections," and that patients in other, non-VA acute care hospitals might benefit from a similar intervention, the investigators said.

Dr. Huskins’ study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, Merck, Elan Pharmaceuticals, Roche Diagnostics, and Kimberly Clark. Dr. Huskins and his associates reported ties to Roche, GlaxoSmithKline, Medegen, and BioNeutral Group. Dr. Jain’s study was supported by the Veterans Health Administration, and no financial conflicts of interest were reported.

Two similar interventions to prevent hospital-associated methicillin-resistant Staphylococcus aureus infections produced opposite results: One yielded dramatic reductions in overall, bloodstream, device-associated, and non–device-associated MRSA, whereas the other showed no effect, according to separate reports in the April 14 issue of the New England Journal of Medicine.

Photo credit: Janice Haney Carr/CDC

Both interventions centered on culture-based active surveillance for resistant organisms, the expanded use of barrier precautions, attention to hand hygiene, and substantial "culture change" among health care providers to take action against resistant infections. And both interventions substantially improved in-hospital safety practices.

But only one intervention actually decreased MRSA transmission, leaving the issue of how to reduce hospital-associated resistant infections as unclear as ever.

In one study, researchers in the STAR*ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial compared an infection-control intervention vs. existing, standard safety procedures in 19 adult medical and surgical ICUs during a 6-month period. They analyzed outcomes for 1,356 patients in the intervention group (10 ICUs) and 2,132 patients in the control group (9 ICUs).

The intervention called for obtaining nasal swabs for MRSA cultures and stool or perianal swabs for vancomycin-resistant enterococcus (VRE) cultures within 2 days of admission to the ICU and weekly thereafter, to actively identify patients who carried or were infected with these organisms. Patients who were found to be colonized or infected – along with patients known to have been colonized or infected during the previous year – were assigned to care with contact precautions, which continued for the duration of their ICU stay. All other patients were assigned to care with universal gloving until surveillance cultures were found to be negative, at which time standard ICU practices resumed.

In control ICUs, swabs were taken in an identical manner, but the culture results were not communicated to ICU staff. Standard existing procedures were used to identify patients who were colonized or infected with MRSA or VRE, and they were then treated using contact precautions, said Dr. W. Charles Huskins of the Mayo Clinic, Rochester, Minn., and his associates.

In addition, "intervention ICUs received training in the intervention, door signs describing each category of precautions, and an aggregate report on the providers’ use of universal gloving during the first month of the intervention period."

In all the ICUs, monitors recorded contacts between providers and patients at random times on random dates, and providers’ use of hand hygiene, clean gloves, and gowns was noted.

Patients who carried or were infected with MRSA or VRE were more often identified in the intervention ICUs than in the control ICUs, and thus were more often assigned to expanded barrier precautions (mean, 51% of all patient-days), universal gloving (43%), and either one or the other (92%). In contrast, patients in the control ICUs were assigned to expanded barrier precautions on only 38% of all patient-days, and universal gloving was not used.

A composite measure of caregivers’ hand hygiene and use of clean gloves was nearly twice as high in the intervention ICUs (47% of contacts) as in the control ICUs (25%). In intervention ICUs, clean gloves were used for 82% of contacts, gowns were used in 77%, and hygiene after contact in 69%. In contrast, these proportions were 72%, 59%, and 59%, respectively, in control ICUs.

Nevertheless the primary outcome (ICU-level incidence of new colonization or infection with MRSA or VRE per 1,000 patient-days at risk) was not significantly different between the intervention and control groups, at 40% and 36%, respectively.

This lack of effectiveness was "surprising, given that surveillance cultures identified a sizable subgroup of colonized patients who were not otherwise recognized, and that colonized or infected patients were assigned to either contact precautions or universal gloving for nearly all their ICU patient-days," Dr. Huskins and his colleagues said (N. Engl. J. Med. 2011;364:1407-18).

It is unclear why the intervention failed to reduce the infection rate, but there are several possibilities.

First, the prolonged lag time (an average of 5 days) between admission to the ICU and reporting of the culture results allowed for transmission before the expanded precautions were undertaken. Second, the providers’ use of proper safety measures was greater but still not optimal in the intervention ICUs.

Third, body sites other than those that were cultured – such as the pharynx, open wounds, the skin, respiratory secretions, or the rectum – may have been harboring MRSA or VRE. Fourth, a different route of transmission that wasn’t addressed by this intervention – such as contaminated instruments or colonized care providers – may have been at fault.

And finally, the intervention period may not have been long enough to demonstrate an effect. "Previous studies have observed that a reduction in the incidence of MRSA infection may not be evident until a year or more after initiation of an intervention," the investigators said.

They concluded that "merely improving the identification of colonized patients and expanding the use of barrier precautions ... are measures that are not likely to be broadly effective." Additional interventions that "reduce the density of colonization of body sites or contamination of the environment may be necessary."

In the other study, Dr. Rajiv Jain of the Veterans Health Administration and his associates assessed outcomes after implementation of a nationwide initiative to decrease health care–associated MRSA infections in acute care hospitals. The prevalence of MRSA carriage at hospital admission is much higher among VA patients (approximately 14%) than among patients at non-VA hospitals (6.3%) and in the general population (1.5%), they noted.

The intervention called for surveillance of nasal MRSA colonization for all patients who were admitted to the hospital, transferred from one unit to another within the hospital, or discharged from the hospital, followed by contact precautions for all patients who were found to be either colonized or infected with MRSA. As with the intervention in Dr. Huskins’ study, the VA intervention emphasized hand hygiene and "change in the institutional culture" so that all caregivers were held responsible for infection control.

Outcomes were assessed for 1,934,598 admissions, transfers, or discharges at all the medical, coronary care, or surgical ICUs and all the medical, surgical, rehabilitation medicine, and spinal-cord injury units at 150 VA hospitals across the country in 2007-2010.

After the intervention was implemented in 2007, the rate of hospital-associated MRSA infections in ICUs dropped 62% (from 1.64 per 1,000 patient-days to 0.62). The rate of bloodstream MRSA infections not related to a device declined 79% (from 0.14 per 1,000 patient-days to 0.03). The rate of bloodstream MRSA infections related to a device decreased 62% (from 0.16 to 0.06 per 1,000 patient-days), said Dr. Jain, also of the VA Pittsburgh Healthcare System and the University of Pittsburgh, and his colleagues.

In particular, the rate of ventilator-associated MRSA pneumonia in ICUs decreased 72% (from 1.17 to 0.33 per 1,000 device-days), and that of bloodstream MRSA associated with central venous catheters in ICUs dropped 33% (from 0.46 to 0.31 per 1,000 device-days), Dr. Jain and his associates said (N. Engl. J. Med. 2011;364:1419-30).

The rates of other, non-MRSA ICU infections also decreased significantly. The rate of pneumonia not related to a device declined 37% (from 0.35 to 0.22 per 1,000 patient-days), and that of pneumonia related to a device dropped 75% (from 0.32 to 0.08 per 1,000 patient-days). The rate of urinary tract infections also decreased 75% (from 0.16 to 0.04 per 1,000 patient-day), as did that of skin and soft-tissue infections (from 0.16 to 0.04 per 1,000 patient-days).

The results were similar in non-ICU units, where overall hospital-related MRSA infections declined 45%. Bloodstream infection decreased 58%, pneumonia dropped 38%, UTIs declined 44%, and skin and soft-tissue infections dropped 53%.

Contrary to the findings by Dr. Huskins and colleagues, these results "suggest that proactive efforts to prevent the transmission of MRSA are associated with a reduction in [health care–associated] MRSA infections," and that patients in other, non-VA acute care hospitals might benefit from a similar intervention, the investigators said.

Dr. Huskins’ study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, Merck, Elan Pharmaceuticals, Roche Diagnostics, and Kimberly Clark. Dr. Huskins and his associates reported ties to Roche, GlaxoSmithKline, Medegen, and BioNeutral Group. Dr. Jain’s study was supported by the Veterans Health Administration, and no financial conflicts of interest were reported.

Two similar interventions to prevent hospital-associated methicillin-resistant Staphylococcus aureus infections produced opposite results: One yielded dramatic reductions in overall, bloodstream, device-associated, and non–device-associated MRSA, whereas the other showed no effect, according to separate reports in the April 14 issue of the New England Journal of Medicine.

Photo credit: Janice Haney Carr/CDC

Both interventions centered on culture-based active surveillance for resistant organisms, the expanded use of barrier precautions, attention to hand hygiene, and substantial "culture change" among health care providers to take action against resistant infections. And both interventions substantially improved in-hospital safety practices.

But only one intervention actually decreased MRSA transmission, leaving the issue of how to reduce hospital-associated resistant infections as unclear as ever.

In one study, researchers in the STAR*ICU (Strategies to Reduce Transmission of Antimicrobial-Resistant Bacteria in Intensive Care Units) trial compared an infection-control intervention vs. existing, standard safety procedures in 19 adult medical and surgical ICUs during a 6-month period. They analyzed outcomes for 1,356 patients in the intervention group (10 ICUs) and 2,132 patients in the control group (9 ICUs).

The intervention called for obtaining nasal swabs for MRSA cultures and stool or perianal swabs for vancomycin-resistant enterococcus (VRE) cultures within 2 days of admission to the ICU and weekly thereafter, to actively identify patients who carried or were infected with these organisms. Patients who were found to be colonized or infected – along with patients known to have been colonized or infected during the previous year – were assigned to care with contact precautions, which continued for the duration of their ICU stay. All other patients were assigned to care with universal gloving until surveillance cultures were found to be negative, at which time standard ICU practices resumed.

In control ICUs, swabs were taken in an identical manner, but the culture results were not communicated to ICU staff. Standard existing procedures were used to identify patients who were colonized or infected with MRSA or VRE, and they were then treated using contact precautions, said Dr. W. Charles Huskins of the Mayo Clinic, Rochester, Minn., and his associates.

In addition, "intervention ICUs received training in the intervention, door signs describing each category of precautions, and an aggregate report on the providers’ use of universal gloving during the first month of the intervention period."

In all the ICUs, monitors recorded contacts between providers and patients at random times on random dates, and providers’ use of hand hygiene, clean gloves, and gowns was noted.

Patients who carried or were infected with MRSA or VRE were more often identified in the intervention ICUs than in the control ICUs, and thus were more often assigned to expanded barrier precautions (mean, 51% of all patient-days), universal gloving (43%), and either one or the other (92%). In contrast, patients in the control ICUs were assigned to expanded barrier precautions on only 38% of all patient-days, and universal gloving was not used.

A composite measure of caregivers’ hand hygiene and use of clean gloves was nearly twice as high in the intervention ICUs (47% of contacts) as in the control ICUs (25%). In intervention ICUs, clean gloves were used for 82% of contacts, gowns were used in 77%, and hygiene after contact in 69%. In contrast, these proportions were 72%, 59%, and 59%, respectively, in control ICUs.

Nevertheless the primary outcome (ICU-level incidence of new colonization or infection with MRSA or VRE per 1,000 patient-days at risk) was not significantly different between the intervention and control groups, at 40% and 36%, respectively.

This lack of effectiveness was "surprising, given that surveillance cultures identified a sizable subgroup of colonized patients who were not otherwise recognized, and that colonized or infected patients were assigned to either contact precautions or universal gloving for nearly all their ICU patient-days," Dr. Huskins and his colleagues said (N. Engl. J. Med. 2011;364:1407-18).

It is unclear why the intervention failed to reduce the infection rate, but there are several possibilities.

First, the prolonged lag time (an average of 5 days) between admission to the ICU and reporting of the culture results allowed for transmission before the expanded precautions were undertaken. Second, the providers’ use of proper safety measures was greater but still not optimal in the intervention ICUs.

Third, body sites other than those that were cultured – such as the pharynx, open wounds, the skin, respiratory secretions, or the rectum – may have been harboring MRSA or VRE. Fourth, a different route of transmission that wasn’t addressed by this intervention – such as contaminated instruments or colonized care providers – may have been at fault.

And finally, the intervention period may not have been long enough to demonstrate an effect. "Previous studies have observed that a reduction in the incidence of MRSA infection may not be evident until a year or more after initiation of an intervention," the investigators said.

They concluded that "merely improving the identification of colonized patients and expanding the use of barrier precautions ... are measures that are not likely to be broadly effective." Additional interventions that "reduce the density of colonization of body sites or contamination of the environment may be necessary."

In the other study, Dr. Rajiv Jain of the Veterans Health Administration and his associates assessed outcomes after implementation of a nationwide initiative to decrease health care–associated MRSA infections in acute care hospitals. The prevalence of MRSA carriage at hospital admission is much higher among VA patients (approximately 14%) than among patients at non-VA hospitals (6.3%) and in the general population (1.5%), they noted.

The intervention called for surveillance of nasal MRSA colonization for all patients who were admitted to the hospital, transferred from one unit to another within the hospital, or discharged from the hospital, followed by contact precautions for all patients who were found to be either colonized or infected with MRSA. As with the intervention in Dr. Huskins’ study, the VA intervention emphasized hand hygiene and "change in the institutional culture" so that all caregivers were held responsible for infection control.

Outcomes were assessed for 1,934,598 admissions, transfers, or discharges at all the medical, coronary care, or surgical ICUs and all the medical, surgical, rehabilitation medicine, and spinal-cord injury units at 150 VA hospitals across the country in 2007-2010.

After the intervention was implemented in 2007, the rate of hospital-associated MRSA infections in ICUs dropped 62% (from 1.64 per 1,000 patient-days to 0.62). The rate of bloodstream MRSA infections not related to a device declined 79% (from 0.14 per 1,000 patient-days to 0.03). The rate of bloodstream MRSA infections related to a device decreased 62% (from 0.16 to 0.06 per 1,000 patient-days), said Dr. Jain, also of the VA Pittsburgh Healthcare System and the University of Pittsburgh, and his colleagues.

In particular, the rate of ventilator-associated MRSA pneumonia in ICUs decreased 72% (from 1.17 to 0.33 per 1,000 device-days), and that of bloodstream MRSA associated with central venous catheters in ICUs dropped 33% (from 0.46 to 0.31 per 1,000 device-days), Dr. Jain and his associates said (N. Engl. J. Med. 2011;364:1419-30).

The rates of other, non-MRSA ICU infections also decreased significantly. The rate of pneumonia not related to a device declined 37% (from 0.35 to 0.22 per 1,000 patient-days), and that of pneumonia related to a device dropped 75% (from 0.32 to 0.08 per 1,000 patient-days). The rate of urinary tract infections also decreased 75% (from 0.16 to 0.04 per 1,000 patient-day), as did that of skin and soft-tissue infections (from 0.16 to 0.04 per 1,000 patient-days).

The results were similar in non-ICU units, where overall hospital-related MRSA infections declined 45%. Bloodstream infection decreased 58%, pneumonia dropped 38%, UTIs declined 44%, and skin and soft-tissue infections dropped 53%.

Contrary to the findings by Dr. Huskins and colleagues, these results "suggest that proactive efforts to prevent the transmission of MRSA are associated with a reduction in [health care–associated] MRSA infections," and that patients in other, non-VA acute care hospitals might benefit from a similar intervention, the investigators said.

Dr. Huskins’ study was supported by the National Institute of Allergy and Infectious Diseases, the National Center for Research Resources, Merck, Elan Pharmaceuticals, Roche Diagnostics, and Kimberly Clark. Dr. Huskins and his associates reported ties to Roche, GlaxoSmithKline, Medegen, and BioNeutral Group. Dr. Jain’s study was supported by the Veterans Health Administration, and no financial conflicts of interest were reported.

A four-drug fixed-dose combination regimen for pulmonary tuberculosis was found noninferior to the standard regimen of four separately administered drugs in two of three analyses of data from a clinical trial reported in the April 13 issue of JAMA.

The combo regimen "did not demonstrate full noninferiority" because it met the strict study criteria only in the per-protocol analysis and in a post hoc modified intention-to-treat analysis, but failed to do so in the intention-to-treat analysis. Nevertheless, "the results do support the WHO recommendation for use of fixed-dose combinations because of the potential advantages associated with their administration, compared with separate-drug formulations," said Dr. Christian Lienhardt of the World Health Organization and his associates.

The main advantage is that patients on fixed-dose combo regimens take 3-4 pills per day instead of 9-16 during the first 2 months of treatment. This facilitates adherence, which in turn reduces the risk of developing drug resistance, the researchers noted.

The open-label noninferiority trial was conducted at 11 sites in nine African, Asian, and Latin American countries.

Study subjects were adults with newly diagnosed sputum smear–positive pulmonary tuberculosis who were randomly assigned to receive either separate tablets of rifampin, isoniazid, pyrazinamide, and ethambutol or a single combination tablet of the same drugs every day for an 8-week "intensive" phase of the trial. This was followed by 18 weeks of a combination rifampicin plus isoniazid tablet, three times per week, for both study groups.

Every study subject also received pyridoxine with the study drugs throughout the trial.

The patients were required to attend their treatment facilities and take their drugs under supervision of the medical staff. They were also seen at 2, 3, 5, and 6 months during treatment and at 2-month intervals for up to 30 months during follow-up.

The primary efficacy end point was the proportion of patients with an "unfavorable" outcome, which was defined as bacteriologic failure or relapse within 18 months, treatment change after 5 months because of positive sputum smear results or clinical or radiologic deterioration, or death that was possibly or definitely attributable to active tuberculosis.

In the per-protocol analysis of 591 patients on fixed-dose combo therapy and 579 on standard separate drugs, the proportion of unfavorable outcomes was 6.1% in the first group and 5.4% in the second, a difference that met the criteria for noninferiority.

In the post-hoc modified intention-to-treat analysis of 658 patients on fixed-dose combo therapy and 647 on standard separate drugs, the proportion of unfavorable outcomes was 10.2% in the first group and 9% in the second, a difference that also met the criteria for noninferiority.

However, in the intention-to-treat analysis of 684 patients on fixed-dose combo therapy and 664 on standard separate drugs, the proportion of unfavorable outcomes was 16.7% in the first group and 15.2% in the second, a difference which just missed meeting the criteria for noninferiority, the investigators said (JAMA 2011;305:1415-23).

The number of patients who reported adverse events within the first 2 months of starting treatment was small and similar between the two groups. Most of these events were mild or moderate and "reflected the expected undesirable effects of antituberculosis agents," including nausea, vomiting, diarrhea, rash, pruritus, arthralgia, and myalgia.

This trial was supported by the U.S. Agency for International Development. All the drugs used in this trial were manufactured by Svizera. No financial conflicts of interest were reported.

A four-drug fixed-dose combination regimen for pulmonary tuberculosis was found noninferior to the standard regimen of four separately administered drugs in two of three analyses of data from a clinical trial reported in the April 13 issue of JAMA.

The combo regimen "did not demonstrate full noninferiority" because it met the strict study criteria only in the per-protocol analysis and in a post hoc modified intention-to-treat analysis, but failed to do so in the intention-to-treat analysis. Nevertheless, "the results do support the WHO recommendation for use of fixed-dose combinations because of the potential advantages associated with their administration, compared with separate-drug formulations," said Dr. Christian Lienhardt of the World Health Organization and his associates.

The main advantage is that patients on fixed-dose combo regimens take 3-4 pills per day instead of 9-16 during the first 2 months of treatment. This facilitates adherence, which in turn reduces the risk of developing drug resistance, the researchers noted.

The open-label noninferiority trial was conducted at 11 sites in nine African, Asian, and Latin American countries.

Study subjects were adults with newly diagnosed sputum smear–positive pulmonary tuberculosis who were randomly assigned to receive either separate tablets of rifampin, isoniazid, pyrazinamide, and ethambutol or a single combination tablet of the same drugs every day for an 8-week "intensive" phase of the trial. This was followed by 18 weeks of a combination rifampicin plus isoniazid tablet, three times per week, for both study groups.

Every study subject also received pyridoxine with the study drugs throughout the trial.

The patients were required to attend their treatment facilities and take their drugs under supervision of the medical staff. They were also seen at 2, 3, 5, and 6 months during treatment and at 2-month intervals for up to 30 months during follow-up.

The primary efficacy end point was the proportion of patients with an "unfavorable" outcome, which was defined as bacteriologic failure or relapse within 18 months, treatment change after 5 months because of positive sputum smear results or clinical or radiologic deterioration, or death that was possibly or definitely attributable to active tuberculosis.

In the per-protocol analysis of 591 patients on fixed-dose combo therapy and 579 on standard separate drugs, the proportion of unfavorable outcomes was 6.1% in the first group and 5.4% in the second, a difference that met the criteria for noninferiority.

In the post-hoc modified intention-to-treat analysis of 658 patients on fixed-dose combo therapy and 647 on standard separate drugs, the proportion of unfavorable outcomes was 10.2% in the first group and 9% in the second, a difference that also met the criteria for noninferiority.

However, in the intention-to-treat analysis of 684 patients on fixed-dose combo therapy and 664 on standard separate drugs, the proportion of unfavorable outcomes was 16.7% in the first group and 15.2% in the second, a difference which just missed meeting the criteria for noninferiority, the investigators said (JAMA 2011;305:1415-23).

The number of patients who reported adverse events within the first 2 months of starting treatment was small and similar between the two groups. Most of these events were mild or moderate and "reflected the expected undesirable effects of antituberculosis agents," including nausea, vomiting, diarrhea, rash, pruritus, arthralgia, and myalgia.

This trial was supported by the U.S. Agency for International Development. All the drugs used in this trial were manufactured by Svizera. No financial conflicts of interest were reported.

A four-drug fixed-dose combination regimen for pulmonary tuberculosis was found noninferior to the standard regimen of four separately administered drugs in two of three analyses of data from a clinical trial reported in the April 13 issue of JAMA.

The combo regimen "did not demonstrate full noninferiority" because it met the strict study criteria only in the per-protocol analysis and in a post hoc modified intention-to-treat analysis, but failed to do so in the intention-to-treat analysis. Nevertheless, "the results do support the WHO recommendation for use of fixed-dose combinations because of the potential advantages associated with their administration, compared with separate-drug formulations," said Dr. Christian Lienhardt of the World Health Organization and his associates.

The main advantage is that patients on fixed-dose combo regimens take 3-4 pills per day instead of 9-16 during the first 2 months of treatment. This facilitates adherence, which in turn reduces the risk of developing drug resistance, the researchers noted.

The open-label noninferiority trial was conducted at 11 sites in nine African, Asian, and Latin American countries.

Study subjects were adults with newly diagnosed sputum smear–positive pulmonary tuberculosis who were randomly assigned to receive either separate tablets of rifampin, isoniazid, pyrazinamide, and ethambutol or a single combination tablet of the same drugs every day for an 8-week "intensive" phase of the trial. This was followed by 18 weeks of a combination rifampicin plus isoniazid tablet, three times per week, for both study groups.

Every study subject also received pyridoxine with the study drugs throughout the trial.

The patients were required to attend their treatment facilities and take their drugs under supervision of the medical staff. They were also seen at 2, 3, 5, and 6 months during treatment and at 2-month intervals for up to 30 months during follow-up.

The primary efficacy end point was the proportion of patients with an "unfavorable" outcome, which was defined as bacteriologic failure or relapse within 18 months, treatment change after 5 months because of positive sputum smear results or clinical or radiologic deterioration, or death that was possibly or definitely attributable to active tuberculosis.

In the per-protocol analysis of 591 patients on fixed-dose combo therapy and 579 on standard separate drugs, the proportion of unfavorable outcomes was 6.1% in the first group and 5.4% in the second, a difference that met the criteria for noninferiority.

In the post-hoc modified intention-to-treat analysis of 658 patients on fixed-dose combo therapy and 647 on standard separate drugs, the proportion of unfavorable outcomes was 10.2% in the first group and 9% in the second, a difference that also met the criteria for noninferiority.

However, in the intention-to-treat analysis of 684 patients on fixed-dose combo therapy and 664 on standard separate drugs, the proportion of unfavorable outcomes was 16.7% in the first group and 15.2% in the second, a difference which just missed meeting the criteria for noninferiority, the investigators said (JAMA 2011;305:1415-23).

The number of patients who reported adverse events within the first 2 months of starting treatment was small and similar between the two groups. Most of these events were mild or moderate and "reflected the expected undesirable effects of antituberculosis agents," including nausea, vomiting, diarrhea, rash, pruritus, arthralgia, and myalgia.

This trial was supported by the U.S. Agency for International Development. All the drugs used in this trial were manufactured by Svizera. No financial conflicts of interest were reported.

A four-drug fixed-dose combination regimen for pulmonary tuberculosis was found noninferior to the standard regimen of four separately administered drugs in two of three analyses of data from a clinical trial reported in the April 13 issue of JAMA.

The combo regimen "did not demonstrate full noninferiority" because it met the strict study criteria only in the per-protocol analysis and in a post hoc modified intention-to-treat analysis, but failed to do so in the intention-to-treat analysis. Nevertheless, "the results do support the WHO recommendation for use of fixed-dose combinations because of the potential advantages associated with their administration, compared with separate-drug formulations," said Dr. Christian Lienhardt of the World Health Organization and his associates.

The main advantage is that patients on fixed-dose combo regimens take 3-4 pills per day instead of 9-16 during the first 2 months of treatment. This facilitates adherence, which in turn reduces the risk of developing drug resistance, the researchers noted.

The open-label noninferiority trial was conducted at 11 sites in nine African, Asian, and Latin American countries.

Study subjects were adults with newly diagnosed sputum smear–positive pulmonary tuberculosis who were randomly assigned to receive either separate tablets of rifampin, isoniazid, pyrazinamide, and ethambutol or a single combination tablet of the same drugs every day for an 8-week "intensive" phase of the trial. This was followed by 18 weeks of a combination rifampicin plus isoniazid tablet, three times per week, for both study groups.

Every study subject also received pyridoxine with the study drugs throughout the trial.

The patients were required to attend their treatment facilities and take their drugs under supervision of the medical staff. They were also seen at 2, 3, 5, and 6 months during treatment and at 2-month intervals for up to 30 months during follow-up.

The primary efficacy end point was the proportion of patients with an "unfavorable" outcome, which was defined as bacteriologic failure or relapse within 18 months, treatment change after 5 months because of positive sputum smear results or clinical or radiologic deterioration, or death that was possibly or definitely attributable to active tuberculosis.

In the per-protocol analysis of 591 patients on fixed-dose combo therapy and 579 on standard separate drugs, the proportion of unfavorable outcomes was 6.1% in the first group and 5.4% in the second, a difference that met the criteria for noninferiority.

In the post-hoc modified intention-to-treat analysis of 658 patients on fixed-dose combo therapy and 647 on standard separate drugs, the proportion of unfavorable outcomes was 10.2% in the first group and 9% in the second, a difference that also met the criteria for noninferiority.

However, in the intention-to-treat analysis of 684 patients on fixed-dose combo therapy and 664 on standard separate drugs, the proportion of unfavorable outcomes was 16.7% in the first group and 15.2% in the second, a difference which just missed meeting the criteria for noninferiority, the investigators said (JAMA 2011;305:1415-23).

The number of patients who reported adverse events within the first 2 months of starting treatment was small and similar between the two groups. Most of these events were mild or moderate and "reflected the expected undesirable effects of antituberculosis agents," including nausea, vomiting, diarrhea, rash, pruritus, arthralgia, and myalgia.

This trial was supported by the U.S. Agency for International Development. All the drugs used in this trial were manufactured by Svizera. No financial conflicts of interest were reported.

A four-drug fixed-dose combination regimen for pulmonary tuberculosis was found noninferior to the standard regimen of four separately administered drugs in two of three analyses of data from a clinical trial reported in the April 13 issue of JAMA.

The combo regimen "did not demonstrate full noninferiority" because it met the strict study criteria only in the per-protocol analysis and in a post hoc modified intention-to-treat analysis, but failed to do so in the intention-to-treat analysis. Nevertheless, "the results do support the WHO recommendation for use of fixed-dose combinations because of the potential advantages associated with their administration, compared with separate-drug formulations," said Dr. Christian Lienhardt of the World Health Organization and his associates.

The main advantage is that patients on fixed-dose combo regimens take 3-4 pills per day instead of 9-16 during the first 2 months of treatment. This facilitates adherence, which in turn reduces the risk of developing drug resistance, the researchers noted.

The open-label noninferiority trial was conducted at 11 sites in nine African, Asian, and Latin American countries.

Study subjects were adults with newly diagnosed sputum smear–positive pulmonary tuberculosis who were randomly assigned to receive either separate tablets of rifampin, isoniazid, pyrazinamide, and ethambutol or a single combination tablet of the same drugs every day for an 8-week "intensive" phase of the trial. This was followed by 18 weeks of a combination rifampicin plus isoniazid tablet, three times per week, for both study groups.

Every study subject also received pyridoxine with the study drugs throughout the trial.

The patients were required to attend their treatment facilities and take their drugs under supervision of the medical staff. They were also seen at 2, 3, 5, and 6 months during treatment and at 2-month intervals for up to 30 months during follow-up.

The primary efficacy end point was the proportion of patients with an "unfavorable" outcome, which was defined as bacteriologic failure or relapse within 18 months, treatment change after 5 months because of positive sputum smear results or clinical or radiologic deterioration, or death that was possibly or definitely attributable to active tuberculosis.

In the per-protocol analysis of 591 patients on fixed-dose combo therapy and 579 on standard separate drugs, the proportion of unfavorable outcomes was 6.1% in the first group and 5.4% in the second, a difference that met the criteria for noninferiority.

In the post-hoc modified intention-to-treat analysis of 658 patients on fixed-dose combo therapy and 647 on standard separate drugs, the proportion of unfavorable outcomes was 10.2% in the first group and 9% in the second, a difference that also met the criteria for noninferiority.

However, in the intention-to-treat analysis of 684 patients on fixed-dose combo therapy and 664 on standard separate drugs, the proportion of unfavorable outcomes was 16.7% in the first group and 15.2% in the second, a difference which just missed meeting the criteria for noninferiority, the investigators said (JAMA 2011;305:1415-23).

The number of patients who reported adverse events within the first 2 months of starting treatment was small and similar between the two groups. Most of these events were mild or moderate and "reflected the expected undesirable effects of antituberculosis agents," including nausea, vomiting, diarrhea, rash, pruritus, arthralgia, and myalgia.

This trial was supported by the U.S. Agency for International Development. All the drugs used in this trial were manufactured by Svizera. No financial conflicts of interest were reported.

A four-drug fixed-dose combination regimen for pulmonary tuberculosis was found noninferior to the standard regimen of four separately administered drugs in two of three analyses of data from a clinical trial reported in the April 13 issue of JAMA.

The combo regimen "did not demonstrate full noninferiority" because it met the strict study criteria only in the per-protocol analysis and in a post hoc modified intention-to-treat analysis, but failed to do so in the intention-to-treat analysis. Nevertheless, "the results do support the WHO recommendation for use of fixed-dose combinations because of the potential advantages associated with their administration, compared with separate-drug formulations," said Dr. Christian Lienhardt of the World Health Organization and his associates.

The main advantage is that patients on fixed-dose combo regimens take 3-4 pills per day instead of 9-16 during the first 2 months of treatment. This facilitates adherence, which in turn reduces the risk of developing drug resistance, the researchers noted.

The open-label noninferiority trial was conducted at 11 sites in nine African, Asian, and Latin American countries.

Study subjects were adults with newly diagnosed sputum smear–positive pulmonary tuberculosis who were randomly assigned to receive either separate tablets of rifampin, isoniazid, pyrazinamide, and ethambutol or a single combination tablet of the same drugs every day for an 8-week "intensive" phase of the trial. This was followed by 18 weeks of a combination rifampicin plus isoniazid tablet, three times per week, for both study groups.

Every study subject also received pyridoxine with the study drugs throughout the trial.

The patients were required to attend their treatment facilities and take their drugs under supervision of the medical staff. They were also seen at 2, 3, 5, and 6 months during treatment and at 2-month intervals for up to 30 months during follow-up.

The primary efficacy end point was the proportion of patients with an "unfavorable" outcome, which was defined as bacteriologic failure or relapse within 18 months, treatment change after 5 months because of positive sputum smear results or clinical or radiologic deterioration, or death that was possibly or definitely attributable to active tuberculosis.

In the per-protocol analysis of 591 patients on fixed-dose combo therapy and 579 on standard separate drugs, the proportion of unfavorable outcomes was 6.1% in the first group and 5.4% in the second, a difference that met the criteria for noninferiority.

In the post-hoc modified intention-to-treat analysis of 658 patients on fixed-dose combo therapy and 647 on standard separate drugs, the proportion of unfavorable outcomes was 10.2% in the first group and 9% in the second, a difference that also met the criteria for noninferiority.

However, in the intention-to-treat analysis of 684 patients on fixed-dose combo therapy and 664 on standard separate drugs, the proportion of unfavorable outcomes was 16.7% in the first group and 15.2% in the second, a difference which just missed meeting the criteria for noninferiority, the investigators said (JAMA 2011;305:1415-23).

The number of patients who reported adverse events within the first 2 months of starting treatment was small and similar between the two groups. Most of these events were mild or moderate and "reflected the expected undesirable effects of antituberculosis agents," including nausea, vomiting, diarrhea, rash, pruritus, arthralgia, and myalgia.

This trial was supported by the U.S. Agency for International Development. All the drugs used in this trial were manufactured by Svizera. No financial conflicts of interest were reported.

A four-drug fixed-dose combination regimen for pulmonary tuberculosis was found noninferior to the standard regimen of four separately administered drugs in two of three analyses of data from a clinical trial reported in the April 13 issue of JAMA.

The combo regimen "did not demonstrate full noninferiority" because it met the strict study criteria only in the per-protocol analysis and in a post hoc modified intention-to-treat analysis, but failed to do so in the intention-to-treat analysis. Nevertheless, "the results do support the WHO recommendation for use of fixed-dose combinations because of the potential advantages associated with their administration, compared with separate-drug formulations," said Dr. Christian Lienhardt of the World Health Organization and his associates.

The main advantage is that patients on fixed-dose combo regimens take 3-4 pills per day instead of 9-16 during the first 2 months of treatment. This facilitates adherence, which in turn reduces the risk of developing drug resistance, the researchers noted.

The open-label noninferiority trial was conducted at 11 sites in nine African, Asian, and Latin American countries.

Study subjects were adults with newly diagnosed sputum smear–positive pulmonary tuberculosis who were randomly assigned to receive either separate tablets of rifampin, isoniazid, pyrazinamide, and ethambutol or a single combination tablet of the same drugs every day for an 8-week "intensive" phase of the trial. This was followed by 18 weeks of a combination rifampicin plus isoniazid tablet, three times per week, for both study groups.

Every study subject also received pyridoxine with the study drugs throughout the trial.

The patients were required to attend their treatment facilities and take their drugs under supervision of the medical staff. They were also seen at 2, 3, 5, and 6 months during treatment and at 2-month intervals for up to 30 months during follow-up.

The primary efficacy end point was the proportion of patients with an "unfavorable" outcome, which was defined as bacteriologic failure or relapse within 18 months, treatment change after 5 months because of positive sputum smear results or clinical or radiologic deterioration, or death that was possibly or definitely attributable to active tuberculosis.

In the per-protocol analysis of 591 patients on fixed-dose combo therapy and 579 on standard separate drugs, the proportion of unfavorable outcomes was 6.1% in the first group and 5.4% in the second, a difference that met the criteria for noninferiority.

In the post-hoc modified intention-to-treat analysis of 658 patients on fixed-dose combo therapy and 647 on standard separate drugs, the proportion of unfavorable outcomes was 10.2% in the first group and 9% in the second, a difference that also met the criteria for noninferiority.

However, in the intention-to-treat analysis of 684 patients on fixed-dose combo therapy and 664 on standard separate drugs, the proportion of unfavorable outcomes was 16.7% in the first group and 15.2% in the second, a difference which just missed meeting the criteria for noninferiority, the investigators said (JAMA 2011;305:1415-23).

The number of patients who reported adverse events within the first 2 months of starting treatment was small and similar between the two groups. Most of these events were mild or moderate and "reflected the expected undesirable effects of antituberculosis agents," including nausea, vomiting, diarrhea, rash, pruritus, arthralgia, and myalgia.

This trial was supported by the U.S. Agency for International Development. All the drugs used in this trial were manufactured by Svizera. No financial conflicts of interest were reported.

A four-drug fixed-dose combination regimen for pulmonary tuberculosis was found noninferior to the standard regimen of four separately administered drugs in two of three analyses of data from a clinical trial reported in the April 13 issue of JAMA.

The combo regimen "did not demonstrate full noninferiority" because it met the strict study criteria only in the per-protocol analysis and in a post hoc modified intention-to-treat analysis, but failed to do so in the intention-to-treat analysis. Nevertheless, "the results do support the WHO recommendation for use of fixed-dose combinations because of the potential advantages associated with their administration, compared with separate-drug formulations," said Dr. Christian Lienhardt of the World Health Organization and his associates.

The main advantage is that patients on fixed-dose combo regimens take 3-4 pills per day instead of 9-16 during the first 2 months of treatment. This facilitates adherence, which in turn reduces the risk of developing drug resistance, the researchers noted.

The open-label noninferiority trial was conducted at 11 sites in nine African, Asian, and Latin American countries.

Study subjects were adults with newly diagnosed sputum smear–positive pulmonary tuberculosis who were randomly assigned to receive either separate tablets of rifampin, isoniazid, pyrazinamide, and ethambutol or a single combination tablet of the same drugs every day for an 8-week "intensive" phase of the trial. This was followed by 18 weeks of a combination rifampicin plus isoniazid tablet, three times per week, for both study groups.

Every study subject also received pyridoxine with the study drugs throughout the trial.

The patients were required to attend their treatment facilities and take their drugs under supervision of the medical staff. They were also seen at 2, 3, 5, and 6 months during treatment and at 2-month intervals for up to 30 months during follow-up.

The primary efficacy end point was the proportion of patients with an "unfavorable" outcome, which was defined as bacteriologic failure or relapse within 18 months, treatment change after 5 months because of positive sputum smear results or clinical or radiologic deterioration, or death that was possibly or definitely attributable to active tuberculosis.

In the per-protocol analysis of 591 patients on fixed-dose combo therapy and 579 on standard separate drugs, the proportion of unfavorable outcomes was 6.1% in the first group and 5.4% in the second, a difference that met the criteria for noninferiority.

In the post-hoc modified intention-to-treat analysis of 658 patients on fixed-dose combo therapy and 647 on standard separate drugs, the proportion of unfavorable outcomes was 10.2% in the first group and 9% in the second, a difference that also met the criteria for noninferiority.

However, in the intention-to-treat analysis of 684 patients on fixed-dose combo therapy and 664 on standard separate drugs, the proportion of unfavorable outcomes was 16.7% in the first group and 15.2% in the second, a difference which just missed meeting the criteria for noninferiority, the investigators said (JAMA 2011;305:1415-23).

The number of patients who reported adverse events within the first 2 months of starting treatment was small and similar between the two groups. Most of these events were mild or moderate and "reflected the expected undesirable effects of antituberculosis agents," including nausea, vomiting, diarrhea, rash, pruritus, arthralgia, and myalgia.

This trial was supported by the U.S. Agency for International Development. All the drugs used in this trial were manufactured by Svizera. No financial conflicts of interest were reported.

A four-drug fixed-dose combination regimen for pulmonary tuberculosis was found noninferior to the standard regimen of four separately administered drugs in two of three analyses of data from a clinical trial reported in the April 13 issue of JAMA.

The combo regimen "did not demonstrate full noninferiority" because it met the strict study criteria only in the per-protocol analysis and in a post hoc modified intention-to-treat analysis, but failed to do so in the intention-to-treat analysis. Nevertheless, "the results do support the WHO recommendation for use of fixed-dose combinations because of the potential advantages associated with their administration, compared with separate-drug formulations," said Dr. Christian Lienhardt of the World Health Organization and his associates.

The main advantage is that patients on fixed-dose combo regimens take 3-4 pills per day instead of 9-16 during the first 2 months of treatment. This facilitates adherence, which in turn reduces the risk of developing drug resistance, the researchers noted.

The open-label noninferiority trial was conducted at 11 sites in nine African, Asian, and Latin American countries.

Study subjects were adults with newly diagnosed sputum smear–positive pulmonary tuberculosis who were randomly assigned to receive either separate tablets of rifampin, isoniazid, pyrazinamide, and ethambutol or a single combination tablet of the same drugs every day for an 8-week "intensive" phase of the trial. This was followed by 18 weeks of a combination rifampicin plus isoniazid tablet, three times per week, for both study groups.

Every study subject also received pyridoxine with the study drugs throughout the trial.

The patients were required to attend their treatment facilities and take their drugs under supervision of the medical staff. They were also seen at 2, 3, 5, and 6 months during treatment and at 2-month intervals for up to 30 months during follow-up.

The primary efficacy end point was the proportion of patients with an "unfavorable" outcome, which was defined as bacteriologic failure or relapse within 18 months, treatment change after 5 months because of positive sputum smear results or clinical or radiologic deterioration, or death that was possibly or definitely attributable to active tuberculosis.

In the per-protocol analysis of 591 patients on fixed-dose combo therapy and 579 on standard separate drugs, the proportion of unfavorable outcomes was 6.1% in the first group and 5.4% in the second, a difference that met the criteria for noninferiority.

In the post-hoc modified intention-to-treat analysis of 658 patients on fixed-dose combo therapy and 647 on standard separate drugs, the proportion of unfavorable outcomes was 10.2% in the first group and 9% in the second, a difference that also met the criteria for noninferiority.

However, in the intention-to-treat analysis of 684 patients on fixed-dose combo therapy and 664 on standard separate drugs, the proportion of unfavorable outcomes was 16.7% in the first group and 15.2% in the second, a difference which just missed meeting the criteria for noninferiority, the investigators said (JAMA 2011;305:1415-23).

The number of patients who reported adverse events within the first 2 months of starting treatment was small and similar between the two groups. Most of these events were mild or moderate and "reflected the expected undesirable effects of antituberculosis agents," including nausea, vomiting, diarrhea, rash, pruritus, arthralgia, and myalgia.

This trial was supported by the U.S. Agency for International Development. All the drugs used in this trial were manufactured by Svizera. No financial conflicts of interest were reported.

Giving the quadrivalent HPV vaccine on two of three alternative dosing schedules that are better suited to resource-poor regions than is the standard schedule was found to be "noninferior" among young adolescent girls in an underserved region in Vietnam, according to a report in the April 13 issue of JAMA.

In this clinical trial involving 903 girls aged 11-13 years, the quadrivalent HPV vaccine proved to be noninferior when given at 0, 3, and 9 months and at 0, 6, and 12 months, compared with the standard 0-, 2-, and 6-month dosing schedule.

When given on the third alternative dosing schedule at 0, 12, and 24 months, the vaccine did not meet the strict study criteria for noninferiority but was still found to be "highly immunogenic," said Dr. Kathleen M. Neuzil of PATH, an international nonprofit organization that addresses global health problems and is headquartered in Seattle.

"The similarity of the immunogenicity and reactogenicity profiles of the HPV vaccine reported from this predominantly ethnic minority population in a low-resource area of Vietnam ... is reassuring, and supports more widespread introduction of the vaccine," Dr. Neuzil and her colleagues reported. "The option of delivering HPV vaccine on flexible schedules will allow countries to minimize costs and maximize feasibility according to local vaccination practices" (JAMA 2011;305:1424-31).

Dr. Neuzil and her colleagues performed the open-label, randomized trial at 21 schools in predominantly rural northwestern Vietnam in 2007-2010.

The first alternative dosing schedule they assessed – at 0, 3, and 9 months – would be less restrictive than would the standard schedule because it would fit into the region's existing schedule for medical outreach services to isolated areas.

The second alternative schedule – at 0, 6, and 12 months – would be more useful because it could coincide with the semiannual "health days" often held in resource-poor nations.

The third alternative schedule – at 0, 12, and 24 months – could be incorporated into other countries’ annual health programs, particularly those given at schools, the researchers noted.

The primary end point was immunogenicity to HPV-16 and HPV-18 at 1 month after receipt of the final dose. According to the strict study definitions, the first two alternative dosing schedules met noninferiority criteria for HPV-16 and HPV-18, but the third (annual) schedule met the criteria only for HPV-18.

A secondary outcome was immunogenicity to the other two virus types, HPV-6 and HPV-11, which are covered by the quadrivalent vaccine. Again the first two alternative dosing schedules met the strict noninferiority criteria for HPV-6 and HPV-11, but the annual schedule met the criteria only for HPV-11.

Although the antibody concentrations against HPV-16 and HPV-6 were lower with the annual schedule than with the other dosing schedules assessed in this study, they still were higher than those that have been reported among women aged 16-26 years. "It is difficult to know if these lower anti-HPV [titers] will translate to significantly different efficacies against important clinical outcomes, such as high-grade precancerous lesions," Dr. Neuzil and her associates noted.

Extended follow-up is underway to answer this question and to determine whether longer-term antibody responses are affected by dosing schedule, they added.

The vaccine was well tolerated, and the proportion of subjects with adverse events was comparable across all the study groups. No serious adverse events were reported.

This study was funded by the Bill and Melinda Gates Foundation. Merck & Co. provided the vaccine and the immunogenicity testing at no charge. The researchers reported no relevant financial disclosures.

Giving the quadrivalent HPV vaccine on two of three alternative dosing schedules that are better suited to resource-poor regions than is the standard schedule was found to be "noninferior" among young adolescent girls in an underserved region in Vietnam, according to a report in the April 13 issue of JAMA.

In this clinical trial involving 903 girls aged 11-13 years, the quadrivalent HPV vaccine proved to be noninferior when given at 0, 3, and 9 months and at 0, 6, and 12 months, compared with the standard 0-, 2-, and 6-month dosing schedule.

When given on the third alternative dosing schedule at 0, 12, and 24 months, the vaccine did not meet the strict study criteria for noninferiority but was still found to be "highly immunogenic," said Dr. Kathleen M. Neuzil of PATH, an international nonprofit organization that addresses global health problems and is headquartered in Seattle.

"The similarity of the immunogenicity and reactogenicity profiles of the HPV vaccine reported from this predominantly ethnic minority population in a low-resource area of Vietnam ... is reassuring, and supports more widespread introduction of the vaccine," Dr. Neuzil and her colleagues reported. "The option of delivering HPV vaccine on flexible schedules will allow countries to minimize costs and maximize feasibility according to local vaccination practices" (JAMA 2011;305:1424-31).

Dr. Neuzil and her colleagues performed the open-label, randomized trial at 21 schools in predominantly rural northwestern Vietnam in 2007-2010.

The first alternative dosing schedule they assessed – at 0, 3, and 9 months – would be less restrictive than would the standard schedule because it would fit into the region's existing schedule for medical outreach services to isolated areas.

The second alternative schedule – at 0, 6, and 12 months – would be more useful because it could coincide with the semiannual "health days" often held in resource-poor nations.

The third alternative schedule – at 0, 12, and 24 months – could be incorporated into other countries’ annual health programs, particularly those given at schools, the researchers noted.

The primary end point was immunogenicity to HPV-16 and HPV-18 at 1 month after receipt of the final dose. According to the strict study definitions, the first two alternative dosing schedules met noninferiority criteria for HPV-16 and HPV-18, but the third (annual) schedule met the criteria only for HPV-18.

A secondary outcome was immunogenicity to the other two virus types, HPV-6 and HPV-11, which are covered by the quadrivalent vaccine. Again the first two alternative dosing schedules met the strict noninferiority criteria for HPV-6 and HPV-11, but the annual schedule met the criteria only for HPV-11.

Although the antibody concentrations against HPV-16 and HPV-6 were lower with the annual schedule than with the other dosing schedules assessed in this study, they still were higher than those that have been reported among women aged 16-26 years. "It is difficult to know if these lower anti-HPV [titers] will translate to significantly different efficacies against important clinical outcomes, such as high-grade precancerous lesions," Dr. Neuzil and her associates noted.

Extended follow-up is underway to answer this question and to determine whether longer-term antibody responses are affected by dosing schedule, they added.

The vaccine was well tolerated, and the proportion of subjects with adverse events was comparable across all the study groups. No serious adverse events were reported.

This study was funded by the Bill and Melinda Gates Foundation. Merck & Co. provided the vaccine and the immunogenicity testing at no charge. The researchers reported no relevant financial disclosures.

Giving the quadrivalent HPV vaccine on two of three alternative dosing schedules that are better suited to resource-poor regions than is the standard schedule was found to be "noninferior" among young adolescent girls in an underserved region in Vietnam, according to a report in the April 13 issue of JAMA.

In this clinical trial involving 903 girls aged 11-13 years, the quadrivalent HPV vaccine proved to be noninferior when given at 0, 3, and 9 months and at 0, 6, and 12 months, compared with the standard 0-, 2-, and 6-month dosing schedule.

When given on the third alternative dosing schedule at 0, 12, and 24 months, the vaccine did not meet the strict study criteria for noninferiority but was still found to be "highly immunogenic," said Dr. Kathleen M. Neuzil of PATH, an international nonprofit organization that addresses global health problems and is headquartered in Seattle.

"The similarity of the immunogenicity and reactogenicity profiles of the HPV vaccine reported from this predominantly ethnic minority population in a low-resource area of Vietnam ... is reassuring, and supports more widespread introduction of the vaccine," Dr. Neuzil and her colleagues reported. "The option of delivering HPV vaccine on flexible schedules will allow countries to minimize costs and maximize feasibility according to local vaccination practices" (JAMA 2011;305:1424-31).

Dr. Neuzil and her colleagues performed the open-label, randomized trial at 21 schools in predominantly rural northwestern Vietnam in 2007-2010.

The first alternative dosing schedule they assessed – at 0, 3, and 9 months – would be less restrictive than would the standard schedule because it would fit into the region's existing schedule for medical outreach services to isolated areas.

The second alternative schedule – at 0, 6, and 12 months – would be more useful because it could coincide with the semiannual "health days" often held in resource-poor nations.

The third alternative schedule – at 0, 12, and 24 months – could be incorporated into other countries’ annual health programs, particularly those given at schools, the researchers noted.

The primary end point was immunogenicity to HPV-16 and HPV-18 at 1 month after receipt of the final dose. According to the strict study definitions, the first two alternative dosing schedules met noninferiority criteria for HPV-16 and HPV-18, but the third (annual) schedule met the criteria only for HPV-18.

A secondary outcome was immunogenicity to the other two virus types, HPV-6 and HPV-11, which are covered by the quadrivalent vaccine. Again the first two alternative dosing schedules met the strict noninferiority criteria for HPV-6 and HPV-11, but the annual schedule met the criteria only for HPV-11.

Although the antibody concentrations against HPV-16 and HPV-6 were lower with the annual schedule than with the other dosing schedules assessed in this study, they still were higher than those that have been reported among women aged 16-26 years. "It is difficult to know if these lower anti-HPV [titers] will translate to significantly different efficacies against important clinical outcomes, such as high-grade precancerous lesions," Dr. Neuzil and her associates noted.

Extended follow-up is underway to answer this question and to determine whether longer-term antibody responses are affected by dosing schedule, they added.

The vaccine was well tolerated, and the proportion of subjects with adverse events was comparable across all the study groups. No serious adverse events were reported.

This study was funded by the Bill and Melinda Gates Foundation. Merck & Co. provided the vaccine and the immunogenicity testing at no charge. The researchers reported no relevant financial disclosures.

Giving the quadrivalent HPV vaccine on two of three alternative dosing schedules that are better suited to resource-poor regions than is the standard schedule was found to be "noninferior" among young adolescent girls in an underserved region in Vietnam, according to a report in the April 13 issue of JAMA.

In this clinical trial involving 903 girls aged 11-13 years, the quadrivalent HPV vaccine proved to be noninferior when given at 0, 3, and 9 months and at 0, 6, and 12 months, compared with the standard 0-, 2-, and 6-month dosing schedule. When given on the third alternative dosing schedule at 0, 12, and 24 months, the vaccine did not meet the strict study criteria for noninferiority but was still found to be "highly immunogenic," said Dr. Kathleen M. Neuzil of PATH, an international nonprofit organization that addresses global health problems and is headquartered in Seattle.

"The similarity of the immunogenicity and reactogenicity profiles of the HPV vaccine reported from this predominantly ethnic minority population in a low-resource area of Vietnam ... is reassuring, and supports more widespread introduction of the vaccine," Dr. Neuzil and her colleagues reported. "The option of delivering HPV vaccine on flexible schedules will allow countries to minimize costs and maximize feasibility according to local vaccination practices" (JAMA 2011;305:1424-31).

Dr. Neuzil and her colleagues performed the open-label, randomized trial at 21 schools in predominantly rural northwestern Vietnam in 2007-2010.

The first alternative dosing schedule they assessed – at 0, 3, and 9 months – would be less restrictive than would the standard schedule because it would fit into the region’s existing schedule for medical outreach services to isolated areas. The second alternative schedule – at 0, 6, and 12 months – would be more useful because it could coincide with the semiannual "health days" often held in resource-poor nations. The third alternative schedule – at 0, 12, and 24 months – could be incorporated into other countries’ annual health programs, particularly those given at schools, the researchers noted.

The primary end point was immunogenicity to HPV-16 and HPV-18 at 1 month after receipt of the final dose. According to the strict study definitions, the first two alternative dosing schedules met noninferiority criteria for HPV-16 and HPV-18, but the third (annual) schedule met the criteria only for HPV-18.

A secondary outcome was immunogenicity to the other two virus types, HPV-6 and HPV-11, which are covered by the quadrivalent vaccine. Again the first two alternative dosing schedules met the strict noninferiority criteria for HPV-6 and HPV-11, but the annual schedule met the criteria only for HPV-11.

Although the antibody concentrations against HPV-16 and HPV-6 were lower with the annual schedule than with the other dosing schedules assessed in this study, they still were higher than those that have been reported among women aged 16-26 years. "It is difficult to know if these lower anti-HPV [titers] will translate to significantly different efficacies against important clinical outcomes, such as high-grade precancerous lesions," Dr. Neuzil and her associates noted.

Extended follow-up is underway to answer this question and to determine whether longer-term antibody responses are affected by dosing schedule, they added.

The vaccine was well tolerated, and the proportion of subjects with adverse events was comparable across all the study groups. No serious adverse events were reported.

This study was funded by the Bill and Melinda Gates Foundation. Merck & Co. provided the vaccine and the immunogenicity testing at no charge. The researchers reported no relevant financial disclosures.

Giving the quadrivalent HPV vaccine on two of three alternative dosing schedules that are better suited to resource-poor regions than is the standard schedule was found to be "noninferior" among young adolescent girls in an underserved region in Vietnam, according to a report in the April 13 issue of JAMA.

In this clinical trial involving 903 girls aged 11-13 years, the quadrivalent HPV vaccine proved to be noninferior when given at 0, 3, and 9 months and at 0, 6, and 12 months, compared with the standard 0-, 2-, and 6-month dosing schedule. When given on the third alternative dosing schedule at 0, 12, and 24 months, the vaccine did not meet the strict study criteria for noninferiority but was still found to be "highly immunogenic," said Dr. Kathleen M. Neuzil of PATH, an international nonprofit organization that addresses global health problems and is headquartered in Seattle.

"The similarity of the immunogenicity and reactogenicity profiles of the HPV vaccine reported from this predominantly ethnic minority population in a low-resource area of Vietnam ... is reassuring, and supports more widespread introduction of the vaccine," Dr. Neuzil and her colleagues reported. "The option of delivering HPV vaccine on flexible schedules will allow countries to minimize costs and maximize feasibility according to local vaccination practices" (JAMA 2011;305:1424-31).

Dr. Neuzil and her colleagues performed the open-label, randomized trial at 21 schools in predominantly rural northwestern Vietnam in 2007-2010.

The first alternative dosing schedule they assessed – at 0, 3, and 9 months – would be less restrictive than would the standard schedule because it would fit into the region’s existing schedule for medical outreach services to isolated areas. The second alternative schedule – at 0, 6, and 12 months – would be more useful because it could coincide with the semiannual "health days" often held in resource-poor nations. The third alternative schedule – at 0, 12, and 24 months – could be incorporated into other countries’ annual health programs, particularly those given at schools, the researchers noted.

The primary end point was immunogenicity to HPV-16 and HPV-18 at 1 month after receipt of the final dose. According to the strict study definitions, the first two alternative dosing schedules met noninferiority criteria for HPV-16 and HPV-18, but the third (annual) schedule met the criteria only for HPV-18.

A secondary outcome was immunogenicity to the other two virus types, HPV-6 and HPV-11, which are covered by the quadrivalent vaccine. Again the first two alternative dosing schedules met the strict noninferiority criteria for HPV-6 and HPV-11, but the annual schedule met the criteria only for HPV-11.

Although the antibody concentrations against HPV-16 and HPV-6 were lower with the annual schedule than with the other dosing schedules assessed in this study, they still were higher than those that have been reported among women aged 16-26 years. "It is difficult to know if these lower anti-HPV [titers] will translate to significantly different efficacies against important clinical outcomes, such as high-grade precancerous lesions," Dr. Neuzil and her associates noted.

Extended follow-up is underway to answer this question and to determine whether longer-term antibody responses are affected by dosing schedule, they added.

The vaccine was well tolerated, and the proportion of subjects with adverse events was comparable across all the study groups. No serious adverse events were reported.

This study was funded by the Bill and Melinda Gates Foundation. Merck & Co. provided the vaccine and the immunogenicity testing at no charge. The researchers reported no relevant financial disclosures.

Giving the quadrivalent HPV vaccine on two of three alternative dosing schedules that are better suited to resource-poor regions than is the standard schedule was found to be "noninferior" among young adolescent girls in an underserved region in Vietnam, according to a report in the April 13 issue of JAMA.

In this clinical trial involving 903 girls aged 11-13 years, the quadrivalent HPV vaccine proved to be noninferior when given at 0, 3, and 9 months and at 0, 6, and 12 months, compared with the standard 0-, 2-, and 6-month dosing schedule. When given on the third alternative dosing schedule at 0, 12, and 24 months, the vaccine did not meet the strict study criteria for noninferiority but was still found to be "highly immunogenic," said Dr. Kathleen M. Neuzil of PATH, an international nonprofit organization that addresses global health problems and is headquartered in Seattle.

"The similarity of the immunogenicity and reactogenicity profiles of the HPV vaccine reported from this predominantly ethnic minority population in a low-resource area of Vietnam ... is reassuring, and supports more widespread introduction of the vaccine," Dr. Neuzil and her colleagues reported. "The option of delivering HPV vaccine on flexible schedules will allow countries to minimize costs and maximize feasibility according to local vaccination practices" (JAMA 2011;305:1424-31).

Dr. Neuzil and her colleagues performed the open-label, randomized trial at 21 schools in predominantly rural northwestern Vietnam in 2007-2010.

The first alternative dosing schedule they assessed – at 0, 3, and 9 months – would be less restrictive than would the standard schedule because it would fit into the region’s existing schedule for medical outreach services to isolated areas. The second alternative schedule – at 0, 6, and 12 months – would be more useful because it could coincide with the semiannual "health days" often held in resource-poor nations. The third alternative schedule – at 0, 12, and 24 months – could be incorporated into other countries’ annual health programs, particularly those given at schools, the researchers noted.

The primary end point was immunogenicity to HPV-16 and HPV-18 at 1 month after receipt of the final dose. According to the strict study definitions, the first two alternative dosing schedules met noninferiority criteria for HPV-16 and HPV-18, but the third (annual) schedule met the criteria only for HPV-18.

A secondary outcome was immunogenicity to the other two virus types, HPV-6 and HPV-11, which are covered by the quadrivalent vaccine. Again the first two alternative dosing schedules met the strict noninferiority criteria for HPV-6 and HPV-11, but the annual schedule met the criteria only for HPV-11.

Although the antibody concentrations against HPV-16 and HPV-6 were lower with the annual schedule than with the other dosing schedules assessed in this study, they still were higher than those that have been reported among women aged 16-26 years. "It is difficult to know if these lower anti-HPV [titers] will translate to significantly different efficacies against important clinical outcomes, such as high-grade precancerous lesions," Dr. Neuzil and her associates noted.

Extended follow-up is underway to answer this question and to determine whether longer-term antibody responses are affected by dosing schedule, they added.

The vaccine was well tolerated, and the proportion of subjects with adverse events was comparable across all the study groups. No serious adverse events were reported.

This study was funded by the Bill and Melinda Gates Foundation. Merck & Co. provided the vaccine and the immunogenicity testing at no charge. The researchers reported no relevant financial disclosures.

Giving the quadrivalent HPV vaccine on two of three alternative dosing schedules that are better suited to resource-poor regions than is the standard schedule was found to be "noninferior" among young adolescent girls in an underserved region in Vietnam, according to a report in the April 13 issue of JAMA.

In this clinical trial involving 903 girls aged 11-13 years, the quadrivalent HPV vaccine proved to be noninferior when given at 0, 3, and 9 months and at 0, 6, and 12 months, compared with the standard 0-, 2-, and 6-month dosing schedule. When given on the third alternative dosing schedule at 0, 12, and 24 months, the vaccine did not meet the strict study criteria for noninferiority but was still found to be "highly immunogenic," said Dr. Kathleen M. Neuzil of PATH, an international nonprofit organization that addresses global health problems and is headquartered in Seattle.

"The similarity of the immunogenicity and reactogenicity profiles of the HPV vaccine reported from this predominantly ethnic minority population in a low-resource area of Vietnam ... is reassuring, and supports more widespread introduction of the vaccine," Dr. Neuzil and her colleagues reported. "The option of delivering HPV vaccine on flexible schedules will allow countries to minimize costs and maximize feasibility according to local vaccination practices" (JAMA 2011;305:1424-31).

Dr. Neuzil and her colleagues performed the open-label, randomized trial at 21 schools in predominantly rural northwestern Vietnam in 2007-2010.

The first alternative dosing schedule they assessed – at 0, 3, and 9 months – would be less restrictive than would the standard schedule because it would fit into the region’s existing schedule for medical outreach services to isolated areas. The second alternative schedule – at 0, 6, and 12 months – would be more useful because it could coincide with the semiannual "health days" often held in resource-poor nations. The third alternative schedule – at 0, 12, and 24 months – could be incorporated into other countries’ annual health programs, particularly those given at schools, the researchers noted.

The primary end point was immunogenicity to HPV-16 and HPV-18 at 1 month after receipt of the final dose. According to the strict study definitions, the first two alternative dosing schedules met noninferiority criteria for HPV-16 and HPV-18, but the third (annual) schedule met the criteria only for HPV-18.

A secondary outcome was immunogenicity to the other two virus types, HPV-6 and HPV-11, which are covered by the quadrivalent vaccine. Again the first two alternative dosing schedules met the strict noninferiority criteria for HPV-6 and HPV-11, but the annual schedule met the criteria only for HPV-11.

Although the antibody concentrations against HPV-16 and HPV-6 were lower with the annual schedule than with the other dosing schedules assessed in this study, they still were higher than those that have been reported among women aged 16-26 years. "It is difficult to know if these lower anti-HPV [titers] will translate to significantly different efficacies against important clinical outcomes, such as high-grade precancerous lesions," Dr. Neuzil and her associates noted.

Extended follow-up is underway to answer this question and to determine whether longer-term antibody responses are affected by dosing schedule, they added.

The vaccine was well tolerated, and the proportion of subjects with adverse events was comparable across all the study groups. No serious adverse events were reported.

This study was funded by the Bill and Melinda Gates Foundation. Merck & Co. provided the vaccine and the immunogenicity testing at no charge. The researchers reported no relevant financial disclosures.

Giving the quadrivalent HPV vaccine on two of three alternative dosing schedules that are better suited to resource-poor regions than is the standard schedule was found to be "noninferior" among young adolescent girls in an underserved region in Vietnam, according to a report in the April 13 issue of JAMA.

In this clinical trial involving 903 girls aged 11-13 years, the quadrivalent HPV vaccine proved to be noninferior when given at 0, 3, and 9 months and at 0, 6, and 12 months, compared with the standard 0-, 2-, and 6-month dosing schedule. When given on the third alternative dosing schedule at 0, 12, and 24 months, the vaccine did not meet the strict study criteria for noninferiority but was still found to be "highly immunogenic," said Dr. Kathleen M. Neuzil of PATH, an international nonprofit organization that addresses global health problems and is headquartered in Seattle.

"The similarity of the immunogenicity and reactogenicity profiles of the HPV vaccine reported from this predominantly ethnic minority population in a low-resource area of Vietnam ... is reassuring, and supports more widespread introduction of the vaccine," Dr. Neuzil and her colleagues reported. "The option of delivering HPV vaccine on flexible schedules will allow countries to minimize costs and maximize feasibility according to local vaccination practices" (JAMA 2011;305:1424-31).

Dr. Neuzil and her colleagues performed the open-label, randomized trial at 21 schools in predominantly rural northwestern Vietnam in 2007-2010.

The first alternative dosing schedule they assessed – at 0, 3, and 9 months – would be less restrictive than would the standard schedule because it would fit into the region’s existing schedule for medical outreach services to isolated areas. The second alternative schedule – at 0, 6, and 12 months – would be more useful because it could coincide with the semiannual "health days" often held in resource-poor nations. The third alternative schedule – at 0, 12, and 24 months – could be incorporated into other countries’ annual health programs, particularly those given at schools, the researchers noted.

The primary end point was immunogenicity to HPV-16 and HPV-18 at 1 month after receipt of the final dose. According to the strict study definitions, the first two alternative dosing schedules met noninferiority criteria for HPV-16 and HPV-18, but the third (annual) schedule met the criteria only for HPV-18.

A secondary outcome was immunogenicity to the other two virus types, HPV-6 and HPV-11, which are covered by the quadrivalent vaccine. Again the first two alternative dosing schedules met the strict noninferiority criteria for HPV-6 and HPV-11, but the annual schedule met the criteria only for HPV-11.

Although the antibody concentrations against HPV-16 and HPV-6 were lower with the annual schedule than with the other dosing schedules assessed in this study, they still were higher than those that have been reported among women aged 16-26 years. "It is difficult to know if these lower anti-HPV [titers] will translate to significantly different efficacies against important clinical outcomes, such as high-grade precancerous lesions," Dr. Neuzil and her associates noted.

Extended follow-up is underway to answer this question and to determine whether longer-term antibody responses are affected by dosing schedule, they added.

The vaccine was well tolerated, and the proportion of subjects with adverse events was comparable across all the study groups. No serious adverse events were reported.

This study was funded by the Bill and Melinda Gates Foundation. Merck & Co. provided the vaccine and the immunogenicity testing at no charge. The researchers reported no relevant financial disclosures.

Giving the quadrivalent HPV vaccine on two of three alternative dosing schedules that are better suited to resource-poor regions than is the standard schedule was found to be "noninferior" among young adolescent girls in an underserved region in Vietnam, according to a report in the April 13 issue of JAMA.

In this clinical trial involving 903 girls aged 11-13 years, the quadrivalent HPV vaccine proved to be noninferior when given at 0, 3, and 9 months and at 0, 6, and 12 months, compared with the standard 0-, 2-, and 6-month dosing schedule. When given on the third alternative dosing schedule at 0, 12, and 24 months, the vaccine did not meet the strict study criteria for noninferiority but was still found to be "highly immunogenic," said Dr. Kathleen M. Neuzil of PATH, an international nonprofit organization that addresses global health problems and is headquartered in Seattle.

"The similarity of the immunogenicity and reactogenicity profiles of the HPV vaccine reported from this predominantly ethnic minority population in a low-resource area of Vietnam ... is reassuring, and supports more widespread introduction of the vaccine," Dr. Neuzil and her colleagues reported. "The option of delivering HPV vaccine on flexible schedules will allow countries to minimize costs and maximize feasibility according to local vaccination practices" (JAMA 2011;305:1424-31).

Dr. Neuzil and her colleagues performed the open-label, randomized trial at 21 schools in predominantly rural northwestern Vietnam in 2007-2010.

The first alternative dosing schedule they assessed – at 0, 3, and 9 months – would be less restrictive than would the standard schedule because it would fit into the region’s existing schedule for medical outreach services to isolated areas. The second alternative schedule – at 0, 6, and 12 months – would be more useful because it could coincide with the semiannual "health days" often held in resource-poor nations. The third alternative schedule – at 0, 12, and 24 months – could be incorporated into other countries’ annual health programs, particularly those given at schools, the researchers noted.

The primary end point was immunogenicity to HPV-16 and HPV-18 at 1 month after receipt of the final dose. According to the strict study definitions, the first two alternative dosing schedules met noninferiority criteria for HPV-16 and HPV-18, but the third (annual) schedule met the criteria only for HPV-18.

A secondary outcome was immunogenicity to the other two virus types, HPV-6 and HPV-11, which are covered by the quadrivalent vaccine. Again the first two alternative dosing schedules met the strict noninferiority criteria for HPV-6 and HPV-11, but the annual schedule met the criteria only for HPV-11.

Although the antibody concentrations against HPV-16 and HPV-6 were lower with the annual schedule than with the other dosing schedules assessed in this study, they still were higher than those that have been reported among women aged 16-26 years. "It is difficult to know if these lower anti-HPV [titers] will translate to significantly different efficacies against important clinical outcomes, such as high-grade precancerous lesions," Dr. Neuzil and her associates noted.

Extended follow-up is underway to answer this question and to determine whether longer-term antibody responses are affected by dosing schedule, they added.

The vaccine was well tolerated, and the proportion of subjects with adverse events was comparable across all the study groups. No serious adverse events were reported.

This study was funded by the Bill and Melinda Gates Foundation. Merck & Co. provided the vaccine and the immunogenicity testing at no charge. The researchers reported no relevant financial disclosures.