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Hospital-acquired conditions drop 8% since 2014, saving 8,000 lives and $3 billion
From 2014 to 2016, the rate of potentially deadly hospital-acquired conditions in the United States dropped by 8% – a change that translated into 350,000 fewer such conditions, 8,000 fewer inpatient deaths, and a national savings of almost $3 billion.
The preliminary new baseline rate for hospital-acquired conditions (HACs) is 90 per 1,000 discharges – down from 98 per 1,000 discharges at the end of 2014, according to the Agency for Healthcare Research and Quality’s new report, “AHRQ National Scorecard on Hospital-Acquired Conditions – Updated Baseline Rates and Preliminary Results 2014-2016.”
The largest improvements occurred in central line–associated bloodstream infections (down 31% from 2014), postoperative venous thromboembolism (21% decline), adverse drug events (15% decline), and pressure ulcers (10% decline). A new category, C. difficile infections, also showed a large decline over 2014 (11%).
These numbers build on earlier successes associated with a national goal set by the Centers for Medicare & Medicaid Services to reduce HACs by 20% by 2019. They should be hailed as proof that attention to prevention strategies can save lives and money, said Seema Verma, CMS administrator.
“Today’s results show that this is a tremendous accomplishment by America’s hospitals in delivering high-quality, affordable healthcare,” Ms. Verma said in a press statement. “CMS is committed to moving the healthcare system to one that improves quality and fosters innovation while reducing administrative burden and lowering costs. This work could not be accomplished without the concerted effort of our many hospital, patient, provider, private, and federal partners – all working together to ensure the best possible care by protecting patients from harm and making care safer.”
The numbers continue to go in the right direction, the report noted. Data reported in late 2016 found a 17% decline in HACs from 2010 to 2014. This equated to 2.1 million HACs, 87,000 fewer deaths, and a savings of $19.9 billion.
Much work remains to be done to achieve the stated 2019 goal, the report noted, but the rewards are great. Reaching the 20% reduction goal would secure a total decrease in the HAC rate from 98 to 78 per 1,000 discharges. This would result in 1.78 million fewer HAC in the years from 2015-2019. That decrease would ultimately save 53,000 lives and $19.1 billion over 5 years.
From 2014 to 2016, the rate of potentially deadly hospital-acquired conditions in the United States dropped by 8% – a change that translated into 350,000 fewer such conditions, 8,000 fewer inpatient deaths, and a national savings of almost $3 billion.
The preliminary new baseline rate for hospital-acquired conditions (HACs) is 90 per 1,000 discharges – down from 98 per 1,000 discharges at the end of 2014, according to the Agency for Healthcare Research and Quality’s new report, “AHRQ National Scorecard on Hospital-Acquired Conditions – Updated Baseline Rates and Preliminary Results 2014-2016.”
The largest improvements occurred in central line–associated bloodstream infections (down 31% from 2014), postoperative venous thromboembolism (21% decline), adverse drug events (15% decline), and pressure ulcers (10% decline). A new category, C. difficile infections, also showed a large decline over 2014 (11%).
These numbers build on earlier successes associated with a national goal set by the Centers for Medicare & Medicaid Services to reduce HACs by 20% by 2019. They should be hailed as proof that attention to prevention strategies can save lives and money, said Seema Verma, CMS administrator.
“Today’s results show that this is a tremendous accomplishment by America’s hospitals in delivering high-quality, affordable healthcare,” Ms. Verma said in a press statement. “CMS is committed to moving the healthcare system to one that improves quality and fosters innovation while reducing administrative burden and lowering costs. This work could not be accomplished without the concerted effort of our many hospital, patient, provider, private, and federal partners – all working together to ensure the best possible care by protecting patients from harm and making care safer.”
The numbers continue to go in the right direction, the report noted. Data reported in late 2016 found a 17% decline in HACs from 2010 to 2014. This equated to 2.1 million HACs, 87,000 fewer deaths, and a savings of $19.9 billion.
Much work remains to be done to achieve the stated 2019 goal, the report noted, but the rewards are great. Reaching the 20% reduction goal would secure a total decrease in the HAC rate from 98 to 78 per 1,000 discharges. This would result in 1.78 million fewer HAC in the years from 2015-2019. That decrease would ultimately save 53,000 lives and $19.1 billion over 5 years.
From 2014 to 2016, the rate of potentially deadly hospital-acquired conditions in the United States dropped by 8% – a change that translated into 350,000 fewer such conditions, 8,000 fewer inpatient deaths, and a national savings of almost $3 billion.
The preliminary new baseline rate for hospital-acquired conditions (HACs) is 90 per 1,000 discharges – down from 98 per 1,000 discharges at the end of 2014, according to the Agency for Healthcare Research and Quality’s new report, “AHRQ National Scorecard on Hospital-Acquired Conditions – Updated Baseline Rates and Preliminary Results 2014-2016.”
The largest improvements occurred in central line–associated bloodstream infections (down 31% from 2014), postoperative venous thromboembolism (21% decline), adverse drug events (15% decline), and pressure ulcers (10% decline). A new category, C. difficile infections, also showed a large decline over 2014 (11%).
These numbers build on earlier successes associated with a national goal set by the Centers for Medicare & Medicaid Services to reduce HACs by 20% by 2019. They should be hailed as proof that attention to prevention strategies can save lives and money, said Seema Verma, CMS administrator.
“Today’s results show that this is a tremendous accomplishment by America’s hospitals in delivering high-quality, affordable healthcare,” Ms. Verma said in a press statement. “CMS is committed to moving the healthcare system to one that improves quality and fosters innovation while reducing administrative burden and lowering costs. This work could not be accomplished without the concerted effort of our many hospital, patient, provider, private, and federal partners – all working together to ensure the best possible care by protecting patients from harm and making care safer.”
The numbers continue to go in the right direction, the report noted. Data reported in late 2016 found a 17% decline in HACs from 2010 to 2014. This equated to 2.1 million HACs, 87,000 fewer deaths, and a savings of $19.9 billion.
Much work remains to be done to achieve the stated 2019 goal, the report noted, but the rewards are great. Reaching the 20% reduction goal would secure a total decrease in the HAC rate from 98 to 78 per 1,000 discharges. This would result in 1.78 million fewer HAC in the years from 2015-2019. That decrease would ultimately save 53,000 lives and $19.1 billion over 5 years.
For Gram-negative bacteremias, 7 days of antibiotics is enough
MADRID – Seven days of antibiotic therapy was just as effective as 14 days for patients with Gram-negative bacteremias.
The shorter course was associated with similar cure rates and a faster return to normal activities, Dafna Yahav, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“In patients hospitalized with Gram-negative bacteremia and sepsis, a course of 7 antibiotic days was not inferior to 14 days, and resulted in a more rapid return to baseline activity, “ said Dr. Yahav of the Rabin Medical Center, Petah Tikva, Israel. “This could lead to a change in accepted management algorithms and shortened antibiotic therapy. Potentially, though we did not show this in our trial, it may lead to reduced cost, reduced development of resistance, and fewer adverse events.”
During the past few years, a new dogma has emerged in antibiotic treatment paradigms, she said: Shorter is better. Brad Spellberg, MD, described this concept in his 2016 editorial in JAMA Internal Medicine, “The new antibiotic mantra” (Sep 1;176[9]:1254-5).
In it, Dr. Spellberg, of the University of Southern California, Los Angeles, addressed the long-held view that a full 10- or 14-day course of antibiotics was necessary to decrease the risk of creating a resistant strain, even if clinical symptoms were long resolved.
However, he noted, there is little evidence supporting the idea that longer courses suppress the rise of resistance – and, in fact, some data support the opposite.
“To the contrary, specifically for pneumonia, studies have shown that longer courses of therapy result in more emergence of antibiotic resistance, which is consistent with everything we know about natural selection, the driver of antibiotic resistance,” he noted. “In only a few types of infections does resistance emerge at the site of infection; rather, resistance typically emerges off target, among colonizing flora away from the site of infection. Thus, all that is achieved by treating an infection with antibiotics for longer than the patient has symptoms is increased selective pressure driving antibiotic resistance among our colonizing microbial flora.”
The European Union and Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America have all recently updated their antibiotic stewardship guidelines to include a strong recommendation for the shortest effective duration of antimicrobial therapy.
However, most of the supporting data were drawn from randomized, controlled studies of patients with lung, skin, and kidney infections. Short-course treatments have not been adequately studied in bacteremia patients, Dr. Yahav said.
The aim of her study, which was investigator initiated and received no external funding, was to demonstrate the noninferiority of 7 days of antibiotic therapy, compared with 14 days, in patients with bacteremia arising from Gram-negative infections.
The randomized, open-label study comprised 604 patients in three hospitals: two in Israel and one in Italy. Patients were eligible if they had an aerobic Gram-negative bacteremia of any infection source that was either community- or hospital acquired. The medication choice was left up to the treating physician. Patients were assessed at discharge, and at days 30 and 90.
The primary outcome was a composite 90-day endpoint of all-cause mortality, clinical failure (relapse, new local complications, or distant complications), and readmission or hospital stay longer than 14 days. There were a number of secondary outcomes, including new infection, emergence of antibiotic resistance, total hospital and total antibiotic days, time to return to baseline activity, and adverse events.
The cohort was a mean of 71 years old. About 60% were functionally independent, and the mean Charlson comorbidity score was 2. Most of the infections (90%) were nosocomial. The urinary tract was the largest source of infection (69%). Other sources were abdominal, respiratory, central venous catheter, and skin or soft tissue.
Escherichia coli was the most common infective organism (62%), followed by Klebsiella species and Enterobacteriaceae. A small number of patients had Acinetobacter and Pseudomonas infections.
In the intent-to-treat analysis, the primary composite outcome of all-cause mortality or extended hospital stay occurred in 46% of the 7-day group and 50% of the 14-day group – not significantly different. The results were nearly identical in the per-protocol analysis (46% vs. 49.6%).
Likewise, none of the secondary outcomes posted a significant difference in favor of one treatment arm, including relapse (2.9% vs. 2.7%) and resistance development (10.8% vs. 9.7%).
Dr. Yahav pointed out that total antibiotic-use days were significantly less in the 7-day group, (5 days) than in the 14-day group (10 days). Patients in the short-duration group returned to their normal activities a day earlier than those in the longer-term group (2 days vs. 3 days), a difference that was statistically significant.
The total hospital stay from randomization to day 90 was only half a day shorter in the short-term group (mean, 3 days vs. 3.5 days). That was not a significant finding.
There were some differences in adverse events, although none was statistically significant. The short-duration arm had slightly more cases of kidney injury (0.5%), fewer cases of liver function abnormalities (–1.5%), and half as many rashes (two vs. four). There were two cases of Clostridium difficile in the short-use arm and one in the long-use arm, also not a significant difference.
A subgroup analysis looked at outcomes among the different sources of infection (urinary tract vs. other), whether empirical antibiotics were used, and whether the induced resistance was multdrug or non–multidrug. All of those differences hovered close to the null, but generally favored short antibiotic treatment, Dr. Yahav noted.
“I would conclude from these data that is generally safe to stop antibiotics after 7 days of covering antibiotics for Gram-negative bacteremia patients, if they are hemodynamically stable and nonneutropenic at 7 days, and have no uncontrolled source of infection,” she concluded.
The investigator-initiated study had no outside funding.
SOURCE: Yahav D et al. ECCMID 2018. Oral abstract O1120.
MADRID – Seven days of antibiotic therapy was just as effective as 14 days for patients with Gram-negative bacteremias.
The shorter course was associated with similar cure rates and a faster return to normal activities, Dafna Yahav, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“In patients hospitalized with Gram-negative bacteremia and sepsis, a course of 7 antibiotic days was not inferior to 14 days, and resulted in a more rapid return to baseline activity, “ said Dr. Yahav of the Rabin Medical Center, Petah Tikva, Israel. “This could lead to a change in accepted management algorithms and shortened antibiotic therapy. Potentially, though we did not show this in our trial, it may lead to reduced cost, reduced development of resistance, and fewer adverse events.”
During the past few years, a new dogma has emerged in antibiotic treatment paradigms, she said: Shorter is better. Brad Spellberg, MD, described this concept in his 2016 editorial in JAMA Internal Medicine, “The new antibiotic mantra” (Sep 1;176[9]:1254-5).
In it, Dr. Spellberg, of the University of Southern California, Los Angeles, addressed the long-held view that a full 10- or 14-day course of antibiotics was necessary to decrease the risk of creating a resistant strain, even if clinical symptoms were long resolved.
However, he noted, there is little evidence supporting the idea that longer courses suppress the rise of resistance – and, in fact, some data support the opposite.
“To the contrary, specifically for pneumonia, studies have shown that longer courses of therapy result in more emergence of antibiotic resistance, which is consistent with everything we know about natural selection, the driver of antibiotic resistance,” he noted. “In only a few types of infections does resistance emerge at the site of infection; rather, resistance typically emerges off target, among colonizing flora away from the site of infection. Thus, all that is achieved by treating an infection with antibiotics for longer than the patient has symptoms is increased selective pressure driving antibiotic resistance among our colonizing microbial flora.”
The European Union and Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America have all recently updated their antibiotic stewardship guidelines to include a strong recommendation for the shortest effective duration of antimicrobial therapy.
However, most of the supporting data were drawn from randomized, controlled studies of patients with lung, skin, and kidney infections. Short-course treatments have not been adequately studied in bacteremia patients, Dr. Yahav said.
The aim of her study, which was investigator initiated and received no external funding, was to demonstrate the noninferiority of 7 days of antibiotic therapy, compared with 14 days, in patients with bacteremia arising from Gram-negative infections.
The randomized, open-label study comprised 604 patients in three hospitals: two in Israel and one in Italy. Patients were eligible if they had an aerobic Gram-negative bacteremia of any infection source that was either community- or hospital acquired. The medication choice was left up to the treating physician. Patients were assessed at discharge, and at days 30 and 90.
The primary outcome was a composite 90-day endpoint of all-cause mortality, clinical failure (relapse, new local complications, or distant complications), and readmission or hospital stay longer than 14 days. There were a number of secondary outcomes, including new infection, emergence of antibiotic resistance, total hospital and total antibiotic days, time to return to baseline activity, and adverse events.
The cohort was a mean of 71 years old. About 60% were functionally independent, and the mean Charlson comorbidity score was 2. Most of the infections (90%) were nosocomial. The urinary tract was the largest source of infection (69%). Other sources were abdominal, respiratory, central venous catheter, and skin or soft tissue.
Escherichia coli was the most common infective organism (62%), followed by Klebsiella species and Enterobacteriaceae. A small number of patients had Acinetobacter and Pseudomonas infections.
In the intent-to-treat analysis, the primary composite outcome of all-cause mortality or extended hospital stay occurred in 46% of the 7-day group and 50% of the 14-day group – not significantly different. The results were nearly identical in the per-protocol analysis (46% vs. 49.6%).
Likewise, none of the secondary outcomes posted a significant difference in favor of one treatment arm, including relapse (2.9% vs. 2.7%) and resistance development (10.8% vs. 9.7%).
Dr. Yahav pointed out that total antibiotic-use days were significantly less in the 7-day group, (5 days) than in the 14-day group (10 days). Patients in the short-duration group returned to their normal activities a day earlier than those in the longer-term group (2 days vs. 3 days), a difference that was statistically significant.
The total hospital stay from randomization to day 90 was only half a day shorter in the short-term group (mean, 3 days vs. 3.5 days). That was not a significant finding.
There were some differences in adverse events, although none was statistically significant. The short-duration arm had slightly more cases of kidney injury (0.5%), fewer cases of liver function abnormalities (–1.5%), and half as many rashes (two vs. four). There were two cases of Clostridium difficile in the short-use arm and one in the long-use arm, also not a significant difference.
A subgroup analysis looked at outcomes among the different sources of infection (urinary tract vs. other), whether empirical antibiotics were used, and whether the induced resistance was multdrug or non–multidrug. All of those differences hovered close to the null, but generally favored short antibiotic treatment, Dr. Yahav noted.
“I would conclude from these data that is generally safe to stop antibiotics after 7 days of covering antibiotics for Gram-negative bacteremia patients, if they are hemodynamically stable and nonneutropenic at 7 days, and have no uncontrolled source of infection,” she concluded.
The investigator-initiated study had no outside funding.
SOURCE: Yahav D et al. ECCMID 2018. Oral abstract O1120.
MADRID – Seven days of antibiotic therapy was just as effective as 14 days for patients with Gram-negative bacteremias.
The shorter course was associated with similar cure rates and a faster return to normal activities, Dafna Yahav, MD, said at the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“In patients hospitalized with Gram-negative bacteremia and sepsis, a course of 7 antibiotic days was not inferior to 14 days, and resulted in a more rapid return to baseline activity, “ said Dr. Yahav of the Rabin Medical Center, Petah Tikva, Israel. “This could lead to a change in accepted management algorithms and shortened antibiotic therapy. Potentially, though we did not show this in our trial, it may lead to reduced cost, reduced development of resistance, and fewer adverse events.”
During the past few years, a new dogma has emerged in antibiotic treatment paradigms, she said: Shorter is better. Brad Spellberg, MD, described this concept in his 2016 editorial in JAMA Internal Medicine, “The new antibiotic mantra” (Sep 1;176[9]:1254-5).
In it, Dr. Spellberg, of the University of Southern California, Los Angeles, addressed the long-held view that a full 10- or 14-day course of antibiotics was necessary to decrease the risk of creating a resistant strain, even if clinical symptoms were long resolved.
However, he noted, there is little evidence supporting the idea that longer courses suppress the rise of resistance – and, in fact, some data support the opposite.
“To the contrary, specifically for pneumonia, studies have shown that longer courses of therapy result in more emergence of antibiotic resistance, which is consistent with everything we know about natural selection, the driver of antibiotic resistance,” he noted. “In only a few types of infections does resistance emerge at the site of infection; rather, resistance typically emerges off target, among colonizing flora away from the site of infection. Thus, all that is achieved by treating an infection with antibiotics for longer than the patient has symptoms is increased selective pressure driving antibiotic resistance among our colonizing microbial flora.”
The European Union and Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America have all recently updated their antibiotic stewardship guidelines to include a strong recommendation for the shortest effective duration of antimicrobial therapy.
However, most of the supporting data were drawn from randomized, controlled studies of patients with lung, skin, and kidney infections. Short-course treatments have not been adequately studied in bacteremia patients, Dr. Yahav said.
The aim of her study, which was investigator initiated and received no external funding, was to demonstrate the noninferiority of 7 days of antibiotic therapy, compared with 14 days, in patients with bacteremia arising from Gram-negative infections.
The randomized, open-label study comprised 604 patients in three hospitals: two in Israel and one in Italy. Patients were eligible if they had an aerobic Gram-negative bacteremia of any infection source that was either community- or hospital acquired. The medication choice was left up to the treating physician. Patients were assessed at discharge, and at days 30 and 90.
The primary outcome was a composite 90-day endpoint of all-cause mortality, clinical failure (relapse, new local complications, or distant complications), and readmission or hospital stay longer than 14 days. There were a number of secondary outcomes, including new infection, emergence of antibiotic resistance, total hospital and total antibiotic days, time to return to baseline activity, and adverse events.
The cohort was a mean of 71 years old. About 60% were functionally independent, and the mean Charlson comorbidity score was 2. Most of the infections (90%) were nosocomial. The urinary tract was the largest source of infection (69%). Other sources were abdominal, respiratory, central venous catheter, and skin or soft tissue.
Escherichia coli was the most common infective organism (62%), followed by Klebsiella species and Enterobacteriaceae. A small number of patients had Acinetobacter and Pseudomonas infections.
In the intent-to-treat analysis, the primary composite outcome of all-cause mortality or extended hospital stay occurred in 46% of the 7-day group and 50% of the 14-day group – not significantly different. The results were nearly identical in the per-protocol analysis (46% vs. 49.6%).
Likewise, none of the secondary outcomes posted a significant difference in favor of one treatment arm, including relapse (2.9% vs. 2.7%) and resistance development (10.8% vs. 9.7%).
Dr. Yahav pointed out that total antibiotic-use days were significantly less in the 7-day group, (5 days) than in the 14-day group (10 days). Patients in the short-duration group returned to their normal activities a day earlier than those in the longer-term group (2 days vs. 3 days), a difference that was statistically significant.
The total hospital stay from randomization to day 90 was only half a day shorter in the short-term group (mean, 3 days vs. 3.5 days). That was not a significant finding.
There were some differences in adverse events, although none was statistically significant. The short-duration arm had slightly more cases of kidney injury (0.5%), fewer cases of liver function abnormalities (–1.5%), and half as many rashes (two vs. four). There were two cases of Clostridium difficile in the short-use arm and one in the long-use arm, also not a significant difference.
A subgroup analysis looked at outcomes among the different sources of infection (urinary tract vs. other), whether empirical antibiotics were used, and whether the induced resistance was multdrug or non–multidrug. All of those differences hovered close to the null, but generally favored short antibiotic treatment, Dr. Yahav noted.
“I would conclude from these data that is generally safe to stop antibiotics after 7 days of covering antibiotics for Gram-negative bacteremia patients, if they are hemodynamically stable and nonneutropenic at 7 days, and have no uncontrolled source of infection,” she concluded.
The investigator-initiated study had no outside funding.
SOURCE: Yahav D et al. ECCMID 2018. Oral abstract O1120.
REPORTING FROM ECCMID 2018
Key clinical point: Two weeks of antibiotic treatment conferred no benefits over 7 days of treatment in patients with Gram-negative bacteremias.
Major finding: All-cause mortality and extended hospital stay occurred in 46% of the 7-day group and 50% of the 14-day group – not significantly different.
Study details: The randomized, open-label trial comprised 604 patients.
Disclosures: The investigator-initiated study had no external funding. Dr. Yahav had no financial disclosures.
Source: Yahav D et al. ECCMID 2018. Oral Abstract O1120.
ESBL-resistant bacteria spread in hospital despite strict contact precautions
MADRID – even when staff employed an active surveillance screening protocol to identify every carrier at admission.
The failure of precautions may have root in two thorny issues, said Friederike Maechler, MD, who presented the data at the the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“Adherence to strict contact isolation and hand hygiene is never 100% in a real-life scenario,” said Dr. Maechler, of Charite University Hospital, Berlin. Also, she said, contact isolation can only be effective in a ward if all, or at least most, of the ESBL-E carriers are identified. “Even with an extensive surveillance screening program established, many carriers remained unknown to the health care staff.”
The 25-month study, dubbed R-Gnosis, was conducted in 20 Western European hospitals in Madrid, Berlin, Utrecht, and Geneva. It compared 12 months of contact precaution with standard precaution infection control strategies in medical and surgical non-ICUs.
The entire study hinged on a strict protocol to identify as many ESBL-E carriers as possible. This was done by screening upon admission to the unit, screening once per week during the hospital stay, and screening on discharge. Each patient underwent deep rectal swabs that were cultured on agar and screened for resistance.
The crossover design trial randomized each unit to either contact precautions or standard precautions for 12 months, followed by a 1-month washout period, after which they began the other protocol.
In all, 50,870 patients were entered into the study. By the end, Dr. Maechler had data on 11,367 patients with full screening and follow-up.
Standard precautions did not require a private bedroom, with gloves, gowns, and apron needed for direct contact to body fluids or wounds only, and consistent hand hygiene. Contact precautions required a private bedroom and strict hand hygiene, with gloves, gowns, and aprons used for any patient contact. Study staff monitored compliance with these procedures monthly.
The primary outcome was the ESBL-E acquisition rate per 1,000 patient days. This was defined as a new ESBL-E detection after the patient had a prior negative screen. Dr. Maechler noted that by epidemiological definition, acquisition does not necessarily imply cross-transmission from other patients.
Adherence to the study protocols was good, she said. Adherence to both contact and standard precautions was about 85%, while adherence to hand hygiene was less at around 62%.
Admission ESBL-E screenings revealed that about 12% of the study population was colonized with the strain at admission. The proportion was nearly identical in the contact and standard precaution groups (11.6%, 12.2%).
The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6 in both intervention periods, regardless of the type of precaution taken. Contact precautions appeared to be slightly less effective for Escherichia coli (3.6 per 1,000 patient-days in contact precautions vs. 3.5 in standard), compared with Klebsiella pneumoniae (1.8 vs. 2.2).
A multivariate analysis controlled for screening compliance, colonization pressure, and length of stay, study site, and season of year. It showed that strict contact precautions did not reduce the risk of ward-acquired ESBL-E carriage.
Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
SOURCE: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
MADRID – even when staff employed an active surveillance screening protocol to identify every carrier at admission.
The failure of precautions may have root in two thorny issues, said Friederike Maechler, MD, who presented the data at the the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“Adherence to strict contact isolation and hand hygiene is never 100% in a real-life scenario,” said Dr. Maechler, of Charite University Hospital, Berlin. Also, she said, contact isolation can only be effective in a ward if all, or at least most, of the ESBL-E carriers are identified. “Even with an extensive surveillance screening program established, many carriers remained unknown to the health care staff.”
The 25-month study, dubbed R-Gnosis, was conducted in 20 Western European hospitals in Madrid, Berlin, Utrecht, and Geneva. It compared 12 months of contact precaution with standard precaution infection control strategies in medical and surgical non-ICUs.
The entire study hinged on a strict protocol to identify as many ESBL-E carriers as possible. This was done by screening upon admission to the unit, screening once per week during the hospital stay, and screening on discharge. Each patient underwent deep rectal swabs that were cultured on agar and screened for resistance.
The crossover design trial randomized each unit to either contact precautions or standard precautions for 12 months, followed by a 1-month washout period, after which they began the other protocol.
In all, 50,870 patients were entered into the study. By the end, Dr. Maechler had data on 11,367 patients with full screening and follow-up.
Standard precautions did not require a private bedroom, with gloves, gowns, and apron needed for direct contact to body fluids or wounds only, and consistent hand hygiene. Contact precautions required a private bedroom and strict hand hygiene, with gloves, gowns, and aprons used for any patient contact. Study staff monitored compliance with these procedures monthly.
The primary outcome was the ESBL-E acquisition rate per 1,000 patient days. This was defined as a new ESBL-E detection after the patient had a prior negative screen. Dr. Maechler noted that by epidemiological definition, acquisition does not necessarily imply cross-transmission from other patients.
Adherence to the study protocols was good, she said. Adherence to both contact and standard precautions was about 85%, while adherence to hand hygiene was less at around 62%.
Admission ESBL-E screenings revealed that about 12% of the study population was colonized with the strain at admission. The proportion was nearly identical in the contact and standard precaution groups (11.6%, 12.2%).
The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6 in both intervention periods, regardless of the type of precaution taken. Contact precautions appeared to be slightly less effective for Escherichia coli (3.6 per 1,000 patient-days in contact precautions vs. 3.5 in standard), compared with Klebsiella pneumoniae (1.8 vs. 2.2).
A multivariate analysis controlled for screening compliance, colonization pressure, and length of stay, study site, and season of year. It showed that strict contact precautions did not reduce the risk of ward-acquired ESBL-E carriage.
Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
SOURCE: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
MADRID – even when staff employed an active surveillance screening protocol to identify every carrier at admission.
The failure of precautions may have root in two thorny issues, said Friederike Maechler, MD, who presented the data at the the European Society of Clinical Microbiology and Infectious Diseases annual congress.
“Adherence to strict contact isolation and hand hygiene is never 100% in a real-life scenario,” said Dr. Maechler, of Charite University Hospital, Berlin. Also, she said, contact isolation can only be effective in a ward if all, or at least most, of the ESBL-E carriers are identified. “Even with an extensive surveillance screening program established, many carriers remained unknown to the health care staff.”
The 25-month study, dubbed R-Gnosis, was conducted in 20 Western European hospitals in Madrid, Berlin, Utrecht, and Geneva. It compared 12 months of contact precaution with standard precaution infection control strategies in medical and surgical non-ICUs.
The entire study hinged on a strict protocol to identify as many ESBL-E carriers as possible. This was done by screening upon admission to the unit, screening once per week during the hospital stay, and screening on discharge. Each patient underwent deep rectal swabs that were cultured on agar and screened for resistance.
The crossover design trial randomized each unit to either contact precautions or standard precautions for 12 months, followed by a 1-month washout period, after which they began the other protocol.
In all, 50,870 patients were entered into the study. By the end, Dr. Maechler had data on 11,367 patients with full screening and follow-up.
Standard precautions did not require a private bedroom, with gloves, gowns, and apron needed for direct contact to body fluids or wounds only, and consistent hand hygiene. Contact precautions required a private bedroom and strict hand hygiene, with gloves, gowns, and aprons used for any patient contact. Study staff monitored compliance with these procedures monthly.
The primary outcome was the ESBL-E acquisition rate per 1,000 patient days. This was defined as a new ESBL-E detection after the patient had a prior negative screen. Dr. Maechler noted that by epidemiological definition, acquisition does not necessarily imply cross-transmission from other patients.
Adherence to the study protocols was good, she said. Adherence to both contact and standard precautions was about 85%, while adherence to hand hygiene was less at around 62%.
Admission ESBL-E screenings revealed that about 12% of the study population was colonized with the strain at admission. The proportion was nearly identical in the contact and standard precaution groups (11.6%, 12.2%).
The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6 in both intervention periods, regardless of the type of precaution taken. Contact precautions appeared to be slightly less effective for Escherichia coli (3.6 per 1,000 patient-days in contact precautions vs. 3.5 in standard), compared with Klebsiella pneumoniae (1.8 vs. 2.2).
A multivariate analysis controlled for screening compliance, colonization pressure, and length of stay, study site, and season of year. It showed that strict contact precautions did not reduce the risk of ward-acquired ESBL-E carriage.
Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
SOURCE: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
REPORTING FROM ECCMID 2018
Key clinical point: A protocol of strict contact precautions and hand hygiene was no better than standard contact precautions at preventing the spread of extended-spectrum, beta-lactamase–resistant Enterobacteriaceae.
Major finding: The incidence density of ward-acquired ESBL-E per 1,000 patient-days at risk was 4.6, regardless of precaution.
Study details: The 25-month crossover trial comprised more than 11,000 patients.
Disclosures: Dr. Maechler had no financial disclosures. The R-Gnosis study was funded by the European Community’s Seventh Framework Programme.
Source: Maechler F et al. ECCMID 2018, Oral Abstract O1130.
Adding vasopressin in distributive shock may cut AF risk
In patients with distributive shock, the risk of atrial fibrillation may be lower when vasopressin is administered along with catecholamine vasopressors, results of a recent systematic review and meta-analysis suggest.
The relative risk of atrial fibrillation was reduced for the combination of vasopressin and catecholamines versus the current standard of care, which is catecholamines alone, according to study results published in JAMA.
Beyond atrial fibrillation, however, findings of the meta-analysis were consistent with regard to other endpoints, including mortality, according to William F. McIntyre, MD, of McMaster University, Hamilton, Ont., and his coinvestigators.
Mortality was lower with the combination approach when all studies were analyzed together. Yet, when the analysis was limited to the studies with the lowest risk of bias, the difference in mortality versus catecholamines alone was not statistically significant, investigators said.
Nevertheless, the meta-analysis does suggest that vasopressin may offer a clinical advantage regarding prevention of atrial fibrillation in patients with distributive shock, a frequently fatal condition most often seen in patients with sepsis.
Vasopressin is an endogenous peptide hormone that decreases stimulation of certain myocardial receptors associated with cardiac arrhythmia, the authors noted.
“This, among other mechanisms, may translate into a reduction in adverse events, including atrial fibrillation, injury to other organs, and death,” they said in their report.
Dr. McIntyre and his colleagues included 23 trials that had enrolled a total of 3,088 patients with distributive shock, a condition in which widespread vasodilation lowers vascular resistances and mean arterial pressure. Sepsis is its most common cause. The current study is one of the first to directly compare the combination of vasopressin and catecholamine to catecholamines alone, which is the current standard of care, the investigators wrote.
They found that the administration of vasopressin was associated with a significant 23% reduction in risk of atrial fibrillation.
“The absolute effect is that 68 fewer people per 1,000 patients will experience atrial fibrillation when vasopressin is added to catecholaminergic vasopressors,” Dr. McIntyre and his coauthors said of the results.
The atrial fibrillation finding was judged to be high-quality evidence, they said, noting that two separate sensitivity analyses confirmed the benefit.
Mortality data were less consistent, they said.
Pooled data showed administration of vasopressin along with catecholamines was associated an 11% relative reduction in mortality. In absolute terms, 45 lives would be saved for every 1,000 patients receiving vasopressin, they noted.
However, the mortality findings were different when the analysis was limited to the two studies with low risk of bias. That analysis yielded a relative risk of 0.96 and was not statistically significant.
Studies show patients with distributive shock have a relative vasopressin deficiency, providing a theoretical basis for vasopressin administration as part of care, investigators said.
The current Surviving Sepsis guidelines suggest either adding vasopressin to norepinephrine to help raise mean arterial pressure to target or adding vasopressin to decrease the dosage of norepinephrine. Those are considered weak recommendations based on moderate quality of evidence, Dr. McIntyre and colleagues noted in their report.
Authors of the study reported disclosures related to Tenax Therapeutics, Orion Pharma, Ferring Pharmaceuticals, GlaxoSmithKline, and Bristol-Myers Squibb, among other entities.
SOURCE: McIntyre WF et al. JAMA. 2018;319(18):1889-900.
In patients with distributive shock, the risk of atrial fibrillation may be lower when vasopressin is administered along with catecholamine vasopressors, results of a recent systematic review and meta-analysis suggest.
The relative risk of atrial fibrillation was reduced for the combination of vasopressin and catecholamines versus the current standard of care, which is catecholamines alone, according to study results published in JAMA.
Beyond atrial fibrillation, however, findings of the meta-analysis were consistent with regard to other endpoints, including mortality, according to William F. McIntyre, MD, of McMaster University, Hamilton, Ont., and his coinvestigators.
Mortality was lower with the combination approach when all studies were analyzed together. Yet, when the analysis was limited to the studies with the lowest risk of bias, the difference in mortality versus catecholamines alone was not statistically significant, investigators said.
Nevertheless, the meta-analysis does suggest that vasopressin may offer a clinical advantage regarding prevention of atrial fibrillation in patients with distributive shock, a frequently fatal condition most often seen in patients with sepsis.
Vasopressin is an endogenous peptide hormone that decreases stimulation of certain myocardial receptors associated with cardiac arrhythmia, the authors noted.
“This, among other mechanisms, may translate into a reduction in adverse events, including atrial fibrillation, injury to other organs, and death,” they said in their report.
Dr. McIntyre and his colleagues included 23 trials that had enrolled a total of 3,088 patients with distributive shock, a condition in which widespread vasodilation lowers vascular resistances and mean arterial pressure. Sepsis is its most common cause. The current study is one of the first to directly compare the combination of vasopressin and catecholamine to catecholamines alone, which is the current standard of care, the investigators wrote.
They found that the administration of vasopressin was associated with a significant 23% reduction in risk of atrial fibrillation.
“The absolute effect is that 68 fewer people per 1,000 patients will experience atrial fibrillation when vasopressin is added to catecholaminergic vasopressors,” Dr. McIntyre and his coauthors said of the results.
The atrial fibrillation finding was judged to be high-quality evidence, they said, noting that two separate sensitivity analyses confirmed the benefit.
Mortality data were less consistent, they said.
Pooled data showed administration of vasopressin along with catecholamines was associated an 11% relative reduction in mortality. In absolute terms, 45 lives would be saved for every 1,000 patients receiving vasopressin, they noted.
However, the mortality findings were different when the analysis was limited to the two studies with low risk of bias. That analysis yielded a relative risk of 0.96 and was not statistically significant.
Studies show patients with distributive shock have a relative vasopressin deficiency, providing a theoretical basis for vasopressin administration as part of care, investigators said.
The current Surviving Sepsis guidelines suggest either adding vasopressin to norepinephrine to help raise mean arterial pressure to target or adding vasopressin to decrease the dosage of norepinephrine. Those are considered weak recommendations based on moderate quality of evidence, Dr. McIntyre and colleagues noted in their report.
Authors of the study reported disclosures related to Tenax Therapeutics, Orion Pharma, Ferring Pharmaceuticals, GlaxoSmithKline, and Bristol-Myers Squibb, among other entities.
SOURCE: McIntyre WF et al. JAMA. 2018;319(18):1889-900.
In patients with distributive shock, the risk of atrial fibrillation may be lower when vasopressin is administered along with catecholamine vasopressors, results of a recent systematic review and meta-analysis suggest.
The relative risk of atrial fibrillation was reduced for the combination of vasopressin and catecholamines versus the current standard of care, which is catecholamines alone, according to study results published in JAMA.
Beyond atrial fibrillation, however, findings of the meta-analysis were consistent with regard to other endpoints, including mortality, according to William F. McIntyre, MD, of McMaster University, Hamilton, Ont., and his coinvestigators.
Mortality was lower with the combination approach when all studies were analyzed together. Yet, when the analysis was limited to the studies with the lowest risk of bias, the difference in mortality versus catecholamines alone was not statistically significant, investigators said.
Nevertheless, the meta-analysis does suggest that vasopressin may offer a clinical advantage regarding prevention of atrial fibrillation in patients with distributive shock, a frequently fatal condition most often seen in patients with sepsis.
Vasopressin is an endogenous peptide hormone that decreases stimulation of certain myocardial receptors associated with cardiac arrhythmia, the authors noted.
“This, among other mechanisms, may translate into a reduction in adverse events, including atrial fibrillation, injury to other organs, and death,” they said in their report.
Dr. McIntyre and his colleagues included 23 trials that had enrolled a total of 3,088 patients with distributive shock, a condition in which widespread vasodilation lowers vascular resistances and mean arterial pressure. Sepsis is its most common cause. The current study is one of the first to directly compare the combination of vasopressin and catecholamine to catecholamines alone, which is the current standard of care, the investigators wrote.
They found that the administration of vasopressin was associated with a significant 23% reduction in risk of atrial fibrillation.
“The absolute effect is that 68 fewer people per 1,000 patients will experience atrial fibrillation when vasopressin is added to catecholaminergic vasopressors,” Dr. McIntyre and his coauthors said of the results.
The atrial fibrillation finding was judged to be high-quality evidence, they said, noting that two separate sensitivity analyses confirmed the benefit.
Mortality data were less consistent, they said.
Pooled data showed administration of vasopressin along with catecholamines was associated an 11% relative reduction in mortality. In absolute terms, 45 lives would be saved for every 1,000 patients receiving vasopressin, they noted.
However, the mortality findings were different when the analysis was limited to the two studies with low risk of bias. That analysis yielded a relative risk of 0.96 and was not statistically significant.
Studies show patients with distributive shock have a relative vasopressin deficiency, providing a theoretical basis for vasopressin administration as part of care, investigators said.
The current Surviving Sepsis guidelines suggest either adding vasopressin to norepinephrine to help raise mean arterial pressure to target or adding vasopressin to decrease the dosage of norepinephrine. Those are considered weak recommendations based on moderate quality of evidence, Dr. McIntyre and colleagues noted in their report.
Authors of the study reported disclosures related to Tenax Therapeutics, Orion Pharma, Ferring Pharmaceuticals, GlaxoSmithKline, and Bristol-Myers Squibb, among other entities.
SOURCE: McIntyre WF et al. JAMA. 2018;319(18):1889-900.
FROM JAMA
Key clinical point: For patients with distributive shock, the addition of vasopressin to catecholamine vasopressors may reduce atrial fibrillation risk, compared with catecholamines alone.
Major finding: Vasopressin was associated with a 23% lower risk of atrial fibrillation.
Study details: A systematic review and meta-analysis including 23 randomized clinical trials enrolling a total of 3,088 patients.
Disclosures: Authors reported disclosures related to Tenax Therapeutics, Orion Pharma, Ferring Pharmaceuticals, GlaxoSmithKline, and Bristol-Myers Squibb, among other entities.
Source: McIntyre WF et al. JAMA. 2018;319(18):1889-900.
Ertapenem slashes surgical site infections in carriers of ESBL-producing bacteria
MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.
The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.
He presented the results of the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in gram-negative organisms: Studying intervention strategies” is a 12 million euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multidrug resistant Gram-negative bacteria. Several of the studies reported at ECCMID 2018.
During 2012-2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures). All patients were screened for ESBL-producing bacteria from 2 weeks to 2 days before their operation. In the first phase, carriers were treated with the standard presurgical prophylaxis of 1.5 g cefuroxime and 500 mg metronidazole intravenously. In phase 2, carriers received targeted prophylaxis with IV ertapenem 1 g. Both interventions were given 30 minutes before surgery commenced.
All patients underwent regular surgical site infection surveillance until hospital discharge, then followed up 30 days later by phone or in person.
The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.
ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.
Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.
Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.
Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.
There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:
- E. coli (thirteen in the routine and one in the ertapenem group).
- Klebsiella species (four and one, respectively).
- Proteus species (one in the ertapenem group).
Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.
In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).
Dr. Nutman made no financial declarations.
SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.
MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.
The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.
He presented the results of the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in gram-negative organisms: Studying intervention strategies” is a 12 million euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multidrug resistant Gram-negative bacteria. Several of the studies reported at ECCMID 2018.
During 2012-2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures). All patients were screened for ESBL-producing bacteria from 2 weeks to 2 days before their operation. In the first phase, carriers were treated with the standard presurgical prophylaxis of 1.5 g cefuroxime and 500 mg metronidazole intravenously. In phase 2, carriers received targeted prophylaxis with IV ertapenem 1 g. Both interventions were given 30 minutes before surgery commenced.
All patients underwent regular surgical site infection surveillance until hospital discharge, then followed up 30 days later by phone or in person.
The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.
ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.
Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.
Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.
Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.
There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:
- E. coli (thirteen in the routine and one in the ertapenem group).
- Klebsiella species (four and one, respectively).
- Proteus species (one in the ertapenem group).
Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.
In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).
Dr. Nutman made no financial declarations.
SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.
MADRID – A targeted antibiotic strategy that employed ertapenem in carriers of extended-spectrum beta-lactamase–producing Enterobacteriaceae reduced infections after colorectal surgery by 41%, compared with routine treatment with cefuroxime and metronidazole.
The strategy was even more effective at preventing surgical site infections caused by ESBL-producing bacteria, cutting the rate by 87%, Amir Nutman, MD, said at the European Congress of Clinical Microbiology and Infectious Diseases.
He presented the results of the WP4 study, which was carried out in three hospitals in Serbia, Switzerland, and Israel. Designed as a before-and-after trial, it tested the theory that identifying ESBL carriers and targeting presurgical antibiotic prophylaxis could improve their surgical outcomes.
WP4 was one of five studies in the multinational R-GNOSIS project. “Resistance in gram-negative organisms: Studying intervention strategies” is a 12 million euro, 5-year European collaborative research project designed to identify effective interventions for reducing the carriage, infection, and spread of multidrug resistant Gram-negative bacteria. Several of the studies reported at ECCMID 2018.
During 2012-2017, WP4 enrolled almost 4,000 adults scheduled to undergo colorectal surgery (excluding appendectomy or minor anorectal procedures). All patients were screened for ESBL-producing bacteria from 2 weeks to 2 days before their operation. In the first phase, carriers were treated with the standard presurgical prophylaxis of 1.5 g cefuroxime and 500 mg metronidazole intravenously. In phase 2, carriers received targeted prophylaxis with IV ertapenem 1 g. Both interventions were given 30 minutes before surgery commenced.
All patients underwent regular surgical site infection surveillance until hospital discharge, then followed up 30 days later by phone or in person.
The primary outcome was surgical site infection at 30 days. Secondary outcomes were the type of any surgical site infection (superficial, deep, or organ/space), and infections caused by ESBL-producing bacteria.
ESBL screening was carried out on 3,626 patients; carriage prevalence was 13.8%, but varied by center from 9% to 29%. Of the carriers, 468 were included in the study; 247 received routine prophylaxis and 221 received ertapenem.
Patients were a mean of 63 years old; 98% were living at home before admission. About 20% had diabetes; 5% had some type of immunodeficiency. The most common surgical indication was colon cancer (68%), and about a third had undergone prior colon surgery. Most of the surgeries were open, and about half involved a colectomy.
Patients in the ertapenem group had overall better scores on the National Nosocomial Infections Surveillance Basic SSI Risk Index and were less likely to have an intraoperative finding of colon dilation (20.8% vs. 27%).There were no other clinically compelling intraoperative differences between the two groups, including bleeding, bowel spillage, the need for drains, or stoma placement.
Patients who received prophylactic ertapenem had significantly better 30-day outcomes on all measures of infection than did patients who had standard prophylaxis, Dr. Nutman said.
There were 34 surgical site infections in the routine prophylaxis group and 19 in the ertapenem group. Among these, 17 in the routine group and three in the ertapenem group were caused by ESBL-producing bacteria. The ESBL-positive infections were as follows:
- E. coli (thirteen in the routine and one in the ertapenem group).
- Klebsiella species (four and one, respectively).
- Proteus species (one in the ertapenem group).
Other infections were caused by ESBL-nonproducers, including E. coli, Klebsiella, Proteus, Enterococci, Pseudomonas aeruginosa, Staphylococcus aureus, and other unspecified organisms. Polymicrobial infections occurred in 25 patients.
In an analysis that controlled for National Nosocomial Infections Surveillance score and colon dilation, patients who received ertapenem were 41% less likely to develop any surgical site infection (15.8% vs. 22.7%; odds ratio, 0.59); 17% less likely to develop a deep infection (9.5% vs. 11.3%; OR, 0.83); and 87% less likely to develop an infection caused by an ESBL-producing bacteria (0.9% vs. 6.5%; OR, 0.13).
Dr. Nutman made no financial declarations.
SOURCE: Nutman et al. ECCMID 2018, Abstract O1129.
REPORTING FROM ECCMID 2018
Key clinical point: A targeted presurgical antibiotic prophylaxis significantly cut rates of surgical site infections in carriers of extended beta-lactamase–producing bacteria.
Major finding: Ertapenem reduced the rate of surgical site infection by 41% , and the rate of ESBL-producing infections by 87%, compared to routine prophylaxis.
Study details: The study comprised 468 patients.
Disclosures: The study was funded by the European Commission under the Seventh Framework Programme (FP7) for Research and Technology. Dr. Nutman had no financial disclosures.
Source: Nutman A et al. ECCMID 2018, Abstract O1129
Preoperative penicillin allergy tests could decrease SSI
Patients with reported penicillin allergies are significantly more likely to develop surgical site infections, according to a study conducted at Massachusetts General Hospital in Boston.
With new evidence reporting 90%-99% of patients with a reported allergy are not actually allergic, conducting a preoperative allergy test could improve treatment choice and decrease the risk of SSI, as well as the notable financial burden associated with it. Thus, “systematic, preoperative penicillin allergy evaluations in surgical patients may not only improve antibiotic choice but also decrease SSI risk,” according to Kimberly Blumenthal, MD, the quality director for the department of allergy and immunology at Massachusetts General Hospital, and her fellow investigators.
Surgeries performed were hip arthroplasty, knee arthroplasty, hysterectomy, colon surgery, or coronary artery bypass grafting.
Of the patients studied, 922 (11%) reported a penicillin allergy; most had minor reactions, such as rashes (37.5%) or urticaria (18%). “Only 5 reactions to penicillin represented contraindications to receiving a beta-lactam; the vast majority of patients would have tolerated first-line recommended cephalosporin prophylaxis had allergy evaluation been pursued,“ according to Dr. Blumenthal and her colleagues.
Overall, a total of 241 (2.7%) patients contracted an SSI. In a multivariate analysis, patients who had reported a penicillin allergy were 50% more likely to develop an SSI than those who had no reported allergy (adjusted odds ratio, 1.5; P = .04).
Risk may even be higher than 50% in the general health care population because this health center has a relatively low rate of SSIs, compared with many other hospitals, Dr. Blumenthal and her fellow investigators stated.
The increased risk primarily concerns the treatment used because those with a reported allergy were more likely than those without the allergy to be given clindamycin (48.8% vs. 3.1%, respectively), vancomycin (34.7% vs. 3.3%), gentamicin (24% vs. 2.8%), or fluoroquinolones (6.8% vs. 1.3%) instead of the most commonly used antibiotic, cefazolin (12.2% vs. 92.4%).
Patients given antibiotics other than cefazolin were usually given treatment outside of the perioperative window, which could severely increase the likelihood for developing an SSI, according to investigators. Of patients given vancomycin, 97.5% did not receive their treatment in the recommended time frame, compared with 1.7% of those given cefazolin.
“Increased odds of SSI among patients reporting a penicillin allergy in this cohort was entirely due to the use of beta-lactam–alternative perioperative antibiotics,” wrote to Dr. Blumenthal and her colleagues. “Patients with reported penicillin allergy in this study were not only less likely to receive the most effective perioperative antibiotic, they were also less likely to receive prophylaxis in the recommended time frame for optimal tissue concentration.”
While allergy assessments before surgery are currently recommended, there are no specifically outlined methods for these evaluations, which leads many providers to take what has been deemed the safer route of giving patients beta-lactam–alternative antibiotics instead, Dr. Blumenthal and her colleagues suggested.
The research was supported by the National Institutes of Health, and the investigators reported having no relevant conflicts.
ezimmerman@frontlinemedcom.com
SOURCE: Blumenthal K et al. Clin Infect Dis. 2018 Jan 18;66(3):329-36.
Patients with reported penicillin allergies are significantly more likely to develop surgical site infections, according to a study conducted at Massachusetts General Hospital in Boston.
With new evidence reporting 90%-99% of patients with a reported allergy are not actually allergic, conducting a preoperative allergy test could improve treatment choice and decrease the risk of SSI, as well as the notable financial burden associated with it. Thus, “systematic, preoperative penicillin allergy evaluations in surgical patients may not only improve antibiotic choice but also decrease SSI risk,” according to Kimberly Blumenthal, MD, the quality director for the department of allergy and immunology at Massachusetts General Hospital, and her fellow investigators.
Surgeries performed were hip arthroplasty, knee arthroplasty, hysterectomy, colon surgery, or coronary artery bypass grafting.
Of the patients studied, 922 (11%) reported a penicillin allergy; most had minor reactions, such as rashes (37.5%) or urticaria (18%). “Only 5 reactions to penicillin represented contraindications to receiving a beta-lactam; the vast majority of patients would have tolerated first-line recommended cephalosporin prophylaxis had allergy evaluation been pursued,“ according to Dr. Blumenthal and her colleagues.
Overall, a total of 241 (2.7%) patients contracted an SSI. In a multivariate analysis, patients who had reported a penicillin allergy were 50% more likely to develop an SSI than those who had no reported allergy (adjusted odds ratio, 1.5; P = .04).
Risk may even be higher than 50% in the general health care population because this health center has a relatively low rate of SSIs, compared with many other hospitals, Dr. Blumenthal and her fellow investigators stated.
The increased risk primarily concerns the treatment used because those with a reported allergy were more likely than those without the allergy to be given clindamycin (48.8% vs. 3.1%, respectively), vancomycin (34.7% vs. 3.3%), gentamicin (24% vs. 2.8%), or fluoroquinolones (6.8% vs. 1.3%) instead of the most commonly used antibiotic, cefazolin (12.2% vs. 92.4%).
Patients given antibiotics other than cefazolin were usually given treatment outside of the perioperative window, which could severely increase the likelihood for developing an SSI, according to investigators. Of patients given vancomycin, 97.5% did not receive their treatment in the recommended time frame, compared with 1.7% of those given cefazolin.
“Increased odds of SSI among patients reporting a penicillin allergy in this cohort was entirely due to the use of beta-lactam–alternative perioperative antibiotics,” wrote to Dr. Blumenthal and her colleagues. “Patients with reported penicillin allergy in this study were not only less likely to receive the most effective perioperative antibiotic, they were also less likely to receive prophylaxis in the recommended time frame for optimal tissue concentration.”
While allergy assessments before surgery are currently recommended, there are no specifically outlined methods for these evaluations, which leads many providers to take what has been deemed the safer route of giving patients beta-lactam–alternative antibiotics instead, Dr. Blumenthal and her colleagues suggested.
The research was supported by the National Institutes of Health, and the investigators reported having no relevant conflicts.
ezimmerman@frontlinemedcom.com
SOURCE: Blumenthal K et al. Clin Infect Dis. 2018 Jan 18;66(3):329-36.
Patients with reported penicillin allergies are significantly more likely to develop surgical site infections, according to a study conducted at Massachusetts General Hospital in Boston.
With new evidence reporting 90%-99% of patients with a reported allergy are not actually allergic, conducting a preoperative allergy test could improve treatment choice and decrease the risk of SSI, as well as the notable financial burden associated with it. Thus, “systematic, preoperative penicillin allergy evaluations in surgical patients may not only improve antibiotic choice but also decrease SSI risk,” according to Kimberly Blumenthal, MD, the quality director for the department of allergy and immunology at Massachusetts General Hospital, and her fellow investigators.
Surgeries performed were hip arthroplasty, knee arthroplasty, hysterectomy, colon surgery, or coronary artery bypass grafting.
Of the patients studied, 922 (11%) reported a penicillin allergy; most had minor reactions, such as rashes (37.5%) or urticaria (18%). “Only 5 reactions to penicillin represented contraindications to receiving a beta-lactam; the vast majority of patients would have tolerated first-line recommended cephalosporin prophylaxis had allergy evaluation been pursued,“ according to Dr. Blumenthal and her colleagues.
Overall, a total of 241 (2.7%) patients contracted an SSI. In a multivariate analysis, patients who had reported a penicillin allergy were 50% more likely to develop an SSI than those who had no reported allergy (adjusted odds ratio, 1.5; P = .04).
Risk may even be higher than 50% in the general health care population because this health center has a relatively low rate of SSIs, compared with many other hospitals, Dr. Blumenthal and her fellow investigators stated.
The increased risk primarily concerns the treatment used because those with a reported allergy were more likely than those without the allergy to be given clindamycin (48.8% vs. 3.1%, respectively), vancomycin (34.7% vs. 3.3%), gentamicin (24% vs. 2.8%), or fluoroquinolones (6.8% vs. 1.3%) instead of the most commonly used antibiotic, cefazolin (12.2% vs. 92.4%).
Patients given antibiotics other than cefazolin were usually given treatment outside of the perioperative window, which could severely increase the likelihood for developing an SSI, according to investigators. Of patients given vancomycin, 97.5% did not receive their treatment in the recommended time frame, compared with 1.7% of those given cefazolin.
“Increased odds of SSI among patients reporting a penicillin allergy in this cohort was entirely due to the use of beta-lactam–alternative perioperative antibiotics,” wrote to Dr. Blumenthal and her colleagues. “Patients with reported penicillin allergy in this study were not only less likely to receive the most effective perioperative antibiotic, they were also less likely to receive prophylaxis in the recommended time frame for optimal tissue concentration.”
While allergy assessments before surgery are currently recommended, there are no specifically outlined methods for these evaluations, which leads many providers to take what has been deemed the safer route of giving patients beta-lactam–alternative antibiotics instead, Dr. Blumenthal and her colleagues suggested.
The research was supported by the National Institutes of Health, and the investigators reported having no relevant conflicts.
ezimmerman@frontlinemedcom.com
SOURCE: Blumenthal K et al. Clin Infect Dis. 2018 Jan 18;66(3):329-36.
FROM CLINICAL INFECTIOUS DISEASES
Key clinical point: Patients with reported penicillin allergies are at higher risk of developing a surgical site infection.
Major finding: Having a penicillin allergy was associated with a 50% increased risk of developing a surgical site infection, compared with those without the allergy (adjusted odds ratio, 1.5; P = .04).
Study details: Retrospective cohort study of 8,385 patients operated on at Massachusetts General Hospital, Boston, during 2010-2014.
Disclosures: The research was supported by the National Institutes of Health, and the investigators reported having no relevant conflicts.
Source: Blumenthal K et al. Clin Infect Dis. 2018 Jan 18;66(3):329-36.
Combo therapy does not improve outcomes for A. Baumannii
, based on data from 406 patients.
In a study published online in The Lancet Infectious Diseases, Mical Paul, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues randomized 198 patients to colistin alone and 208 to colistin plus meropenem (Lancet Infect Dis. 2018 Feb 15. doi: 10.1016/S1473-3099[18]30099-9).
The demographics were similar between the groups and approximately 77% of patients in each group were infected with A. baumannii.
The results highlight “the necessity of assessing combination therapy in randomized trials before adopting it into clinical use,” the researchers said.
The study was not designed to examine the effect of the two types of therapy on bacteria other than A. baumannii, the researchers noted. However, based on the findings, “we recommend against the routine use of carbapenems for the treatment of carbapenem-resistant A. baumannii infections,” they said.
The study was supported by EU AIDA grant Health-F3-2011-278348. Dr. Paul had no financial conflicts to disclose.
SOURCE: Paul M et al. Lancet Infect Dis. 2018 Feb 15. doi: 10.1016/S1473-3099(18)30099-9.
, based on data from 406 patients.
In a study published online in The Lancet Infectious Diseases, Mical Paul, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues randomized 198 patients to colistin alone and 208 to colistin plus meropenem (Lancet Infect Dis. 2018 Feb 15. doi: 10.1016/S1473-3099[18]30099-9).
The demographics were similar between the groups and approximately 77% of patients in each group were infected with A. baumannii.
The results highlight “the necessity of assessing combination therapy in randomized trials before adopting it into clinical use,” the researchers said.
The study was not designed to examine the effect of the two types of therapy on bacteria other than A. baumannii, the researchers noted. However, based on the findings, “we recommend against the routine use of carbapenems for the treatment of carbapenem-resistant A. baumannii infections,” they said.
The study was supported by EU AIDA grant Health-F3-2011-278348. Dr. Paul had no financial conflicts to disclose.
SOURCE: Paul M et al. Lancet Infect Dis. 2018 Feb 15. doi: 10.1016/S1473-3099(18)30099-9.
, based on data from 406 patients.
In a study published online in The Lancet Infectious Diseases, Mical Paul, MD, of Rambam Health Care Campus, Haifa, Israel, and colleagues randomized 198 patients to colistin alone and 208 to colistin plus meropenem (Lancet Infect Dis. 2018 Feb 15. doi: 10.1016/S1473-3099[18]30099-9).
The demographics were similar between the groups and approximately 77% of patients in each group were infected with A. baumannii.
The results highlight “the necessity of assessing combination therapy in randomized trials before adopting it into clinical use,” the researchers said.
The study was not designed to examine the effect of the two types of therapy on bacteria other than A. baumannii, the researchers noted. However, based on the findings, “we recommend against the routine use of carbapenems for the treatment of carbapenem-resistant A. baumannii infections,” they said.
The study was supported by EU AIDA grant Health-F3-2011-278348. Dr. Paul had no financial conflicts to disclose.
SOURCE: Paul M et al. Lancet Infect Dis. 2018 Feb 15. doi: 10.1016/S1473-3099(18)30099-9.
FROM THE LANCET INFECTIOUS DISEASES
Duodenoscope redesign prompts voluntary recall by Pentax
Pentax has issued a voluntary recall for Pentax ED-3490TK duodenoscopes because of infections associated with reprocessed duodenoscopes, and the Food and Drug Administration has cleared the 510(k) to improve the device. The new design will, it is hoped, improve cleaning and disinfection for these devices.
“Reducing infections associated with duodenoscopes remains a top priority for the FDA, and we believe the new design changes to the Pentax duodenoscope will make these devices easier to clean and high-level disinfect to help enhance their safety,” said Suzanne Schwartz, MD, associate director for science and strategic partnerships at the FDA’s Center for Devices and Radiological Health. “We will continue to encourage new innovations for these devices to protect public health while enabling patients to have continued access to minimally invasive, life-saving endoscopy procedures.”
. In one study, even after double high-level disinfection or standard high-level disinfection followed by ethylene oxide gas sterilization, duodenoscopes had similar rates of contamination. These contamination events were associated with outbreaks of carbapenem-resistant Enterobacteriaceae infections. One of the culprits behind residual contamination may be the presence of biofilms, which are notoriously difficult to clean with standard disinfection methods.
Prior to the clearance of the elevator channel sealing mechanism, the first duodenoscope with a disposable distal cap was introduced, the Pentax ED34-i10T. The use of a disposable tip for the duodenoscope is meant to decrease the risk of future infections associated with these devices. The use of a disposable tip also improves cleaning and reprocessing of the duodenoscopes.
The FDA continues to work with manufacturers to improve the safety of duodenscopes and other reusable medical devices to protect patients from bacterial infections.
Pentax has issued a voluntary recall for Pentax ED-3490TK duodenoscopes because of infections associated with reprocessed duodenoscopes, and the Food and Drug Administration has cleared the 510(k) to improve the device. The new design will, it is hoped, improve cleaning and disinfection for these devices.
“Reducing infections associated with duodenoscopes remains a top priority for the FDA, and we believe the new design changes to the Pentax duodenoscope will make these devices easier to clean and high-level disinfect to help enhance their safety,” said Suzanne Schwartz, MD, associate director for science and strategic partnerships at the FDA’s Center for Devices and Radiological Health. “We will continue to encourage new innovations for these devices to protect public health while enabling patients to have continued access to minimally invasive, life-saving endoscopy procedures.”
. In one study, even after double high-level disinfection or standard high-level disinfection followed by ethylene oxide gas sterilization, duodenoscopes had similar rates of contamination. These contamination events were associated with outbreaks of carbapenem-resistant Enterobacteriaceae infections. One of the culprits behind residual contamination may be the presence of biofilms, which are notoriously difficult to clean with standard disinfection methods.
Prior to the clearance of the elevator channel sealing mechanism, the first duodenoscope with a disposable distal cap was introduced, the Pentax ED34-i10T. The use of a disposable tip for the duodenoscope is meant to decrease the risk of future infections associated with these devices. The use of a disposable tip also improves cleaning and reprocessing of the duodenoscopes.
The FDA continues to work with manufacturers to improve the safety of duodenscopes and other reusable medical devices to protect patients from bacterial infections.
Pentax has issued a voluntary recall for Pentax ED-3490TK duodenoscopes because of infections associated with reprocessed duodenoscopes, and the Food and Drug Administration has cleared the 510(k) to improve the device. The new design will, it is hoped, improve cleaning and disinfection for these devices.
“Reducing infections associated with duodenoscopes remains a top priority for the FDA, and we believe the new design changes to the Pentax duodenoscope will make these devices easier to clean and high-level disinfect to help enhance their safety,” said Suzanne Schwartz, MD, associate director for science and strategic partnerships at the FDA’s Center for Devices and Radiological Health. “We will continue to encourage new innovations for these devices to protect public health while enabling patients to have continued access to minimally invasive, life-saving endoscopy procedures.”
. In one study, even after double high-level disinfection or standard high-level disinfection followed by ethylene oxide gas sterilization, duodenoscopes had similar rates of contamination. These contamination events were associated with outbreaks of carbapenem-resistant Enterobacteriaceae infections. One of the culprits behind residual contamination may be the presence of biofilms, which are notoriously difficult to clean with standard disinfection methods.
Prior to the clearance of the elevator channel sealing mechanism, the first duodenoscope with a disposable distal cap was introduced, the Pentax ED34-i10T. The use of a disposable tip for the duodenoscope is meant to decrease the risk of future infections associated with these devices. The use of a disposable tip also improves cleaning and reprocessing of the duodenoscopes.
The FDA continues to work with manufacturers to improve the safety of duodenscopes and other reusable medical devices to protect patients from bacterial infections.
REPROVE: Ceftazidime-avibactam noninferior to meropenem for nosocomial pneumonia
Ceftazidime-avibactam was noninferior to meropenem for nosocomial pneumonia including ventilator-associated pneumonia from gram-negative organisms, results from the REPROVE trial demonstrated.
Nosocomial or hospital-acquired pneumonia is a common hospital-acquired infection associated with increased cost and mortality. Further, nosocomial pneumonia is associated with gram-negative pathogens such as Pseudomonas aeruginosa and Enterobacteriaceae that may carry extended-spectrum beta-lactamases and carbapenemase, thereby limiting the treatment options. However, ceftazidime-avibactam has both antipseudomonal and extended beta-lactamase coverage for multidrug-resistant gram-negative infections, and may provide an alternative to meropenem.
Antoni Torres, MD, of the University of Barcelona and his colleagues sought to compare the safety and efficacy of ceftazidime-avibactam to meropenem in patients with nosocomial and ventilator-associated pneumonia. The REPROVE study was a phase 3, double-blind, noninferiority trial performed at 136 centers in 23 countries. Patients were randomly assigned 1:1 to receive either ceftazidime-avibactam (500-2,000 mg every 8 hours) or meropenem (1,000 mg every 8 hours) with adjustment as needed for renal function.
Participants included in the study were 18-90 years of age with nosocomial pneumonia as evidenced by pneumonia 48 hours or more after admission or within 7 days after discharge from an inpatient facility. Patients with ventilator-associated pneumonia had lung infection within 48 hours of intubation and mechanical ventilation. Sputum culture and gram stains were obtained within 48 hours before randomization, and patients were excluded for evidence of gram-positive–only pathogens or those not expected to respond to meropenem or ceftazidime-avibactam.
The study involved a safety population (808 patients), a clinically modified intention-to-treat population (726), and a clinically evaluable population (527). The intention-to-treat population demonstrated a predominance of Klebsiella pneumoniae (37%), and Pseudomonas aeruginosa (30%); 28% of the intention-to-treat population were identified as not susceptible to ceftazidime.
Overall, the clinically modified intention-to-treat group demonstrated a clinical cure rate of 68.8% (245/356) in the ceftazidime-avibactam and 73.0% (270/370) for the meropenem group (difference, –4.2%; 95% confidence interval, –10.8 to 2.5). The evaluable population demonstrated a clinical cure rate of 77.4% (199/257) in the ceftazidime-avibactam group and 78.1% (211/270) in the meropenem group (–0.7%; 95% CI, –7.9 to 6.4).
The all-cause mortality rate was similar between groups at the test-of-cure date and at day 28. The clinically modified intention-to-treat population demonstrated a mortality of 8.1% vs. 6.8% at the test-of-cure date and 8.4% vs. 7.3% at day 28 for ceftazidime-avibactam and meropenem, respectively.
Adverse events were noted in 75% vs. 74% of patients in the ceftazidime-avibactam groups and meropenem groups, respectively. Most adverse events were rated as mild to moderate and deemed likely unrelated to the treatment.
However, serious adverse events occurred in 19% (n = 75) in the ceftazidime-avibactam group and 13% (n = 54) in the meropenem group. Four serious adverse events were thought to be possibly related to the study drug ceftazidime-avibactam and included diarrhea, acute coronary syndrome, subacute hepatic failure, and abnormal liver function test results. The authors noted the adverse events in the trial were consistent and detected no new safety concerns for ceftazidime-avibactam.
Limitations of the study included an inability to establish the optimal duration of treatment for nosocomial pneumonia treated with meropenem or ceftazidime-avibactam.
“Our results show noninferiority for the treatment of nosocomial pneumonia caused by ceftazidime-nonsusceptible or ceftazidime-susceptible gram-negative aerobic pathogens,” the authors concluded.
The study was initially funded by AstraZeneca until the rights to ceftazidime-avibactam were acquired by Pfizer. Multiple authors reported financial relationships with AstraZeneca including grant funding, employment, and shareholding.
SOURCE: Torres A et al. Lancet Infect Dis. 2017. doi: 10.1016/S1473-3099(17)30747-8.
Ceftazidime-avibactam was noninferior to meropenem for nosocomial pneumonia including ventilator-associated pneumonia from gram-negative organisms, results from the REPROVE trial demonstrated.
Nosocomial or hospital-acquired pneumonia is a common hospital-acquired infection associated with increased cost and mortality. Further, nosocomial pneumonia is associated with gram-negative pathogens such as Pseudomonas aeruginosa and Enterobacteriaceae that may carry extended-spectrum beta-lactamases and carbapenemase, thereby limiting the treatment options. However, ceftazidime-avibactam has both antipseudomonal and extended beta-lactamase coverage for multidrug-resistant gram-negative infections, and may provide an alternative to meropenem.
Antoni Torres, MD, of the University of Barcelona and his colleagues sought to compare the safety and efficacy of ceftazidime-avibactam to meropenem in patients with nosocomial and ventilator-associated pneumonia. The REPROVE study was a phase 3, double-blind, noninferiority trial performed at 136 centers in 23 countries. Patients were randomly assigned 1:1 to receive either ceftazidime-avibactam (500-2,000 mg every 8 hours) or meropenem (1,000 mg every 8 hours) with adjustment as needed for renal function.
Participants included in the study were 18-90 years of age with nosocomial pneumonia as evidenced by pneumonia 48 hours or more after admission or within 7 days after discharge from an inpatient facility. Patients with ventilator-associated pneumonia had lung infection within 48 hours of intubation and mechanical ventilation. Sputum culture and gram stains were obtained within 48 hours before randomization, and patients were excluded for evidence of gram-positive–only pathogens or those not expected to respond to meropenem or ceftazidime-avibactam.
The study involved a safety population (808 patients), a clinically modified intention-to-treat population (726), and a clinically evaluable population (527). The intention-to-treat population demonstrated a predominance of Klebsiella pneumoniae (37%), and Pseudomonas aeruginosa (30%); 28% of the intention-to-treat population were identified as not susceptible to ceftazidime.
Overall, the clinically modified intention-to-treat group demonstrated a clinical cure rate of 68.8% (245/356) in the ceftazidime-avibactam and 73.0% (270/370) for the meropenem group (difference, –4.2%; 95% confidence interval, –10.8 to 2.5). The evaluable population demonstrated a clinical cure rate of 77.4% (199/257) in the ceftazidime-avibactam group and 78.1% (211/270) in the meropenem group (–0.7%; 95% CI, –7.9 to 6.4).
The all-cause mortality rate was similar between groups at the test-of-cure date and at day 28. The clinically modified intention-to-treat population demonstrated a mortality of 8.1% vs. 6.8% at the test-of-cure date and 8.4% vs. 7.3% at day 28 for ceftazidime-avibactam and meropenem, respectively.
Adverse events were noted in 75% vs. 74% of patients in the ceftazidime-avibactam groups and meropenem groups, respectively. Most adverse events were rated as mild to moderate and deemed likely unrelated to the treatment.
However, serious adverse events occurred in 19% (n = 75) in the ceftazidime-avibactam group and 13% (n = 54) in the meropenem group. Four serious adverse events were thought to be possibly related to the study drug ceftazidime-avibactam and included diarrhea, acute coronary syndrome, subacute hepatic failure, and abnormal liver function test results. The authors noted the adverse events in the trial were consistent and detected no new safety concerns for ceftazidime-avibactam.
Limitations of the study included an inability to establish the optimal duration of treatment for nosocomial pneumonia treated with meropenem or ceftazidime-avibactam.
“Our results show noninferiority for the treatment of nosocomial pneumonia caused by ceftazidime-nonsusceptible or ceftazidime-susceptible gram-negative aerobic pathogens,” the authors concluded.
The study was initially funded by AstraZeneca until the rights to ceftazidime-avibactam were acquired by Pfizer. Multiple authors reported financial relationships with AstraZeneca including grant funding, employment, and shareholding.
SOURCE: Torres A et al. Lancet Infect Dis. 2017. doi: 10.1016/S1473-3099(17)30747-8.
Ceftazidime-avibactam was noninferior to meropenem for nosocomial pneumonia including ventilator-associated pneumonia from gram-negative organisms, results from the REPROVE trial demonstrated.
Nosocomial or hospital-acquired pneumonia is a common hospital-acquired infection associated with increased cost and mortality. Further, nosocomial pneumonia is associated with gram-negative pathogens such as Pseudomonas aeruginosa and Enterobacteriaceae that may carry extended-spectrum beta-lactamases and carbapenemase, thereby limiting the treatment options. However, ceftazidime-avibactam has both antipseudomonal and extended beta-lactamase coverage for multidrug-resistant gram-negative infections, and may provide an alternative to meropenem.
Antoni Torres, MD, of the University of Barcelona and his colleagues sought to compare the safety and efficacy of ceftazidime-avibactam to meropenem in patients with nosocomial and ventilator-associated pneumonia. The REPROVE study was a phase 3, double-blind, noninferiority trial performed at 136 centers in 23 countries. Patients were randomly assigned 1:1 to receive either ceftazidime-avibactam (500-2,000 mg every 8 hours) or meropenem (1,000 mg every 8 hours) with adjustment as needed for renal function.
Participants included in the study were 18-90 years of age with nosocomial pneumonia as evidenced by pneumonia 48 hours or more after admission or within 7 days after discharge from an inpatient facility. Patients with ventilator-associated pneumonia had lung infection within 48 hours of intubation and mechanical ventilation. Sputum culture and gram stains were obtained within 48 hours before randomization, and patients were excluded for evidence of gram-positive–only pathogens or those not expected to respond to meropenem or ceftazidime-avibactam.
The study involved a safety population (808 patients), a clinically modified intention-to-treat population (726), and a clinically evaluable population (527). The intention-to-treat population demonstrated a predominance of Klebsiella pneumoniae (37%), and Pseudomonas aeruginosa (30%); 28% of the intention-to-treat population were identified as not susceptible to ceftazidime.
Overall, the clinically modified intention-to-treat group demonstrated a clinical cure rate of 68.8% (245/356) in the ceftazidime-avibactam and 73.0% (270/370) for the meropenem group (difference, –4.2%; 95% confidence interval, –10.8 to 2.5). The evaluable population demonstrated a clinical cure rate of 77.4% (199/257) in the ceftazidime-avibactam group and 78.1% (211/270) in the meropenem group (–0.7%; 95% CI, –7.9 to 6.4).
The all-cause mortality rate was similar between groups at the test-of-cure date and at day 28. The clinically modified intention-to-treat population demonstrated a mortality of 8.1% vs. 6.8% at the test-of-cure date and 8.4% vs. 7.3% at day 28 for ceftazidime-avibactam and meropenem, respectively.
Adverse events were noted in 75% vs. 74% of patients in the ceftazidime-avibactam groups and meropenem groups, respectively. Most adverse events were rated as mild to moderate and deemed likely unrelated to the treatment.
However, serious adverse events occurred in 19% (n = 75) in the ceftazidime-avibactam group and 13% (n = 54) in the meropenem group. Four serious adverse events were thought to be possibly related to the study drug ceftazidime-avibactam and included diarrhea, acute coronary syndrome, subacute hepatic failure, and abnormal liver function test results. The authors noted the adverse events in the trial were consistent and detected no new safety concerns for ceftazidime-avibactam.
Limitations of the study included an inability to establish the optimal duration of treatment for nosocomial pneumonia treated with meropenem or ceftazidime-avibactam.
“Our results show noninferiority for the treatment of nosocomial pneumonia caused by ceftazidime-nonsusceptible or ceftazidime-susceptible gram-negative aerobic pathogens,” the authors concluded.
The study was initially funded by AstraZeneca until the rights to ceftazidime-avibactam were acquired by Pfizer. Multiple authors reported financial relationships with AstraZeneca including grant funding, employment, and shareholding.
SOURCE: Torres A et al. Lancet Infect Dis. 2017. doi: 10.1016/S1473-3099(17)30747-8.
FROM THE LANCET INFECTIOUS DISEASES
Key clinical point: Ceftazidime-avibactam was noninferior to meropenem for nosocomial pneumonia.
Major finding: The clinically modified intention-to-treat group demonstrated clinical cure rates of 69% and 73% in the ceftazidime-avibactam vs. the meropenem group, respectively.
Data source: A phase 3, double-blind, noninferiority trial performed at 136 centers in 23 countries.
Disclosures: The study was initially funded by AstraZeneca until the rights to ceftazidime-avibactam were acquired by Pfizer. Multiple authors reported financial relationships with AstraZeneca including grant funding, employment, and shareholding.
Source: Torres A et al. Lancet Infect Dis. 2017. doi: 10.1016/S1473-3099(17)30747-8.
Drug combo indicated for bacterial pneumonia
(Avycaz) to include hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults.
Specifically, the approved indication is for infections caused by certain Gram-negative bacteria – some of which are increasingly resistant to available antibiotics – including, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae.
There have not been new treatment options for HABP/VABP caused by Gram-negative bacteria in more than 15 years, according to Allergan, the drug’s manufacturer.
This is the third approved indication for ceftazidime/avibactam; the other two indications are for complicated intra-abdominal infections (in combination with metronidazole) and for complicated urinary tract infections.
(Avycaz) to include hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults.
Specifically, the approved indication is for infections caused by certain Gram-negative bacteria – some of which are increasingly resistant to available antibiotics – including, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae.
There have not been new treatment options for HABP/VABP caused by Gram-negative bacteria in more than 15 years, according to Allergan, the drug’s manufacturer.
This is the third approved indication for ceftazidime/avibactam; the other two indications are for complicated intra-abdominal infections (in combination with metronidazole) and for complicated urinary tract infections.
(Avycaz) to include hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults.
Specifically, the approved indication is for infections caused by certain Gram-negative bacteria – some of which are increasingly resistant to available antibiotics – including, Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae.
There have not been new treatment options for HABP/VABP caused by Gram-negative bacteria in more than 15 years, according to Allergan, the drug’s manufacturer.
This is the third approved indication for ceftazidime/avibactam; the other two indications are for complicated intra-abdominal infections (in combination with metronidazole) and for complicated urinary tract infections.