Antimicrobial-resistant infections

SAN DIEGO – Thirty-day mortality associated with Staphylococcus aureus bacteremia is reduced if there is guidance from either an antimicrobial stewardship team (AST) or an infectious disease consultant (IDC), according to a multivariate experience at Yale New Haven Hospital presented at an annual scientific meeting on infectious diseases.

“This has been a hot area, because there have been a lot of recent studies suggesting that expert infectious disease advice improves care, but not every study has associated expert advice with a mortality benefit,” said Jacqueline Sherbuk, MD, a fellow in the division of infectious diseases and international health at the University of Virginia, Charlottesville. She was a resident at Yale University when this study was conducted.

In this study, the impact of an IDC on outcome in patients with S. aureus bacteremia was evaluated relative to no expert advice. By itself, an IDC was associated with improved adherence to standards of care for S. aureus bacteremia management, but the reduction in mortality was not statistically significant for those who received IDC guidance relative to those who did not.

“Given that patient care may be guided by consultations from the AST independent of IDC, we looked at the overall impact of expert opinion versus no expert involvement, and this achieved significance on multivariate analysis,” Dr. Sherbuk reported.

For adherence to guidelines, IDC guidance was better than no expert advice on multiple measures, including proportion obtaining an echocardiogram (89% vs. 67%; P less than .001), appropriate definitive antibiotics (98% vs. 80%; P less than .001), and appropriate treatment duration (92% vs. 35%; P less than .001). However, the advantage for 30-day mortality rates was only a trend (11% vs. 21%, P = .07). It was only when patients who received IDC guidance or a consultation from the AST were combined that the difference climbed to significance (11% vs. 23%; P = .04).

“On multivariate analysis, the OR [odds ratio] was substantial, predicting a 60% reduction [OR 0.40; P = .03) in 30-day mortality for expert advice vs. no expert advice,” Dr. Sherbuk reported.

In this retrospective observational study, 261 unique cases of S. aureus bacteremia cases in adult patients established with positive blood cultures were evaluated. The cases were collected over a 1-year period at Yale New Haven Hospital. After exclusion of those who died within 3 days of the initial positive culture or who were transferred to other facilities, 236 were included in this analysis.

IDC guidance, which is not required for S. aureus bacteremia at Yale New Haven Hospital, was provided for 74.5% of the patients. Another 4% of patients received guidance from the AST, which is an independent service often provided prior to IDC guidance, according to Dr. Sherbuk.

copyright Thomas Northcut/Thinkstock

When those who received expert advice were compared with those who were not, there were no differences in age, sex, clinical diagnosis, or rate of methicillin-resistant S. aureus. While the IDC group had a lower rate of immunosuppressed patients relative to the non–expert advice group, it had a higher proportion of patients with orthopedic prostheses.

Relapse (3% vs. 5%) and reinfection (6% vs. 4%) rates were low in both those who did and did not receive expert advice, respectively. These rates were not significantly different. On multivariate analysis, the two factors associated with increased 30-day mortality were patient age greater than 60 years and sepsis based on sequential organ failure assessment.

Several previous studies have associated IDC advice with improved outcomes in S. aureus bacteremia, according to Dr. Sherbuk, but this study suggests that the AST “can be a meaningful adjunct” to IDC guidance to improve outcomes. She noted that several other sets of data presented at this year’s ID Week also associated AST with improved infection management.

SAN DIEGO – Thirty-day mortality associated with Staphylococcus aureus bacteremia is reduced if there is guidance from either an antimicrobial stewardship team (AST) or an infectious disease consultant (IDC), according to a multivariate experience at Yale New Haven Hospital presented at an annual scientific meeting on infectious diseases.

“This has been a hot area, because there have been a lot of recent studies suggesting that expert infectious disease advice improves care, but not every study has associated expert advice with a mortality benefit,” said Jacqueline Sherbuk, MD, a fellow in the division of infectious diseases and international health at the University of Virginia, Charlottesville. She was a resident at Yale University when this study was conducted.

In this study, the impact of an IDC on outcome in patients with S. aureus bacteremia was evaluated relative to no expert advice. By itself, an IDC was associated with improved adherence to standards of care for S. aureus bacteremia management, but the reduction in mortality was not statistically significant for those who received IDC guidance relative to those who did not.

“Given that patient care may be guided by consultations from the AST independent of IDC, we looked at the overall impact of expert opinion versus no expert involvement, and this achieved significance on multivariate analysis,” Dr. Sherbuk reported.

For adherence to guidelines, IDC guidance was better than no expert advice on multiple measures, including proportion obtaining an echocardiogram (89% vs. 67%; P less than .001), appropriate definitive antibiotics (98% vs. 80%; P less than .001), and appropriate treatment duration (92% vs. 35%; P less than .001). However, the advantage for 30-day mortality rates was only a trend (11% vs. 21%, P = .07). It was only when patients who received IDC guidance or a consultation from the AST were combined that the difference climbed to significance (11% vs. 23%; P = .04).

“On multivariate analysis, the OR [odds ratio] was substantial, predicting a 60% reduction [OR 0.40; P = .03) in 30-day mortality for expert advice vs. no expert advice,” Dr. Sherbuk reported.

In this retrospective observational study, 261 unique cases of S. aureus bacteremia cases in adult patients established with positive blood cultures were evaluated. The cases were collected over a 1-year period at Yale New Haven Hospital. After exclusion of those who died within 3 days of the initial positive culture or who were transferred to other facilities, 236 were included in this analysis.

IDC guidance, which is not required for S. aureus bacteremia at Yale New Haven Hospital, was provided for 74.5% of the patients. Another 4% of patients received guidance from the AST, which is an independent service often provided prior to IDC guidance, according to Dr. Sherbuk.

copyright Thomas Northcut/Thinkstock

When those who received expert advice were compared with those who were not, there were no differences in age, sex, clinical diagnosis, or rate of methicillin-resistant S. aureus. While the IDC group had a lower rate of immunosuppressed patients relative to the non–expert advice group, it had a higher proportion of patients with orthopedic prostheses.

Relapse (3% vs. 5%) and reinfection (6% vs. 4%) rates were low in both those who did and did not receive expert advice, respectively. These rates were not significantly different. On multivariate analysis, the two factors associated with increased 30-day mortality were patient age greater than 60 years and sepsis based on sequential organ failure assessment.

Several previous studies have associated IDC advice with improved outcomes in S. aureus bacteremia, according to Dr. Sherbuk, but this study suggests that the AST “can be a meaningful adjunct” to IDC guidance to improve outcomes. She noted that several other sets of data presented at this year’s ID Week also associated AST with improved infection management.

SAN DIEGO – Thirty-day mortality associated with Staphylococcus aureus bacteremia is reduced if there is guidance from either an antimicrobial stewardship team (AST) or an infectious disease consultant (IDC), according to a multivariate experience at Yale New Haven Hospital presented at an annual scientific meeting on infectious diseases.

“This has been a hot area, because there have been a lot of recent studies suggesting that expert infectious disease advice improves care, but not every study has associated expert advice with a mortality benefit,” said Jacqueline Sherbuk, MD, a fellow in the division of infectious diseases and international health at the University of Virginia, Charlottesville. She was a resident at Yale University when this study was conducted.

In this study, the impact of an IDC on outcome in patients with S. aureus bacteremia was evaluated relative to no expert advice. By itself, an IDC was associated with improved adherence to standards of care for S. aureus bacteremia management, but the reduction in mortality was not statistically significant for those who received IDC guidance relative to those who did not.

“Given that patient care may be guided by consultations from the AST independent of IDC, we looked at the overall impact of expert opinion versus no expert involvement, and this achieved significance on multivariate analysis,” Dr. Sherbuk reported.

For adherence to guidelines, IDC guidance was better than no expert advice on multiple measures, including proportion obtaining an echocardiogram (89% vs. 67%; P less than .001), appropriate definitive antibiotics (98% vs. 80%; P less than .001), and appropriate treatment duration (92% vs. 35%; P less than .001). However, the advantage for 30-day mortality rates was only a trend (11% vs. 21%, P = .07). It was only when patients who received IDC guidance or a consultation from the AST were combined that the difference climbed to significance (11% vs. 23%; P = .04).

“On multivariate analysis, the OR [odds ratio] was substantial, predicting a 60% reduction [OR 0.40; P = .03) in 30-day mortality for expert advice vs. no expert advice,” Dr. Sherbuk reported.

In this retrospective observational study, 261 unique cases of S. aureus bacteremia cases in adult patients established with positive blood cultures were evaluated. The cases were collected over a 1-year period at Yale New Haven Hospital. After exclusion of those who died within 3 days of the initial positive culture or who were transferred to other facilities, 236 were included in this analysis.

IDC guidance, which is not required for S. aureus bacteremia at Yale New Haven Hospital, was provided for 74.5% of the patients. Another 4% of patients received guidance from the AST, which is an independent service often provided prior to IDC guidance, according to Dr. Sherbuk.

copyright Thomas Northcut/Thinkstock

When those who received expert advice were compared with those who were not, there were no differences in age, sex, clinical diagnosis, or rate of methicillin-resistant S. aureus. While the IDC group had a lower rate of immunosuppressed patients relative to the non–expert advice group, it had a higher proportion of patients with orthopedic prostheses.

Relapse (3% vs. 5%) and reinfection (6% vs. 4%) rates were low in both those who did and did not receive expert advice, respectively. These rates were not significantly different. On multivariate analysis, the two factors associated with increased 30-day mortality were patient age greater than 60 years and sepsis based on sequential organ failure assessment.

Several previous studies have associated IDC advice with improved outcomes in S. aureus bacteremia, according to Dr. Sherbuk, but this study suggests that the AST “can be a meaningful adjunct” to IDC guidance to improve outcomes. She noted that several other sets of data presented at this year’s ID Week also associated AST with improved infection management.

SAN DIEGO – Thirty-one percent of multidrug-resistant infections were acquired from the community in a prospective single-center study of a regional hospital.

“Multidrug-resistant organisms have escaped the hospital,” Nicholas A. Turner, MD, of Duke University Medical Center, Durham, N.C., and his associates wrote in a poster presented at an annual scientific meeting on infectious diseases. “Community acquisition of multidrug-resistant organisms [MDROs] is increasing, not just within referral centers but also community hospitals. Providers will need to be increasingly aware of this trend.”

Infections of MDROs cause about 2,000,000 illnesses and 23,000 deaths annually in the United States, according to the Centers for Disease Control and Prevention. Until recently, MDROs were considered a plague of hospitals. Amid reports of increasing levels of community acquisition, the researchers studied adults admitted to a 202-bed regional hospital between 2013 and 2016. They defined MDROs as infections of methicillin-resistant Staphylococcus aureus (MRSA), gram-negative bacteria resistant to more than three antimicrobial classes, vancomycin-resistant Enterococcus (VRE), or diarrhea with a positive stool culture for Clostridium difficile.

A total of 285 patients had MDROs. Clostridium difficile (45%) and MRSA (35%) were most common. In all, 88 (31%) MDROs were community-acquired – that is, diagnosed within 48 hours of admission in patients who were not on dialysis, did not live in a long-term care facility, and had not been hospitalized for more than 48 hours in the past 90 days. A total of 36% of MRSA and multidrug-resistant gram-negative infections were community acquired, as were 25% of Clostridium difficile infections. There were only 10 VRE infections, of which none were community-acquired.

National Institute of Allergy and Infectious Diseases

After the researchers controlled for clinical and demographic variables, the only significant predictor of community-acquired MDRO was cancer (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.02-5.2). Surgery within the previous 12 months was significantly associated with hospital-acquired MDRO (OR, 0.16; 95% CI, 0.05-0.5).

Traditional risk factors for community-acquired MRSA or C. difficile infection did not achieve statistical significance in the multivariable analysis, the researchers noted. “Similar to data from large tertiary care centers, our findings suggest that MDROs are increasingly acquired in the community setting, even at smaller regional hospitals,” they concluded. “Further study is needed to track the expansion of MDROs in the community setting.”

Dr. Turner reported having no conflicts of interest.

SAN DIEGO – Thirty-one percent of multidrug-resistant infections were acquired from the community in a prospective single-center study of a regional hospital.

“Multidrug-resistant organisms have escaped the hospital,” Nicholas A. Turner, MD, of Duke University Medical Center, Durham, N.C., and his associates wrote in a poster presented at an annual scientific meeting on infectious diseases. “Community acquisition of multidrug-resistant organisms [MDROs] is increasing, not just within referral centers but also community hospitals. Providers will need to be increasingly aware of this trend.”

Infections of MDROs cause about 2,000,000 illnesses and 23,000 deaths annually in the United States, according to the Centers for Disease Control and Prevention. Until recently, MDROs were considered a plague of hospitals. Amid reports of increasing levels of community acquisition, the researchers studied adults admitted to a 202-bed regional hospital between 2013 and 2016. They defined MDROs as infections of methicillin-resistant Staphylococcus aureus (MRSA), gram-negative bacteria resistant to more than three antimicrobial classes, vancomycin-resistant Enterococcus (VRE), or diarrhea with a positive stool culture for Clostridium difficile.

A total of 285 patients had MDROs. Clostridium difficile (45%) and MRSA (35%) were most common. In all, 88 (31%) MDROs were community-acquired – that is, diagnosed within 48 hours of admission in patients who were not on dialysis, did not live in a long-term care facility, and had not been hospitalized for more than 48 hours in the past 90 days. A total of 36% of MRSA and multidrug-resistant gram-negative infections were community acquired, as were 25% of Clostridium difficile infections. There were only 10 VRE infections, of which none were community-acquired.

National Institute of Allergy and Infectious Diseases

After the researchers controlled for clinical and demographic variables, the only significant predictor of community-acquired MDRO was cancer (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.02-5.2). Surgery within the previous 12 months was significantly associated with hospital-acquired MDRO (OR, 0.16; 95% CI, 0.05-0.5).

Traditional risk factors for community-acquired MRSA or C. difficile infection did not achieve statistical significance in the multivariable analysis, the researchers noted. “Similar to data from large tertiary care centers, our findings suggest that MDROs are increasingly acquired in the community setting, even at smaller regional hospitals,” they concluded. “Further study is needed to track the expansion of MDROs in the community setting.”

Dr. Turner reported having no conflicts of interest.

SAN DIEGO – Thirty-one percent of multidrug-resistant infections were acquired from the community in a prospective single-center study of a regional hospital.

“Multidrug-resistant organisms have escaped the hospital,” Nicholas A. Turner, MD, of Duke University Medical Center, Durham, N.C., and his associates wrote in a poster presented at an annual scientific meeting on infectious diseases. “Community acquisition of multidrug-resistant organisms [MDROs] is increasing, not just within referral centers but also community hospitals. Providers will need to be increasingly aware of this trend.”

Infections of MDROs cause about 2,000,000 illnesses and 23,000 deaths annually in the United States, according to the Centers for Disease Control and Prevention. Until recently, MDROs were considered a plague of hospitals. Amid reports of increasing levels of community acquisition, the researchers studied adults admitted to a 202-bed regional hospital between 2013 and 2016. They defined MDROs as infections of methicillin-resistant Staphylococcus aureus (MRSA), gram-negative bacteria resistant to more than three antimicrobial classes, vancomycin-resistant Enterococcus (VRE), or diarrhea with a positive stool culture for Clostridium difficile.

A total of 285 patients had MDROs. Clostridium difficile (45%) and MRSA (35%) were most common. In all, 88 (31%) MDROs were community-acquired – that is, diagnosed within 48 hours of admission in patients who were not on dialysis, did not live in a long-term care facility, and had not been hospitalized for more than 48 hours in the past 90 days. A total of 36% of MRSA and multidrug-resistant gram-negative infections were community acquired, as were 25% of Clostridium difficile infections. There were only 10 VRE infections, of which none were community-acquired.

National Institute of Allergy and Infectious Diseases

After the researchers controlled for clinical and demographic variables, the only significant predictor of community-acquired MDRO was cancer (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.02-5.2). Surgery within the previous 12 months was significantly associated with hospital-acquired MDRO (OR, 0.16; 95% CI, 0.05-0.5).

Traditional risk factors for community-acquired MRSA or C. difficile infection did not achieve statistical significance in the multivariable analysis, the researchers noted. “Similar to data from large tertiary care centers, our findings suggest that MDROs are increasingly acquired in the community setting, even at smaller regional hospitals,” they concluded. “Further study is needed to track the expansion of MDROs in the community setting.”

Dr. Turner reported having no conflicts of interest.

SAN DIEGO – Ciprofloxacin cured 100% of gyrase A wild-type Neisseria gonorrhoeae infections, and physicians prescribed it significantly more frequently when they received electronic reminders of test results and recommendations, in a single-center study.

“Recent reports of untreatable gonorrhea have caused great concern. Treatment with ceftriaxone may be a major driver of resistance, and reducing its use may curb the emergence of resistant infections,” Lao-Tzu Allan-Blitz, a medical student at the David Geffen School of Medicine at the University of California, Los Angeles, said at an annual scientific meeting on infectious diseases.

The Centers for Disease Control and Prevention ranks multidrug-resistant N. gonorrhoeae third among all drug-resistant threats in the United States, Mr. Allan-Blitz noted during an oral presentation at the meeting. Beginning in the late 1990s, strains of N. gonorrhoeae developed resistance to sulfanilamides, penicillin, tetracycline, and fluoroquinolones, leaving only the extended-spectrum cephalosporins for empiric treatment. Recent reports of cephalosporin-resistant N. gonorrhoeae in other countries have raised the specter of untreatable gonorrhea.

Because antimicrobial resistance can shift in response to selective pressure, experts are exploring the use of antibiotics once considered ineffective for treating N. gonorrhoeae infections. At UCLA, researchers developed a real-time reverse transcription polymerase chain reaction test for a mutation of codon 91 in the gyrase A (gyrA) gene in N. gonorrhoeae that reliably predicts resistance to ciprofloxacin.

Test results take 24-48 hours. The test is not Food and Drug Administration approved but has been validated in accordance with Clinical Laboratory Improvement Amendments, Mr. Allan-Blitz said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

In November 2015, UCLA Health began gyrA genotyping all N. gonorrhoeae positive specimens, and in May 2016, it began sending providers electronic reminders of genotype results and treatment recommendations. For gyrA wild-type infections, UCLA Health recommends 500 mg oral ciprofloxacin, Mr. Allan-Blitz said.

Centers for Disease Control and Prevention

Genotyping of 582 cases tested between January 2015 and November 2016 showed that 43% were wild-type. Another 27% cases were mutant (resistant) and 30% had an indeterminate genotype. Before UCLA Health implemented its electronic reminder system, physicians treated only 3% of cases with ciprofloxacin. After the reminder system went into effect, this proportion rose to 18% (P = .002).

Initial test-of-cure data are promising. All 25 patients with wild-type infections who received ciprofloxacin and returned 7-90 days later tested negative for N. gonorrhoeae. Culture sites included the urethra (seven cases), pharynx (seven cases), rectum (seven cases), and genitals (four cases), Mr. Allan-Blitz said. “Prior studies have demonstrated that reminder notifications improve uptake of antimicrobial stewardship,” he said. “Other health centers should consider implementing the gyrA assay, and using reminder notifications may improve uptake by providers.”

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

SAN DIEGO – Ciprofloxacin cured 100% of gyrase A wild-type Neisseria gonorrhoeae infections, and physicians prescribed it significantly more frequently when they received electronic reminders of test results and recommendations, in a single-center study.

“Recent reports of untreatable gonorrhea have caused great concern. Treatment with ceftriaxone may be a major driver of resistance, and reducing its use may curb the emergence of resistant infections,” Lao-Tzu Allan-Blitz, a medical student at the David Geffen School of Medicine at the University of California, Los Angeles, said at an annual scientific meeting on infectious diseases.

The Centers for Disease Control and Prevention ranks multidrug-resistant N. gonorrhoeae third among all drug-resistant threats in the United States, Mr. Allan-Blitz noted during an oral presentation at the meeting. Beginning in the late 1990s, strains of N. gonorrhoeae developed resistance to sulfanilamides, penicillin, tetracycline, and fluoroquinolones, leaving only the extended-spectrum cephalosporins for empiric treatment. Recent reports of cephalosporin-resistant N. gonorrhoeae in other countries have raised the specter of untreatable gonorrhea.

Because antimicrobial resistance can shift in response to selective pressure, experts are exploring the use of antibiotics once considered ineffective for treating N. gonorrhoeae infections. At UCLA, researchers developed a real-time reverse transcription polymerase chain reaction test for a mutation of codon 91 in the gyrase A (gyrA) gene in N. gonorrhoeae that reliably predicts resistance to ciprofloxacin.

Test results take 24-48 hours. The test is not Food and Drug Administration approved but has been validated in accordance with Clinical Laboratory Improvement Amendments, Mr. Allan-Blitz said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

In November 2015, UCLA Health began gyrA genotyping all N. gonorrhoeae positive specimens, and in May 2016, it began sending providers electronic reminders of genotype results and treatment recommendations. For gyrA wild-type infections, UCLA Health recommends 500 mg oral ciprofloxacin, Mr. Allan-Blitz said.

Centers for Disease Control and Prevention

Genotyping of 582 cases tested between January 2015 and November 2016 showed that 43% were wild-type. Another 27% cases were mutant (resistant) and 30% had an indeterminate genotype. Before UCLA Health implemented its electronic reminder system, physicians treated only 3% of cases with ciprofloxacin. After the reminder system went into effect, this proportion rose to 18% (P = .002).

Initial test-of-cure data are promising. All 25 patients with wild-type infections who received ciprofloxacin and returned 7-90 days later tested negative for N. gonorrhoeae. Culture sites included the urethra (seven cases), pharynx (seven cases), rectum (seven cases), and genitals (four cases), Mr. Allan-Blitz said. “Prior studies have demonstrated that reminder notifications improve uptake of antimicrobial stewardship,” he said. “Other health centers should consider implementing the gyrA assay, and using reminder notifications may improve uptake by providers.”

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

SAN DIEGO – Ciprofloxacin cured 100% of gyrase A wild-type Neisseria gonorrhoeae infections, and physicians prescribed it significantly more frequently when they received electronic reminders of test results and recommendations, in a single-center study.

“Recent reports of untreatable gonorrhea have caused great concern. Treatment with ceftriaxone may be a major driver of resistance, and reducing its use may curb the emergence of resistant infections,” Lao-Tzu Allan-Blitz, a medical student at the David Geffen School of Medicine at the University of California, Los Angeles, said at an annual scientific meeting on infectious diseases.

The Centers for Disease Control and Prevention ranks multidrug-resistant N. gonorrhoeae third among all drug-resistant threats in the United States, Mr. Allan-Blitz noted during an oral presentation at the meeting. Beginning in the late 1990s, strains of N. gonorrhoeae developed resistance to sulfanilamides, penicillin, tetracycline, and fluoroquinolones, leaving only the extended-spectrum cephalosporins for empiric treatment. Recent reports of cephalosporin-resistant N. gonorrhoeae in other countries have raised the specter of untreatable gonorrhea.

Because antimicrobial resistance can shift in response to selective pressure, experts are exploring the use of antibiotics once considered ineffective for treating N. gonorrhoeae infections. At UCLA, researchers developed a real-time reverse transcription polymerase chain reaction test for a mutation of codon 91 in the gyrase A (gyrA) gene in N. gonorrhoeae that reliably predicts resistance to ciprofloxacin.

Test results take 24-48 hours. The test is not Food and Drug Administration approved but has been validated in accordance with Clinical Laboratory Improvement Amendments, Mr. Allan-Blitz said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

In November 2015, UCLA Health began gyrA genotyping all N. gonorrhoeae positive specimens, and in May 2016, it began sending providers electronic reminders of genotype results and treatment recommendations. For gyrA wild-type infections, UCLA Health recommends 500 mg oral ciprofloxacin, Mr. Allan-Blitz said.

Centers for Disease Control and Prevention

Genotyping of 582 cases tested between January 2015 and November 2016 showed that 43% were wild-type. Another 27% cases were mutant (resistant) and 30% had an indeterminate genotype. Before UCLA Health implemented its electronic reminder system, physicians treated only 3% of cases with ciprofloxacin. After the reminder system went into effect, this proportion rose to 18% (P = .002).

Initial test-of-cure data are promising. All 25 patients with wild-type infections who received ciprofloxacin and returned 7-90 days later tested negative for N. gonorrhoeae. Culture sites included the urethra (seven cases), pharynx (seven cases), rectum (seven cases), and genitals (four cases), Mr. Allan-Blitz said. “Prior studies have demonstrated that reminder notifications improve uptake of antimicrobial stewardship,” he said. “Other health centers should consider implementing the gyrA assay, and using reminder notifications may improve uptake by providers.”

The National Institutes of Health provided funding. The investigators reported having no conflicts of interest.

SAN DIEGO – Among patients with serious infections due to Enterobacteriaceae, delayed appropriate therapy has a stronger association with outcomes, relative to presence of carbapenem-resistant Enterobacteriaceae, according to an analysis of national hospital data.

“We need to reconsider how we approach patients with serious Gram-negative infections,” lead study author Thomas Lodise, PharmD, PhD, said at an annual scientific meeting on infectious diseases. “We kind of take this wait-and-see approach in infectious diseases; we wait a couple of days, then we get aggressive. You would never do this in oncology. I don’t know how many more studies we need to show that early therapy matters. We talk about antibiotic stewardship. One of the fundamental pillars of stewardship is getting it right the first time, and we fail to do this in the majority of patients with serious Gram-negative infections.”

Doug Brunk/Frontline Medical News

At the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society, he noted that delayed appropriate therapy is associated with increased rates of clinical failure and mortality, longer lengths of stay, longer durations of antibiotic treatment, and greater in-hospital costs. “Similarly, patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) have poorer outcomes, such as increased risk of mortality or of being discharged to a long-term care facility, compared with patients with infections caused by carbapenem-susceptible Enterobacteriaceae isolates,” said Dr. Lodise of the Albany (N.Y.) College of Pharmacy and Health Sciences. “Although CRE and delayed appropriate therapy have both been associated with worse outcomes, the impact of each of these factors on clinical and economic outcomes is not well understood.”

In an effort to assess the independent and combined impact of CRE and delayed appropriate therapy on clinical and economic outcomes among hospitalized U.S. patients with serious infections due to Enterobacteriaceae, Dr. Lodise and his associates drew from the Premier Hospital Database, which includes information for about 500 acute-care hospitals in the United States, including the 150 hospitals that provided admission records and microbiological data assessed in the current analysis.

The researchers evaluated adults hospitalized between July 2011 and September 2014. The index date was defined as the earliest culture positive for at least one Gram-negative bacteria of interest, and patients were stratified based on whether the pathogen was CRE or non-CRE. Appropriate therapy was defined as receipt of an antibiotic regimen with microbiological activity against all pathogens identified within the index culture on the index date or within the subsequent 2-day period. All subsequent receipt of such therapy was defined as delayed appropriate therapy.

In all, 50,069 patients with a mean age of 66 years were included in the study. Of these, 514 (1%) harbored infections caused by CRE, and 49,555 (99%) had infections caused by a pathogen other than CRE. Multivariate adjusted analysis revealed significant differences between the CRE group and the non-CRE group in duration of antibiotic therapy (a mean of 8.5 days vs. 7.5 days, respectively); length of stay (a mean of 8.4 days vs. 7.6 days), and in-hospital cost (a mean of $19,816 vs. a mean of $15,165; P less than .01 for all associations). In addition, CRE patients were less likely to be discharged home (odds ratio [OR], .3) and more likely to die in the hospital or be discharged to hospice (OR, 2.2).

When outcomes of patients infections due to Enterobacteriaceae species were stratified by timing of appropriate therapy (timely vs. delayed) and CRE status (CRE vs. non-CRE), without exception the burden of serious infections was least among patients with infections due to non-CRE who received timely appropriate therapy, and greatest among patients with infections due to CRE in whom appropriate therapy was delayed. A gradient effect was observed across strata, and weighted towards timing of receipt of initial therapy. For example, the mean LOS post index culture date rank was lowest among non-CRE patients who received timely appropriate therapy (a mean of 5 days) and greatest among patients infected with CRE who received delayed appropriate therapy (a mean of 8.8 days). Similarly, mean in-hospital costs post index culture date rank was lowest among non-CRE patients who received timely appropriate therapy (a mean of $9,875) and greatest among patients infected with CRE who received delayed appropriate therapy (a mean of $25,506).

“This study demonstrates the importance of early identification of patients at risk for delayed appropriate therapy, through the use of clinical criteria for risk stratification or rapid diagnostic tools,” Dr. Lodise concluded. “The findings also highlight the need to shift current treatment practices away from antibiotic escalation strategies that contribute to delayed appropriate therapy and toward early aggressive, appropriate therapy in patients at risk for CRE infection.”

Allergan funded the study. Dr. Lodise disclosed that he has received consulting fees or honoraria from Allergan. He has also been a consultant for Merck, Achaogen, Zavante, and The Medicines Company.

[email protected]

SAN DIEGO – Among patients with serious infections due to Enterobacteriaceae, delayed appropriate therapy has a stronger association with outcomes, relative to presence of carbapenem-resistant Enterobacteriaceae, according to an analysis of national hospital data.

“We need to reconsider how we approach patients with serious Gram-negative infections,” lead study author Thomas Lodise, PharmD, PhD, said at an annual scientific meeting on infectious diseases. “We kind of take this wait-and-see approach in infectious diseases; we wait a couple of days, then we get aggressive. You would never do this in oncology. I don’t know how many more studies we need to show that early therapy matters. We talk about antibiotic stewardship. One of the fundamental pillars of stewardship is getting it right the first time, and we fail to do this in the majority of patients with serious Gram-negative infections.”

Doug Brunk/Frontline Medical News

At the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society, he noted that delayed appropriate therapy is associated with increased rates of clinical failure and mortality, longer lengths of stay, longer durations of antibiotic treatment, and greater in-hospital costs. “Similarly, patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) have poorer outcomes, such as increased risk of mortality or of being discharged to a long-term care facility, compared with patients with infections caused by carbapenem-susceptible Enterobacteriaceae isolates,” said Dr. Lodise of the Albany (N.Y.) College of Pharmacy and Health Sciences. “Although CRE and delayed appropriate therapy have both been associated with worse outcomes, the impact of each of these factors on clinical and economic outcomes is not well understood.”

In an effort to assess the independent and combined impact of CRE and delayed appropriate therapy on clinical and economic outcomes among hospitalized U.S. patients with serious infections due to Enterobacteriaceae, Dr. Lodise and his associates drew from the Premier Hospital Database, which includes information for about 500 acute-care hospitals in the United States, including the 150 hospitals that provided admission records and microbiological data assessed in the current analysis.

The researchers evaluated adults hospitalized between July 2011 and September 2014. The index date was defined as the earliest culture positive for at least one Gram-negative bacteria of interest, and patients were stratified based on whether the pathogen was CRE or non-CRE. Appropriate therapy was defined as receipt of an antibiotic regimen with microbiological activity against all pathogens identified within the index culture on the index date or within the subsequent 2-day period. All subsequent receipt of such therapy was defined as delayed appropriate therapy.

In all, 50,069 patients with a mean age of 66 years were included in the study. Of these, 514 (1%) harbored infections caused by CRE, and 49,555 (99%) had infections caused by a pathogen other than CRE. Multivariate adjusted analysis revealed significant differences between the CRE group and the non-CRE group in duration of antibiotic therapy (a mean of 8.5 days vs. 7.5 days, respectively); length of stay (a mean of 8.4 days vs. 7.6 days), and in-hospital cost (a mean of $19,816 vs. a mean of $15,165; P less than .01 for all associations). In addition, CRE patients were less likely to be discharged home (odds ratio [OR], .3) and more likely to die in the hospital or be discharged to hospice (OR, 2.2).

When outcomes of patients infections due to Enterobacteriaceae species were stratified by timing of appropriate therapy (timely vs. delayed) and CRE status (CRE vs. non-CRE), without exception the burden of serious infections was least among patients with infections due to non-CRE who received timely appropriate therapy, and greatest among patients with infections due to CRE in whom appropriate therapy was delayed. A gradient effect was observed across strata, and weighted towards timing of receipt of initial therapy. For example, the mean LOS post index culture date rank was lowest among non-CRE patients who received timely appropriate therapy (a mean of 5 days) and greatest among patients infected with CRE who received delayed appropriate therapy (a mean of 8.8 days). Similarly, mean in-hospital costs post index culture date rank was lowest among non-CRE patients who received timely appropriate therapy (a mean of $9,875) and greatest among patients infected with CRE who received delayed appropriate therapy (a mean of $25,506).

“This study demonstrates the importance of early identification of patients at risk for delayed appropriate therapy, through the use of clinical criteria for risk stratification or rapid diagnostic tools,” Dr. Lodise concluded. “The findings also highlight the need to shift current treatment practices away from antibiotic escalation strategies that contribute to delayed appropriate therapy and toward early aggressive, appropriate therapy in patients at risk for CRE infection.”

Allergan funded the study. Dr. Lodise disclosed that he has received consulting fees or honoraria from Allergan. He has also been a consultant for Merck, Achaogen, Zavante, and The Medicines Company.

[email protected]

SAN DIEGO – Among patients with serious infections due to Enterobacteriaceae, delayed appropriate therapy has a stronger association with outcomes, relative to presence of carbapenem-resistant Enterobacteriaceae, according to an analysis of national hospital data.

“We need to reconsider how we approach patients with serious Gram-negative infections,” lead study author Thomas Lodise, PharmD, PhD, said at an annual scientific meeting on infectious diseases. “We kind of take this wait-and-see approach in infectious diseases; we wait a couple of days, then we get aggressive. You would never do this in oncology. I don’t know how many more studies we need to show that early therapy matters. We talk about antibiotic stewardship. One of the fundamental pillars of stewardship is getting it right the first time, and we fail to do this in the majority of patients with serious Gram-negative infections.”

Doug Brunk/Frontline Medical News

At the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society, he noted that delayed appropriate therapy is associated with increased rates of clinical failure and mortality, longer lengths of stay, longer durations of antibiotic treatment, and greater in-hospital costs. “Similarly, patients with infections caused by carbapenem-resistant Enterobacteriaceae (CRE) have poorer outcomes, such as increased risk of mortality or of being discharged to a long-term care facility, compared with patients with infections caused by carbapenem-susceptible Enterobacteriaceae isolates,” said Dr. Lodise of the Albany (N.Y.) College of Pharmacy and Health Sciences. “Although CRE and delayed appropriate therapy have both been associated with worse outcomes, the impact of each of these factors on clinical and economic outcomes is not well understood.”

In an effort to assess the independent and combined impact of CRE and delayed appropriate therapy on clinical and economic outcomes among hospitalized U.S. patients with serious infections due to Enterobacteriaceae, Dr. Lodise and his associates drew from the Premier Hospital Database, which includes information for about 500 acute-care hospitals in the United States, including the 150 hospitals that provided admission records and microbiological data assessed in the current analysis.

The researchers evaluated adults hospitalized between July 2011 and September 2014. The index date was defined as the earliest culture positive for at least one Gram-negative bacteria of interest, and patients were stratified based on whether the pathogen was CRE or non-CRE. Appropriate therapy was defined as receipt of an antibiotic regimen with microbiological activity against all pathogens identified within the index culture on the index date or within the subsequent 2-day period. All subsequent receipt of such therapy was defined as delayed appropriate therapy.

In all, 50,069 patients with a mean age of 66 years were included in the study. Of these, 514 (1%) harbored infections caused by CRE, and 49,555 (99%) had infections caused by a pathogen other than CRE. Multivariate adjusted analysis revealed significant differences between the CRE group and the non-CRE group in duration of antibiotic therapy (a mean of 8.5 days vs. 7.5 days, respectively); length of stay (a mean of 8.4 days vs. 7.6 days), and in-hospital cost (a mean of $19,816 vs. a mean of $15,165; P less than .01 for all associations). In addition, CRE patients were less likely to be discharged home (odds ratio [OR], .3) and more likely to die in the hospital or be discharged to hospice (OR, 2.2).

When outcomes of patients infections due to Enterobacteriaceae species were stratified by timing of appropriate therapy (timely vs. delayed) and CRE status (CRE vs. non-CRE), without exception the burden of serious infections was least among patients with infections due to non-CRE who received timely appropriate therapy, and greatest among patients with infections due to CRE in whom appropriate therapy was delayed. A gradient effect was observed across strata, and weighted towards timing of receipt of initial therapy. For example, the mean LOS post index culture date rank was lowest among non-CRE patients who received timely appropriate therapy (a mean of 5 days) and greatest among patients infected with CRE who received delayed appropriate therapy (a mean of 8.8 days). Similarly, mean in-hospital costs post index culture date rank was lowest among non-CRE patients who received timely appropriate therapy (a mean of $9,875) and greatest among patients infected with CRE who received delayed appropriate therapy (a mean of $25,506).

“This study demonstrates the importance of early identification of patients at risk for delayed appropriate therapy, through the use of clinical criteria for risk stratification or rapid diagnostic tools,” Dr. Lodise concluded. “The findings also highlight the need to shift current treatment practices away from antibiotic escalation strategies that contribute to delayed appropriate therapy and toward early aggressive, appropriate therapy in patients at risk for CRE infection.”

Allergan funded the study. Dr. Lodise disclosed that he has received consulting fees or honoraria from Allergan. He has also been a consultant for Merck, Achaogen, Zavante, and The Medicines Company.

[email protected]

SAN DIEGO – Only 0.2% of intensive care unit patients developed MRSA infections after testing negative on nasal surveillance swabs, said Darunee Chotiprasitsakul, MD, of Johns Hopkins Medicine in Baltimore.

But physicians often prescribed vancomycin anyway, accumulating nearly 7,400 potentially avoidable treatment days over a 19-month period, she said during an oral presentation at an annual meeting on infectious diseases.

Current guidelines recommend empiric vancomycin to cover MRSA infection when ill patients have a history of MRSA colonization or recent hospitalization or exposure to antibiotics. Patients whose nasal screening swabs are negative for MRSA have been shown to be at low risk of subsequent infection, but guidelines don’t address how to use swab results to guide decisions about empiric vancomycin, Dr. Chotiprasitsakul said.

Therefore, she and her associates studied 11,882 adults without historical MRSA infection or colonization who received nasal swabs for routine surveillance in adult ICUs at Johns Hopkins. A total of 441 patients (4%) had positive swabs, while 96% tested negative.

Among patients with negative swabs, only 25 (0.22%) developed MRSA infection requiring treatment. Thus, the negative predictive value of a nasal swab for MRSA was 99%, making the probability of infection despite a negative swab “exceedingly low,” Dr. Chotiprasitsakul said.

But clinicians seemed not to use negative swab results to curtail vancomycin therapy, she found. Rates of empiric vancomycin use were 36% among patients with positive swabs and 39% among those with negative swabs. Over 19 months, ICU patients received 7,371 avoidable days of vancomycin, a median of 3 days per patient.

Matching patients by ICU and days at risk identified no significant predictors of MRSA infection, Dr. Chotiprasitsakul said. Johns Hopkins Medicine has robust infection control practices, high compliance with hand hygiene and contact precautions, and low rates of nosocomial MRSA transmission, she noted. The predictive value of a negative MRSA nasal swab could be lower at institutions where that isn’t the case, she said.

Johns Hopkins is working to curtail unnecessary use of vancomycin, said senior author Sara Cosgrove, MD, professor of medicine in infectious diseases and director of the department of antimicrobial stewardship. The team has added the findings to its guidelines for antibiotic use, which are available in an app for Johns Hopkins providers, she said in an interview.

The stewardship also highlights the data when discussing starting and stopping vancomycin in patients at very low risk for MRSA infections, she said. “In general, providers have responded favorably to acting upon this new information,” Dr. Cosgrove noted.

Johns Hopkins continues to track median days of vancomycin use per patient and per 1,000 days in its units. “[We] will assess if there is an impact on vancomycin use over the coming year,” said Dr. Cosgrove.

The investigators had no conflicts of interest. The event marked the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

[email protected]

SAN DIEGO – Only 0.2% of intensive care unit patients developed MRSA infections after testing negative on nasal surveillance swabs, said Darunee Chotiprasitsakul, MD, of Johns Hopkins Medicine in Baltimore.

But physicians often prescribed vancomycin anyway, accumulating nearly 7,400 potentially avoidable treatment days over a 19-month period, she said during an oral presentation at an annual meeting on infectious diseases.

Current guidelines recommend empiric vancomycin to cover MRSA infection when ill patients have a history of MRSA colonization or recent hospitalization or exposure to antibiotics. Patients whose nasal screening swabs are negative for MRSA have been shown to be at low risk of subsequent infection, but guidelines don’t address how to use swab results to guide decisions about empiric vancomycin, Dr. Chotiprasitsakul said.

Therefore, she and her associates studied 11,882 adults without historical MRSA infection or colonization who received nasal swabs for routine surveillance in adult ICUs at Johns Hopkins. A total of 441 patients (4%) had positive swabs, while 96% tested negative.

Among patients with negative swabs, only 25 (0.22%) developed MRSA infection requiring treatment. Thus, the negative predictive value of a nasal swab for MRSA was 99%, making the probability of infection despite a negative swab “exceedingly low,” Dr. Chotiprasitsakul said.

But clinicians seemed not to use negative swab results to curtail vancomycin therapy, she found. Rates of empiric vancomycin use were 36% among patients with positive swabs and 39% among those with negative swabs. Over 19 months, ICU patients received 7,371 avoidable days of vancomycin, a median of 3 days per patient.

Matching patients by ICU and days at risk identified no significant predictors of MRSA infection, Dr. Chotiprasitsakul said. Johns Hopkins Medicine has robust infection control practices, high compliance with hand hygiene and contact precautions, and low rates of nosocomial MRSA transmission, she noted. The predictive value of a negative MRSA nasal swab could be lower at institutions where that isn’t the case, she said.

Johns Hopkins is working to curtail unnecessary use of vancomycin, said senior author Sara Cosgrove, MD, professor of medicine in infectious diseases and director of the department of antimicrobial stewardship. The team has added the findings to its guidelines for antibiotic use, which are available in an app for Johns Hopkins providers, she said in an interview.

The stewardship also highlights the data when discussing starting and stopping vancomycin in patients at very low risk for MRSA infections, she said. “In general, providers have responded favorably to acting upon this new information,” Dr. Cosgrove noted.

Johns Hopkins continues to track median days of vancomycin use per patient and per 1,000 days in its units. “[We] will assess if there is an impact on vancomycin use over the coming year,” said Dr. Cosgrove.

The investigators had no conflicts of interest. The event marked the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

[email protected]

SAN DIEGO – Only 0.2% of intensive care unit patients developed MRSA infections after testing negative on nasal surveillance swabs, said Darunee Chotiprasitsakul, MD, of Johns Hopkins Medicine in Baltimore.

But physicians often prescribed vancomycin anyway, accumulating nearly 7,400 potentially avoidable treatment days over a 19-month period, she said during an oral presentation at an annual meeting on infectious diseases.

Current guidelines recommend empiric vancomycin to cover MRSA infection when ill patients have a history of MRSA colonization or recent hospitalization or exposure to antibiotics. Patients whose nasal screening swabs are negative for MRSA have been shown to be at low risk of subsequent infection, but guidelines don’t address how to use swab results to guide decisions about empiric vancomycin, Dr. Chotiprasitsakul said.

Therefore, she and her associates studied 11,882 adults without historical MRSA infection or colonization who received nasal swabs for routine surveillance in adult ICUs at Johns Hopkins. A total of 441 patients (4%) had positive swabs, while 96% tested negative.

Among patients with negative swabs, only 25 (0.22%) developed MRSA infection requiring treatment. Thus, the negative predictive value of a nasal swab for MRSA was 99%, making the probability of infection despite a negative swab “exceedingly low,” Dr. Chotiprasitsakul said.

But clinicians seemed not to use negative swab results to curtail vancomycin therapy, she found. Rates of empiric vancomycin use were 36% among patients with positive swabs and 39% among those with negative swabs. Over 19 months, ICU patients received 7,371 avoidable days of vancomycin, a median of 3 days per patient.

Matching patients by ICU and days at risk identified no significant predictors of MRSA infection, Dr. Chotiprasitsakul said. Johns Hopkins Medicine has robust infection control practices, high compliance with hand hygiene and contact precautions, and low rates of nosocomial MRSA transmission, she noted. The predictive value of a negative MRSA nasal swab could be lower at institutions where that isn’t the case, she said.

Johns Hopkins is working to curtail unnecessary use of vancomycin, said senior author Sara Cosgrove, MD, professor of medicine in infectious diseases and director of the department of antimicrobial stewardship. The team has added the findings to its guidelines for antibiotic use, which are available in an app for Johns Hopkins providers, she said in an interview.

The stewardship also highlights the data when discussing starting and stopping vancomycin in patients at very low risk for MRSA infections, she said. “In general, providers have responded favorably to acting upon this new information,” Dr. Cosgrove noted.

Johns Hopkins continues to track median days of vancomycin use per patient and per 1,000 days in its units. “[We] will assess if there is an impact on vancomycin use over the coming year,” said Dr. Cosgrove.

The investigators had no conflicts of interest. The event marked the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

[email protected]

SAN DIEGO – Patients colonized with MRSA are at high risk of MRSA infection both in the predischarge and postdischarge time periods, results from an 8-year Veterans Affairs study showed.

“MRSA colonization is recognized as being a strong predictor of subsequent infection,” Richard E. Nelson, PhD, said at an annual scientific meeting on infectious diseases. “What’s less understood is, are there differences in infection rates among patients who are colonized at different times? And, is there a difference between patients who import colonization with them to a hospital versus those who acquire it during a hospital stay? In addition, infection control efforts mainly focus on the predischarge time period. What about infections that develop post discharge?”

In an effort to investigate these questions, Dr. Nelson of the VA Salt Lake City Healthcare System, and his associates, evaluated more than 1.3 million acute care inpatient admissions to 125 VA hospitals nationwide from January 2008 through December 2015 who had surveillance tests performed for MRSA carriage.

copyright Pixland/Thinkstock

The researchers restricted admissions to individuals with at least 365 days of VA activity prior to admission and categorized them into three groups: no colonization (defined as those who had no positive surveillance tests (n = 1,196,928); importation (defined as those who tested positive for MRSA colonization on admission (n = 95,833); and acquisition (defined as those who did not test positive for MRSA on admission but tested positive on a subsequent surveillance test during their admission (n = 15,146). Next, they captured MRSA infections in these individuals prior to discharge and at 30 and 90 days post discharge. Infections were defined as positive MRSA cultures taken from sterile sites, including blood, catheter site, or bone.

Overall, patients were in their mid-60s, and those who imported MRSA and those who acquired it were more likely to be male, less likely to be married, and more likely to not have health insurance. “The acquirers had by far the highest rates of predischarge infections, which peaked in 2010 and declined through 2015,” said Dr. Nelson, who also holds a faculty position in University of Utah’s department of internal medicine, in the division of epidemiology. Specifically, the proportion of predischarge MRSA infections, compared with 30 days post discharge, were 40.4% vs. 59.6%, respectively, in the no colonization group; 63% vs. 37% in the importation group, and 80.8% vs. 19.2% in the acquisition group.

He also reported that the proportion of predischarge MRSA infections, compared with 90 days post discharge, were 20.5% vs. 79.5%, respectively, in the no colonization group; 47.3% vs. 52.7% in the importation group, and 70.5% vs. 29.5% in the acquisition group. The time from acquisition to infection was a mean of 8.7 days in the 30-day analysis and a mean of 22.4 days in the 90-day analysis.

Multivariate logistic regression revealed that the impact of colonization status on infection was highest in the acquisition group, compared with the importation group. Specifically, the odds ratio of developing a MRSA infection among the importation group was 29.22 in the predischarge period, OR 10.87 at post discharge 30 days, and OR 7.64 at post discharge 90 days (P less than .001 for all). Meanwhile, the OR among the acquisition group was 85.19 in the predischarge period, OR 13.01 at post discharge 30 days, and OR 8.26 at post discharge 90 days (P less than .001 for all).

Dr. Nelson acknowledged certain limitations of the study, including the fact that it only identified postdischarge infections that were detected in a VA facility. “This is likely an underestimate of postdischarge infections, because we’re missing the infection that occur in non-VA facilities,” he said at the event, which marked the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. “Also, patients can be colonized in many different body locations, but the VA protocol is that the surveillance test be done in the nostrils. So we may have misclassified patients who were colonized in a different body location as being uncolonized, when in fact they were colonized.”

The study was funded by a grant from the VA. Dr. Nelson reported having no financial disclosures.

[email protected]

SAN DIEGO – Patients colonized with MRSA are at high risk of MRSA infection both in the predischarge and postdischarge time periods, results from an 8-year Veterans Affairs study showed.

“MRSA colonization is recognized as being a strong predictor of subsequent infection,” Richard E. Nelson, PhD, said at an annual scientific meeting on infectious diseases. “What’s less understood is, are there differences in infection rates among patients who are colonized at different times? And, is there a difference between patients who import colonization with them to a hospital versus those who acquire it during a hospital stay? In addition, infection control efforts mainly focus on the predischarge time period. What about infections that develop post discharge?”

In an effort to investigate these questions, Dr. Nelson of the VA Salt Lake City Healthcare System, and his associates, evaluated more than 1.3 million acute care inpatient admissions to 125 VA hospitals nationwide from January 2008 through December 2015 who had surveillance tests performed for MRSA carriage.

copyright Pixland/Thinkstock

The researchers restricted admissions to individuals with at least 365 days of VA activity prior to admission and categorized them into three groups: no colonization (defined as those who had no positive surveillance tests (n = 1,196,928); importation (defined as those who tested positive for MRSA colonization on admission (n = 95,833); and acquisition (defined as those who did not test positive for MRSA on admission but tested positive on a subsequent surveillance test during their admission (n = 15,146). Next, they captured MRSA infections in these individuals prior to discharge and at 30 and 90 days post discharge. Infections were defined as positive MRSA cultures taken from sterile sites, including blood, catheter site, or bone.

Overall, patients were in their mid-60s, and those who imported MRSA and those who acquired it were more likely to be male, less likely to be married, and more likely to not have health insurance. “The acquirers had by far the highest rates of predischarge infections, which peaked in 2010 and declined through 2015,” said Dr. Nelson, who also holds a faculty position in University of Utah’s department of internal medicine, in the division of epidemiology. Specifically, the proportion of predischarge MRSA infections, compared with 30 days post discharge, were 40.4% vs. 59.6%, respectively, in the no colonization group; 63% vs. 37% in the importation group, and 80.8% vs. 19.2% in the acquisition group.

He also reported that the proportion of predischarge MRSA infections, compared with 90 days post discharge, were 20.5% vs. 79.5%, respectively, in the no colonization group; 47.3% vs. 52.7% in the importation group, and 70.5% vs. 29.5% in the acquisition group. The time from acquisition to infection was a mean of 8.7 days in the 30-day analysis and a mean of 22.4 days in the 90-day analysis.

Multivariate logistic regression revealed that the impact of colonization status on infection was highest in the acquisition group, compared with the importation group. Specifically, the odds ratio of developing a MRSA infection among the importation group was 29.22 in the predischarge period, OR 10.87 at post discharge 30 days, and OR 7.64 at post discharge 90 days (P less than .001 for all). Meanwhile, the OR among the acquisition group was 85.19 in the predischarge period, OR 13.01 at post discharge 30 days, and OR 8.26 at post discharge 90 days (P less than .001 for all).

Dr. Nelson acknowledged certain limitations of the study, including the fact that it only identified postdischarge infections that were detected in a VA facility. “This is likely an underestimate of postdischarge infections, because we’re missing the infection that occur in non-VA facilities,” he said at the event, which marked the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. “Also, patients can be colonized in many different body locations, but the VA protocol is that the surveillance test be done in the nostrils. So we may have misclassified patients who were colonized in a different body location as being uncolonized, when in fact they were colonized.”

The study was funded by a grant from the VA. Dr. Nelson reported having no financial disclosures.

[email protected]

SAN DIEGO – Patients colonized with MRSA are at high risk of MRSA infection both in the predischarge and postdischarge time periods, results from an 8-year Veterans Affairs study showed.

“MRSA colonization is recognized as being a strong predictor of subsequent infection,” Richard E. Nelson, PhD, said at an annual scientific meeting on infectious diseases. “What’s less understood is, are there differences in infection rates among patients who are colonized at different times? And, is there a difference between patients who import colonization with them to a hospital versus those who acquire it during a hospital stay? In addition, infection control efforts mainly focus on the predischarge time period. What about infections that develop post discharge?”

In an effort to investigate these questions, Dr. Nelson of the VA Salt Lake City Healthcare System, and his associates, evaluated more than 1.3 million acute care inpatient admissions to 125 VA hospitals nationwide from January 2008 through December 2015 who had surveillance tests performed for MRSA carriage.

copyright Pixland/Thinkstock

The researchers restricted admissions to individuals with at least 365 days of VA activity prior to admission and categorized them into three groups: no colonization (defined as those who had no positive surveillance tests (n = 1,196,928); importation (defined as those who tested positive for MRSA colonization on admission (n = 95,833); and acquisition (defined as those who did not test positive for MRSA on admission but tested positive on a subsequent surveillance test during their admission (n = 15,146). Next, they captured MRSA infections in these individuals prior to discharge and at 30 and 90 days post discharge. Infections were defined as positive MRSA cultures taken from sterile sites, including blood, catheter site, or bone.

Overall, patients were in their mid-60s, and those who imported MRSA and those who acquired it were more likely to be male, less likely to be married, and more likely to not have health insurance. “The acquirers had by far the highest rates of predischarge infections, which peaked in 2010 and declined through 2015,” said Dr. Nelson, who also holds a faculty position in University of Utah’s department of internal medicine, in the division of epidemiology. Specifically, the proportion of predischarge MRSA infections, compared with 30 days post discharge, were 40.4% vs. 59.6%, respectively, in the no colonization group; 63% vs. 37% in the importation group, and 80.8% vs. 19.2% in the acquisition group.

He also reported that the proportion of predischarge MRSA infections, compared with 90 days post discharge, were 20.5% vs. 79.5%, respectively, in the no colonization group; 47.3% vs. 52.7% in the importation group, and 70.5% vs. 29.5% in the acquisition group. The time from acquisition to infection was a mean of 8.7 days in the 30-day analysis and a mean of 22.4 days in the 90-day analysis.

Multivariate logistic regression revealed that the impact of colonization status on infection was highest in the acquisition group, compared with the importation group. Specifically, the odds ratio of developing a MRSA infection among the importation group was 29.22 in the predischarge period, OR 10.87 at post discharge 30 days, and OR 7.64 at post discharge 90 days (P less than .001 for all). Meanwhile, the OR among the acquisition group was 85.19 in the predischarge period, OR 13.01 at post discharge 30 days, and OR 8.26 at post discharge 90 days (P less than .001 for all).

Dr. Nelson acknowledged certain limitations of the study, including the fact that it only identified postdischarge infections that were detected in a VA facility. “This is likely an underestimate of postdischarge infections, because we’re missing the infection that occur in non-VA facilities,” he said at the event, which marked the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. “Also, patients can be colonized in many different body locations, but the VA protocol is that the surveillance test be done in the nostrils. So we may have misclassified patients who were colonized in a different body location as being uncolonized, when in fact they were colonized.”

The study was funded by a grant from the VA. Dr. Nelson reported having no financial disclosures.

[email protected]

SAN DIEGO – Hospitalized patients who received the investigational oral agent ribaxamase had a 71% reduction in the development of new Clostridium difficile infection, results from a phase 2b study showed.

At an annual scientific meeting on infectious diseases, lead investigator John F. Kokai-Kun, PhD, said that the finding represents a paradigm shift in the use of intravenous beta-lactam antibiotics to prevent opportunistic infections. “We currently treat Clostridium difficile infection (CDI) with antibiotics, which attack the vegetative cells,” said Dr. Kokai-Kun, vice president of nonclinical affairs for Rockville, Md.–based Synthetic Biologics, which is developing ribaxamase. “Since C. diff. is primarily a toxin-mediated disease, certain products seem to neutralize the toxin. There’s also been work with probiotics and prebiotics to try to strengthen and repair the dysbiotic colon. Fecal replacement therapy has been shown to be fairly effective for treatment of recurrent C. diff. infection. What if we could simply block the initial insult that leads to this cascade? That’s the damage caused to the gut microbiome by the antibiotic that’s excreted to the intestine.”

Doug Brunk/Frontline Medical News

That’s where ribaxamase comes in, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. Ribaxamase is an orally administered beta-lactamase designed to degrade penicillin and cephalosporins in the intestinal lumen. It’s formulated for release in the proximal small intestine and is expected to be given during or a short time after administration of IV beta-lactam antibiotics such as ceftriaxone. “This is expected to degrade the excess antibiotics that are excreted into the small intestine via the bile,” Dr. Kokai-Kun explained. “It’s designed to prevent disruption of the gut microbiome and thus protect from opportunistic GI infections like CDI.” Early-stage clinical studies demonstrated that ribaxamase was well tolerated and that it is not systemically absorbed, while phase 2 studies showed that ribaxamase degrades ceftriaxone in the intestine to below the level of detection while not affecting the pharmacokinetics of ceftriaxone in the plasma.
 

For the current study, 412 patients were enrolled at 84 multinational clinical sites. These patients were admitted to the hospital for treatment of a lower respiratory tract infection and were randomized 1:1 to receive ceftriaxone plus 150 mg ribaxamase or ceftriaxone plus placebo. Patients in both groups could also receive an oral macrolide at the discretion of the clinical investigator. The researchers also obtained fecal samples at screening, 72 hours post antibiotic treatment, and at the end of a 4-week follow-up visit, to determine colonization by opportunistic pathogens and to examine changes in the gut microbiome. Patients were monitored for 6 weeks for diarrhea and CDI. Diarrhea was defined as three or more loose or watery stools in a 24-hour period. “If that occurred, then we collected a sample, which was sent to the local lab to determine the presence of C. difficile toxins,” Dr. Kokai-Kun said.

The average age of study participants was 70 years, and about one-third in each arm received oral macrolides. The number of adverse events and serious adverse events were similar between active and placebo arms, and there was no trend associated with ribaxamase use. The lower respiratory tract infection cure rate to the ceftriaxone treatment was about 99% in both arms at 72 hours post treatment and at 2 weeks post treatment.

To analyze changes in the gut microbiome, the researchers conducted 16S rRNA sequencing of DNA extracted from fecal samples. In all, 652 samples were sequenced from 229 patients. Results from that analysis suggests that ribaxamase “appears to protect the gut microbiome from the onslaught of the ceftriaxone,” he said.

Ribaxamase reduced the incidence of new-onset CDI by 71%, compared with placebo (P = .045). “It apparently did this by protecting the integrity of the gut microbiome,” Dr. Kokai-Kun said. “There was also a significant reduction of new colonization by vancomycin-resistant enterococci at 72 hours and 4 weeks (P = .0001 and P = .0002, respectively) which is an opportunistic pathogen that is known to be able to inhabit gut microbiome when there is dysbiosis.”

The study was sponsored by Synthetic Biologics. Dr. Kokai-Kun is an employee of the company.

[email protected]

SAN DIEGO – Hospitalized patients who received the investigational oral agent ribaxamase had a 71% reduction in the development of new Clostridium difficile infection, results from a phase 2b study showed.

At an annual scientific meeting on infectious diseases, lead investigator John F. Kokai-Kun, PhD, said that the finding represents a paradigm shift in the use of intravenous beta-lactam antibiotics to prevent opportunistic infections. “We currently treat Clostridium difficile infection (CDI) with antibiotics, which attack the vegetative cells,” said Dr. Kokai-Kun, vice president of nonclinical affairs for Rockville, Md.–based Synthetic Biologics, which is developing ribaxamase. “Since C. diff. is primarily a toxin-mediated disease, certain products seem to neutralize the toxin. There’s also been work with probiotics and prebiotics to try to strengthen and repair the dysbiotic colon. Fecal replacement therapy has been shown to be fairly effective for treatment of recurrent C. diff. infection. What if we could simply block the initial insult that leads to this cascade? That’s the damage caused to the gut microbiome by the antibiotic that’s excreted to the intestine.”

Doug Brunk/Frontline Medical News

That’s where ribaxamase comes in, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. Ribaxamase is an orally administered beta-lactamase designed to degrade penicillin and cephalosporins in the intestinal lumen. It’s formulated for release in the proximal small intestine and is expected to be given during or a short time after administration of IV beta-lactam antibiotics such as ceftriaxone. “This is expected to degrade the excess antibiotics that are excreted into the small intestine via the bile,” Dr. Kokai-Kun explained. “It’s designed to prevent disruption of the gut microbiome and thus protect from opportunistic GI infections like CDI.” Early-stage clinical studies demonstrated that ribaxamase was well tolerated and that it is not systemically absorbed, while phase 2 studies showed that ribaxamase degrades ceftriaxone in the intestine to below the level of detection while not affecting the pharmacokinetics of ceftriaxone in the plasma.
 

For the current study, 412 patients were enrolled at 84 multinational clinical sites. These patients were admitted to the hospital for treatment of a lower respiratory tract infection and were randomized 1:1 to receive ceftriaxone plus 150 mg ribaxamase or ceftriaxone plus placebo. Patients in both groups could also receive an oral macrolide at the discretion of the clinical investigator. The researchers also obtained fecal samples at screening, 72 hours post antibiotic treatment, and at the end of a 4-week follow-up visit, to determine colonization by opportunistic pathogens and to examine changes in the gut microbiome. Patients were monitored for 6 weeks for diarrhea and CDI. Diarrhea was defined as three or more loose or watery stools in a 24-hour period. “If that occurred, then we collected a sample, which was sent to the local lab to determine the presence of C. difficile toxins,” Dr. Kokai-Kun said.

The average age of study participants was 70 years, and about one-third in each arm received oral macrolides. The number of adverse events and serious adverse events were similar between active and placebo arms, and there was no trend associated with ribaxamase use. The lower respiratory tract infection cure rate to the ceftriaxone treatment was about 99% in both arms at 72 hours post treatment and at 2 weeks post treatment.

To analyze changes in the gut microbiome, the researchers conducted 16S rRNA sequencing of DNA extracted from fecal samples. In all, 652 samples were sequenced from 229 patients. Results from that analysis suggests that ribaxamase “appears to protect the gut microbiome from the onslaught of the ceftriaxone,” he said.

Ribaxamase reduced the incidence of new-onset CDI by 71%, compared with placebo (P = .045). “It apparently did this by protecting the integrity of the gut microbiome,” Dr. Kokai-Kun said. “There was also a significant reduction of new colonization by vancomycin-resistant enterococci at 72 hours and 4 weeks (P = .0001 and P = .0002, respectively) which is an opportunistic pathogen that is known to be able to inhabit gut microbiome when there is dysbiosis.”

The study was sponsored by Synthetic Biologics. Dr. Kokai-Kun is an employee of the company.

[email protected]

SAN DIEGO – Hospitalized patients who received the investigational oral agent ribaxamase had a 71% reduction in the development of new Clostridium difficile infection, results from a phase 2b study showed.

At an annual scientific meeting on infectious diseases, lead investigator John F. Kokai-Kun, PhD, said that the finding represents a paradigm shift in the use of intravenous beta-lactam antibiotics to prevent opportunistic infections. “We currently treat Clostridium difficile infection (CDI) with antibiotics, which attack the vegetative cells,” said Dr. Kokai-Kun, vice president of nonclinical affairs for Rockville, Md.–based Synthetic Biologics, which is developing ribaxamase. “Since C. diff. is primarily a toxin-mediated disease, certain products seem to neutralize the toxin. There’s also been work with probiotics and prebiotics to try to strengthen and repair the dysbiotic colon. Fecal replacement therapy has been shown to be fairly effective for treatment of recurrent C. diff. infection. What if we could simply block the initial insult that leads to this cascade? That’s the damage caused to the gut microbiome by the antibiotic that’s excreted to the intestine.”

Doug Brunk/Frontline Medical News

That’s where ribaxamase comes in, he said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society. Ribaxamase is an orally administered beta-lactamase designed to degrade penicillin and cephalosporins in the intestinal lumen. It’s formulated for release in the proximal small intestine and is expected to be given during or a short time after administration of IV beta-lactam antibiotics such as ceftriaxone. “This is expected to degrade the excess antibiotics that are excreted into the small intestine via the bile,” Dr. Kokai-Kun explained. “It’s designed to prevent disruption of the gut microbiome and thus protect from opportunistic GI infections like CDI.” Early-stage clinical studies demonstrated that ribaxamase was well tolerated and that it is not systemically absorbed, while phase 2 studies showed that ribaxamase degrades ceftriaxone in the intestine to below the level of detection while not affecting the pharmacokinetics of ceftriaxone in the plasma.
 

For the current study, 412 patients were enrolled at 84 multinational clinical sites. These patients were admitted to the hospital for treatment of a lower respiratory tract infection and were randomized 1:1 to receive ceftriaxone plus 150 mg ribaxamase or ceftriaxone plus placebo. Patients in both groups could also receive an oral macrolide at the discretion of the clinical investigator. The researchers also obtained fecal samples at screening, 72 hours post antibiotic treatment, and at the end of a 4-week follow-up visit, to determine colonization by opportunistic pathogens and to examine changes in the gut microbiome. Patients were monitored for 6 weeks for diarrhea and CDI. Diarrhea was defined as three or more loose or watery stools in a 24-hour period. “If that occurred, then we collected a sample, which was sent to the local lab to determine the presence of C. difficile toxins,” Dr. Kokai-Kun said.

The average age of study participants was 70 years, and about one-third in each arm received oral macrolides. The number of adverse events and serious adverse events were similar between active and placebo arms, and there was no trend associated with ribaxamase use. The lower respiratory tract infection cure rate to the ceftriaxone treatment was about 99% in both arms at 72 hours post treatment and at 2 weeks post treatment.

To analyze changes in the gut microbiome, the researchers conducted 16S rRNA sequencing of DNA extracted from fecal samples. In all, 652 samples were sequenced from 229 patients. Results from that analysis suggests that ribaxamase “appears to protect the gut microbiome from the onslaught of the ceftriaxone,” he said.

Ribaxamase reduced the incidence of new-onset CDI by 71%, compared with placebo (P = .045). “It apparently did this by protecting the integrity of the gut microbiome,” Dr. Kokai-Kun said. “There was also a significant reduction of new colonization by vancomycin-resistant enterococci at 72 hours and 4 weeks (P = .0001 and P = .0002, respectively) which is an opportunistic pathogen that is known to be able to inhabit gut microbiome when there is dysbiosis.”

The study was sponsored by Synthetic Biologics. Dr. Kokai-Kun is an employee of the company.

[email protected]

 

SAN DIEGO – After other strategies to reduce inappropriate testing for Clostridium difficile infection did not provide adequate reductions in inappropriate orders, a “hard stop” protocol, which prevents testing if specific conditions are not met, reduced the rate of testing by 42% without any incidence of delayed diagnosis, according to data presented at ID Week 2017.

“Testing stewardship is really critical to minimize the frequency of false-positive [Clostridium difficile infection] cases, which of course lead to harm. They lead to inappropriate treatment, prolonged length of stay, and patient dissatisfaction,” reported Marci L. Drees, MD, Infection Prevention Officer and Hospital Epidemiologist, Christiana Care Health System, Newark, Del.

Ted Bowsworth/Frontline Medical News

The move to a hard stop protocol occurred after several events. The first of these was a switch to an all-Polymerase chain reaction (PCR) testing protocol. Previously, PCR was employed as a second step after an initial positive enzyme immunoassay (EIA). Almost immediately, there was a 20% to 25% jump in the proportion of positive tests due to colonization rather than active infection.

“Of course, we did, at the time, educate our clinicians about this new testing algorithm, explaining how it is so much more sensitive and that they need to be smarter about who they are testing. But as we saw the cases roll in, we noticed that many of the [colonization] cases were in patients with a history of recent laxative use,” Dr. Drees recounted.

This led initially to a “soft stop” protocol in which clinicians ordering C. difficile–infection testing received an alert if laxatives had been ordered within the previous 24 hours. The alert provided details about the laxatives and suggested that the order for C. difficile–infection testing be reconsidered. This alert was no more than a suggestion, but it did reduce C. difficile–infection testing orders by 25% at first.

“The problem was that the alert lost effect over time as people got used to seeing it and clicked right through it,” Dr. Drees explained.

Despite the diminishing effect of the soft stop, no further steps were planned until a new set of data alerted the infectious disease department that C. difficile–infection rates were higher than benchmarks. This prompted concern among the hospital leadership and led to creation of a multidisciplinary team that was given the task to dig deeper for the source of problems and develop strategies to lower rates of inappropriate testing.

When that team did their initial analysis, what really came to the front was that about half the cases that had been identified as hospital-onset C. difficile were likely only C. difficile colonizations. They either had received laxatives prior to their test or they did not have significant diarrhea,” Dr. Drees said.

It was this finding that prompted a hard stop protocol to be built into C. difficile–infection test orders. In this protocol, which is executed only in patients who have been hospitalized for at least 36 hours, two conditions must be met sequentially for the testing order to proceed. The first is there must be documentation of at least two episodes of diarrhea in the prior 24 hours. If this condition is met, then the ordering system asks for verification that the patient has not received a laxative in the prior 24 hours.

“If either of these criteria are not met, the order can only proceed if the clinician calls the lab for an override,” Dr. Drees explained. Although the person answering the phone in the laboratory does not require any additional documentation or justification, the person ordering the test must enter the name of the person in the laboratory with whom they spoke. If this field is not filled in, the order will not proceed.

Prior to the hard stop, there was an average of 12 C. difficile–infection tests ordered per day. After the hard stop, the average fell to 7 per day, a 42% decline, according to Dr. Drees. C. difficile-infection cases did not increase, and there were no incidences of delayed diagnosis resulting in adverse clinical consequences.

Of the 157 overrides on the hard stop, representing 15% of all orders, only 11% produced a positive C. difficile-infection result. It was noted that almost one third of the overrides did not follow the protocol.

“What I mean is that they did not actually call the lab. They put in their own name [for the field requiring the name of a lab worker] or they put in Mickey Mouse or they put in something, so the order would proceed,” Dr. Drees said. After followup in those cases, “we have not had repeat offenders.”

Even a hard stop is likely to have diminishing efficacy over time as clinicians identify work-arounds, Dr. Drees acknowledged. For example, there is concern that therapy for CDI will be ordered without testing, although this has not yet been detected. However, the hard stop has been more effective and shown a longer duration of effect than the soft stop, according to Dr. Drees. Although Dr. Drees acknowledged that there have been exceptions, the hard stop has “generally been well accepted.”

Dr. Drees reported that she has no financial relationships relevant to this topic.

 

SAN DIEGO – After other strategies to reduce inappropriate testing for Clostridium difficile infection did not provide adequate reductions in inappropriate orders, a “hard stop” protocol, which prevents testing if specific conditions are not met, reduced the rate of testing by 42% without any incidence of delayed diagnosis, according to data presented at ID Week 2017.

“Testing stewardship is really critical to minimize the frequency of false-positive [Clostridium difficile infection] cases, which of course lead to harm. They lead to inappropriate treatment, prolonged length of stay, and patient dissatisfaction,” reported Marci L. Drees, MD, Infection Prevention Officer and Hospital Epidemiologist, Christiana Care Health System, Newark, Del.

Ted Bowsworth/Frontline Medical News

The move to a hard stop protocol occurred after several events. The first of these was a switch to an all-Polymerase chain reaction (PCR) testing protocol. Previously, PCR was employed as a second step after an initial positive enzyme immunoassay (EIA). Almost immediately, there was a 20% to 25% jump in the proportion of positive tests due to colonization rather than active infection.

“Of course, we did, at the time, educate our clinicians about this new testing algorithm, explaining how it is so much more sensitive and that they need to be smarter about who they are testing. But as we saw the cases roll in, we noticed that many of the [colonization] cases were in patients with a history of recent laxative use,” Dr. Drees recounted.

This led initially to a “soft stop” protocol in which clinicians ordering C. difficile–infection testing received an alert if laxatives had been ordered within the previous 24 hours. The alert provided details about the laxatives and suggested that the order for C. difficile–infection testing be reconsidered. This alert was no more than a suggestion, but it did reduce C. difficile–infection testing orders by 25% at first.

“The problem was that the alert lost effect over time as people got used to seeing it and clicked right through it,” Dr. Drees explained.

Despite the diminishing effect of the soft stop, no further steps were planned until a new set of data alerted the infectious disease department that C. difficile–infection rates were higher than benchmarks. This prompted concern among the hospital leadership and led to creation of a multidisciplinary team that was given the task to dig deeper for the source of problems and develop strategies to lower rates of inappropriate testing.

When that team did their initial analysis, what really came to the front was that about half the cases that had been identified as hospital-onset C. difficile were likely only C. difficile colonizations. They either had received laxatives prior to their test or they did not have significant diarrhea,” Dr. Drees said.

It was this finding that prompted a hard stop protocol to be built into C. difficile–infection test orders. In this protocol, which is executed only in patients who have been hospitalized for at least 36 hours, two conditions must be met sequentially for the testing order to proceed. The first is there must be documentation of at least two episodes of diarrhea in the prior 24 hours. If this condition is met, then the ordering system asks for verification that the patient has not received a laxative in the prior 24 hours.

“If either of these criteria are not met, the order can only proceed if the clinician calls the lab for an override,” Dr. Drees explained. Although the person answering the phone in the laboratory does not require any additional documentation or justification, the person ordering the test must enter the name of the person in the laboratory with whom they spoke. If this field is not filled in, the order will not proceed.

Prior to the hard stop, there was an average of 12 C. difficile–infection tests ordered per day. After the hard stop, the average fell to 7 per day, a 42% decline, according to Dr. Drees. C. difficile-infection cases did not increase, and there were no incidences of delayed diagnosis resulting in adverse clinical consequences.

Of the 157 overrides on the hard stop, representing 15% of all orders, only 11% produced a positive C. difficile-infection result. It was noted that almost one third of the overrides did not follow the protocol.

“What I mean is that they did not actually call the lab. They put in their own name [for the field requiring the name of a lab worker] or they put in Mickey Mouse or they put in something, so the order would proceed,” Dr. Drees said. After followup in those cases, “we have not had repeat offenders.”

Even a hard stop is likely to have diminishing efficacy over time as clinicians identify work-arounds, Dr. Drees acknowledged. For example, there is concern that therapy for CDI will be ordered without testing, although this has not yet been detected. However, the hard stop has been more effective and shown a longer duration of effect than the soft stop, according to Dr. Drees. Although Dr. Drees acknowledged that there have been exceptions, the hard stop has “generally been well accepted.”

Dr. Drees reported that she has no financial relationships relevant to this topic.

 

SAN DIEGO – After other strategies to reduce inappropriate testing for Clostridium difficile infection did not provide adequate reductions in inappropriate orders, a “hard stop” protocol, which prevents testing if specific conditions are not met, reduced the rate of testing by 42% without any incidence of delayed diagnosis, according to data presented at ID Week 2017.

“Testing stewardship is really critical to minimize the frequency of false-positive [Clostridium difficile infection] cases, which of course lead to harm. They lead to inappropriate treatment, prolonged length of stay, and patient dissatisfaction,” reported Marci L. Drees, MD, Infection Prevention Officer and Hospital Epidemiologist, Christiana Care Health System, Newark, Del.

Ted Bowsworth/Frontline Medical News

The move to a hard stop protocol occurred after several events. The first of these was a switch to an all-Polymerase chain reaction (PCR) testing protocol. Previously, PCR was employed as a second step after an initial positive enzyme immunoassay (EIA). Almost immediately, there was a 20% to 25% jump in the proportion of positive tests due to colonization rather than active infection.

“Of course, we did, at the time, educate our clinicians about this new testing algorithm, explaining how it is so much more sensitive and that they need to be smarter about who they are testing. But as we saw the cases roll in, we noticed that many of the [colonization] cases were in patients with a history of recent laxative use,” Dr. Drees recounted.

This led initially to a “soft stop” protocol in which clinicians ordering C. difficile–infection testing received an alert if laxatives had been ordered within the previous 24 hours. The alert provided details about the laxatives and suggested that the order for C. difficile–infection testing be reconsidered. This alert was no more than a suggestion, but it did reduce C. difficile–infection testing orders by 25% at first.

“The problem was that the alert lost effect over time as people got used to seeing it and clicked right through it,” Dr. Drees explained.

Despite the diminishing effect of the soft stop, no further steps were planned until a new set of data alerted the infectious disease department that C. difficile–infection rates were higher than benchmarks. This prompted concern among the hospital leadership and led to creation of a multidisciplinary team that was given the task to dig deeper for the source of problems and develop strategies to lower rates of inappropriate testing.

When that team did their initial analysis, what really came to the front was that about half the cases that had been identified as hospital-onset C. difficile were likely only C. difficile colonizations. They either had received laxatives prior to their test or they did not have significant diarrhea,” Dr. Drees said.

It was this finding that prompted a hard stop protocol to be built into C. difficile–infection test orders. In this protocol, which is executed only in patients who have been hospitalized for at least 36 hours, two conditions must be met sequentially for the testing order to proceed. The first is there must be documentation of at least two episodes of diarrhea in the prior 24 hours. If this condition is met, then the ordering system asks for verification that the patient has not received a laxative in the prior 24 hours.

“If either of these criteria are not met, the order can only proceed if the clinician calls the lab for an override,” Dr. Drees explained. Although the person answering the phone in the laboratory does not require any additional documentation or justification, the person ordering the test must enter the name of the person in the laboratory with whom they spoke. If this field is not filled in, the order will not proceed.

Prior to the hard stop, there was an average of 12 C. difficile–infection tests ordered per day. After the hard stop, the average fell to 7 per day, a 42% decline, according to Dr. Drees. C. difficile-infection cases did not increase, and there were no incidences of delayed diagnosis resulting in adverse clinical consequences.

Of the 157 overrides on the hard stop, representing 15% of all orders, only 11% produced a positive C. difficile-infection result. It was noted that almost one third of the overrides did not follow the protocol.

“What I mean is that they did not actually call the lab. They put in their own name [for the field requiring the name of a lab worker] or they put in Mickey Mouse or they put in something, so the order would proceed,” Dr. Drees said. After followup in those cases, “we have not had repeat offenders.”

Even a hard stop is likely to have diminishing efficacy over time as clinicians identify work-arounds, Dr. Drees acknowledged. For example, there is concern that therapy for CDI will be ordered without testing, although this has not yet been detected. However, the hard stop has been more effective and shown a longer duration of effect than the soft stop, according to Dr. Drees. Although Dr. Drees acknowledged that there have been exceptions, the hard stop has “generally been well accepted.”

Dr. Drees reported that she has no financial relationships relevant to this topic.

 

SAN DIEGO – Bacteria with favorable susceptibility profiles don’t always translate reliably into treatment successes, according to a detailed study of six isolates.

“Both patient and microbe factors can contribute to treatment failure, even involving pan-susceptible isolates,” Andrew Berti, PharmD, PhD, said in an interview prior to an annual scientific meeting on infectious diseases.

Courtesy of Dr. Andrew Berti

Although clinicians can employ suppressive antimicrobial therapy in patients with persistent or relapsing bacteremia, bacteria with favorable susceptibility profiles may be able to survive in high concentrations of antibiotics. “The antimicrobial tolerance phenotype can thwart efforts to prevent bacteremia recurrence with prolonged exposure to antimicrobials and may contribute to breakthrough bacteremias while the patient is receiving active therapy,” Dr. Berti, of the department of pharmacy practice at Wayne State University, Detroit, and his associates wrote in their abstract of the research they presented at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

The researchers presented the case of a patient who experienced multiple episodes of breakthrough Staphylococcus aureus bacteremia over a period of 5 years in the setting of appropriately dosed antimicrobial suppressive therapy. They recovered six clinical bloodstream isolates from the patient during distinct episodes of methicillin-susceptible S. aureus (MSSA) bacteremia, and it was determined that a central line infection was the source for each episode. Isolates recovered were susceptible to the individual therapies received, which included oxacillin, daptomycin, and dalbavancin. The researchers used Illumina technology to collect bacterial whole genome sequence data. “Relatively little is known about bacterial evolution during human infection as these tend to be acute, rapidly resolved events,” Dr. Berti said. “This case was unique in that we could observe changes to a pathogen over a more than 6 years period as it adapted to survive host defenses and multiple antibiotic interventions.”

The researchers discovered that the first two isolates (ST256) and the last four isolates (ST5) “represent distinct populations and suggest that a distinct MSSA strain displaced the previous population between bacteremia episodes 2 and 3,” they wrote in their abstract. “Of note, all of these strains were able to survive and establish breakthrough bacteremias despite favorable susceptibility profiles to the agents used as suppressive therapy. Although the MICs remain low and in the susceptible range to oxacillin, daptomycin, and dalbavancin, these isolates progressively developed significant antimicrobial tolerance phenotypes, which coincided with mutations in walK (yycG), htrA2, ftsW, ebh, and ileS that may be advantageous to survival under antibiotic pressure.”

Dr. Berti acknowledged certain limitations of the analysis, including the inability to test for heteroresistance to some antibiotics, which may also contribute to treatment failure. “Specific therapeutic interventions that coincide with bacterial population changes are not necessarily causative of those changes,” he said. One of the study authors, Warren Rose, PharmD, disclosed having received research grants, speaker honoraria, and/or consulting fees from Theravance, Merck, The Medicines Company and Visante, Inc. All other authors reported having no financial disclosures.

[email protected]

 

SAN DIEGO – Bacteria with favorable susceptibility profiles don’t always translate reliably into treatment successes, according to a detailed study of six isolates.

“Both patient and microbe factors can contribute to treatment failure, even involving pan-susceptible isolates,” Andrew Berti, PharmD, PhD, said in an interview prior to an annual scientific meeting on infectious diseases.

Courtesy of Dr. Andrew Berti

Although clinicians can employ suppressive antimicrobial therapy in patients with persistent or relapsing bacteremia, bacteria with favorable susceptibility profiles may be able to survive in high concentrations of antibiotics. “The antimicrobial tolerance phenotype can thwart efforts to prevent bacteremia recurrence with prolonged exposure to antimicrobials and may contribute to breakthrough bacteremias while the patient is receiving active therapy,” Dr. Berti, of the department of pharmacy practice at Wayne State University, Detroit, and his associates wrote in their abstract of the research they presented at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

The researchers presented the case of a patient who experienced multiple episodes of breakthrough Staphylococcus aureus bacteremia over a period of 5 years in the setting of appropriately dosed antimicrobial suppressive therapy. They recovered six clinical bloodstream isolates from the patient during distinct episodes of methicillin-susceptible S. aureus (MSSA) bacteremia, and it was determined that a central line infection was the source for each episode. Isolates recovered were susceptible to the individual therapies received, which included oxacillin, daptomycin, and dalbavancin. The researchers used Illumina technology to collect bacterial whole genome sequence data. “Relatively little is known about bacterial evolution during human infection as these tend to be acute, rapidly resolved events,” Dr. Berti said. “This case was unique in that we could observe changes to a pathogen over a more than 6 years period as it adapted to survive host defenses and multiple antibiotic interventions.”

The researchers discovered that the first two isolates (ST256) and the last four isolates (ST5) “represent distinct populations and suggest that a distinct MSSA strain displaced the previous population between bacteremia episodes 2 and 3,” they wrote in their abstract. “Of note, all of these strains were able to survive and establish breakthrough bacteremias despite favorable susceptibility profiles to the agents used as suppressive therapy. Although the MICs remain low and in the susceptible range to oxacillin, daptomycin, and dalbavancin, these isolates progressively developed significant antimicrobial tolerance phenotypes, which coincided with mutations in walK (yycG), htrA2, ftsW, ebh, and ileS that may be advantageous to survival under antibiotic pressure.”

Dr. Berti acknowledged certain limitations of the analysis, including the inability to test for heteroresistance to some antibiotics, which may also contribute to treatment failure. “Specific therapeutic interventions that coincide with bacterial population changes are not necessarily causative of those changes,” he said. One of the study authors, Warren Rose, PharmD, disclosed having received research grants, speaker honoraria, and/or consulting fees from Theravance, Merck, The Medicines Company and Visante, Inc. All other authors reported having no financial disclosures.

[email protected]

 

SAN DIEGO – Bacteria with favorable susceptibility profiles don’t always translate reliably into treatment successes, according to a detailed study of six isolates.

“Both patient and microbe factors can contribute to treatment failure, even involving pan-susceptible isolates,” Andrew Berti, PharmD, PhD, said in an interview prior to an annual scientific meeting on infectious diseases.

Courtesy of Dr. Andrew Berti

Although clinicians can employ suppressive antimicrobial therapy in patients with persistent or relapsing bacteremia, bacteria with favorable susceptibility profiles may be able to survive in high concentrations of antibiotics. “The antimicrobial tolerance phenotype can thwart efforts to prevent bacteremia recurrence with prolonged exposure to antimicrobials and may contribute to breakthrough bacteremias while the patient is receiving active therapy,” Dr. Berti, of the department of pharmacy practice at Wayne State University, Detroit, and his associates wrote in their abstract of the research they presented at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

The researchers presented the case of a patient who experienced multiple episodes of breakthrough Staphylococcus aureus bacteremia over a period of 5 years in the setting of appropriately dosed antimicrobial suppressive therapy. They recovered six clinical bloodstream isolates from the patient during distinct episodes of methicillin-susceptible S. aureus (MSSA) bacteremia, and it was determined that a central line infection was the source for each episode. Isolates recovered were susceptible to the individual therapies received, which included oxacillin, daptomycin, and dalbavancin. The researchers used Illumina technology to collect bacterial whole genome sequence data. “Relatively little is known about bacterial evolution during human infection as these tend to be acute, rapidly resolved events,” Dr. Berti said. “This case was unique in that we could observe changes to a pathogen over a more than 6 years period as it adapted to survive host defenses and multiple antibiotic interventions.”

The researchers discovered that the first two isolates (ST256) and the last four isolates (ST5) “represent distinct populations and suggest that a distinct MSSA strain displaced the previous population between bacteremia episodes 2 and 3,” they wrote in their abstract. “Of note, all of these strains were able to survive and establish breakthrough bacteremias despite favorable susceptibility profiles to the agents used as suppressive therapy. Although the MICs remain low and in the susceptible range to oxacillin, daptomycin, and dalbavancin, these isolates progressively developed significant antimicrobial tolerance phenotypes, which coincided with mutations in walK (yycG), htrA2, ftsW, ebh, and ileS that may be advantageous to survival under antibiotic pressure.”

Dr. Berti acknowledged certain limitations of the analysis, including the inability to test for heteroresistance to some antibiotics, which may also contribute to treatment failure. “Specific therapeutic interventions that coincide with bacterial population changes are not necessarily causative of those changes,” he said. One of the study authors, Warren Rose, PharmD, disclosed having received research grants, speaker honoraria, and/or consulting fees from Theravance, Merck, The Medicines Company and Visante, Inc. All other authors reported having no financial disclosures.

[email protected]

 

Clinical question: How effective is an antimicrobial stewardship approach grounded in behavioral theory and focused on preserving prescriber autonomy and participation in improving appropriateness of antimicrobial prescribing in hospitals?

Background: Antimicrobial stewardship programs aim to achieve the goal of improving antimicrobial prescribing. This leads to significant benefits, including decreased antimicrobial resistance, improved clinical outcomes (lower morbidity and mortality), and lower health care costs. Stewardship programs do not often focus on the human behavior element of the prescribing physicians. Changing antimicrobial prescribing is a complex behavioral process, and there is a known persistent resistance between prescribers and the stewardship team. In a simple sense, this resistance is generated by tension created when prescribers do not have autonomy.

Previous studies that used interventions based on behavioral theory found promising results, but none of them were in a hospital setting. Rather, most of these studies had a narrow focus of respiratory tract infections in outpatient clinics.

Study design: Prospective, stepped-wedge, participatory intervention study.

Setting: Seven clinical departments (two medical, three surgical, and two pediatric) in a tertiary care medical center and a general teaching hospital, both in Amsterdam. The first hospital was a 700-bed tertiary care center with salaried specialists, while the second hospital was a 550-bed general medical center with self-employed specialists.

Synopsis: During a baseline period of 16 months and an intervention period of 12 months, physicians who prescribed systemic antimicrobial drugs for any indication were included in the study. In all, 1,121 patient cases with 700 prescriptions were studied during the baseline period and 882 patient cases with 531 prescriptions were studied during the intervention period. The intervention was as follows: Prescribers were offered a free choice of how to improve their antimicrobial prescribing. They were stimulated to choose interventions with higher potential for success based on a root cause analysis of inappropriate prescribing. The study was inspired by the participatory action research paradigm, which focuses on collaboration and empowerment of the stakeholders in the change process. In this study, prescribers were given reports of root cause analysis of their prior prescribing patterns. Then, they were invited to choose and codevelop one or more interventions that were tailored and individualized to improve their own prescribing. This approach draws on the following three behavioral principles: 1) respect for the prescriber’s autonomy to avoid feelings of resistance; 2) the inclination that people have to value a product higher and feel more ownership of it if they made it themselves (the IKEA effect); 3) the tendency of people to follow up on an active and public commitment.

The primary outcome was antimicrobial appropriateness, measured with a validated appropriateness assessment instrument. One of three infectious disease specialists assessed the adult prescriptions, and one of three infectious disease/immunology pediatricians assessed the pediatric prescriptions for appropriateness. Appropriateness criteria were as follows: indication, choice of antimicrobial, dosage, route, and duration. A secondary outcome was antimicrobial consumption, reported as days of therapy per 100 admissions per month. Other outcomes were changes in specific appropriateness categories, intravenous antimicrobial consumption, consumption of specific antimicrobial subgroups, and length of hospital stay.

The mean antimicrobial appropriateness increased from 64.1% at intervention start to 77.4% at 12-month follow-up (+13.3%; relative risk, 1.17; 95% CI, 1.04-1.27), without a change in slope. Antimicrobial consumption remained the same during both study periods. Length of hospital stay did not change relative to the start of the intervention approach.

This is the first study of its kind, as a hospital antimicrobial stewardship program study grounded in behavioral science, with the key element being the free choice allowed to the prescribers, who made their own autonomous decisions about how to improve their prescribing. The authors hypothesize that the prescribers felt relatively nonthreatened by their approach since the prescribers maintained their free will to change their own behavior if so desired. The prescribers were given a free intervention choice. For example, they could have just chosen “education” as an easy out; however, the root cause analysis seemed to be an impetus for the prescribers to choose interventions that would be more effective. A prior study in a nursing home setting was unsuccessful; aside from other differences, that study used a predetermined set of interventions, thus lacking the autonomy and IKEA effect seen in this study.

Bottom line: Use of a behavioral approach that preserves prescriber autonomy resulted in an increase in antimicrobial appropriateness sustained for at least 12 months. The intervention is effective, inexpensive, and transferable to various health care settings.

Citation: Sikkens JJ, van Agtmael MA, Peters EJG, et al. Behavioral approach to appropriate antimicrobial prescribing in hospitals: The dutch unique method for antimicrobial stewardship (DUMAS) participatoryintervention study. JAMA Intern Med. Published online May 1, 2017. doi: 10.1001/jamainternmed.2017.0946.

Dr. Ramee is a hospitalist at Ochsner Health System, New Orleans.

 

Clinical question: How effective is an antimicrobial stewardship approach grounded in behavioral theory and focused on preserving prescriber autonomy and participation in improving appropriateness of antimicrobial prescribing in hospitals?

Background: Antimicrobial stewardship programs aim to achieve the goal of improving antimicrobial prescribing. This leads to significant benefits, including decreased antimicrobial resistance, improved clinical outcomes (lower morbidity and mortality), and lower health care costs. Stewardship programs do not often focus on the human behavior element of the prescribing physicians. Changing antimicrobial prescribing is a complex behavioral process, and there is a known persistent resistance between prescribers and the stewardship team. In a simple sense, this resistance is generated by tension created when prescribers do not have autonomy.

Previous studies that used interventions based on behavioral theory found promising results, but none of them were in a hospital setting. Rather, most of these studies had a narrow focus of respiratory tract infections in outpatient clinics.

Study design: Prospective, stepped-wedge, participatory intervention study.

Setting: Seven clinical departments (two medical, three surgical, and two pediatric) in a tertiary care medical center and a general teaching hospital, both in Amsterdam. The first hospital was a 700-bed tertiary care center with salaried specialists, while the second hospital was a 550-bed general medical center with self-employed specialists.

Synopsis: During a baseline period of 16 months and an intervention period of 12 months, physicians who prescribed systemic antimicrobial drugs for any indication were included in the study. In all, 1,121 patient cases with 700 prescriptions were studied during the baseline period and 882 patient cases with 531 prescriptions were studied during the intervention period. The intervention was as follows: Prescribers were offered a free choice of how to improve their antimicrobial prescribing. They were stimulated to choose interventions with higher potential for success based on a root cause analysis of inappropriate prescribing. The study was inspired by the participatory action research paradigm, which focuses on collaboration and empowerment of the stakeholders in the change process. In this study, prescribers were given reports of root cause analysis of their prior prescribing patterns. Then, they were invited to choose and codevelop one or more interventions that were tailored and individualized to improve their own prescribing. This approach draws on the following three behavioral principles: 1) respect for the prescriber’s autonomy to avoid feelings of resistance; 2) the inclination that people have to value a product higher and feel more ownership of it if they made it themselves (the IKEA effect); 3) the tendency of people to follow up on an active and public commitment.

The primary outcome was antimicrobial appropriateness, measured with a validated appropriateness assessment instrument. One of three infectious disease specialists assessed the adult prescriptions, and one of three infectious disease/immunology pediatricians assessed the pediatric prescriptions for appropriateness. Appropriateness criteria were as follows: indication, choice of antimicrobial, dosage, route, and duration. A secondary outcome was antimicrobial consumption, reported as days of therapy per 100 admissions per month. Other outcomes were changes in specific appropriateness categories, intravenous antimicrobial consumption, consumption of specific antimicrobial subgroups, and length of hospital stay.

The mean antimicrobial appropriateness increased from 64.1% at intervention start to 77.4% at 12-month follow-up (+13.3%; relative risk, 1.17; 95% CI, 1.04-1.27), without a change in slope. Antimicrobial consumption remained the same during both study periods. Length of hospital stay did not change relative to the start of the intervention approach.

This is the first study of its kind, as a hospital antimicrobial stewardship program study grounded in behavioral science, with the key element being the free choice allowed to the prescribers, who made their own autonomous decisions about how to improve their prescribing. The authors hypothesize that the prescribers felt relatively nonthreatened by their approach since the prescribers maintained their free will to change their own behavior if so desired. The prescribers were given a free intervention choice. For example, they could have just chosen “education” as an easy out; however, the root cause analysis seemed to be an impetus for the prescribers to choose interventions that would be more effective. A prior study in a nursing home setting was unsuccessful; aside from other differences, that study used a predetermined set of interventions, thus lacking the autonomy and IKEA effect seen in this study.

Bottom line: Use of a behavioral approach that preserves prescriber autonomy resulted in an increase in antimicrobial appropriateness sustained for at least 12 months. The intervention is effective, inexpensive, and transferable to various health care settings.

Citation: Sikkens JJ, van Agtmael MA, Peters EJG, et al. Behavioral approach to appropriate antimicrobial prescribing in hospitals: The dutch unique method for antimicrobial stewardship (DUMAS) participatoryintervention study. JAMA Intern Med. Published online May 1, 2017. doi: 10.1001/jamainternmed.2017.0946.

Dr. Ramee is a hospitalist at Ochsner Health System, New Orleans.

 

Clinical question: How effective is an antimicrobial stewardship approach grounded in behavioral theory and focused on preserving prescriber autonomy and participation in improving appropriateness of antimicrobial prescribing in hospitals?

Background: Antimicrobial stewardship programs aim to achieve the goal of improving antimicrobial prescribing. This leads to significant benefits, including decreased antimicrobial resistance, improved clinical outcomes (lower morbidity and mortality), and lower health care costs. Stewardship programs do not often focus on the human behavior element of the prescribing physicians. Changing antimicrobial prescribing is a complex behavioral process, and there is a known persistent resistance between prescribers and the stewardship team. In a simple sense, this resistance is generated by tension created when prescribers do not have autonomy.

Previous studies that used interventions based on behavioral theory found promising results, but none of them were in a hospital setting. Rather, most of these studies had a narrow focus of respiratory tract infections in outpatient clinics.

Study design: Prospective, stepped-wedge, participatory intervention study.

Setting: Seven clinical departments (two medical, three surgical, and two pediatric) in a tertiary care medical center and a general teaching hospital, both in Amsterdam. The first hospital was a 700-bed tertiary care center with salaried specialists, while the second hospital was a 550-bed general medical center with self-employed specialists.

Synopsis: During a baseline period of 16 months and an intervention period of 12 months, physicians who prescribed systemic antimicrobial drugs for any indication were included in the study. In all, 1,121 patient cases with 700 prescriptions were studied during the baseline period and 882 patient cases with 531 prescriptions were studied during the intervention period. The intervention was as follows: Prescribers were offered a free choice of how to improve their antimicrobial prescribing. They were stimulated to choose interventions with higher potential for success based on a root cause analysis of inappropriate prescribing. The study was inspired by the participatory action research paradigm, which focuses on collaboration and empowerment of the stakeholders in the change process. In this study, prescribers were given reports of root cause analysis of their prior prescribing patterns. Then, they were invited to choose and codevelop one or more interventions that were tailored and individualized to improve their own prescribing. This approach draws on the following three behavioral principles: 1) respect for the prescriber’s autonomy to avoid feelings of resistance; 2) the inclination that people have to value a product higher and feel more ownership of it if they made it themselves (the IKEA effect); 3) the tendency of people to follow up on an active and public commitment.

The primary outcome was antimicrobial appropriateness, measured with a validated appropriateness assessment instrument. One of three infectious disease specialists assessed the adult prescriptions, and one of three infectious disease/immunology pediatricians assessed the pediatric prescriptions for appropriateness. Appropriateness criteria were as follows: indication, choice of antimicrobial, dosage, route, and duration. A secondary outcome was antimicrobial consumption, reported as days of therapy per 100 admissions per month. Other outcomes were changes in specific appropriateness categories, intravenous antimicrobial consumption, consumption of specific antimicrobial subgroups, and length of hospital stay.

The mean antimicrobial appropriateness increased from 64.1% at intervention start to 77.4% at 12-month follow-up (+13.3%; relative risk, 1.17; 95% CI, 1.04-1.27), without a change in slope. Antimicrobial consumption remained the same during both study periods. Length of hospital stay did not change relative to the start of the intervention approach.

This is the first study of its kind, as a hospital antimicrobial stewardship program study grounded in behavioral science, with the key element being the free choice allowed to the prescribers, who made their own autonomous decisions about how to improve their prescribing. The authors hypothesize that the prescribers felt relatively nonthreatened by their approach since the prescribers maintained their free will to change their own behavior if so desired. The prescribers were given a free intervention choice. For example, they could have just chosen “education” as an easy out; however, the root cause analysis seemed to be an impetus for the prescribers to choose interventions that would be more effective. A prior study in a nursing home setting was unsuccessful; aside from other differences, that study used a predetermined set of interventions, thus lacking the autonomy and IKEA effect seen in this study.

Bottom line: Use of a behavioral approach that preserves prescriber autonomy resulted in an increase in antimicrobial appropriateness sustained for at least 12 months. The intervention is effective, inexpensive, and transferable to various health care settings.

Citation: Sikkens JJ, van Agtmael MA, Peters EJG, et al. Behavioral approach to appropriate antimicrobial prescribing in hospitals: The dutch unique method for antimicrobial stewardship (DUMAS) participatoryintervention study. JAMA Intern Med. Published online May 1, 2017. doi: 10.1001/jamainternmed.2017.0946.

Dr. Ramee is a hospitalist at Ochsner Health System, New Orleans.