Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
UK study supports whole-genome sequencing for resistance surveillance
New research by a team of scientists from the United Kingdom suggests that whole-genome sequencing (WGS) should be considered as an alternative to traditional phenotypic testing for national surveillance of antibiotic resistance.
In a study published yesterday in Eurosurveillance, researchers from the UK's Animal and Plant Health Agency and the University of East Anglia performed WGS on a collection of 515 Escherichia coli isolates collected from pigs on 57 UK farms. They also tested their susceptibility to a panel of nine antibiotics, using the minimal inhibitory concentration (MIC) to determine phenotypic resistance or susceptibility. The aim of the study was to determine whether the presence of antibiotic resistance genes and mutations in the E coli isolates could accurately predict their resistance to antibiotics of human clinical and veterinary importance.
Overall, correlation of WGS results with susceptibility to the nine antibiotics was 98.9% for test specificity, and 97.5% for the positive predictive value of a test. The overall kappa score (k = 0.914) indicated the presence of antibiotic resistance genes was highly predictive of reduced susceptibility and showed excellent correlation with the phenotypic MIC data from the isolates. However, there was variation for each antibiotic; five showed "almost perfect" agreement, three showed strong agreement, and one showed moderate agreement. Suggested epidemiologic cutoff adjustments increased concordance between genotypic data and kappa values for the four strong-to-moderate agreement antibiotics.
The authors of the study say WGS provides the additional benefit of being able to detect genes that confer resistance to antibiotics that aren't routinely tested in MIC panels, and can identify other elements of bacterial strains—such as multilocus sequence types and plasmids—that are important for assessing their ability to transmit antibiotic resistance.
Dec 12 Eurosurveill study
Asymptomatic C diff carriage found in nearly 10% of hospital patients
A study conducted at a New York hospital has found that asymptomatic carriage of Clostridioides difficile is prevalent among admitted patients and confers a significant risk of developing into C difficile infection (CDI), researchers reported this week in Infection Control and Hospital Epidemiology.
In the study, conducted from March 2017 to July 2018, researchers at Montefiore Medical Center created a pilot screening program to test patients being admitted to the hospital without diarrhea for C difficile. Eligible subjects, including adult patients from the community and nursing facility residents, underwent swabbing of their perirectal area. The swabs were tested by polymerase chain reaction within 24 hours of admission, and the patients were then observed for 6 months. Development of clinical CDI was compared among the C difficile carriers and non-carriers.
Of the 220 patients tested, 21 (9.6%) were asymptomatic C difficile carriers, with 17 of 168 nursing facility residents (10.2%) and 4 of 52 community residents (7.7%) testing positive. Among the 21 C difficile carriers, 8 (38.1%) progressed to clinical CDI within 6 months, compared with 4 of 199 (2.0%) non-carriers. In the time-to-event analysis, C difficile carriers had significantly increased risk of developing clinical CDI compared with non-carriers (hazard ratio, 23.9; 95% confidence interval, 7.2 to 79.6; P < .001).
The authors of the study say that identifying asymptomatic carriers is important because, even without diarrhea, they still shed spores that can contaminate hospital surfaces, and could represent a significant reservoir for C difficile transmission.
"Therefore, identification of asymptomatic carriers could reduce the spread of C. difficile," they write. "Specific environmental, isolation, and stewardship strategies to prevent spread of C. difficile from carriers to uninfected patients as well as prevent progression to symptomatic CDI warrant further study."
Dec 11 Infect Control Hosp Epidemiol abstract
Report details 19-case XDR Klebsiella pneumoniae outbreak in Germany
Originally published by CIDRAP News Dec 12
Additional surveillance following a 17-case outbreak in northeastern Germany of extensively drug-resistant (XDR) Klebsiella pneumoniae has revealed 2 additional cases and details on the XDR strain, according to a study today in Eurosurveillance.
The outbreak was first detailed by the European Centre for Disease Prevention and Control (ECDC) on Oct 28. From June through the end of October, investigators reported 6 infected and 11 colonized patients in four Western Pomerania medical facilities, including a university hospital. The XDR K pneumoniae strain (ST307) produced carbapenemases NDM-1 and OXA-48, and was susceptible only to chloramphenicol, tigecycline, and cefiderocol, according to today's report. The authors also note synergistic activity against the strain for aztreonam combined with ceftazidime-avibactam.
As noted by the ECDC in October, the outbreak strain was similar to a previously reported patient from Finland who was hospitalized in St. Petersburg, Russia, but no epidemiologic links were found to the German outbreak.
The authors write in today's study, "The first case (index patient) presented no typical risk factors for K. pneumoniae infection such as a recent hospital stay or recent travel, and is therefore unlikely to be the primary case that brought the outbreak strain into the university hospital."
The investigators said the outbreak seemed controlled until the last week of October, when a new case was detected through admission screening at the university hospital. The patient had been hospitalized in July and September. A second new case was detected through rectal screening the following week.
The authors conclude, "Clinical and laboratory staff need to increase vigilance in order to improve early detection of XDR outbreaks. Early extensive screening and a high level of isolation precautions are needed to avoid further spread of these pathogens."
Dec 12 Eurosurveillance report
Oct 28 CIDRAP News scan on ECDC report
New antibiotic narrowly misses the mark in phase 3 clinical
Originally published by CIDRAP News Dec 12
Drug maker Iterum Therapautics announced this week that its lead antibiotic candidate, sulopenem, narrowly failed to demonstrate non-inferiority to ertapenem in a phase 3 clinical trial in patients with complicated intra-abdominal infections (cIAIs).
According to a press release from Iterum, of Dublin, Ireland, the primary US Food and Drug Administration (FDA) endpoint in the Sulopenem for Resistant Enterobacteriaceae (SURE) trial was clinical response on day 28 in the microbiologic-modified intent to treat (micro-MITT) population. The trial randomized patients to receive either intravenous (IV) sulopenem followed by oral sulopenem or IV ertapenem followed by oral ciprofloxacin and oral metronidazole (patients with ciprofloxacin-resistant organisms at baseline received amoxicillin-clavulanate).
The difference in outcomes on this population was 4.7% (85.5% for sulopenem vs 90.2% for ertapenem), with a 95% confidence interval of -10.3% to 1.0%. To achieve non-inferiority, however, the lower limit of the difference in the outcome rates had to be greater than -10.0%. The company said the difference in outcomes was one patient shy of the target.
Company officials say that despite the results, they remain hopeful that the drug, which is also being evaluated for treating complicated and uncomplicated urinary tract infections, will ultimately receive FDA approval.
“We believe that these topline results, while narrowly missing the primary endpoint, provide data that emphasize the potential for sulopenem to help address the growing challenge of antibiotic resistance,” said Corey Fishman, CEO of Iterum Therapeutics. “If we obtain positive results in Q1 2020 from our Phase 3 complicated and uncomplicated urinary tract trials, we believe that the overall safety and efficacy results from this cIAI trial would be supportive in an FDA filing for oral and IV sulopenem and that sulopenem’s market potential remains robust.”
Dec 10 Iterum Therapeutics press release
Study probes increasing use of cefdinir in Kentucky children
Originally published by CIDRAP News Dec 11
A review of Medicaid claims in Kentucky from 2012 through 2016 found that cefdinir prescriptions for treating outpatient pediatric infections has increased over the study period, researchers based at the University of Kentucky reported today in the Journal of the Pediatric Infectious Diseases Society.
Cefdinir is an oral third-generation cephalosporin that, despite its ease of prescribing in children, isn't recommended as first-line therapy because of pharmacokinetics concerns and unnecessarily broad and mismatched coverage. The authors looked at cefdinir prescribing patterns as part of an effort to understand why Kentucky has the highest rate of antibiotic prescribing for children. The researchers had previously found an overall decrease in antibiotic use in Kentucky; however, the number of cefdinir prescriptions rose over that period.
In the current study, the researchers linked pharmacy claims to medical claims to better understand diagnoses related to cefdinir use. Of 3.6 million antibiotic prescriptions filled over the 5-year study period, 10% were for cefdinir, which led to a cost of $18 million—22% of all Medicaid antibiotic spending. Rates of use rose from 140 per 1,000 children in 2012 to 209 per 1,000 in 2016. During the same timeframe, amoxicillin use was stable and rates of azithromycin and amoxicillin-clavulanate declined.
Upper respiratory infections accounted for most cefdinir use, and the team saw a shift toward higher prescribing in young children and provider type from physicians to nurse practitioners, consistent with overall antibiotic prescribing in Kentucky's Medicaid recipients.
Given that much of the use was probably inappropriate and that the drug is costly, the authors wrote, "Cefdinir is the ideal target for outpatient stewardship; it is both inappropriately prescribed and also expensive, so reducing use may lead to better patient care as well as substantial cost savings.
Dec 11 J Pediatric Infect Dis Soc abstract
Colistin resistance MCR genes found in Ecuador, China clusters
Originally published by CIDRAP News Dec 11
In the latest in colistin resistance genes, Ecuadorian researchers yesterday reported a household animal-human cluster of MCR-1, and Chinese investigators today report a cluster of colistin- and carbapenem-resistant K pneumoniae carrying both NDM-1 and MCR-8 resistance genes.
In the first study, published in the Journal of Global Antimicrobial Resistance, the scientists attempted to detect possible sources of colistin-resistant Escherichia coli after a boy was determined to have Ecuador's first case of MCR-1–containing E coli carriage. They collected fecal swabs and soil fecal samples from domestic animals in the boy's home.
The researchers found MCR-1.1 in three isolates, from two dogs and a chicken. The three isolates were on three different E coli sequence types, and the human isolate was found on a fourth sequence type.
The authors conclude, "Our results indicate a polyclonal dissemination of mcr-1.1 in the environment surrounding the first MCR-producing E. coli strain reported in Ecuador."
Dec 10 J Glob Antimicrob Resist study
In the second study, researchers in Chengdu, the capital of Sichuan province, detail a cluster of five carbapenem-resistant K pneumoniae strains from patients in two hospitals, four of which were also resistant to colistin. The findings appear in the Journal of Infectious Diseases.
Whole-genome sequencing identified NDM-1 (New Delhi metal-beta-lactamase), which confers resistance to carbapenem antibiotics. The four colistin-resistant strains harbored a new variant of MCR-8, called MCR-8.2, which differs from MCR-8.1 by four amino acid substitutions. The authors say the findings represent an emerging threat for clinical management.
Dec 11 J Infect Dis abstract
Stewardship intervention at VA clinics shows durable success, study finds
Originally published by CIDRAP News Dec 9
A multifaceted outpatient stewardship intervention at Veterans Affairs primary care clinics in Pennsylvania was associated with sustained reductions in overall, unnecessary, and suboptimal antibiotic prescription rates for up to a year after some components were discontinued, researchers reported today in Clinical Infectious Diseases.
The intervention at seven primary care clinics in the Veterans Affairs Pittsburgh Healthcare System (VAPHS), implemented in response to high rates of inappropriate antibiotic use, involved clinician education, peer comparisons of overall antibiotic prescribing rates (provided to prescribers in monthly emails), and a clinical decision support electronic order set, and was directed against all antibiotic prescribing.
The intervention was tied to a significant reduction in total and unnecessary antibiotic prescribing, but after 6 months, peer comparisons were discontinued. To evaluate whether benefits of the intervention were sustained after ending peer comparisons, researchers from VAPHS, the University of Pittsburgh, and Allegheny Health Network analyzed overall, unnecessary, and suboptimal antibiotic prescribing during the baseline period (January to June 2016), the intervention period (January to June 2017), and the post-intervention period (January to June 2018).
When adjusted for seasonality, the results showed that the mean antibiotic prescribing rate fell from 76.9 prescriptions per 1,000 office visits during the baseline period to 49.5 per 1,000 office visits (a 35.6% reduction) and remained significantly lower during the post-intervention period (56.3 per 1,000 office visits, 26.8% lower than the baseline). The rate of unnecessary antibiotic prescribing fell from 58.8% during baseline to 37.8% during the intervention and 44.3% post-intervention. Overall, 19.9% of antibiotics were prescribed optimally during the baseline period, compared with 36.6% during the intervention and 34.9% during the post-intervention period.
Although the results show the intervention achieved durable success, the authors note that roughly 40% of antibiotic prescriptions were still not indicated and 65% were suboptimal. In response to the data, they have reinstituted an ongoing education and peer-comparison based approach.
"While we observed long-term benefits after withdrawing peer comparison, our experience suggests that best results will be attained with sustained rather than time-limited interventions," they write.
Dec 9 Clin Infect Dis abstract
Hospital stewardship program linked to lower antibiotic use, AMR
Originally published by CIDRAP News Dec 9
In another study published today in Clinical Infectious Diseases, Canadian researchers reported that implementation of a comprehensive hospital-based antibiotic stewardship program (ASP) at a Toronto hospital resulted in reduced antibiotic use and was associated with a significant decline in institutional antimicrobial resistance (AMR).
The controlled interrupted time series study by researchers from the University of Toronto and Sunnybrook Health Sciences Centre looked at 14 years (October 2002 to September 2016) of data from Sunnybrook's Bayview Campus, a 627-bed teaching hospital where an ASP was implemented in 2009. The ASP involved dedicated infectious diseases physicians and pharmacists providing regular service-specific education, hospital-wide antibiotic guidelines, formulary restrictions, and pharmacist-led prospective audit-and-feedback for targeted antibiotics. The primary outcome analyzed in the study was the change in incidence of hospital-acquired antibiotic-resistant organisms (HA-AROs) and multidrug-resistant organisms (HA-MDROs) among clinical isolates.
The analysis found statistically significant shifts in consumption of targeted antibiotics (incidence rate ratio [IRR], 0.98; 90% confidence interval [CI], 0.87 to 1.10), non-targeted antibiotics (IRR, 0.93; 95% CI, 0.83 to 1.04), and total antibiotics (IRR, 0.94; 95% CI, 0.85 to 1.04) during the intervention period, corresponding with a 9% reduction in HA-ARO burden (IRR, 0.91; 95% CI, 0.83 to 0.99) and 13% reduction in HA-MDRO burden (IRR, 0.87; 95% CI, 0.73 to 1.04).
This occurred despite an upward trajectory in community associated (CA) antibiotic resistance rates throughout the baseline and intervention periods, during which CA-ARO burden rose by 40% (IRR, 1.40; 95% CI, 1.28 to 1.54) and CA-MDRO burden rose by 68% (IRR, 1.68; 95% CI, 1.57 to 1.82).
Dec 9 Clin Infect Dis abstract
Review of penicillin allergy may lower use of non–beta-lactams
Originally published by CIDRAP News Dec 9
More than two thirds of patients with reported penicillin allergies at a Miami hospital were able to take other beta-lactam antibiotics, according to research presented today at the midyear clinical meeting of the American Society of Health System Pharmacists (ASHP).
In the study, pharmacists from Baptist Hospital of Miami interviewed 63 patients with reported penicillin allergies and then reviewed their medication histories prior to verifying orders for alternative antibiotics. The reviews revealed that 43 of the 63 patients (68%) had previously and successfully used other beta-lactam antibiotics, most often cephalosporins, and that aztreonam and levofloxacin were the most commonly prescribed non–beta-lactam antibiotics before the assessment. The pharmacists recommended switching these patients to a beta-lactam antibiotic, and the substitution saved the hospital $21,500 over 3 months.
Penicillin allergies are reported by up to 10% of the population, but research has shown that more than 95% of patients reporting penicillin allergy are not truly allergic. Non–beta-lactam substitutions are frequently more expensive, broader spectrum, and associated with more side effects.
"The prevalence of this perceived allergy makes our study particularly useful to hospitals and healthcare systems as they look at better patient care and cost reductions," Rita Chamoun, PharmD, clinical staff pharmacist at Baptist Hospital of Miami and lead author of the study, said in an ASHP press release. "Working together, pharmacists and other medical professionals can find alternatives that work for some patients. A multi-disciplinary approach is key to optimizing therapy in patients with a reported penicillin allergy."
Chamoun said the study also illustrates the importance of evaluating and improving antibiotic allergy documentation.
Dec 9 ASHP press release
