In vitro susceptibility of carbapenem resistant Enterobacterales to meropenem-vaborbactam and ceftazidime-avibactam at a single academic medical centre.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are considered an urgent threat. Ceftazidime-avibactam and meropenem-vaborbactam contain ß-lactamase inhibitors active against CRE isolates including those that produce Klebsiella pneumoniae carbapenemases (KPC). METHODS: Retrospective chart review of CRE isolates from 1 January 2016 to 1 November 2018. Collected data includes a descriptive overview of measured MIC values, resistance mechanism via a polymerase chain reaction test (Xpert Carba-R, Cepheid, Sunnyvale CA), as well as clinical outcomes. RESULTS: Of 106 isolates reviewed, 86 isolates met the inclusion criteria from 85 individual subjects. The breakpoint:MIC ratio for ceftazidime-avibactam overall was 4, while for meropenem-vaborbactam this ratio was 32 (p < 0.0001). For KPC isolates, ceftazidime-avibactam MIC50/MIC90 in 2016, 2017, and 2018 were 2/4 mg/L (n = 32), 2/4 mg/L (n = 17), and 2/8 mg/L (n = 30), respectively. The meropenem-vaborbactam MIC50/MIC90, for KPC isolates in 2016, 2017, and 2018 were 0.06/0.125 mg/L (n = 32), 0.06/0.1 mg/L (n = 17), and 0.06/0.5 mg/L (n = 30), respectively. Microbiologic cure was 75% (n = 16) in ceftazidime-avibactam subjects and 58.3% (n = 12) in subjects treated with alternative agents (p = 0.43). The 14- and 30-day mortality was numerically higher in subjects treated with alternate agents when compared ceftazidime-avibactam 2/9 (22.2%) vs 3/17 (17.6%) (p = 1.00) and 4/9 (44.4%) vs 4/17 (28.6%) (p = 0.38), respectively. For ceftazidime-avibactam, 30-day mortality in 2016, 2017, and 2018 was 0/5 (0%), 0/2 (0%), and 4/10 (40%). CONCLUSION: Selective pressure from the use of ceftazidime-avibactam at our institution may be decreasing its utility as a first-line agent for CRE infections. Meropenem-vaborbactam maintained low MIC values and may be a promising treatment option for CRE.

Introducing antimicrobial stewardship to the outpatient clinics of a suburban academic health system.

Objective: To establish an antimicrobial stewardship program in the outpatient setting. Design: Prescribers of antimicrobials were asked to complete a survey regarding antimicrobial stewardship. We also monitored their compliance with appropriate prescribing practices, which were shared in monthly quality improvement reports. Setting: The study was performed at Loyola University Health System, an academic teaching healthcare system in a metropolitan suburban environment. Participants: Prescribers of antimicrobials across 19 primary care and 3 immediate- and urgent-care clinics. Methods: The voluntary survey was developed using SurveyMonkeyand was distributed via e-mail. Data were collected anonymously. Rates of compliance with appropriate prescribing practices were abstracted from electronic health records and assessed by 3 metrics: (1) avoidance of antibiotics in adult acute bronchitis and appropriate antibiotic treatment in (2) patients tested for pharyngitis and (3) children with upper respiratory tract infections. Results: Prescribers were highly knowledgeable about what constitutes appropriate prescribing; verified compliance rates were highly concordant with self-reported rates. Nearly all prescribers were concerned about resistance, but fewer than half believed antibiotics were overprescribed in their office. Among respondents, 74% reported intense pressure from patients to prescribe antimicrobials inappropriately. Immediate- and urgent-care prescribers had higher rates of compliance than primary-care prescribers, and the latter group responded well to monthly reports and online educational resources. Conclusions: Intense pressure from patients to prescribe antimicrobials when they are not indicated leads to overprescribing, an effect compounded by the importance of patient satisfaction scores. Compliance reporting improved the number of appropriate antibiotics prescribed in the primary care setting.