1964. Microbiological Outcomes With Plazomicin (PLZ) vs. Colistin (CST) in Patients With Bloodstream Infections (BSI) Caused by Carbapenem-Resistant Enterobacteriaceae (CRE) in the CARE Study

Abstract

Background. PLZ is a next-generation aminoglycoside with structural modifications that protect it from aminoglycoside-modifying enzymes (AMEs) and in vitro activity against multidrug-resistant (MDR) Enterobacteriaceae, including aminoglycoside-and carbapenem-resistant strains. In the CARE study, PLZ was associated with improvement in 28-day all-cause mortality vs. CST in patients with CRE BSI. We report the microbiological outcomes in the CARE study by pathogen and key resistance mechanism. Methods. CARE was a multinational, open-label trial that enrolled BSI patients with documented or presumed CRE into two cohorts. Patients in the randomized cohort received PLZ (15 mg/kg q24h IV) or CST (300-mg load [CST base activity] then 5 mg/kg/day IV) plus adjunctive tigecycline or meropenem. Patients in the observational cohort received PLZ plus investigator's choice of adjunctive agent. Treatment duration was 7-14 days. Isolate identification and susceptibility testing were conducted by a central laboratory. Whole-genome sequencing was used to identify AME and carbapenemase genes. Microbiological outcomes were assessed in patients with confirmed CRE who received ≥1 dose of study drug (mMITT population). Results. Of 45 BSI patients enrolled, 43 had confirmed CRE (mMITT), including Klebsiella pneumoniae (n = 42) and Enterobacter aerogenes (n = 1). Against CRE, PLZ MICs ranged from 0.12 to >128 μg/mL; 25/28 (89.3%) isolates from PLZtreated patients had a PLZ MIC ≤4 μg/mL, while 3 had a PLZ MIC ≥128 μg/mL and a confirmed 16S ribosomal methyltransferase gene. CST MICs ranged from 0.25 to >128 μg/mL; 6/16 (37.5%) isolates from CST-treated patients had an MIC >2 μg/mL. There were 47 distinct Enterobacteriaceae pathogens isolated from 43 patients, and of these, AME genes were detected in 43/47 (91.5%), most commonly aac(6')-Ib (n = 29). Carbapenemase genes were detected in 45/47 (95.7%) isolates, most commonly blaKPC (n = 33). PLZ demonstrated higher microbiological eradication rates than CST against CRE, including AME-and carbapenemase-producing isolates (table). Conclusion. The results provide evidence of the efficacy of PLZ-based therapy for patients with BSI due to MDR Enterobacteriaceae, including AME-and carbapenemase-producing organisms. (Table Presented).