Antimicrobial Activity of Ceftolozane–Tazobactam Tested against Contemporary (2012–2016) Enterobacteriaceae and Pseudomonas aeruginosa from ICU vs. non-ICU Isolates Collected in US Medical Centers

Abstract

BackgroundCeftolozane-tazobactam (C-T) is a combination of a novel antipseudomonal cephalosporin and a well-described β-lactamase inhibitor. C-T was approved by the United States (US) Food and Drug Administration in 2014 for complicated urinary tract infections, including acute pyelonephritis and complicated intra-abdominal infections. C-T is currently in clinical trials for the treatment of hospital-acquired pneumonia. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide. This study compares the activities of C-T and comparators against GN isolates from ICU patients and non-ICU patients.MethodsA total of 3,100 GN ICU isolates and 3,271 isolates from non-ICU patients were collected from 30 US hospitals in 2012–2016. Isolates were tested for susceptibility (S) to C-T and comparators by CLSI broth microdilution methodology in a central monitoring laboratory. Other antibiotics tested included amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), meropenem (MER), and piperacillin-tazobactam (TZP). CLSI (2017) interpretive criteria were used for all except COL with Enterobacteriaceae (ENT), for which EUCAST (2017) criteria were used.ResultsThe most common ENT species from ICU and non-ICU patients were similar. The 3 most common ENT for ICU and non-ICU isolates were Klebsiella pneumoniae, 24.1% and 25.8%; Escherichia coli, 19.4% and 18.2%; and Serratia marcescens, 14.7% and 14.3%, respectively. The most common non-enteric species was Pseudomonas aeruginosa (PSA) for ICU and non-ICU (72.7% and 78.2%). ICU ENT isolates generally had a lower %S than non-ICU (Table). ENT showed more variability than PSA for %S between ICU and non-ICU.ConclusionFor ENT overall, MER and AMK were the most active, followed by C-T. Comparing ICU and non-ICU, MER and C-T were slightly more active vs. non-ICU ENT, while AMK %S was similar for both. For PSA, COL was the most active; C-T and AMK were similar. Activities between ICU and non-ICU isolates were similar for C-T and COL while AMK was more active vs. ICU isolates, and MER was more active vs. non-ICU. C-T showed potent activity against ICU and non-ICU isolates for ENT and PSA.Disclosures D. Shortridge, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; M. A. Pfaller, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant