1485. Antimicrobial Activity of Ceftolozane-Tazobactam Tested Against Contemporary (2015–2017) Gram-Negative Isolates from Patients with Pneumonia in US Medical Centers

Abstract

BackgroundCeftolozane-tazobactam (C-T) is a combination antipseudomonal cephalosporin and β-lactamase inhibitor. C-T has been approved in >50 countries for treating adults with complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections in combination with metronidazole. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance among Gram-negative (GN) isolates worldwide. In the current study, isolates were collected from US patients hospitalized with pneumonia (PIHP) from 2015–2017.MethodsA total of 4,337 GN isolates, including 2,102 Enterobacteriaceae (ENT) and 1,528 Pseudomonas aeruginosa (PSA) isolates, were collected in 2015–2017 from 30 US hospitals and tested for C-T susceptibility (S) by CLSI broth microdilution at JMI Laboratories. Only 1 isolate per patient per infection episode was included. Other antibiotics tested were amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), levofloxacin (LVX), meropenem (MEM), and piperacillin–tazobactam (TZP).-resistant (R) phenotypes analyzed were ENT R to doripenem, imipenem, or meropenem (CRE) and extended-spectrum β-lactamase (ESBL, non-CRE). Multidrug-resistant (MDR) isolates were identified as nonsusceptible (NS) to 3 or more antimicrobial classes. PSA phenotypes analyzed were CAZ-NS, MEM-NS, and TZP-NS.ResultsOf the 4,337 GN isolates, 3,820 (88.1%) had a C-T MIC ≤8 mg/L. The three most prevalent GN species isolated from PIHP were PSA (n = 1,528; 35.2%), Klebsiella pneumoniae (KPN, n = 562; 13.0%), and Escherichia coli (EC, n = 434; 10.0%). The %S of C-T and comparators for the top 3 pathogens are shown in the table. C-T showed activity against these isolates with %S of 96.5, 88.6, and 97.5% against EC, KPN, and PSA, respectively.ConclusionC-T demonstrated activity against the most prevalent contemporary GN isolates from PIHP in the US. C-T was the only β-lactam that had >88%S against all 3 species: EC, KPN, and PSA. C-T and COL were the only agents tested that had >95%S for EC and PSA pathogens in PIHP. For PSA, C-T maintained activity against isolates resistant to CAZ, TZP, and MEM. These data suggest that C-T may be a useful treatment for GN infections causing PIHP. Disclosures S. J. R. Arends, Merck: Research Contractor, Research support. D. Shortridge, Merck: Research Contractor, Research support. L. R. Duncan, Merck: Research Contractor, Research support. J. M. Streit, Merck: Research Contractor, Research support. R. K. Flamm, Merck: Research Contractor, Research support.