Background: Ceftolozane-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.
Materials/Methods: A 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.
Results: Of the 4,337 GN isolates, 3,820 (88.1%) had a C-T MIC ≤ 8 mg/L. The 3 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.
Conclusion: C-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.
S. J. R. Arends,
L. R. Duncan, Merck: Research Contractor , Research support .
J. M. Streit, Merck: Research Contractor , Research support .
R. K. Flamm, Merck: Research Contractor , Research support .