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

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...

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Detalles Bibliográficos
Autores principales: Arends, S J Ryan, Shortridge, Dee, Duncan, Leonard R, Streit, Jennifer M, Flamm, Robert K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6252399/
http://dx.doi.org/10.1093/ofid/ofy210.1314
Descripción
Sumario: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. 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 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. 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. [Image: see text] 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.