Activity of Ceftolozane-Tazobactam and Comparators When Tested against Bacterial Surveillance Isolates Collected from Pediatric Patients in the US during 2012–2016 as Part of a Global Surveillance Program

Abstract

Background. Cefolozane-tazobactam (C-T) is an antibacterial combination of a novel antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T was approved by the US Food and Drug Administration in 2014 and by the European Medicine Agency in 2015 to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections in adults. The Program to Assess Cefolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide. Methods. A total of 4121 GN isolates were collected during 2012-2016 from pediatric patients (<18 years old) in 31 US hospitals and tested for C-T susceptibility (S) by CLSI broth microdilution method in a central monitoring laboratory (JMI Laboratories). Other antibiotics tested were amikacin (AMK), cefepime (FEP), cef-tazidime (CAZ), colistin (COL), levofoxacin (LVX), meropenem (FOS), and pip-eracillin-tazobactam (TZP). Antibiotic-resistant phenotypes identified using CLSI (2017) clinical breakpoints included: carbapenem-resistant Enterobacteriaceae (CRE), non-CRE extended-spectrum β-lactamase screen positive (ESBL, non-CRE), cefazi-dime-nonsusceptible (CAZ-NS), and meropenem-NS (MER-NS). EUCAST (2017) COL clinical breakpoints were used for Enterobacteriaceae (ENT). Results. The most common infection type in hospitalized pediatric patients was pneumonia (n = 1,488) followed by urinary tract infection (n = 1,143) and bloodstream infection (n = 767). A total of 2,969 ENT and 1,152 non-enterics were isolated. The 5 most common species were Escherichia coli (EC: 1,311), Pseudomonas aeruginosa (PSA: 821 isolates), Klebsiella pneumoniae (KPN: 429), Enterobacter cloacae complex (ECC: 360), and Serratia marcescens (SM: 264). Susceptibilities of C-T and comparators for the main species and resistant phenotypes are shown in the Table. Only 7 isolates were CRE in this study. Conclusion. C-T demonstrated good activity against pediatric ENT isolates (96.1%S), EC (99.2%S), and KPN (97.9%S). For ENT, all agents but COL had >90% S. For PSA, C-T demonstrated potent activity (99.5%S) and was the most potent antibiotic tested with activity similar to COL.