1273. Activity of Ceftolozane/Tazobactam and Comparators Against Enterobacterales and P. aeruginosa Isolates from Pediatric Patients—SMART United States 2017-2019

Abstract

BackgroundCeftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor approved by FDA and EMA for complicated urinary tract (cUTI) and complicated intraabdominal infections (cIAI), as well as hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP) in patients ≥18 years. Clinical trials studying the use of C/T for pediatric patients with cUTI and cIAI are completed, and HABP/VABP pediatric studies are underway. We evaluated the antimicrobial activity of C/T against gram-negative isolates collected from patients ≤17 years in the United States (US) as part of the global SMART surveillance program.MethodsIn 2017-2019, 27 US clinical labs each collected up to 250 consecutive gram-negative pathogens per year. A total of 1336 isolates were collected from pediatric patients. MICs were determined using CLSI broth microdilution and breakpoints. C/T-nonsusceptible Enterobacterales (Ebact) and P. aeruginosa were screened for genes encoding β-lactamases.ResultsAmong the 944 collected Ebact and 220 P. aeruginosa isolates, 40.7% and 76.4%, respectively, were collected from patients with respiratory tract infections, 37.0% and 10.0% from UTI, 13.7% and 8.2% from IAI, and 8.3% and 5.0% from bloodstream infections. The table shows antimicrobial susceptibility of Ebact, P. aeruginosa, and select phenotypes. C/T was active against 98% of Ebact, including 50 of 51 and 12 of 13 ESBL-non-CRE phenotype E. coli and K. pneumoniae, respectively. Among P. aeruginosa, C/T was active against 95% of isolates, 9-21 percentage points higher than the comparator β-lactams, and it maintained activity against 71-75% of P. aeruginosa isolates nonsusceptible to commonly used β-lactams. Among the 21 C/T-nonsusceptible Ebact, 2 isolates carried KPC and ESBL and 3 isolates carried only ESBL; in 16 isolates no β-lactamases were detected, of which 15 were species with intrinsic AmpC. Among 12 C/T-nonsusceptible P. aeruginosa, no acquired β-lactamases were detected, likely indicating chromosomally-mediated resistance mechanisms.Results Table ConclusionC/T could be a potential new treatment option for US pediatric patients with infections caused by Ebact and P. aeruginosa, including resistant phenotypes.Disclosures Sibylle Lob, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor) Meredith Hackel, PhD MPH, IHMA (Employee)Pfizer, Inc. (Independent Contractor) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Kelly Harris, PharmD, BCPS, Merck & Co. Inc (Employee) Katherine Young, MS, Merck (Employee) Mary Motyl, PhD, Merck & Co., Inc. (Employee, Shareholder) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Independent Contractor)