1602. Comparative Activity of Ceftolozane-Tazobactam (C/T) and Ceftazidime-Avibactam (CZA) against Pseudomonas aeruginosa (PSA) from Patients with Cystic Fibrosis (CF)

Abstract

BackgroundAcute pulmonary exacerbations (APE) are a frequent cause of hospitalization for patients with CF. PSA is among the most common pathogen implicated in CF APE. Due to repetitive antibiotic courses, multidrug resistance (MDR) must be considered leaving few available intravenous antibiotic options. CZA and C/T are newer anti-PSA antibiotics that have been used to treat CF APE, but little data are available to compare their in vitro activity.MethodsNon-duplicate, contemporary, clinical PSA (n=105) isolates were acquired from 85 patients during CF APE from 3 US hospital systems. MICs were assessed in at least triplicate by reference broth microdilution for C/T, CZA, aztreonam (ATM), cefepime (FEP), ceftazidime (CAZ), ciprofloxacin (CIP), levofloxacin (LVX), meropenem (MEM), piperacillin/tazobactam (TZP), and tobramycin (TOB). Current CLSI breakpoints were used to define susceptibility. Activity was further assessed in MDR, CAZ and MEM non-susceptible (NS) phenotypes.ResultsThe mean patient age at isolate retrieval was 31 years (IQR: 21-43), and 20% were under 18 years. Mucoid morphology was observed in 48 (46%) isolates, and MDR defined in 41 (39%). Rates of susceptibility (MIC50/MIC90/%S) were: C/T (1/4/92%), CZA (2/8/90%), CAZ (4/64/68%), TZP (8/256/67%), TOB (2/32/63%), MEM (1/32/58%), ATM (8/64/57%), FEP (8/≥128/50%), CIP (2/8/27%), and LVX (4/16/24%). A mucoid phenotype did not alter %S (non-mucoid vs. mucoid) for C/T (93 vs. 92%) or CZA (91 vs. 88%). Among the 41 MDR PSA, activity was 2/16/83% and 4/16/76% for C/T and CZA, respectively. C/T, CZA, and MEM %S was 77, 69, and 23% for the 35 CAZ-NS isolates. C/T, CZA, and CAZ %S was 84, 77, and 39% for MEM-NS isolates.ConclusionThese contemporary PSA from patients with CF displayed low susceptibility rates to most β-lactams, fluoroquinolones, and tobramycin, and MDR was common. C/T and CZA retained similarly high susceptibility against these isolates, including MDR strains and CAZ-NS/MEM-NS phenotypes. These data justify that both CT and CZA may be considered for CF APE due to PSA non-susceptible to current standard of care treatment options.Disclosures David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support) Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)bioMérieux (Research Grant or Support, Other Financial or Material Support, Speaker Honorarium)Melinta (Research Grant or Support)Merck & Co., Inc. (Research Grant or Support)Paratek (Speaker’s Bureau)Summit (Other Financial or Material Support, Research funding (clinical trials))