Antimicrobial Activity of Ceftolozane/Tazobactam and Comparator Agents Tested Against Pseudomonas aeruginosa Isolates From United States Medical Centers (2013)

BACKGROUND: Ceftolozane/tazobactam (TOL/TAZ) is a novel antibacterial with activity against P. aeruginosa (PSA) and most ESBL-producing Enterobacteriaceae. TOL/TAZ is currently under review by the FDA. Studies in VAP/HAP are ongoing. METHODS: 1081 PSA isolates were consecutively collected in 2013 from 30 USA medical centers by the Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS). Susceptibility (S) testing was performed by CLSI broth microdilution methods (TOL/TAZ at a fixed 4 µg/mL of TAZ). RESULTS: TOL/TAZ (MIC 50/90 , 0.5/2 µg/mL) was 4- to 16-fold more active than ceftazidime (CAZ; MIC 50/90 , 2/32 µg/mL; 84.7% S) and inhibited 98.2 and 96.4% of isolates at MIC of ≤8 and ≤4 µg/mL, respectively (Table summarizes the activities of anti-PSA agents). The highest TOL/TAZ MIC among CAZ-S strains was 8 µg/mL (99.3% inhibited at ≤2 µg/mL). TOL/TAZ inhibited 88.5% of CAZ non-S (MIC 50/90 , 2/16 µg/mL) and 92.8% of meropenem (MEM) non-S (MIC 50/90 , 1/8 µg/mL) PSA at ≤8 µg/mL. Among PSA strains non-S to both CAZ and MEM (85 strains), TOL/TAZ (MIC 50/90 , 4/>32 µg/mL) inhibited 82.4% at ≤8 µg/mL. TOL/TAZ was also active against strains non-S to MEM, CAZ, and piperacillin/tazobactam (P/T; 84.2% inhibited at ≤8 µg/mL). At MIC ≤8 µg/mL, TOL/TAZ inhibited 89.2 and 93.7% of PSA non-S to gentamicin (GEN) and ciprofloxacin (CIP), respectively. Among PSA strains non-S to both GEN and CIP (85 strains), TOL/TAZ inhibited 87.1% at ≤8 µg/mL. Further, 82.7% (43/52) of strains non-S to CIP, GEN, and MEM had TOL/TAZ MIC of ≤8 µg/mL. Overall, the most active agents were TOL/TAZ (MIC 50/90 , 0.5/2 µg/mL), colistin (MIC 50/90 , 1/2 µg/mL; 99.9% S), and amikacin (MIC 50/90 , 2/8 µg/mL; 96.8% S). S rates for CAZ (84.7%), cefepime (83.5%), P/T (78.5%), MEM (80.6%), doripenem (84.2%), CIP (76.6%), and GEN (88.9%) were lower than TOL/TAZ at ≤8 (98.2%) or ≤4 µg/mL (96.4%).