Background: Ceftolozane/tazobactam (TOL/TAZ) is an antipseudomonal cephalosporin with a beta-lactamase inhibitor currently in clinical development in patients with ventilated nosocomial bacterial pneumonia, and recently approved for complicated intra-abdominal infections (in combination with metronidazole) and complicated urinary tract infections in the United States (USA).
Methods: 1,052 Gram-negative (GN) pathogens were consecutively collected from various infection sources in patients in intensive care units (ICU) in 26 USA hospitals in 2013 and 2014, were tested for susceptibility (S) by CLSI broth microdilution methods (TOL/TAZ at a fixed 4 µg/mL of TAZ). USA-FDA breakpoints for S were applied (≤2 µg/mL for Enterobacteriaceae [ENT]; ≤4 µg/mL for P. aeruginosa [PSA]).
Results: The most frequently isolated GN organisms were PSA (27.1%), E. coli (EC; 20.2%), K. pneumoniae (KPN; 15.2%), and Enterobacter spp. (ESP; 12.3%). MIC90 and %S to TOL/TAZ, piperacillin/tazobactam (PIP/TAZ), ceftazidime (CAZ), cefepime (FEP) and meropenem (MEM) are summarized in the Table. Against PSA, TOL/TAZ (95.8 %S) was the most active beta-lactam (B-L) agent tested, being up to eight-fold more potent than FEP (the next most active agent). MEM was the most active B-L agent tested against ENT 94.3% followed by TOL/TAZ 88.4% and CEF 87.2. S to EC was high (>97%) TOL/TAZ and MEM and lower (85.4 to 91.5%) for FEP, CAZ and PIP/TAZ. Only 80.0% of KPN were S to MEM and this was reflected in the activity of the other agents tested (S ranged from 73.8% for CAZ to 76.9% for TOL/TAZ). ESBL phenotype was observed among 17.9 and 28.1% of EC and KPN, respectively. The rank order of activity against ESP was MEM>FEP>TOL/TAZ>PIP/TAZ>CAZ.
Conclusion: TOL/TAZ was the most active B-L agent tested (including MEM) against the most prevalent GN pathogen (PSA), and second to MEM in activity against ENT collected from patients in ICU in USA hospitals during 2013 and 2014.
D. J. Farrell,
Merck & Co., Inc.:
M. Castanheira, Merck & Co., Inc.: Research Contractor , Research support
R. N. Jones, Merck & Co., Inc.: Research Contractor , Research support