247Antimicrobial Activity of Ceftolozane/Tazobactam Tested against Gram-negative Bacterial Isolates from Hospitalized Patients with Pneumonia in United States Hospitals (2013)

David J. Farrell, Helio S. Sader, Robert K. Flamm, Ronald N. Jones
2014 Open Forum Infectious Diseases  
■ Ceftolozane/tazobactam is an antibacterial consisting of ceftolozane, a novel antipseudomonal cephalosporin, with tazobactam, a well-established β-lactamase inhibitor. ■ Ceftolozane exerts its bactericidal activity by inhibiting essential penicillin-binding proteins, resulting in inhibition of cell-wall synthesis and subsequent cell death. Ceftolozane has demonstrated greater activity against Pseudomonas aeruginosa when directly compared with ceftazidime and cefepime. ■ Tazobactam is a potent
more » ... obactam is a potent inhibitor of most common Class A and some Class C β-lactamases that protects ceftolozane from hydrolysis, by binding to the active site of these enzymes, and broadens coverage to include most extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and some AmpC-derepressed Enterobacteriaceae. ■ In clinical trials, ceftolozane/tazobactam demonstrated superior clinical efficacy to high-dose levofloxacin for the treatment of patients with complicated lower urinary tract infection/pyelonephritis. Ceftolozane/tazobactam plus metronidazole was as efficacious as meropenem in patients with complicated intra-abdominal infection (cIAI). RESULTS ■ P. aeruginosa was the most common pathogen (40.4%) and ceftolozane/tazobactam was the most active β-lactam tested against P. aeruginosa (MIC required to inhibit the growth of 50%/90% of organisms [MIC 50/90 ], 0.5/2 µg/mL; 97.6% inhibited at ≤8 µg/mL; Tables 1 to 3). P. aeruginosa was moderately susceptible to ceftazidime (83.0%), cefepime (81.2%), meropenem (78.1%), piperacillin/tazobactam (75.7%), levofloxacin (72.6%), and gentamicin (86.0%). Most isolates were susceptible to amikacin (95.2%) and colistin (99.8%; Table 3). ■ Ceftolozane/tazobactam showed activity against ceftazidime-non-susceptible (85.9% inhibited at ≤8 µg/mL), cefepime-non-susceptible (88.1% inhibited at ≤8 µg/mL), meropenem-non-susceptible P. aeruginosa (91.3% inhibited at ≤8 µg/mL), and isolates non-susceptible to meropenem + ceftazidime + piperacillin/tazobactam (78.3% inhibited at ≤8 µg/mL), and other antimicrobial agents (Tables 1, 2; Figure 1). Ceftolozane/tazobactam inhibited 86.2% of MDR (16.2% of all P. aeruginosa isolates) and 77.1% of XDR (8.3% of all P. aeruginosa isolates) P. aeruginosa isolates at MICs of ≤8 µg/mL (Table 1). No PDR strains of P. aeruginosa were found. ■ Ceftolozane/tazobactam was very active (MIC 50/90 , 0.5/4 µg/mL; 90.6/92.3% inhibited at ≤4/≤8 µg/mL) against 776 Enterobacteriaceae and retained activity against many MDR (13.3% of all Enterobacteriaceae isolates) and XDR (3.6% of all Enterobacteriaceae isolates), inhibiting 49.5% of MDR isolates and 17.9% of XDR isolates at MIC values of ≤8 µg/mL (Table 1). ■ Ceftolozane/tazobactam was active against E. coli (MIC 50/90 , 0.25/0.5 µg/mL; 99.3/100.0% inhibited at ≤4/≤8 µg/mL), including ESBL-phenotype isolates (MIC 50/90 , 0.25/1 µg/mL; 95.0/100.0% inhibited at ≤4/≤8 µg/mL; Table 1). All E. coli isolates were susceptible ■ Ceftolozane/tazobactam demonstrated greater in vitro activity, and susceptibility at ≤8 µg/mL, than currently available cephalosporins, carbapenems, and piperacillin/tazobactam when tested against P. aeruginosa. ■ Ceftolozane/tazobactam exhibited activity against many MDR and XDR P. aeruginosa. ■ Against Enterobacteriaceae (including MDR and XDR strains), ceftolozane/ tazobactam activity was greater than those of the other cephalosporins tested and piperacillin/tazobactam. ■ Ceftolozane/tazobactam may represent a valuable treatment option for Gram-negative infections, including pneumonia caused by MDR and XDR P. aeruginosa.
doi:10.1093/ofid/ofu052.113 fatcat:avkuljz5pbbfhn3k5axx7czoiq