title: Antimicrobial Activity of High-Proportion Cefepime-Tazobactam (WCK 4282) against a Large Number of Gram-Negative Isolates Collected Worldwide in 2014.
abstract: Cefepime-tazobactam (WCK 4282) is currently under clinical development for use at a dosage of 2 g/2 g every 8 h. A total of 7,981 isolates were collected from 146 medical centers (39 countries) in 2014 as a part of the SENTRY Antimicrobial Surveillance Program, and their susceptibilities to cefepime-tazobactam (with tazobactam at fixed concentrations of 4 and 8 μg/ml) were tested by a reference broth microdilution method. Isolates were mainly from patients with pneumonia (29.5%) and bloodstream infections (26.9%). Cefepime-tazobactam (with tazobactam at a fixed concentration of 8 μg/ml) and cefepime inhibited 96.9 and 87.9% ofEnterobacteriaceaestrains at ≤8 μg/ml. The activity of cefepime-tazobactam againstEnterobacteriaceaestrains was comparable to that of meropenem (96.7% of isolates were susceptible) and greater than that of piperacillin-tazobactam (87.7% susceptible). AllEnterobacteriaceaespecies from the United States exceptKlebsiella pneumoniaehad >99.0% of isolates inhibited by cefepime-tazobactam at ≤8/8 μg/ml. The prevalence of the extended-spectrum β-lactamase (ESBL)-screening-positive phenotype was the highest amongEscherichia coliisolates in China (66.3%) and amongK. pneumoniaeisolates (58.0%) in Latin America. Cefepime-tazobactam at ≤8/8 μg/ml inhibited 98.7 and 71.3% of ESBL-screening-positive phenotypeE. colistrains andK. pneumoniaestrains, respectively. Meropenem showed limited activity against ESBL-screening-positive phenotypeK. pneumoniaestrains (69.6% susceptible). Cefepime-tazobactam was active againstEnterobacterspp. (MIC50and MIC90, 0.06 and 0.5 μg/ml, respectively), including ceftazidime-nonsusceptible isolates (96.1% of isolates were inhibited by cefepime-tazobactam at ≤8/8 μg/ml). The activity of cefepime-tazobactam againstPseudomonas aeruginosa(82.4 and 91.6% of isolates were inhibited by cefepime-tazobactam at ≤8/8 and ≤16/8 μg/ml, respectively) was comparable to that of meropenem and piperacillin-tazobactam (79.2% susceptible). In summary, cefepime-tazobactam was highly active againstP. aeruginosaandEnterobacteriaceaestrains, including ESBL-screening-positive phenotypeE. colistrains and ceftazidime-nonsusceptibleEnterobacterspp. These results support the further clinical development of the cefepime-tazobactam combination.
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA helio-sader@jmilabs.com.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Rodrigo E
authors.initials: RE
authors.lastname: Mendes
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000077723:Cefepime; D002511:Cephalosporins / Q000494:pharmacology*; D004755:Enterobacteriaceae / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D007711:Klebsiella pneumoniae / Q000187:drug effects; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D000077725:Piperacillin, Tazobactam Drug Combination; D000078142:Tazobactam; D013845:Thienamycins / Q000494:pharmacology; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D013845:Thienamycins; D000077725:Piperacillin, Tazobactam Drug Combination; D000077723:Cefepime; D010397:Penicillanic Acid; D001618:beta-Lactamases; D000077731:Meropenem; D000078142:Tazobactam; D010878:Piperacillin
keywords: cefepime-tazobactam