title: Ceftazidime-avibactam activity when tested against ceftazidime-nonsusceptible Citrobacter spp., Enterobacter spp., Serratia marcescens, and Pseudomonas aeruginosa from Unites States medical centers (2011-2014).
abstract: A total of 6910 Enterobacteriaceae with inducible AmpC β-lactamases and 5328 Pseudomonas aeruginosa were collected from 71 US hospitals in 2011-2014 and were susceptibility tested using the reference broth microdilution method. Ceftazidime-avibactam demonstrated potent in vitro activity against all 3 Enterobacteriaceae genus groups evaluated, with MIC(50)/MIC(90) values of 0.12/0.5 μg/mL for Enterobacter spp. and Serratia marcescens and 0.12/0.25 μg/mL for Citrobacter spp. (99.8-99.9% susceptibility rates at ≤8 μg/mL). Furthermore, 99.3% of ceftazidime-nonsusceptible Enterobacteriaceae isolates (1015 of 1022) were susceptible to ceftazidime-avibactam (MIC(50)/MIC(90) of 0.25-0.5/1-2 μg/mL), whereas susceptibility rates for cefepime ranged from 45.9% (Citrobacter spp.) to 80.0% (S. marcescens). Ceftazidime-avibactam was also very active against P. aeruginosa (MIC(50)/MIC(90), 2/4 μg/mL; 96.8% inhibited at ≤8 μg/mL). P. aeruginosa susceptibility rates to other antipseudomonal β-lactams ranged from 79.6% for piperacillin-tazobactam to 84.5% for cefepime. Ceftazidime-avibactam inhibited 67.4% of isolates at ≤8 μg/mL (MIC(50)/MIC(90), 8/32 μg/mL) that were nonsusceptible to ceftazidime, cefepime, piperacillin-tazobactam, and meropenem.
authors.affiliation: JMI Laboratories, North Liberty, IA, USA. Electronic address: helio-sader@jmilabs.com.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, North Liberty, IA, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
authors.affiliation: JMI Laboratories, North Liberty, IA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.affiliation: JMI Laboratories, North Liberty, IA, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
authors.affiliation: JMI Laboratories, North Liberty, IA, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D004338:Drug Combinations; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology*; D006761:Hospitals; D006801:Humans; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D014481:United States
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D002442:Ceftazidime
keywords: Class C beta-lactamases; Derepressed AmpC; Gram-negative bacilli; cephalosporinases