title: Antimicrobial activity of ceftolozane/tazobactam tested against Pseudomonas aeruginosa and Enterobacteriaceae with various resistance patterns isolated in European hospitals (2011-12).
abstract: OBJECTIVE
  To evaluate the in vitro activity of ceftolozane/tazobactam and comparator agents tested against contemporary Gram-negative bacteria. Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor.
  
  
  METHODS
  A total of 10 532 Gram-negative organisms (2191 Pseudomonas aeruginosa and 8341 Enterobacteriaceae) were consecutively collected from 31 medical centres located in 13 European countries plus Turkey and Israel. The organisms were tested for susceptibility by broth microdilution methods as described by the CLSI M07-A9 document and the results interpreted according to EUCAST as well as CLSI breakpoint criteria. Selected ceftazidime- and/or meropenem-resistant P. aeruginosa isolates were screened for the presence of β-lactamase genes by PCR.
  
  
  RESULTS
  P. aeruginosa exhibited high rates of multidrug-resistant (31.9%) and extensively drug-resistant (24.6%) isolates and 11.6% of isolates were susceptible only to colistin. When tested against P. aeruginosa, ceftolozane/tazobactam (MIC(50), 1 mg/L) was generally 4-fold more active than ceftazidime (MIC(50), 4 mg/L) and inhibited >90% of isolates with an MIC of ≤8 mg/L in nine countries. In contrast, the highest susceptibility rates observed for ceftazidime and meropenem, respectively, were 86.0%/86.0% (UK) and 85.2%/86.1% (Ireland) (67.2%/67.1% overall). Ceftolozane/tazobactam (MIC(50/90), 0.25/2 mg/L; 93.7% and 95.2% inhibited at ≤4 and ≤8 mg/L, respectively), meropenem [MIC(50/90), ≤0.06/≤0.06 mg/L; 98.0% susceptible (EUCAST)] and tigecycline [MIC(50/90), 0.12/1 mg/L; 94.1% susceptible (EUCAST)] were the most active compounds tested against Enterobacteriaceae.
  
  
  CONCLUSIONS
  Ceftolozane/tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than currently available cephalosporins and piperacillin/tazobactam when tested against Enterobacteriaceae.
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA helio-sader@jmilabs.com.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D003428:Cross Infection; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000453:epidemiology / Q000382:microbiology; D005060:Europe; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000453:epidemiology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D000078142:Tazobactam; D018440:beta-Lactam Resistance / Q000235:genetics; D065093:beta-Lactamase Inhibitors / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D065093:beta-Lactamase Inhibitors; C519491:ceftolozane; D010397:Penicillanic Acid; D000078142:Tazobactam
keywords: ESBLs; XDR; cephalosporins; multidrug resistant; β-lactamase inhibitors