title: Susceptibility Profile of Ceftolozane/Tazobactam and Other Parenteral Antimicrobials Against Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa From US Hospitals.
abstract: OBJECTIVE
  Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are frequently isolated pathogens in the hospital setting, and antimicrobial resistance among these organisms is on the rise. In an attempt to meet the challenge of gram-negative resistance, new therapies, including ceftolozane/tazobactam (C/T), were recently approved by the Food and Drug Administration, and others are in late-stage development. The purpose of this study is to describe the in vitro potency of C/T and other parenteral antimicrobials against a geographically diverse population of E coli, K pneumoniae, and P aeruginosa collected in US hospitals.
  
  
  METHODS
  In 2013 to 2014, 44 hospitals provided nonduplicate, nonurine isolates of E coli (n = 1306), K pneumoniae (n = 1205), and P aeruginosa (n = 1257) from adult inpatients. MICs for C/T and 11 other antimicrobials were determined with broth microdilution methods.
  
  
  RESULTS
  The carbapenems, C/T, and colistin displayed the highest percentage of susceptibility and lowest MIC90 against the Enterobacteriaceae, followed by piperacillin/tazobactam (TZP), cefepime, tobramycin, aztreonam, ceftriaxone, and ciprofloxacin. C/T displayed the greatest potency (MIC90 = 2 mg/L) and 97% susceptibility of all compounds against P aeruginosa. In addition, C/T was highly active against P aeruginosa that were nonsusceptible to the carbapenems or TZP or were multidrug resistant and extended-spectrum β-lactamase-producing Enterobacteriaceae.
  
  
  CONCLUSIONS
  This national survey reported high levels of nonsusceptibility to antimicrobials among both Enterobacteriaceae and P aeruginosa. In contrast, many of these resistant pathogens were susceptible to C/T. These data highlight the enhanced potency of C/T and its potential utility for commonly encountered gram-negative nosocomial pathogens.
authors.affiliation: Center for Anti-Infective Research and Development, Hartford, Connecticut.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Sutherland
authors.affiliation: Center for Anti-Infective Research and Development, Hartford, Connecticut; Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut. Electronic address: david.nicolau@hhchealth.org.
authors.forename: David P
authors.initials: DP
authors.lastname: Nicolau
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000077723:Cefepime; D002511:Cephalosporins / Q000494:pharmacology*; D003428:Cross Infection / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial; D004755:Enterobacteriaceae / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects*; D006761:Hospitals; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects*; D008826:Microbial Sensitivity Tests / Q000379:methods; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010878:Piperacillin / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D000078142:Tazobactam; D014481:United States; D001618:beta-Lactamases / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D002511:Cephalosporins; C519491:ceftolozane; D000077723:Cefepime; D010397:Penicillanic Acid; D001618:beta-Lactamases; D000078142:Tazobactam; D010878:Piperacillin
keywords: Enterobacteriaceae; Pseudomonas aeruginosa; ceftolozane/tazobactam; resistance