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Ceftazidime/avibactam tested against Gram-negative bacteria from intensive care unit (ICU) and non-ICU patients, including those with ventilator-associated pneumonia.

Abstract
Ceftazidime/avibactam consists of ceftazidime combined with the novel non-β-lactam β-lactamase inhibitor avibactam, which inhibits Ambler classes A, C and some D enzymes. Clinical isolates were collected from 71 US medical centres in 2012-2013 and were tested for susceptibility at a central laboratory by reference broth microdilution methods. Results for 4381 bacterial isolates from intensive care unit (ICU) patients as well as those from ventilator-associated pneumonia (VAP) (n=435) were analysed and compared with those of 14 483 organisms from non-ICU patients. β-Lactamase-encoding genes were evaluated for 966 Enterobacteriaceae by a microarray-based assay. Ceftazidime/avibactam was active against 99.8/100.0% of Enterobacteriaceae (MIC90, 0.25/0.25mg/L) from ICU/non-ICU patients (2948/10,872 strains), including isolates from VAP (99.1%), multidrug-resistant (MDR) strains (99.3%), extensively drug-resistant (XDR) strains (96.5%) and meropenem-non-susceptible strains (98.0%), at MICs of ≤8mg/L. Against Enterobacteriaceae, susceptibility rates for ceftazidime, piperacillin/tazobactam and meropenem (ICU/non-ICU) were 86.1/91.8%, 88.0/94.3% and 97.8/99.2%, respectively. Meropenem was active against 75.1/85.4% of MDR Enterobacteriaceae and 8.1/27.1% of XDR Enterobacteriaceae from ICU/non-ICU patients. When tested against Pseudomonas aeruginosa, ceftazidime/avibactam inhibited 95.6/97.5% of isolates from ICU/non-ICU (842/2240 isolates), 97.3% of isolates from VAP, 80.7% of ceftazidime-non-susceptible and 80.7% of MDR isolates at ≤8mg/L. Susceptibility rates for P. aeruginosa from ICU/non-ICU were 77.7/86.9% for ceftazidime, 71.2/82.2% for piperacillin/tazobactam and 76.6/84.7% for meropenem. In summary, lower susceptibility rates were observed among ICU compared with non-ICU isolates. Ceftazidime/avibactam exhibited potent activity against a large collection of Gram-negative organisms from ICU and non-ICU patients and provided greater coverage than currently available β-lactams.
AuthorsHelio S Sader, Mariana Castanheira, Robert K Flamm, Rodrigo E Mendes, David J Farrell, Ronald N Jones
JournalInternational journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 46 Issue 1 Pg. 53-9 (Jul 2015) ISSN: 1872-7913 [Electronic] Netherlands
PMID25956844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Chemical References
  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • DNA, Bacterial
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • Ceftazidime
  • beta-Lactamases
Topics
  • Academic Medical Centers
  • Anti-Bacterial Agents (pharmacology)
  • Azabicyclo Compounds (pharmacology)
  • Ceftazidime (pharmacology)
  • Cross Infection (epidemiology, microbiology)
  • DNA, Bacterial (genetics)
  • Drug Combinations
  • Drug Resistance, Bacterial
  • Gram-Negative Bacteria (drug effects, isolation & purification)
  • Gram-Negative Bacterial Infections (epidemiology, microbiology)
  • Humans
  • Intensive Care Units
  • Microarray Analysis
  • Microbial Sensitivity Tests
  • Prevalence
  • United States (epidemiology)
  • beta-Lactamases (genetics)

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