title: 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.
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA. Electronic address: helio-sader@jmilabs.com.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Flamm
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA.
authors.forename: Rodrigo E
authors.initials: RE
authors.lastname: Mendes
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.affiliation: JMI Laboratories, 345 Beaver Kreek Centre, Suite A, North Liberty, IA 52317, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000046:Academic Medical Centers; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D003428:Cross Infection / Q000453:epidemiology / Q000382:microbiology*; D004269:DNA, Bacterial / Q000235:genetics; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000453:epidemiology / Q000382:microbiology*; D006801:Humans; D007362:Intensive Care Units; D046228:Microarray Analysis; D008826:Microbial Sensitivity Tests; D015995:Prevalence; D014481:United States / Q000453:epidemiology; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D004269:DNA, Bacterial; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D002442:Ceftazidime; D001618:beta-Lactamases
keywords: CRE; Carbapenem-resistant Enterobacteriaceae; ESBL; KPC; Pseudomonas aeruginosa