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

• Susceptibility rates were generally lower among isolates from intensive care unit (ICU) compared with non-ICU patients.
• The occurrence of extended-spectrum β-lactamase (ESBL), multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes were clearly higher among Enterobacteriaceae from ICU compared with non-ICU patients.
• Ceftazidime/avibactam exhibited potent activity against a large collection (n = 13,820) of Enterobacteriaceae isolates from ICU and non-ICU patients, including ESBL- and KPC-producing as well as MDR and XDR strains.
• Overall, 99.9% of Enterobacteriaceae were inhibited at a ceftazidime/avibactam MIC of ≤8 mg/L.
• Ceftazidime/avibactam inhibited 97.0% of Pseudomonas aeruginosa at an MIC of ≤8 mg/L, including 80.7% of ceftazidime-non-susceptible and 87.0% of meropenem-non-susceptible isolates.

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, 0.25/0.25 mg/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 ≤8 mg/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 ≤8 mg/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.