Ceftazidime-Avibactam Activity against Aerobic Gram Negative Organisms Isolated from Intra-Abdominal Infections in United States Hospitals, 2012-2014.

Background: Ceftazidime-avibactam is ceftazidime combined with the novel non-β-lactam β-lactamase inhibitor avibactam, which inhibits Ambler class A (e.g., extended-spectrum β-lactamase [ESBL] and KPC), class C, and some class D enzymes. We evaluated the activity of ceftazidime-avibactam against aerobic gram negative bacteria causing intra-abdominal infections (IAI).

Methods: A total of 1,540 isolates were collected, one each from patient, with IAI in 57 United States hospitals in 2012-2014. Susceptibility testing was performed by reference broth microdilution methods, and Enterobacteriaceae isolates with an ESBL phenotype were evaluated by a microarray-based assay for the presence of genes encoding the CTX-M, TEM, SHV, KPC, NDM, and transferable AmpC enzymes.

Results: All Escherichia coli isolates were susceptible to ceftazidime-avibactam, whereas the susceptibility rates for meropenem, piperacillin-tazobactam, and gentamicin were 99.8%, 93.6%, and 85.5%, respectively. Among Klebsiella pneumoniae isolates, the highest ceftazidime-avibactam minimum inhibitory concentration (MIC) value was only 2 mcg/mL (MIC50/90 0.12/0.25 mcg/mL; 100% susceptible), whereas susceptibility rates to meropenem and gentamicin were 94.5% and 91.9%, respectively. The ESBL-phenotype rates among E. coli and K. pneumoniae were 15.8% and 13.3%, respectively. Overall, only one Enterobacteriaceae isolate (Enterobacter cloacae) was not susceptible to ceftazidime-avibactam and had negative results for all β-lactamases tested. Against Pseudomonas aeruginosa, ceftazidime-avibactam (MIC50/90 2/4 mcg/mL; 97.1% susceptible) and amikacin (MIC50/90 2/8 mcg/mL; 99.0% susceptible) were the most active compounds, and ceftazidime-avibactam retained activity against many meropenem-non-susceptible (88.6% susceptible) and piperacillin-tazobactam-non-susceptible (82.9% susceptible) strains.

Conclusions: Ceftazidime-avibactam coverage (98.7% inhibited at ≤8 mcg/mL) of intra-abdominal infection pathogens was greater than that observed for meropenem (95.7% susceptible) and piperacillin-tazobactam (88.4% susceptible).