Background: Ceftazidime-avibactam (CAZ-AVI) consists of CAZ combined with the novel non-β-lactam β-lactamase (BL) inhibitor AVI, a non-β-lactam BL inhibitor that inhibits Ambler classes A (eg, ESBL and KPC), C and some D enzymes.
Methods: 7272 unique patient organisms were collected from 71 USA medical centers from patients with UTI in 2012-2014. Susceptibility (S) testing was performed for CAZ-AVI (AVI at fixed 4 µg/ml) and comparators by reference broth microdilution methods. Enterobacteriaceae (ENT) with an ESBL phenotype were evaluated for the presence of genes encoding ESBLs, KPC, NDM and transferable AmpC enzymes using a microarray-based assay.
Results: An ESBL phenotype was observed among 11.5, 13.9 and 4.7% of E. coli (EC), Klebsiella spp. (KSP) and P. mirabilis (PM), respectively. CAZ-AVI inhibited >99.9% of all ENT, including all EC and PM isolates, at the S breakpoint of ≤8 µg/mL (Table). CAZ-AVI was also highly active against KSP, including ESBL-phenotype (MIC50/90, 0.25/1 µg/mL; 99.5% S) and meropenem (MEM)-non-S K. pneumoniae (KPN; MIC50/90, 0.5/2 µg/ml; 98.6%). Among E. cloacae (ECL; 23.3% CAZ-non-S), 99.7% of isolates, including 98.8% of CAZ-non-S strains, were S to CAZ-AVI. Overall, only 3 of 6773 ENT (0.04%) were non-S to CAZ-AVI, one KPN with VIM-4, KPC-2 and CMY-2, and one ECL and one Providencia spp. with negative results for all BL tested. CAZ-AVI was also highly active against P. aeruginosa (PSA; MIC50/90, 2/4 µg/mL; 97.7% S), including the majority of isolates non-S to MEM (90.5% S to CAZ-AVI) or CAZ (82.7% S). Further, CAZ-AVI inhibited 77.8% (21/27) of isolates non-S to MEM, CAZ and piperacillin/tazobactam at ≤8 μg/mL. CAZ-AVI showed limited activity against Acinetobacter spp. (57 isolates [0.8% of total], MIC50/90, 16/>32 µg/ml).
Conclusion: CAZ-AVI demonstrated potent activity against a large collection of contemporary (2012-2014) Gram-negative bacilli isolated from patients with UTI in USA hospitals, and provided greater coverage than agents currently available in the USA.
H. S. Sader,
R. K. Flamm, Actavis: Research Contractor , Research support
M. Castanheira, Actavis: Research Contractor , Research support
R. N. Jones, Actavis: Research Contractor , Research support