777. Antimicrobial Activity of ceftazidime-avibactam and Comparator Agents Tested against Gram-negative Organisms Isolated from Urinary Tract Infections (UTI): Results from the International Network for Optimal Resistance Monitoring (INFORM) Program
Session: Poster Abstract Session: Antimicrobial Agents: Novel Agents
Friday, October 9, 2015
Room: Poster Hall
  • IDWEEK15 CAZ-AVI UTI 777.pdf (287.3 kB)
  • 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 g/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 g/mL (Table). CAZ-AVI was also highly active against KSP, including ESBL-phenotype (MIC50/90, 0.25/1 g/mL; 99.5% S) and meropenem (MEM)-non-S K. pneumoniae (KPN; MIC50/90, 0.5/2 g/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 g/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 g/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.

    Helio S. Sader, MD, PhD, David J. Farrell, PhD, Robert K. Flamm, PhD, Mariana Castanheira, PhD and Ronald N. Jones, MD, JMI Laboratories, Inc., North Liberty, IA


    H. S. Sader, Actavis: Research Contractor , Research support

    D. J. Farrell, Actavis: Research Contractor , Research support

    R. K. Flamm, Actavis: Research Contractor , Research support

    M. Castanheira, Actavis: Research Contractor , Research support

    R. N. Jones, Actavis: Research Contractor , Research support

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