Ceftazidime-Avibactam Has Potent Activity Against Enterobacteriaceae



PHILADELPHIA, PA—Ceftazidime-avibactam demonstrated “potent activity” against contemporary Enterobacteriaceae (ENT) strains, including those producing prevalent CTX-M-variants, a presentation at IDWeek 2014 concluded.

This included E. coli, K. Pneumoniae, and P. mirabilis displaying an ESBL-phenotype. The investigational ceftazidime-avibactam combination was “also very active against K. pneumoniae strains showing decreased carbapenem susceptibility and ceftazidime-nonsusceptible Enterobacter species,” reported Maria Castanheira, PhD, of JMI Laboratories in North Liberty, IA.

Ron Jones, MD, a study co-author explained that ceftazidime-avibactam is a “near-perfect drug” for the U.S. in covering gram-negative distribution and, as such, represents an “extraordinary advance.” This is especially relevant, he said, in that the FDA recently reevaluated ceftazidime alone for covering ENT, with an MIC of 8.0µg/mL now the breakpoint for ceftazidime 2g every 8 hours.

The study investigators, including Rodrigo Mendes, PhD, evaluated the activity of ceftazidime-avibactam, a cephalosporin combined with a serine-β-lactamase (BL) inhibitor, by conducting susceptibility testing in 20,709 ENT isolates collected from 2011–2013 in 79 U.S. hospitals.

The organisms tested were E. coli (6,486 isolates), K. pneumoniae (4,421 isolates), E. cloacae (2,261 isolates), P. mirabilis (1,626 isolates), KPC-producers (214 isolates), CTX-M-15-like-producers (497 isolates), and CTX-M-14-like-producers (102 isolates).

Overall, they found that ceftazidime-avibactam inhibited 99.9% of isolates at ≤4µg/mL (CLSI CAZ-S breakpoint) and was only less potent than meropenem (MIC90, 0.25 and ≤0.06µg/mL, respectively). Among 25 isolates displaying ceftazidime-avibactam MICs at >4µg/mL, 15 were indole-positive Proteae with MICs of 8-16 µg/mL and 3 K. pneumoniae producing metallo-BLs (ceftazidime-avibactam MIC, >32µg/mL).

Ceftazidime-avibactam was found to inhibit all E. coli isolates, 99.9% of K. pneumoniae, and >99.9% of E. cloacae at ≤4µg/mL. For these species, ceftazidime-avibactam MIC50/90 were 0.06/0.12, 0.12/0.25, and 0.12/0.5µg/mL, respectively; in contrast, ceftazidime MIC90 values were 2, 32, and >32µg/mL, respectively. All but one of the P. mirabilis isolates were inhibited by ceftazidime-avibactam at ≤0.5µg/mL. A total of 214 KPC-producers, 497 CTX-M-15-like, and 102 CTX-M-14-like strains were identified; for these strains, ceftazidime-avibactam MIC50/90 values were 0.5/2, 0.12/0.5, and 0.12/0.25µg/mL, respectively.

The KPC-producers were resistant to all comparators; ceftazidime-avibactam, tigecycline (MIC50/90, 0.5/1µg/mL), and colistin (MIC50/90, 0.5/2µg/mL) were the only agents with acceptable coverage.

“Ceftazidime-avibactam will be an important addition to the armamentarium of antimicrobial agents used for the treatment of serious infections and those infections caused by multi-drug resistant organisms,” the authors concluded.

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