Role of the Outer Membrane and Porins in Susceptibility of beta-Lactamase-Producing Enterobacteriaceae to Ceftazidime-Avibactam.

Article Details

Citation
Copy to clipboard

Pages JM, Peslier S, Keating TA, Lavigne JP, Nichols WW

Role of the Outer Membrane and Porins in Susceptibility of beta-Lactamase-Producing Enterobacteriaceae to Ceftazidime-Avibactam.

Antimicrob Agents Chemother. 2015 Dec 14;60(3):1349-59. doi: 10.1128/AAC.01585-15.

PubMed ID
26666933 [ View in PubMed
]
Abstract

This study examined the activity of the novel antimicrobial combination ceftazidime-avibactam against Enterobacteriaceae exhibiting different outer membrane permeability profiles, specifically with or without porins and with or without expression of the main efflux pump (AcrAB-TolC). The addition of the outer membrane permeabilizer polymyxin B nonapeptide increased the antibacterial activities of avibactam alone, ceftazidime alone, and ceftazidime-avibactam against the characterized clinical isolates of Escherichia coli, Enterobacter aerogenes, and Klebsiella pneumoniae. This enhancement of activities was mainly due to increased passive penetration of compounds since inhibition of efflux by the addition of phenylalanine-arginine beta-naphthylamide affected the MICs minimally. OmpF (OmpK35) or OmpC (OmpK36) pores were not the major route by which avibactam crossed the outer membranes of E. coli and K. pneumoniae. In contrast, Omp35 and Omp36 allowed diffusion of avibactam across the outer membrane of E. aerogenes, although other diffusion channels for avibactam were also present in that species. It was clear that outer membrane permeability and outer membrane pore-forming proteins play a key role in the activity of ceftazidime-avibactam. Nevertheless, the MICs of ceftazidime-avibactam (with 4 mg/liter avibactam) against the ceftazidime-resistant clinical isolates of the three species of Enterobacteriaceae studied were

DrugBank Data that Cites this Article

Drugs