Effect of β-Lactamase inhibitors on in vitro activity of β-Lactam antibiotics against Burkholderia cepacia complex species.

Annelien Everaert,Tom Coenye

doi:10.1186/s13756-016-0142-3

Abstract

BackgroundBacteria belonging to the Burkholderia cepacia complex (Bcc) are an important cause of chronic respiratory tract infections in cystic fibrosis patients. Intrinsic resistance to a wide range of antimicrobial agents, including a variety of β-lactam antibiotics, is frequently observed in Bcc strains. Resistance to β-lactams is most commonly mediated by efflux pumps, alterations in penicillin-binding proteins or the expression of β-lactamases. β-lactamase inhibitors are able to restore the in vitro activity of β-lactam molecules against a variety of Gram-negative species, but the effect of these inhibitors on the activity of β-lactam treatment against Bcc species is still poorly investigated.MethodsIn the present study, the susceptibility of a panel of Bcc strains was determined towards the β-lactam antibiotics ceftazidime, meropenem, amoxicillin, cefoxitin, cefepime and aztreonam; alone or in combination with a β-lactamase inhibitor (clavulanic acid, sulbactam, tazobactam and avibactam). Consequently, β-lactamase activity was determined for active β-lactam/β-lactamase inhibitor combinations.ResultsClavulanic acid had no effect on minimum inhibitory concentrations, but addition of sulbactam, tazobactam or avibactam to ceftazidime, amoxicillin, cefoxitin, cefepime or aztreonam leads to increased susceptibility (at least 4-fold MIC-decrease) in some Bcc strains. The effect of β-lactamase inhibitors on β-lactamase activity is both strain- and/or antibiotic-dependent, and other mechanisms of β-lactam resistance (besides production of β-lactamases) appear to be important.ConclusionsConsiderable differences in susceptibility of Bcc strains to β-lactam antibiotics were observed. Results obtained in the present study suggest that resistance of Bcc strains against β-lactam antibiotics is mediated by both β-lactamases and non-β-lactamase-mediated resistance mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1186/s13756-016-0142-3) contains supplementary material, which is available to authorized users.

Highlights

Bacteria belonging to the Burkholderia cepacia complex (Bcc) are an important cause of chronic respiratory tract infections in cystic fibrosis patients
In the present study we wanted to validate this assumptions for a larger research panel; we systematically investigated the effect of β-lactamase inhibitors on the susceptibility of Bcc species against several β-lactam antibiotics
In vitro activity of CAZ against some Bcc strains was increased when combined with SUL or AVI; e.g. for B. multivorans LMG 17588 the Minimal inhibitory concentration (MIC) for CAZ decreased from 16 mg/L in the absence of a β-lactamase inhibitor to 2 mg/L in the presence of SUL

Summary

Introduction

Bacteria belonging to the Burkholderia cepacia complex (Bcc) are an important cause of chronic respiratory tract infections in cystic fibrosis patients. Intrinsic resistance to a wide range of antimicrobial agents, including a variety of β-lactam antibiotics, is frequently observed in Bcc strains. Despite the impact of these infections, the number of novel antibiotics in the pipeline is small. Bcc species are an important cause of severe chronic respiratory infections in patients with cystic fibrosis (CF) [4]. Bcc infection in CF patients often correlates with a rapid decrease in lung function leading to a poorer prognosis, longer hospital stays and an increased risk of death.

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Results

Conclusion