Effect of β-lactamase inhibitors on in vitro activity of β-lactam antibiotics against Burkholderia cepacia complex species

摘要

Background: 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 beta-lactam antibiotics, is frequently observed in Bcc strains. Resistance to beta-lactams is most commonly mediated by efflux pumps, alterations in penicillin-binding proteins or the expression of beta-lactamases. beta-lactamase inhibitors are able to restore the in vitro activity of beta-lactam molecules against a variety of Gram-negative species, but the effect of these inhibitors on the activity of beta-lactam treatment against Bcc species is still poorly investigated. Methods: In the present study, the susceptibility of a panel of Bcc strains was determined towards the beta-lactam antibiotics ceftazidime, meropenem, amoxicillin, cefoxitin, cefepime and aztreonam; alone or in combination with a beta-lactamase inhibitor (clavulanic acid, sulbactam, tazobactam and avibactam). Consequently, beta-lactamase activity was determined for active beta-lactam/beta-lactamase inhibitor combinations. Results: Clavulanic 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 beta-lactamase inhibitors on beta-lactamase activity is both strain-and/or antibiotic-dependent, and other mechanisms of beta-lactam resistance (besides production of beta-lactamases) appear to be important. Conclusions: Considerable differences in susceptibility of Bcc strains to beta-lactam antibiotics were observed. Results obtained in the present study suggest that resistance of Bcc strains against beta-lactam antibiotics is mediated by both beta-lactamases and non-beta-lactamase-mediated resistance mechanisms.