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

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 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.

METHODS: In 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.

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 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.

CONCLUSIONS: Considerable 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.