title: Effect of β-Lactamase inhibitors on in vitro activity of β-Lactam antibiotics againstBurkholderia cepaciacomplex species.
abstract: BACKGROUND
  Bacteria belonging to theBurkholderia cepaciacomplex (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.
authors.affiliation: Laboratory of Pharmaceutical Microbiology, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Annelien
authors.initials: A
authors.lastname: Everaert
authors.affiliation: Laboratory of Pharmaceutical Microbiology, Ghent University, Ottergemsesteenweg 460, 9000 Ghent, Belgium.
authors.forename: Tom
authors.identifier: 0000-0002-6407-0601
authors.initials: T
authors.lastname: Coenye
keywords: Burkholderia cepacia complex; Resistance; β-lactam; β-lactamase; β-lactamase inhibitors