Activity of Antibiotics againstBurkholderia cepaciacomplex in Artificial Sputum Medium

Abstract

ABSTRACTBurkholderia cepaciacomplex (Bcc) is a collection of intrinsically drug-resistant gram-negative bacteria that cause life-threatening pulmonary disease in people with cystic fibrosis (CF). Standard antimicrobial susceptibility testing methods have poor predictive value for clinical outcomes in people with Bcc infections, likely due in part to the significant differences betweenin vitrotesting conditions and the environment in which Bcc grow in the lungs of people with CF. We tested the activity of six commonly used antibiotics against two clinical Bcc strains grown to high density in an artificial sputum medium in order to assess their activity in conditions mimicking those foundin vivo. There were major discrepancies between standard susceptibility results and activity in our model, with some antibiotics, including ceftazidime, showing minimal activity despite low MICs, while others, notably tobramycin, were more active in high-density growth conditions than in standard assays. This work underscores the urgent need to develop more clinically relevant susceptibility testing approaches for Bcc.