Activity of antibiotics against Staphylococcus aureus in an in vitro model of biofilms in the context of cystic fibrosis: influence of the culture medium.
Antimicrob Agents Chemother. 2019 Apr 29;:
Authors: Diaz Iglesias Y, Wilms T, Vanbever R, Van Bambeke F
Staphylococcus aureus is a highly prevalent pathogen in the respiratory tract of young patients with cystic fibrosis (CF) and causes biofilm-related infections. Here, we set up an in-vitro model of biofilm grown in tryptic soy broth supplemented by glucose and NaCl (TGN) or in artificial sputum medium (ASM) and used it to evaluate on a pharmacodynamic basis the activity of antibiotics used in CF patients and active on staphylococci (meropenem, vancomycin, azithromycin, linezolid, rifampicin, ciprofloxacin, tobramycin). Rheological studies showed that ASM was more elastic than viscous, as also observed for sputa from CF patients, with elastic and viscous moduli respectively similar and slightly lower than those of CF sputa. Biofilms formed by MSSA ATCC 25923 and MRSA ATCC 33591 reached maturity after 24 h, with biomass (measured by crystal violet staining) and metabolic activity (assessed by following resazurin metabolization) being lower in ASM than in TGN, and viability (bacterial counts) being similar in both media. Full concentration-response curves of antibiotics obtained after 24 h incubation of biofilms showed that all antibiotics were drastically less potent and less efficient in ASM than in TGN towards viability, metabolic activity, and biomass. Tobramycin selected for small colony variants, specifically in biofilms grown in ASM; the auxotrophism of these variants could not be established. These data highlight the major influence exerted by the culture medium on S. aureus responsiveness to antibiotics in biofilms. Use of ASM may help to determine effective drug concentrations or to evaluate new therapeutic options against biofilms in CF patients.
PMID: 31036685 [PubMed - as supplied by publisher]