title: Impact of biofilm on the in vitro activity of vancomycin alone and in combination with tigecycline and rifampicin against Staphylococcus aureus.
abstract: OBJECTIVE
  This study evaluated vancomycin susceptibility and activity alone and in combination with rifampicin and tigecycline against low-biofilm- and high-biofilm-producing methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates.
  
  
  METHODS
  Forty MRSA isolates recovered from bloodstream infections were analysed. Susceptibilities were performed in planktonic and biofilm cultures by microbroth dilution. Biofilm production was determined using an adherent plate assay. Time-kill analysis was performed on six low- and six high-biofilm-producing isolates with 15 mg/L vancomycin alone and in combination with rifampicin or tigecycline at 4x MIC.
  
  
  RESULTS
  Vancomycin susceptibility displayed a 4-fold and an 8-fold increase in the MIC(50) and MIC(90), respectively, in the presence of biofilm. Rifampicin and tigecycline susceptibilities also increased in biofilms, but still remained within the susceptibility breakpoints except for a tigecycline MIC(90) of 1 mg/L. High biofilm production was detected in 60% of the isolates. In time-kill analysis, 15 mg/L vancomycin achieved bactericidal activity against only low-biofilm-producing strains with a 1.8 log(10) cfu/mL difference in bacterial kill compared with high-biofilm-producing strains (P < 0.001). Rifampicin alone had minimal activity, resulting in resistance. Tigecycline was minimally effective and was not bactericidal, but no difference was observed in the comparison of biofilm-producing strains. Vancomycin in combination with rifampicin or tigecycline was bactericidal against all strains (mean kill 4.5 +/- 0.5 log(10) cfu/mL), regardless of biofilm production.
  
  
  CONCLUSIONS
  Vancomycin exposures at 15 mg/L may not be adequate in eradicating biofilm-producing S. aureus. Alternative treatments or combination therapy should be explored to optimize outcomes in biofilm-associated infections.
authors.affiliation: Pharmacy Practice Division, School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA. werose@pharmacy.wisc.edu
authors.forename: Warren E
authors.initials: WE
authors.lastname: Rose
authors.forename: Peter T
authors.initials: PT
authors.lastname: Poppens
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology; D018441:Biofilms / Q000187:drug effects*; D015169:Colony Count, Microbial; D004357:Drug Synergism; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D008911:Minocycline / Q000031:analogs & derivatives* / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000382:microbiology; D000078304:Tigecycline; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D000078304:Tigecycline; D008911:Minocycline; D012293:Rifampin