DIFFUSION OF RIFAMPIN AND VANCOMYCIN THROUGH A STAPHYLOCOCCUS-EPIDERMIDIS BIOFILM

Using an equilibrium dialysis chamber, we evaluated the penetration of vancomycin, rifampin, or both through a staphylococcal biofilm to sim ulate treatment of an infected biomedical implant. A biofilm of ATCC 3 5984 (slime-positive Staphylococcus epidermidis; vancomycin MIC and MB C, 1 and 2 mu g/ml, respectively; rifampin MIC and MBC, 0.00003 and 0. 00025 mu g/ml, respectively) was established on the inner aspect of th e dialysis membrane (molecular mass exclusion, 6,000 kDa). Serum conta ining vancomycin (40 mu g/ml), rifampin (20 mu g/ml), or a combination of both was introduced into the inner chamber of the dialysis unit (i n direct contact with the biofilm), and serum alone was added to the o uter chamber. Rifampin and vancomycin concentrations in both chambers were determined over a 72-h period. In the absence of rifampin, the co ncentration of vancomycin in the outer chamber exceeded the MBC for th e organism after 24 h, and the MBC increased to nearly 8.8 mu g/ml by 72 h, demonstrating that therapeutic levels of vancomycin can penetrat e a staphylococcal biofilm. However, viable bacteria were recovered fr om the biofilm after 72 h of treatment with no apparent increase in th e MIC or MBC of vancomycin. Similarly, concentrations of rifampin exce eding the MBC were detected in the outer chamber after 24 h of treatme nt, but viable organisms were recovered from the biofilm after 72 h of treatment. In this case, the rifampin MBCs for surviving organisms in creased from 0.00025 to >128 mu g/ml. The combination of agents preven ted the development of resistance to rifampin, improved the perfusion of vancomycin through the biofilm, and decreased the penetration of ri fampin but did not sterilize the membrane. These observations provide evidence that bactericidal levels of vancomycin, rifampin, or both can be attained at the surface of an infected implant. Despite this, ster ilization of the biofilm was not accomplished after 72 h of treatment.