Diffusion of rifampin and vancomycin through a Staphylococcus epidermidis biofilm

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Abstract
Using an equilibrium dialysis chamber, we evaluated the penetration of vancomycin, rifampin, or both through a staphylococcal biofilm to simulate treatment of an infected biomedical implant. A biofilm of ATCC 35984 (slime-positive Staphylococcus epidermidis; vancomycin MIC and MBC, 1 and 2 micrograms/ml, respectively; rifampin MIC and MBC, 0.00003 and 0.00025 micrograms/ml, respectively) was established on the inner aspect of the dialysis membrane (molecular mass exclusion, 6,000 kDa). Serum containing vancomycin (40 micrograms/ml), rifampin (20 micrograms/ml), or a combination of both was introduced into the inner chamber of the dialysis unit (in direct contact with the biofilm), and serum alone was added to the outer chamber. Rifampin and vancomycin concentrations in both chambers were determined over a 72-h period. In the absence of rifampin, the concentration of vancomycin in the outer chamber exceeded the MBC for the organism after 24 h, and the MBC increased to nearly 8.0 micrograms/ml by 72 h, demonstrating that therapeutic levels of vancomycin can penetrate a staphylococcal biofilm. However, viable bacteria were recovered from the biofilm after 72 h of treatment with no apparent increase in the MIC or MBC of vancomycin. Similarly, concentrations of rifampin exceeding the MBC were detected in the outer chamber after 24 h of treatment, but viable organisms were recovered from the biofilm after 72 h of treatment. In this case, the rifampin MBCs for surviving organisms increased from 0.00025 to > 128 micrograms/ml. The combination of agents prevented the development of resistance to rifampin, improved the perfusion of vancomycin through the biofilm, and decreased the penetration of rifampin 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, sterilization of the biofilm was not accomplished after 72 h of treatment.