DIFFUSION OF RIFAMPIN AND VANCOMYCIN THROUGH A STAPHYLOCOCCUS-EPIDERMIDIS BIOFILM
DIFFUSION OF RIFAMPIN AND VANCOMYCIN THROUGH A STAPHYLOCOCCUS-EPIDERMIDIS BIOFILM
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DOI：
10.1128/aac.37.12.2522
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发表时间：
1993-12-01
影响因子：
4.9
通讯作者：
KAPLAN, SL
中科院分区：
文献类型：
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作者：
DUNNE, WM;MASON, EO;KAPLAN, SL
使用平衡透析室，我们评估了万古霉素、利福平或两者通过葡萄球菌生物膜的渗透，以模拟受感染生物医学植入物的治疗。ATCC 35984的生物膜（粘液阳性表皮葡萄球菌;万古霉素MIC和MBC，分别为1和2 μ g/ml;利福平MIC和MBC，分别为0.00003和0.00025 μ g/ml）建立在透析膜的内部（分子量排阻，6，000 kDa）。将含有万古霉素（40 μ g/ml）、利福平（20 μ g/ml）或两者的组合的血清引入透析单元的内室（与生物膜直接接触），并将单独的血清加入外室。利福平和万古霉素浓度在两个腔室测定超过72小时的时间。在不存在利福平的情况下，24小时后外室中万古霉素的浓度超过了微生物的MBC，到72小时MBC增加到近8.8 μ g/ml，表明治疗水平的万古霉素可以穿透葡萄球菌生物膜。然而，治疗72小时后从生物膜中回收了活菌，万古霉素的MIC或MBC没有明显增加。类似地，在处理24小时后在外室中检测到超过MBC的利福平浓度，但在处理72小时后从生物膜中回收活生物体。在这种情况下，存活生物体的利福平MBC从0.00025 μ g/ml增加到> 128 μ g/ml。药物的组合防止了对利福平的耐药性的发展，改善了万古霉素通过生物膜的灌注，并降低了利福平的渗透，但没有对膜进行灭菌。这些观察结果提供了证据，证明万古霉素、利福平或两者的杀菌水平可以在受感染植入物的表面达到。尽管如此，生物膜的灭菌在处理72小时后没有完成。
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 mu g/ml, respectively; rifampin MIC and MBC, 0.00003 and 0.00025 mu g/ml, respectively) was established on the inner aspect of the dialysis membrane (molecular mass exclusion, 6,000 kDa). Serum containing 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 (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 8.8 mu g/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 mu g/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.