Gagnon R F, Richards G K, Kostiner G B
Department of Medicine, Montreal General Hospital, Quebec, Canada.
Adv Perit Dial. 1994;10:189-92.
Infections associated with implants are frequently resistant to conventional antibiotic therapy. This resistance has been ascribed to the presence of bacteria on the artificial surface within a protective glue-like matrix forming a bacterial biofilm. We have demonstrated that experimental biofilms of Staphylococcus epidermidis, the main pathogen associated with implantation, are exquisitely sensitive to the action of rifampin. This effect of rifampin is incomplete, however, with the emergence of rifampin-resistant survivors that readily repopulate the biofilm. Studies were therefore performed to determine the effect of combinations of 13 different antibiotics with rifampin against standardized S. epidermidis biofilm preparations in an in vitro assay enabling the kinetic measurement of antibiotic action over a five-day period. The antibiotic combinations with rifampin demonstrated unsuspected divergent patterns of antimicrobial activity against the biofilms: 1. rapid synergy with rifampin was observed with cell-wall active antibiotics (cloxacillin, cephalothin, cefazolin, and cefamandole), whereas slower synergy occurred with vancomycin, ciprofloxacin, tetracycline, and amikacin; 2. some antibiotics (tobramycin, erythromycin, clindamycin, fusidic acid) did not influence the outcome; 3. gentamicin unexpectedly showed marked antagonism to rifampin. These results are relevant to the design of optimal therapeutic regimens for the management of resistant implant-associated infections.
与植入物相关的感染通常对传统抗生素治疗具有抗性。这种抗性归因于在形成细菌生物膜的保护性胶状基质内的人工表面上存在细菌。我们已经证明，与植入相关的主要病原体表皮葡萄球菌的实验性生物膜对利福平的作用极为敏感。然而，利福平的这种作用并不完全，会出现对利福平耐药的存活菌，这些存活菌很容易在生物膜中重新繁殖。因此，我们进行了研究，以确定13种不同抗生素与利福平联合使用对标准化表皮葡萄球菌生物膜制剂的作用，该体外试验能够在五天内动态测量抗生素的作用。与利福平联合使用的抗生素对生物膜表现出意想不到的不同抗菌活性模式：1. 与细胞壁活性抗生素（氯唑西林、头孢噻吩、头孢唑林和头孢孟多）观察到与利福平的快速协同作用，而与万古霉素、环丙沙星、四环素和阿米卡星的协同作用较慢；2. 一些抗生素（妥布霉素、红霉素、克林霉素、夫西地酸）不影响结果；3. 庆大霉素出乎意料地显示出对利福平的明显拮抗作用。这些结果与设计用于治疗耐药性植入物相关感染的最佳治疗方案相关。
