Richards G K, Morcos R J, Gagnon R F
Department of Laboratories, South Saskatchewan Hospital Center, Regina, Canada.
Adv Perit Dial. 1994;10:183-8.
Implant-associated infections offer resistance to antibiotic treatment and possibly do so because the causative bacteria which reside on the artificial surface are enclosed in a protective matrix (biofilm) shielding the bacteria against the action of host defenses and antibiotic action. We have investigated in vitro the effect of various antimicrobial agents on biofilms of Staphylococcus epidermidis, which is the main organism responsible for implant-associated infections. Rifampin was found to exert superior activity, albeit incomplete, against S. epidermidis biofilms using an assay system which enabled the determination of the kinetics of antibiotic action over five days. In a large screening study looking for agents capable of completing the action of rifampin, gentamicin was unexpectedly found to be antagonistic to rifampin. The present study was undertaken to investigate further the activity of gentamicin and five other aminoglycoside antibiotics using a wider range of concentrations (2.5-20 micrograms/mL). The main findings were a marked synergy with rifampin demonstrated by streptomycin, producing a bactericidal outcome, which contrasted sharply with the indifference or antagonism shown by the other aminoglycosides. We then studied in further detail the effect of separate combinations of streptomycin and gentamicin with rifampin over a wider concentration range of each agent (1.25-40 micrograms/mL). Streptomycin showed strong rapid synergy with rifampin even at the lowest concentration of each antibiotic. Gentamicin demonstrated a concentration-related antagonism towards rifampin which was independent of rifampin concentration. The data support the conclusion that streptomycin, like cell-wall active antibiotics, exerts a potent synergy with rifampin against S. epidermidis biofilms, and that the other aminoglycosides, predominantly gentamicin, strongly antagonize rifampin action.(ABSTRACT TRUNCATED AT 250 WORDS)
植入物相关感染对抗生素治疗具有抗性，可能是因为存在于人工表面的致病细菌被包裹在保护性基质（生物膜）中，该生物膜可保护细菌免受宿主防御作用和抗生素作用的影响。我们在体外研究了各种抗菌剂对表皮葡萄球菌生物膜的作用，表皮葡萄球菌是植入物相关感染的主要致病菌。使用一种能够测定五天内抗生素作用动力学的检测系统，发现利福平对表皮葡萄球菌生物膜具有较强的活性，尽管并不完全。在一项寻找能够增强利福平作用的药物的大型筛选研究中，意外发现庆大霉素与利福平具有拮抗作用。本研究旨在使用更广泛的浓度范围（2.5 - 20微克/毫升）进一步研究庆大霉素和其他五种氨基糖苷类抗生素的活性。主要发现是链霉素与利福平表现出显著的协同作用，产生杀菌效果，这与其他氨基糖苷类抗生素表现出的无作用或拮抗作用形成鲜明对比。然后我们更详细地研究了链霉素和庆大霉素分别与利福平在更广泛的每种药物浓度范围（1.25 - 40微克/毫升）下的联合作用。即使在每种抗生素的最低浓度下，链霉素与利福平也显示出强烈的快速协同作用。庆大霉素对利福平表现出浓度相关的拮抗作用，且与利福平浓度无关。数据支持以下结论：链霉素与细胞壁活性抗生素一样，与利福平对表皮葡萄球菌生物膜具有强大的协同作用，而其他氨基糖苷类抗生素，主要是庆大霉素，强烈拮抗利福平的作用。（摘要截短至250字）
