Scheld W M, Zak O, Vosbeck K, Sande M A
J Clin Invest. 1981 Nov;68(5):1381-4. doi: 10.1172/jci110388.
Bacterial adhesion to the constituents of nonbacterial thrombotic endocarditis (NBTE) is important in the pathogenesis of endocarditis. Subinhibitory concentrations (subMIC) of some antibiotics decrease bacterial adhesion to epithelial cells in vitro. We utilized an in vitro assay system to study the effect of subMIC of various antibiotics on streptococcal adhesion to a fibrin-platelet matrix (simulating NBTE). The results were (a) bacterial adhesion of Streptococcus sanguis and Streptococcus faecalis to NBTE was significantly reduced by vancomycin, penicillin, tetracycline, chloramphenicol and streptomycin (P less than 0.01 vs. controls) but not rifampin or trimethoprimsulfametrole; (b) the effect was dose-dependent and increased with duration of exposure to antibiotic; (c) reduction in bacterial adhesion did not correlate with altered retention by hydrophobic-interaction chromatography. This reduction in adhesion correlated with a diminished capacity of subMIC exposed Streptococcus sanguis (1/4 vancomycin minimum inhibitory concentration (MIC) X 4 h) to produce endocarditis in vivo. After intravenous inoculation of 10(6) colony-forming units of preincubated organisms into rabbits with traumatized aortic valves, 6 of 22 developed endocarditis vs. 17 of 22 controls (P = 0.03). These results may be relevant to prophylaxis of endocarditis since exposure of bacteria to subMIC of various antibiotics may reduce bacterial adherence both, to mucosal surfaces, and to damaged cardiac valves.
细菌对非细菌性血栓性心内膜炎(NBTE)成分的黏附在感染性心内膜炎的发病机制中具有重要意义。某些抗生素的亚抑菌浓度(subMIC)在体外可降低细菌对上皮细胞的黏附。我们利用体外检测系统研究了各种抗生素的亚抑菌浓度对链球菌黏附于纤维蛋白 - 血小板基质(模拟NBTE)的影响。结果如下:(a)万古霉素、青霉素、四环素、氯霉素和链霉素可显著降低血链球菌和粪肠球菌对NBTE的细菌黏附(与对照组相比,P<0.01),但利福平或甲氧苄啶 - 磺胺甲恶唑则无此作用;(b)这种作用呈剂量依赖性,并随抗生素暴露时间的延长而增强;(c)细菌黏附的降低与疏水相互作用色谱法检测的保留率改变无关。这种黏附的降低与亚抑菌浓度暴露的血链球菌(1/4万古霉素最低抑菌浓度(MIC)×4小时)在体内形成心内膜炎的能力减弱相关。将10⁶个预孵育生物体的菌落形成单位静脉接种到主动脉瓣受损的兔体内后,22只中有6只发生心内膜炎,而对照组22只中有17只发生(P = 0.03)。这些结果可能与心内膜炎的预防相关,因为细菌暴露于各种抗生素的亚抑菌浓度可能会降低细菌对黏膜表面和受损心脏瓣膜的黏附。