Takeoka K, Ichimiya T, Yamasaki T, Nasu M
Second Department of Internal Medicine, Oita Medical University, Japan.
Chemotherapy. 1998 May-Jun;44(3):190-7. doi: 10.1159/000007114.
The in vitro effect of macrolides at concentrations below the minimum inhibitory concentration (sub-MIC) on the interaction between Pseudomonas aeruginosa biofilm and human polymorphonuclear leukocytes (PMNs) was investigated by using a chemiluminescence assay. The PMN response to either mucoid or nonmucoid P. aeruginosa biofilm was strongly reduced compared with the response to planktonic bacteria (p < 0.01, p < 0.001, respectively). When biofilms were treated with erythromycin, clarithromycin, roxithromycin and azithromycin prior to incubation with PMNs, the chemiluminescence response was markedly enhanced as compared to untreated controls, and a dose-dependent effect was noted over the range of sub-MIC concentrations studied. In general, macrolides appeared to be slightly more active against mucoid biofilm. Azithromycin was shown to be the most active macrolide against P. aeruginosa biofilms. However, the treatment with sub-MICs of rokitamycin did not have any effect. On the other hand, treatment of planktonic bacteria with macrolides before being exposed to the PMNs did not affect the chemiluminescence response as compared to untreated controls. These findings suggest that macrolides inhibiting the biofilm formation of P. aeruginosa may facilitate the phagocytosis of bacteria by PMNs.
采用化学发光分析法研究了大环内酯类药物在低于最低抑菌浓度（亚 MIC）时对铜绿假单胞菌生物膜与人类多形核白细胞（PMN）之间相互作用的体外效应。与对浮游细菌的反应相比，PMN 对黏液型或非黏液型铜绿假单胞菌生物膜的反应显著降低（分别为 p < 0.01，p < 0.001）。在用 PMN 孵育之前，用红霉素、克拉霉素、罗红霉素和阿奇霉素处理生物膜，与未处理的对照相比，化学发光反应明显增强，并且在所研究的亚 MIC 浓度范围内观察到剂量依赖性效应。一般来说，大环内酯类药物对黏液型生物膜的活性似乎略高。阿奇霉素被证明是对铜绿假单胞菌生物膜活性最高的大环内酯类药物。然而，用罗他霉素的亚 MIC 处理没有任何效果。另一方面，与未处理的对照相比，在用 PMN 接触之前用大环内酯类药物处理浮游细菌不会影响化学发光反应。这些发现表明，抑制铜绿假单胞菌生物膜形成的大环内酯类药物可能促进 PMN 对细菌的吞噬作用。
