红霉素对下呼吸道铜绿假单胞菌感染菌株生物被膜的影响

The effect of erythromycin on Pseudomonas aeruginosa biofilm in lower respireatory tract infections

目的 :用红霉素抑制下呼吸道铜绿假单胞菌 (PA)感染患者PA菌株生物被膜的合成 ,增强细菌对抗生素的敏感性。方法 :铜绿假单胞菌下呼吸道感染患者 37例 ,随机分为红霉素干预组 (红组 ,n =2 2 )和常规治疗组 (非红组 ,n =1 5 )。红组在2种抗生素治疗的基础上加红霉素 1 .0 g/d ,其他治疗两组基本相似。观察治疗前及治疗后 (1 0d)培养细菌藻酸盐含量的变化、电镜观察细菌形态学变化并评价临床疗效。结果 :红组在红霉素治疗后 ,PA藻酸盐含量较治疗前明显降低 [治疗前为 2 2 .5± 6 .72 μg/ml;治疗后为 (1 6 .8± 6 .2 1 ) μg/ml,P <0 .0 1 ],而非红组则反而升高 [治疗前为 (2 5 .4 8± 2 0 .76 ) μg/ml;治疗后为(5 1 .97± 4 3.4 1 ) μg/ml],说明红霉素在体内可以减少PA藻酸盐的合成。电镜观察表明 ,经红霉素配合敏感抗生素治疗后 ,菌体明显肿胀、胞质疏松 ,核质变淡 ;菌毛、鞭毛消失 ,菌体结板成块 ;而非红组变化则没有红组明显 ,细菌变形轻微 ,损伤不似红组明显。结论 :红霉素在人体下呼吸道PA感染的治疗中 ,作为敏感抗生素的辅助用药 ,可抑制PA藻酸盐的合成 ,减少其生物被膜的形成 ,帮助药物渗入菌体内 。

Objective: To study the influence of erythromycin on the synthesis of biofilm in P. aeruginosa and the ausceptibility of P. aeruginosa to antibiotics. Methods: 37 patients with P. aeruginosa lower respiratory infection were randomly enrolled into erythromycin group ( n =22) or non erythromycin group ( n =15). Both groups received the same abtibiotic therapy except erythromycin. The quantity of alginate, the morphological changes of P. aeruginosa by transmision electron microscope were checked at the baseline and 10 days after treatment. Results: The quantity of alginate produced by P. aeruginosa reduced significantly in erythromycin group after erythromycin treatment compared with that at baseline [(22.5±6.72) μg/ml vs (16.8±6.21) μg/ml, P <0.01)]; while in non erythromycin group, the quantity of alginate increased significantly [(25.48±20.76) μg/ml vs (51.97±43.41) μg/ml, P <0.01]. The morphological changes of P. aeruginosa in erythromycin group showed marked edema of bacteria cells, rarefaction of cytoplasma, nuclear degenerateion, disappearance of bacterial fimbriae and flagella, the germs aggregated to form a mass. Conclusions: Erythromycin as an adjunct drug for the therapy of lower respiratory tract infection coused by P.aeruginosa , can inhibit the synthesis of alginate, and formation of liofilm, thus enhance the bactericidal activity of antibiotics.