口服头孢菌素类药物对肺炎链球菌肺炎大鼠肠道菌群的影响

Influence of oral cephalosporin drugs on intestinal flora in pneumococcal pneumonia rat

目的观察临床常用口服头孢菌素类药物头孢克洛、头孢地尼和头孢克肟对肺炎链球菌感染大鼠肠道菌群的影响。方法选取健康SD大鼠,随机分为五组,其中一组为正常对照组,其余四组采用气管内直接注入菌液的方法建立肺炎链球菌肺炎大鼠模型,造模成功后随机分为未治疗组、头孢克洛组、头孢地尼组和头孢克肟组,灌胃给予不同头孢菌素进行治疗,每日2次,连续用药5 d后取各组大鼠粪便标本进行快速涂片镜检,取大肠内容物进行肠球菌、肠道杆菌和念珠菌的定量培养和肠道内细菌的菌种鉴定,对肠道菌群进行定量分析。结果连续应用头孢克洛、头孢地尼和头孢克肟治疗5 d,能够对肠道菌群中球菌和杆菌的比例产生不同程度的影响。与感染后未治疗组相比,应用头孢菌素类药物均导致肠道双歧杆菌和乳酸杆菌数量显著减少(P<0.05),念珠菌数量增多(P<0.05)。正常对照组中仅检出大肠埃希菌和粪肠球菌。与感染后未治疗组相比,应用头孢菌素治疗后感染大鼠肠道内的大肠埃希菌和粪肠球菌的检出率表现出不同程度的减少,其中头孢地尼治疗后粪肠球菌检出率下降最为显著,由100%降低至50%,仅5例检出粪肠球菌。肺炎链球菌感染后未治疗组,新检出2例肺炎克雷伯杆菌,1例变形杆菌。与感染后未治疗组相比,应用头孢菌素类药物治疗后变形杆菌、铜绿假单胞菌和屎肠球菌的检出例数明显增多,但肠道内优势菌仍是大肠埃希菌和粪肠球菌。结论口服头孢菌素类药物可导致肠道内优势菌群减少,条件致病菌增多,引起肠道微生态环境紊乱。

Objective To observe the influence of oral Cefaclor, Cefdinir and Cefixime on intestinal flora in streptococcus pneumoniae infection rats. Methods Healthy SD rats were selected and randomly assigned to five groups,one normal control group, and the other four groups were established rat model of pneumococcal pneumonia by intratracheal injection of bacteria liquid directly. Then the successful model rats were divided into untreated group,Cefaclor group, Cefdinir group and Cefixime group. The pneumococcal pneumonia rats were treated with the three oral cephalosporin drugs by intragastric administration twice daily for 5 days. After the treatment, stool specimens were collected for smear microscopic examination and colonic contents samples for quantitative analysis of intestinal flora,including quantitative culture and identification of bacterial strains. Results The proportion of coccus and bacillus in intestinal flora were changed after continuous application of Cefaclor, Cefdinir and Cefixime treatment for 5 days.Compared with the untreated group, intestinal Bifidobacteria and Lactobacilli significantly reduced after treatment with cephalosporins（P〈0.05）, and number of Candida increased（P〈0.05）. Moreover, Escherichina coli and Enterococcus faecalis were only detected in the normal control group. Compared with the untreated group, the detection rates of intestinal Escherichina coli and Enterococcus faecalis showed different degrees of reduction after treatment with cephalosporins. Intestinal Enterococcus faecalis reduced with the reduction from 100% to 50% after treatment with Cefdinir, only 5 cases detected Enterococcus faecalis. After Streptococcus pneumoniae infection, in untreated group 2 cases of Klebsiella pneumoniae and 1 case Proteuswere newly detected. Compared with the untreated group, the detection rates of Proteus, Pseudomonas aeruginosa and Enterococcus faecium significantly increased, but Escherichia coli and Enterococcus faecalis were still dominant flora in the intestine. Conclusion Oral cephalosporin drugs can decrease the intestinal dominant microflora and increase the intestinal opportunistic pathogens, causing disorder of intestinal microecology environment.