儿童支原体肺炎耐药性与大环内酯类抗生素应用的关联性研究

Association Study of Drug Resistance of Mycoplasma Pneumoniae Pneumonia and the Application of Macrolides Antibiotics in Children

目的:探讨不规律使用大环内酯类抗生素与肺炎支原体(MP)耐药的相关性及规律使用阿奇霉素序贯疗法治疗儿童支原体肺炎(MPP)的有效性。方法:选取431例MP感染患儿,根据患儿MP感染次数分为观察组217例和对照组214例,观察组咽拭子标本培养结果阳性且对阿奇霉素敏感者与对照组培养结果阳性且对阿奇霉素耐药者提取DNA进行23s rRNA V区基因突变位点检测,对细菌培养阳性者进行药敏试验,根据药敏试验结果选择观察组中对大环内酯类抗菌药物敏感及23s rRNA V区无突变的患儿进行阿奇霉素序贯治疗,观察治疗效果。结果:观察组与对照组患儿MP培养阳性者分别为56例和49例,两组MP对大环内酯类药物耐药率为19.6%vs 75.5%,差异有统计学意义(χ~2=32.868,P<0.01)。对照组患儿不规范使用大环内酯类药物次数与肺炎支原体耐药率呈正相关(χ~2=22.056,P<0.01;r=0.321,P<0.01)。观察组对阿奇霉素敏感且23s rRNA V区基因位点无突变的26例患儿行阿奇霉素序贯治疗2周和4周时MP培养阴性率分别为73.1%和92.3%,基因测序结果显示培养阳性菌株仍未发现23s rRNA V区基因位点突变。结论:不规律应用大环内酯类抗生素可增加MP耐药率,MP耐药性与23s rRNA V区基因位点突变有关;对儿童MP感染在没有药敏结果情况下,规律使用阿奇霉素抗感染治疗,不会诱导耐药菌株出现。

Objective： To discuss the correlation between irregular use of macrolides antibiotics and drug resistance of Mycoplasma pneumonia （ MP）, and infer efficacy of sequential therapy of azithromycin for Mycoplasma pneumoniae pneumonia （MPP） in children. Methods： Four hundreds and thirty-one MP infected children were selected, and were divided into observation group （217 cases） and control group （214 cases） according to MP infection times during past year. DNA was extracted from the observer cases with specimens cultivate positive result and sensitive to azithromycln, also from the control cases with specimens cultivate positive result and resistant to azithromycin, and to examine gene mutations of 23s rRNA, drug sensitive tests were conducted for those strains with culture positive and cases in observer group with sensitive to macrolides antibiotics and with no 23s rRNA V zone mutations were selected and applicated with azithromycin sequential therapy and to observe efficacy. Results： MP cultural positive cases for observation and control group were 56 and 49 cases respectively, two groups with resistant ratio to macrolides antibiotics （19.6% vs 75.5 % ） had significant difference （x^2 = 32. 868, P〈0. 01 ）. In control group, there was positive correlation between irregular using times of macrolides antibiotics and drug resistant ratio （x^2=22. 056, P〈0. 01 ; r=0. 321, P〈0.01 ）. Twenty-two children in observtion group with sensitive to azithromycin and with no 23s rRNA V zone gene locus mutation whose MP cultural negative rate were 73.1% and 92. 3% respectively after azithromycin sequential therapy for 2 weeks and 4 weeks, gene sequencing results showed that cultural positive strains had still not found 23s rRNA V zone gene locus mutation. Conclusion： Irregular use of macrolides antibiotics can increase the MP resistance ratio, which is correlated with 23s rRNA V zone gene locus mutation. Under circumstances of no MP drug susceptibility results, regular use of azithromycin would not induce resistant strains.