大环内酯类、二甲胺四环素、妥舒沙星对大环内酯类抗药性儿童肺炎支原体肺炎疗效与抗菌作用的对比研究

Therapeutic and antimicrobial efficacy of macrolides,minocycline,and tosufloxacin against macrolide-resistant mycoplasma pneumoniae pneumonia in pediatric patients

目的：观察3种不同抗生素-大环内酯类、二甲胺四环素、妥舒沙星-对大环内酯类抗药性肺炎支原体肺炎（macrolide-resistant Mycoplasma pneumoniae，MRMP）的疗效。方法选取海南省第三人民医院收治的188例确诊为肺炎支原体肺炎（mycoplasma pneumoniae，MP）患儿为研究对象。PCR检测患儿是否有大环内脂耐药基因，对检测为MRMR的患儿分成4组，分别采用阿奇霉素、克拉霉素、妥舒沙星、二甲胺四环素4种药物进行治疗，观察各组退热情况。将检测结果中显示为大环内酯类敏感性肺炎支原体肺炎（macrolide-sensitive mycoplasma pneumoniae，MSMP）的患儿分为阿奇霉素组与克拉霉素组，观察MRMP与MSMP在相同治疗方法下的疗效差异。结果共检测出150例MRMR患儿，其中134例为23S rRNA 2063位点A→G突变；38例MSMP患儿。MRMR患儿4组4抗生素治疗后8 h退热患儿比例分别为阿奇霉素41％，克拉霉素48％，妥舒沙星69％，二甲胺四环素87％。其中两大环内酯类抗生素组（阿奇霉素组、克拉霉素组）用药后平均发热天数明显多于妥舒沙星组和二甲胺四环素组（P＜0.01）。通过DNA拷贝数测算，发现经过48～96小时治疗，二甲胺四环素组患者肺炎支原体下降明显（P＝0.016）高于妥舒沙星组（P＝0.049）、阿奇霉素组（P＝0.273）、克拉霉素组（P＝0.107）。结论大环内酯类抗生素对MRMP的抑菌及治疗作用不强。对于年龄≥8岁的MRMP患儿，适合选用二甲胺四环素作为治疗药物。

Objective To observe the differences in the therapeutic efficacies of macrolides,minocycline,and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae(MRMP).Methods A total of 188 children with M.pneumoniae pneumonia confirmed by culture and PCR were analyzed.Of these,150 patients had a strain with an MR gene and 134 had one with an A-to-G mutation at position 2063 of M.pneumoniae 23S rRNA domain V.Azithromycin(n=27),clarithromycin(n=23),tosufloxacin(n=62),or minocycline(n=38)was used for definitive treatment of patients with MR M.pneumoniae.Among the 188 patients,the other 38 patients with macrolide-sensitive Mycoplasma pneumonia (MSMP)were grouped into azithromycin(n =16)and clarithromycin groups(n =22)for observing whether there is differences with respect to efficacy under parallel treatment between patients with MRMP and MSMP. Results Defervescence within 48 h after the initiation of antibiotic therapy was observed in 41%of the patients in the azithromycin group,48% of those in the clarithromycin group,69% of those in the tosufloxacin group,and 87% of those in the minocycline group.The average number of days of fever after the administration of antibiotic treatment was lower in the minocycline and tosufloxacin groups than in the macrolide groups(azithromycin and clarithromycin groups).The decrease in the M.pneumoniae burden,as estimated by the number of DNA copies,after 48 to 96 h of treatment was more rapid in patients receiving minocycline(P=0.016)than in those receiving tosufloxacin(P=0.049),azithromycin(P=0.273),or clarithromycin(P=0.107).Conclusion We found that the clinical and bacteriological efficacies of macrolides against MR M.pneumoniae pneumonia was low.Our results indicated that minocycline rather than tosufloxacin can be considered the first-choice drug for the treatment of M.pneumoniae pneumonia in children aged >8 years.