B组链球菌的耐药性及红霉素耐药基因检测研究

Susceptibility patterns and mechanisms of macrolide resistance in group B streptococcus isolates

目的探讨北京和广州地区B组链球菌(GBS)抗生素耐药菌谱及对红霉素耐药机制。方法GBS菌193株,其中140株和47株GBS分别来自北京和广州地区正常妇女阴道拭子标本,6株GBS菌株来自北京地区新生儿感染性肺炎和脑膜炎患儿体液标本中培养分离。应用标准的KB纸片法对临床常用7种抗生素耐药性检测。应用PCR法对102株(包括57株敏感株及45株耐药株)GBS进行红霉素耐药基因ermB、mefA检测。结果193株GBS菌均对青霉素类、头孢菌素类抗生素敏感;但青霉素和氨苄青霉素中介率均为17%;北京地区GBS的红霉素和林可霉素耐药率从1998年到1999年分别从8%增加到16%和从20%增加到28%;广州地区1999年分离的GBS菌株对红霉素和林可霉素耐药率分别为45%和26%,与北京地区1998、1999年分离的GBS菌株的红霉素耐药率比较,差异有统计学意义(P=0.000)。在45株红霉素耐药GBS菌中有40株同时对林可霉素耐药,5株表现为红霉素耐药而林可霉素敏感。20株GBS红霉素耐药仅含有ermB基因;13株红霉素耐药株仅含有mefA基因;同时含有ermB和mefA基因有6株。6株耐药株未能检测到ermB和mefA基因。结论青霉素、氨苄青霉素可作为治疗GBS感染首选药物;头孢菌素类抗生素可作为二线的选择药物。而红霉素和林可霉素作为预防和治疗GBS感染的药物应用价值应重新给予评价。在我国ermB基因介导的核糖体靶位点改变在GBS耐药机制中可能起主要作用。

Objective To test the antibiotic susceptibility and study mechanisms of macrolide resistance in group B streptococcus isolates （GBS）. Methods The GBS investigated in this study included 140 and 47 colonizing strains isolated from vaginal or cervical swabs from pregnant women in Beijing（ from 1994 to 1999 ） and Guangzhou obstetrics and gynecology hospitals （from 1999 ） and 6 invasive strains isolated from infants in Beijing Children＇s Hospital. Susceptibility to ampicillin, penicillin G, erythromycin, lincomycin, cephazolin, cefuroxime, cefoperazone was assessed by K-B disc diffusion. The mechanisms, methylation or effiux, of macrolide resistant GBS isolates, were analyzed by PCR for ermB and mefA genes. Results Susceptibility testing revealed that none of the GBS isolates were resistant to β-1actam drugs, but 17% isolates showed intermediate susceptibility to penicillin G and ampicillin. The rate of erythromycin resistance increased from 8% in 1998 to 16% in 1999 in Beijing, while the rate of hncomycin resistance increased from 20% to 28% in that period. However, 21 （45%） and 12（26% ） isolates were resistant to erythromycin and lincomycin, respectively in Guangzhou city where erythromycin resistance rate was higher than that in Beijing. Of 45 erythromycin resistant isolates, 20 （20/45, 44% ） possessed the ermB gene and 13 （13/45, 29% ） harbored the mefA gene; 6 isolates harbored both genes, 6 isolates had possessed neither ermB gene nor mefA gene. Conclusion The susceptibility of GBS isolates to penicillin G and ampicillin suggests use of penicillin G or ampicillin as a first-line drug in prophylactic treatment regimes against earlyonset neonatal GBS disease. Erythromycin and lincomycin should not be recommended as the second-llne antimicrobial in Beijing and Guangzhou city. The clinical relevance of macrolide resistant GBS in women treated with macrolides for intrapartum prophylaxis needs to be assessed. Ribosomal modification by a methylase encoded by erm gene may play a major role in the mechanisms of macrolide resistance of GBS isolates in China.