新生儿侵袭性感染B族链球菌的耐药表型及耐药机制

目的通过分析侵袭性感染新生儿的B族链球菌（GBS）临床分离株的耐药性和耐药基因型，为新生儿GBS感染的防治和抗菌药物的合理应用提供理论依据。 方法收集2013年1月至2016年6月就诊于广东省4家医院GBS侵袭性感染< 90 d新生儿病例。使用VITEK-2 Compact全自动细菌鉴定及药敏分析系统对GBS分离株进行鉴定和抗菌药物最小抑菌浓度（MIC）测定；应用PCR方法进行红霉素和四环素耐药基因检测。 结果确诊新生儿GBS侵袭性感染93例，其中34例（36.6%）早发型，59例（63.4%）晚发型。93株GBS分离株药物敏感试验结果显示，GBS对青霉素类、头孢菌素类、利奈唑胺和万古霉素均100%敏感；对左氧氟沙星、氧氟沙星和阿奇霉素的耐药率较低，分别为8.6%、2.2%和1.1%。对红霉素、克林霉素和四环素的耐药率高，分别为60.2%、78.5%和93.5%；耐药表型以固有表型（cMLS_B）为主，占53.9%，其次为L表型（26.3%）、诱导表型（iMLS_B）（15.8%）和M表型（3.9%）。56株红霉素耐药菌株ermB基因的携带率为85.7%，2株（3.6%）耐药菌株同时携带ermB和mefA基因，均未检出ermA。87株四环素耐药菌株中，四环素耐药基因tetO和tetM携带率分别为74.7%和46%，其中25株同时携带tetO和tetM，均未检出tetL和tetK基因。 结论青霉素和氨苄西林仍是治疗新生儿侵袭性GBS感染及高危新生儿预防GBS感染的首选药物。广东地区GBS红霉素耐药机制以ermB基因介导的核糖体靶位改变为主，四环素耐药机制以tetO和tetM基因为主。

Resistance patterns and mechanism of group B Streptococcus isolated from infants with invasive disease

ObjectiveTo investigate the antibiotics resistance rates and the resistance mechanisms of erythromycin and tetracycline among group B Streptococcus (GBS)-positive isolates cultured from infants with invasive infection, and to provide a reliable evidence for the prevention and treatment of infants with invasive GBS infection. MethodsFrom January 2013 to June 2016, the GBS strains isolated from infants with invasive diseases of < 90 days from four teaching hospitals were collected to investigate the current antimicrobial resistance status and resistance genes of these strains. The GBS isolates were identified and the minimum inhibitory concentration (MIC) of the antibiotics was determined by VITEK-2 Compact automatic bacterial identification system. Genes associated with resistance to erythromycin (ermA, ermB, mefA) and tetracycline (tetK, tetL, tetM, tetO) were investigated using PCR amplification and DNA sequencing. ResultsTotal of 93 non-duplicate colonizing GBS isolates were collected from infants with invasive GBS infection, among whom, 34 cases with early-onset infection and 59 cases with late-onset infection were diagnosed. All the isolates were susceptible to penicillins, cephalosporins, linezolid and vancomycin. The resistance of the isolates to levofloxacin, ofloxacin and azithromycin were 8.6 %, 2.2% and 1.1%, respectively. The resistance of isolates to erythromycin, clindamycin and tetracycline were significantly high, which were 60.2%, 78.5% and 93.5%, respectively. The most predominant phenotype was cMLSB (53.9%), followed by L phenotype (26.3%), iMLSB (15.8%) and M phenotype (3.9%). Among the resistance genes investigated, tetM (46%) and tetO (74.7%) were detected among tetracycline-resistant isolates and ermB (85.7%) and mefA (3.6%) were found among macrolide-resistant isolates. But ermA was not detected. ConclusionsFor neonates and young infants, empirical treatment with penicillins and ampicillin at birth for all high-risk neonates were recommended. Ribosomal modification by ermB gene play major role in erythromycin resistance of GBS, and the tetracycline resistance mediated by tetO and tetM genes were dominated.