侵袭性肺炎链球菌β内酰胺类抗菌药物耐药机制研究  

Resistant mechanism of β-lactam antibiotic of invasive Streptococcus pneumoniae

作　　者：张天栋[1] 孔箐[1] 王春[1] 秦惠宏[1] 张泓[1] 

机构地区：[1]上海市儿童医院,上海交通大学附属儿童医院检验科,200040

出　　处：《中华检验医学杂志》2014年第10期748-752,共5页Chinese Journal of Laboratory Medicine

基　　金：上海市自然科学基金（09ZR14275）

摘　　要：目的：了解上海市儿童医院临床分离侵袭性肺炎链球菌的耐药状况、对β内酰胺类抗菌药物的耐药机制，为抗菌药物的合理应用提供参考依据。方法本研究为针对抗菌药物耐药机制的基础性研究。收集上海市儿童医院2005年1月至2011年12月临床分离的侵袭性肺炎链球菌62株，采用E-test法测定分离株对9种抗菌药物的MIC。 PCR扩增肺炎链球菌的青霉素结合蛋白编码基因pbp2x、pbp2b、pbp1a，分析突变与β内酰胺类抗菌药物耐药水平的相关性。 PCR扩增肺炎链球菌的murM基因，分析其突变与β内酰胺类抗菌药物耐药水平的相关性。结果在62株侵袭性肺炎链球菌中，青霉素耐药肺炎链球菌（PRSP）的检出率为43．6％（27/62）。 pbp2b基因保守序列附近的基因突变率，青霉素中介肺炎链球菌（PISP）（100％，25/25）与青霉素敏感肺炎链球菌（PSSP）（3/10）、PSSP（3/10）与PRSP（100％，27/27）之间的差异有统计学意义（χ2分别为21．875和23．310，P均＜0．01）。 pbp2x基因保守序列附近及内部的基因突变率，PISP（84％，21/25）与PSSP（0）、PSSP（0）与PRSP（85．2％，23/27）之间的差异有统计学意义（χ2分别为21．000和22．513，P 均＜0．01）。pbp1a基因保守序列附近及插入序列的基因突变率，PISP（68％，17/25）与PSSP（0）、PRSP（100％，27/27）与PSSP（0）、PRSP（100％，27/27）与PISP（68％，17/25）之间的差异均有统计学意义（χ2分别为13．22、37．000、10．211，P均＜0．01）。 murM基因的碱基突变率，青霉素MIC≥8 mg/L或头孢曲松MIC≥2 mg/L组（95．8％，23/24）和青霉素MIC＜8 mg/L或头孢曲松MIC＜2 mg/L组（0）差异有统计学意义（χ2＝56．2，P＝0．0026）。结论上海市儿童医院分离的侵袭性肺炎链球菌耐药现象严重。pbps基因和murM基因突变在β内酰胺类抗菌药物耐药中均发挥作用，且与抗菌药物耐药水Objective To understand the drug resistance and antibiotic resistance mechanism ofβ-lactam antibiotics of invasive Streptococcus pneumoniae isolated from Shanghai Children′s Hospital, provides the reference for the rational use of antimicrobial agents.Methods This study is based on the research of the mechanism of drug resistance.62 isolates of invasive Streptococcus pneumoniae were collected from Shanghai Children′s Hospital from January 2005 to December 2011.Minimum inhibitory concentrations （ MIC） of strains to 9 antimicrobial agents were determined by E-test method.The penicillin binding protein coding genes pbp2x, pbp2b, and pbp1a of Streptococcus pneumoniae were amplified by PCR.Then, the correlation between the gene mutation andβ-lactam antibiotics resistant level were analyzed.The murM gene of Streptococcus pneumoniae was amplified by PCR and the correlation of mutation and β-lactam antibiotics resistant level was analyzed.Results Out of 62 strains of invasive Streptococcus pneumoniae from children, the detection rate of penicillin resistant Streptococcus pneumoniae was 43.6% （27/62）.Between penicillin intermediate Streptococcus pneumoniae （ PISP ） （ 100%, 25/25 ） and penicillin sensitive Streptococcus＆amp;nbsp;pneumoniae （PSSP） （3/10）, the difference of gene mutation rate near the pbp2b conserved sequence was statistically significant （χ2 =21.875, P〈0.01）.The same situation occurred between penicillin resistant Streptococcus pneumoniae （PRSP）（100%, 27/27）and PSSP （3/10） （χ2 =23.310, P〈0.01）.Also the difference of gene mutation rate of PISP （84%, 21/25） vs PSSP （0） and PSSP （0） vs PRSP （85.2%, 23/27） near or in the pbp2x conserved sequence were statistically significant （χ2 =21.000, P 〈0.01;χ2 =22.513,P〈0.01）.The difference of gene mutation rate near the pbp1a conserved sequence and Insertion sequence, which were statistically significant, occurred between PISP and PSSP （χ2 =13.22,P〈0.01）, between PRSP and PSSP （

关 键 词：链球菌  肺炎 β内酰胺抗药性 基因型 青霉素结合蛋白质类 细菌蛋白质类 

分 类 号：R446.5[医药卫生—诊断学]