福建省耐多药结核分枝杆菌对吡嗪酰胺的耐药水平与基因型特征分析

Phenotypic pyrazinamide resistance and genotypic characteristics among multidrug-resistant Mycobacterium tuberculosis isolates in Fujian Province

目的 了解福建省耐多药结核分枝杆菌（MDR-MTB）对吡嗪酰胺（PZA）的耐药水平及基因型分布情况,分析PZA耐药水平及基因型之间的关系。方法 收集2007—2008年和2010—2011年福建省耐药监测点共119株MDR-MTB临床分离株,采用WHO推荐的方法进行耐药性检测,应用间隔区寡核苷酸分型技术（Spoligotyping）进行基因分型,对分型结果上传至SpolDB4.0数据库,并进行聚类分析。结果 119株MDR-MTB菌株对PZA的耐药率为36.97%（44/119）。耐PZA菌株对链霉素（Sm）的耐药率为70.45%（31/44）,高于PZA敏感菌株对Sm的耐药率[50.67%（38/75）],差异有统计学意义（χ 2=4.45,P=0.035）;耐PZA菌株对乙胺丁醇（EMB）的耐药率为81.82%（36/44）,高于PZA敏感菌株对EMB的耐药率[52.00%（39/75）],差异有统计学意义（χ 2=1.58,P=0.001）。北京基因型菌株占67.23%（80/119）;非北京基因型菌株占32.77%（39/119）,共有16个基因型（含8个新发现的基因型）,其中常见的是H家族（含H和H3）和T家族（含T1、T2、T3和T5）。北京基因型菌株对PZA的耐药率（38.75%,31/80）与非北京基因型菌株对PZA的耐药率（33.33%,13/39）间差异无统计学意义（χ 2=0.33,P=0.566）。 结论 福建省耐多药结核病患者临床分离株对PZA耐药的问题应引起重视,对PZA耐药与对Sm和EMB耐药有关;MDR-MTB菌株主要为北京基因型,北京基因型与非北京基因型菌株对PZA的耐药率未见差异。

Objective In order to detect the phenotypic pyrazinamide （PZA） resistance and the genotypic distribution of MDR Mycobacterium tuberculosis （MTB） isolates from Fujian Province, and analyze the correlation between PZA resistance and genotype.Methods A total of 119 MDR-MTB strains were collected from the drug resistant surveillance sites in Fujian Province among 2007-2008 and 2010-2011. The drug susceptibility test （DST） of PZA recommended by WHO was conducted. Genotyping was performed by using Spoligotyping, and the results were uploaded to SpolDB 4.0 database for cluster analysis.Results The PZA resistant rate of 119 MDR-MTB strains was 36.97% （44/119）. The streptomycin （Sm） resistant rate of PZA resistant strains （70.45%, 31/44） was higher than that of PZA sensitive strains （50.67%, 38/75）, and the difference was statistically significant （χ 2=4.45, P=0.035）. The ethambutol （EMB） resistant rate of PZA resistant strains （81.82%, 36/44） was higher than that of PZA sensitive strains （52.00%, 39/75）, and the difference was statistically significant （χ 2=1.58, P=0.001）. Beijing genotype strains accounted for 67.23% （80/119）. Non Beijing genotype strains （32.77%, 39/119） had 16 genotypes including 8 new genotypes, the most common genotypes of which were H family containing H and H3 and T family containing T1, T2, T3 and T5. The PZA resistant rate of Beijing genotypic strains was 38.75% （31/80）, and that of non Beijing genotypic strains was 33.33% （13/39）; there was no significant difference in PZA resistant rate （χ 2=0.33, P=0.566）. Conclusion We should pay attention to the problem about PZA resistance of MDR-MTB strains in Fujian Province. The resistance to PZA is related to the resistance to Sm and EMB. Beijing genotype is mainly prevalent in Fujian Province, and there is no significant difference in the PZA rate between Beijing genotypic strains and non Beijng genotypic strains.