306株结核分枝杆菌耐药情况及菌型分析

Analysis of the drug resistance of 306 strains of Mycobacterium tuberculosis and bacterial typing

目的分析结核分枝杆菌耐药情况及菌型,指导临床感染防控。方法收集471例骨关节结核患者脓液样本及492例肺结核患者的痰液样本。对患者感染病原学进行监测,对结核分枝杆菌进行分型及耐药情况分析,对人型结核分枝杆菌耐药株的耐药基因进行检测。数据经统计学分析。结果从963例结核患者中,共分离306株结核分枝杆菌,分离率31.78%。从471例骨关节结核患者病灶处脓液样本培养中,分离结核分枝杆菌169株,分离率35.88%;492例肺结核患者痰液培养分离137株结核分枝杆菌,分离率27.85%。不同患者间感染情况差异有统计学意义(χ2=7.1674,P=0.0074)。306株结核分枝杆菌中,人型结核分枝杆菌267株,牛型结核分枝杆菌39株,构成比分别为87.25%和12.75%。72株人型结核分枝杆菌耐药,耐药率26.97%。5株牛型结核分枝杆菌耐药,耐药率12.82%,差异有统计学意义(χ2=116.5974,P=0.0000)。13株人型结核分枝杆菌耐多药,耐药率为4.87%,并未发现耐多药的牛型结核分枝杆菌。72株耐药的人型结核分枝杆菌中31株发生katG基因变异,299位Gly→Ser基因突变率为5.56%,315位Ser→Thr基因突变率为37.5%;4株发生基因突变inhA基因变异,239位Ala→Glyr基因突变率为5.56%。30株发生rpoB基因变异,521位Ser→Leu基因突变率为26.39%,526位His→Leu基因突变率为15.28%;18株发生rpsL基因变异,突变位点为43位Lys→Arg基因突变率为25.00%。22株发生gyrA基因变异,90位Ala→Val基因突变率为11.11%,94位Asp→Gly基因突变率为19.44%。男性患者感染率为36.56%,女性患者感染率为26.23%,差异有统计学意义(χ2=11.7720,P=0.0006)。初治患者感染率为38.20%,复发患者感染率为23.78%,差异有统计学意义(χ2=22.8366,P=0.0000)。农民患者感染率为37.92%,其他职业患者感染率为24.89%,差异有统计学意义(χ2=18.7864,P=0.0000)。有基础疾病患者感染率为38.13%,无基础疾病患者感染率为24.50%,差异有统计学意义(χ2=20.5474,P=0.0000)。结论骨关节结核患者感染率居多,且以人型结核分枝杆菌为主,其临床耐药率较高。多种耐药基因的检出可能是结核分枝杆菌耐多药的主要原因。性别、治疗类型、职业、基础疾病是影响感染发生的相关因素。

Objective To analyze the drug resistance of Mycobacterium tuberculosis and to type that bacterium in order to guide the clinical prevention and control of infection.Methods Pus samples were collected from 471 patients with osteoarthritis tuberculosis and sputum samples were collected from 492 patients with tuberculosis.Pathogens causing an infection were monitored,and M.tuberculosis was typed and its drug resistance was analyzed.Drug-resistant strains of M.tuberculosis were tested for drug resistance genes.The data were analyzed statistically.Results A total of 306 strains of Mycobacterium were isolated from 963 patients with tuberculosis at a rate of 31.78%.One hundred and sixty-nine strains of M.tuberculosis were isolated from pus samples from 471 patients with osteoarticular tuberculosis at a rate of 35.88%.One hundred and thirty-seven strains of M.tuberculosis were isolated from sputum samples from 492 patients with tuberculosis at a rate of 27.85%.The prevalence of infection differed significantly between the two groups of patients(χ~2=7.1674,P=0.0074).The 306 strains of Mycobacteriumincluded 267 strains of M.tuberculosis(87.25%)and 39 strains of M.bovis(12.75%).M.tuberculosis was significantly more prevalent(χ~2=339.7647,P=0.0000).Seventy-two strains of M.tuberculosis were drug-resistant,with a resistance of 26.97%.Five strains of M.bovis were drug-resistant,with a resistance of 12.82%.The drug resistance of the two species differed significantly(χ~2=116.5974,P=0.0000).Thirteen strains of M.tuberculosis were multi-drug-resistant,with a resistance of 4.87%.Multi-drug resistant M.bovis was not found.Multi-drug-resistant M.tuberculosis was significantly more prevalent(χ~2=116.5974,P=0.0000).Of 72 strains of drug-resistant M.tuberculosis,31 had a katG gene mutation.A Gly→Ser mutation at site299 was found in 5.56%of the strains,and an Ser→Thr mutation at site 315 was found in 37.5%.Four strains had an inhA gene mutation.An Ala→Gly mutation at site 239 was found in 5.56%of the strains.Thirty strains had an rpoB gene mutation.An Ser→Leu mutation at site 521 was found in 26.39%of the strains,and an His→Leu mutation at site526 was found in 15.28%.Eighteen strains had an rpsL gene mutation.An Lys→Arg mutation at site 43 was found in25.00%of the strains.Twenty-two strains had a gyrA gene mutation.An Ala→Val mutation at site 90 was found in 11.11%of the strains,and an Asp→Gly mutation at site 94 was found in 19.44%.The rate of infection was 36.56%in male patients and 26.23%in female patients,and the rate of infection differed significantly by sex(χ~2=11.7720,P=0.0006).The rate of infection was 38.20%in patients receiving initial treatment and 23.78%in those receiving treatment for recurrence,and the rate of infection differed significantly between the two groups(χ~2=22.8366,P=0.0000).The rate of infection was 37.92%in farmers and 24.89%in patients in other occupations,and the rate of infection differed significantly by occupation(χ~2=18.7864,P=0.0000).The rate of infection was 38.13%in patients with an underlying illness and 24.50%in patients without an underlying illness,and the rate of infection differed significantly between the two groups(χ~2=20.5474,P=0.0000).Conclusion There was a high rate of infection in patients with osteoarthritis tuberculosis.The main form of a Mycobacteriuminfection was M.tuberculosis,and the bacterium was highly drug-resistant.The detection of multiple drug resistance genes may be the main cause of multi-drug resistance in M.tuberculosis.Sex,type of treatment,occupation,and having an underlying illness are all related factors affecting the incidence of a Mycobacteriuminfection in patients,and attention should be paid to these factors.