摘要
目的探讨脓肿分枝杆菌复合群(MABC)对克拉霉素的耐药机制,为MABC肺病诊治提供依据。方法对广州市胸科医院冻存的191株龟-脓肿分枝杆菌复合群进行hsp65、rpoB、ITS多靶位基因菌种鉴定,确定为MABC的菌株进行克拉霉素最低抑菌浓度(MIC)药敏,延长培养时间至14 d,记录3、7、10、14 d的MIC值,观察MABC对克拉霉素诱导耐药情况,并对耐药相关基因rrl和erm(41)进行测序,研究克拉霉素耐药表型和基因型的关系。结果 191株龟-脓肿分枝杆菌复合群经多靶位基因法鉴定出2株龟分枝杆菌,189株MABC,其中111株脓肿分枝杆菌,78株马赛分枝杆菌。111株脓肿分枝杆菌中,克拉霉素获得性耐药1株,获得性耐药率0.9%;克拉霉素诱导耐药78株,诱导耐药率70.3%;总耐药株79株,总耐药率71.2%;78株马赛分枝杆菌无诱导耐药,克拉霉素获得性耐药5株,获得性耐药率6.4%;总耐药株5株,总耐药率为6.4%;脓肿分枝杆菌和马赛分枝杆菌总耐药率和获得性耐药率差异均有统计学意义(P<0.05)。6株克拉霉素获得性耐药菌株中,rrl突变的菌株5株,突变率为83.3%;所有的脓肿分枝杆菌erm(41)序列完整,所有的马赛分枝杆菌erm(41)序列有短缺;111株脓肿分枝杆菌,T28序列型菌株84株、C28序列型菌株27株。78株马赛分枝杆菌皆为T28序列型。结论 MABC为我国较为常见的非结核分枝杆菌,耐药率高,可用药物有限,治疗困难,主要菌种为脓肿分枝杆菌,根本的原因在于克拉霉素诱导耐药,准确的菌种鉴定、可靠的药敏试验对指导MABC肺病的临床治疗有重要意义。
Objective To investigate the mechanism of resistance of Mycobacterium abscess complex(MABC) to clarithromycin,and provide basis for the diagnosis and treatment of MABC lung disease. Methods Multi target gene PCRsequencing of hsp65,rpoB and ITS was performed to identify 191 clinical isolates of Mycobacterium tortoise-abscess complex frozen in Guangzhou Chest Hospital was carried out.Minimum inhibitory concentration(MIC)were tested for 14 days to assess the drug susceptibility of clarithromycin to MABC. MIC values at 3,7,10,and 14 days were recorded to observe MABC induced clarithromycin resistance. PCR-sequencing of rrl and erm(41)was used to compare the phenotype with genotype of clarithromycin resistance. Results 191 strains of Mycobacterium tortoise-abscess complex were identified by multi-target gene to 2 strains of Mycobacterium tortoises and 189 strains of MABC. Among the 189 MABC strains,111 strains were M.abscessus and 78 strains were M.massiliense. Among 111 strains of M.abscessus,1 strain(0.9%) was clarithromycin acquired resistance,and 78 strains(70.3%)showed clarithromycin induced resistance,and the total drug resistance rate was 71.2%(79/111);none of the 78 strains of M.massiliense showed clarithromycin induced resistant,among the 78 strains of M.massiliense,5 strains(6.4%)were clarithromycin resistant,with a total drug resistance rate of 6.4%(5/111). The total drug resistance rate and acquired drug resistance rate of Mycobacterium abscess and Mycobacterium masai were significantly different(P<0.05). Among 6 strains of clarithromycin acquired resistant,5 strains(83.3%)had rrl mutation.All isolates of M.abscessus harbored an intact erm(41)gene and all isolates of M.massiliense had deletions in erm(41).Furthermore,in 111 strains of Mycobacterium abscess,84 strains were of T28 sequence and 27 strains were of C28 sequence. All the 78 strains of M.massiliense were of T28 sequence type. Conclusions MABC was a relatively common nontuberculous mycobacterium in China. It had a high drug resistance rate,limited available drugs,and difficult treatment. The main strain was Mycobacterium abscessus. The reason for the difficulty of treatment was that clarithromycin induces resistance. Accurate strain identification and reliable drug sensitivity test were of great significance for guiding the clinical treatment of MABC lung disease.
作者
苏碧仪
谭耀驹
刘欣
马品云
许蕴怡
蔡杏珊
SU Bi-yi;TAN Yao-ju;LIU Xin;MA Pin-yun;XU Yun-yi;CAI Xing-shan(Guangzhou Chest Hospital,Guangzhou,Guangdong 510095,China)
出处
《热带医学杂志》
CAS
2021年第6期700-704,共5页
Journal of Tropical Medicine
基金
广州市卫生健康科技项目(20181A010034)。
