龟分枝杆菌和脓肿分枝杆菌药物敏感性分析及E试验法应用评价

Drug sensitivity analysis of Mycobacterium chelonae and Mycobacterium abscessus and evaluation of Etest for susceptibility testing

目的分析深圳地区龟分枝杆菌和脓肿分枝杆菌耐药谱，评价E试验法检测龟分枝杆菌和脓肿分枝杆菌药物敏感性的临床适用性。方法用Geno Type Mycobacterium CM分枝杆菌菌种鉴定系统筛选16株龟分枝杆菌临床菌株、20株脓肿分枝杆菌临床菌株，分别用微量肉汤稀释法和E试验法检测其对阿米卡星、头孢西丁、环丙沙星、克拉霉素、多西环素、亚胺培南、利奈唑胺、磺胺甲嗯唑／甲氧苄啶和妥布霉素9种抗生素的MIC，以微量肉汤稀释法为标准，评价E试验法的MIC值符合率和MIC解释的一致率。两组间率的比较采用，检验。结果龟分枝杆菌和脓肿分枝杆菌对阿米卡星和头孢西丁均敏感（36／36），对克拉霉素的耐药率较低（1／36），对环丙沙星、多西环素、亚胺培南和磺胺甲嗯唑／甲氧苄啶的耐药率较高（29／36）。龟分枝杆菌和脓肿分枝杆菌对利奈唑胺的耐药例数分别为2／16和12／20，对妥布霉素的耐药例数分别为7／16和16／20。E试验法检测9种抗生素的MIC值分布与微量肉汤稀释法MIC值分布的总体符合率为46％（149／324），MIC解释一致率最高的分别为阿米卡星、克拉霉素、多西环素和亚胺培南（35／36），其次为磺胺甲嗯唑／甲氧苄啶（34／36），2例（2／36）解释结果有重大误差；一致率较高的为环丙沙星（31／36）和妥布霉素（26／36）；一致率最低的为头孢西丁和利奈唑胺（14／36），易导致MIC解释出现假阳性。结论阿米卡星、头孢西丁和克拉霉素对龟分枝杆菌和脓肿分枝杆菌有良好的体外抗菌作用，利奈唑胺、妥布霉素对部分龟分枝杆菌有良好的体外抗菌作用。除头孢西丁和利奈唑胺外，阿米卡星、克拉霉素、多西环素、环丙沙星和妥布霉素均适用E试验法检测龟分枝杆菌和脓肿分枝杆菌的体外药物敏感性，需慎重采用E试验法检测磺胺甲嗯唑／甲氧苄啶的药物敏感性。

Objective To study the drug resistance profile of Mycobacterium （M.） chelonae and M. abscessus and to evaluate the clinical application of Etest （epsilometer test ） for susceptibility testing. Methods Twenty clinical isolates of M. abscessus and 16 clinical isolates of M. chelonae from clinical specimens were collected. Strain identification was carried out by GenoType Mycobacterium CM assay （Hain Lifescience, Germany）. The accuracy was evaluated by comparing Etest results to those obtained by broth microdilution. Thirty-six isolates were tested against amikacin, cefnxitin, ciprofloxacin, clarithromycin, doxyeycline, imipenem, linezolid, sulfamethoxazole and tobramycin. The agreement among MICs and interpretive category was evaluated. Chi-squared test was used to compare observed frequency of each of the 2 examples. Results All of the isolates （36/36） were sensitive to amikacin and cefoxitin, and only l isolate （1/36） was resistant to clarithromycin, but more isolates （29/36） were resistant to ciprofloxacin, doxycycline, imipenem and sulfamethoxazole. For M. chelonae, only 2/16 were resistant to linezolid, and 7/16 resistant to tobramycin. For M. abscessus, more than 12/20 were resistant to linezolid and 16/20 resistant to tobramycin. The agreement between broth microdilution M^Cs and Etest MICs for 9 drugs was 149/324. With amikacin, clarithromycin, doxycycline and imipenem, the agreement for interpretive category was excellent（ 35/36 ） , followed by sulfamethoxazole（ 34/36 ） , which corresponded to rarely very major error of 2/36. With ciprofloxacin and tobramycin, agreement for interpretive category was 31/36 and 26/36. With cefoxitin and linezolid, the agreement of Etest MICs was the lowest（14/36） , resulting in the resistant category. Conclusions Isolates of M. chelortae and M. abscessus exhibit far more susceptibility to amikacin, cefoxitin and clarithromyein than any other antimicrobial agents. Linezolid and tobramyein showed sensitivity to some isolates of M. chelortae. It is suitable for the Etest method as a simple reliable method for the drug susceptibility of amikacin, ciprofloxacin, clarithromyein, doxycyeline, imipenem, and tobramycin except to cefoxitin and linezolid. The Etest method of determining sulfamethoxazole susceptibility should be careful.