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快速生長非結核分枝桿菌(Nontuberculous Mycobacteria)台灣分離株的藥敏型式

Antibiograms of Rapidly Growing Nontuberculous Mycobacteria Isolated in Taiwan

摘要


由於快速生長非結核分枝桿菌(non-tuberculous mycobacteria, NTM)在台灣的臨床分離的分枝桿菌中佔甚高比例,近年來更發現此類菌中許多菌株與感染有關,因此檢驗室對臨床分離的快速生長NTM有必要操作藥敏試驗,將其等的藥敏型式提供醫師做為治療的參考。2011年美國臨床及實驗室標準機構(Clinicaland Laboratory Standard Institute, CLSI)建議微量肉湯稀釋方法(microbroth dilution method)為快速NTM藥敏試驗的標準方法,但此方法藥敏試驗培養基的配製甚為繁瑣,且有效期短,因此,並不適合檢驗室的常規操作。為了瞭解快速生長NTM的藥敏型式,本研究室根據CLSI所提出各菌種對不同藥物中間性濃度設計精選大管肉湯稀釋藥敏試驗培養基。操作361株快速生長NTM試驗菌(包括Mycobacterium abscessus、M. chelonae與M. fortuitum各100株,M. mucogenicum 40株,M. smegmatis與M. neoaurum各10株,以及M. peregrinum1株)的藥敏試驗時,除了利用精選大管肉湯稀釋方法外,並同時操作早期建議的瓊脂紙錠釋出方法(agar disk elution method)藥敏試驗,然後將兩種方法所獲得的快速生長NTM藥敏型式進行比較,結果指出所有快速生長NTM的兩種方法測試結果皆顯示:(i)對amikacin(AK)、imipenem(IMP)與cefoxitin (FOX)呈95%以上的感受性。其中,M. chelonae亦對這些抗生素呈高度感受性,此發現與先前的報告有所不同;(ii)對clarithromycin(CLA)約有80%以上的感受性;(iii)對moxifloxacin(MOX)、ciprofloxacin(CIP)以及doxycycline(DO)大多呈抵抗性;(iv)對CLSI新建議的測試藥物tobramycin(TOB)與linezoid(LZD)約有70%的感受性;(v)M. abscessus、M. chelonae與M.fortuitum對sulfamethoxazole-trimethoprim(SXT)的感受性僅為60%~80%,低於對M. mucogenicum、M. smegmatis與M. peregrinum所呈現的90%~100%以及(vi)以精選大管肉湯稀釋方法所獲得的各菌對SXT呈感受性比例高於由瓊脂紙錠釋出(agar disk elution)方法所測出的結果。另外,以快速生長NTM測試各種精選大管肉湯稀釋藥敏試驗培養基的有效期,發現CLA的有效期為4星期,其它藥物為3星期,此值得檢驗人員加以參考。

並列摘要


There have been high clinical isolation rates of nontuberculous mycobacteria (NTM) in Taiwan since 2010. The rapidly growing mycobacteria (RGMs) are most frequently encountered among NTM; therefore, the antibiograms of RGMs would serve as useful references for clinicians in diagnosing and treating NTM infection. However, medium preparation for the conventional microdilution method recommended as the gold standard by the CLSI (Clinical and Laboratory Standards Institute) in 2011 is time-consuming and not appropriate for use in routine clinical laboratory practice. Based on the "intermediate" concentration of antimicrobials recommended by CLSI, we developed a "limited macrobroth dilution method" and conducted this study to investigate whether this method produced comparable susceptible profiles with agar disk elution method from the same isolates in our stock clinical isolates. Ten antimicrobial agents were tested for 361 clinical isolates of RGMs, including 100 isolates of the M. chelonae, M. abscess us and M. fortuitum groups, respectively, 40 M. mucogenicum isolates, 10 M. smegmatis isolates and M. neoaurum, respectively, as well as 1 M. peregrinum isolate. Results showed that nearly all of the RGMs were at least 95% susceptible to amikacin (AK), imepenem (IMP), and cefoxitin (FOX). A discrepancy in M. chelonae to AK, IMP and FOX were noted between past studies and ours which showed high susceptibility. In addition to being resistant to moxifloxacin (MOX), ciprofloxacin (CIP) and doxycycline (DO), there were at least 80% susceptibile to clarithromycin (CLA) and 70% susceptible to tobramycin (TOB) as well as linezoid (LZD), both of which were newly recommended by CLSI were found for RGMs. For M. chelonae, M. abscessus and M. fortuitum, 60%~80% susceptibility to sulfamethoxazoletrimethoprim (SXT) and were lower than what was found for M. mucogenicum, M. smegmatis and M. peregrinum which represented 90%~100% susceptible. The macrobroth dilution method appeared to be a better method than the agar disk elution method in SXT testing. Expiration date of CLA broth medium was 4 weeks while other antimicrobial agents remained only 3 weeks. Our study confirmed that the limited macrobroth dilution method appears to be a reliable method for the susceptibility testing of RGM. Therefore, it is expected that it will be implemented as a routine testing method in clinical laboratories.

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