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某醫院病患結核分枝桿菌培養、抗藥性調查與分子醫學檢測

Antimicrobial Resistance Patterns, Culture Prevalence Rate and Molecular Diagnosis of Mycobacterium Tuberculosis for Patients in a Hospital

摘要


背景:從1990-2000年全世界感染肺結核的新案例約88,000,000個,並有30,000,000死亡。因此早期篩檢與治療及防治更顯重要。 方法:本研究於2003年1月至2004年12月針對至醫院就診的3184位病患進行痰液或相關檢體的結核分枝桿菌的篩檢,總共進行9,366套(3184人)分枝桿菌培養與抗生素鑑定。分子醫學的方法檢測457位病患,共603套TB-PCR。此外28位X光與電腦斷層掃描皆陽性,且已被疾病管制局專家確認為結核菌感染的病患,執行AFB、培養與分子醫學檢測。 結果:病患可分離出結核分枝桿菌的陽性率高達4.2%(132人/3184人)。在陽性的132個病患中,19%(25/132)的病患開立三套以上的培養,36%(47/132)的病患開立三套培養,31%(41/132)的病患開立兩套培養,仍有14%(19/132)的病患僅開立一套培養。在所有陽性開單組套中,第一套不長菌(第二套、第三套或以上才長菌)的佔33%(43/132)。另外,本實驗亦發現,若以培養為標準方法,抗酸性染色(acidfast stain)的敏感性為37%,特異性為98%,陽性預測值為32%,陰性預測值為98%。分子醫學檢測457位病患,共603套TB-PCR,其敏感性為31%,特異性為83%,陽性預測值為10%,陰性預測值為95%。28位X光與電腦斷層掃描皆陽性,且已被疾病管制局專家確認為結核菌感染的病患,發現此28位確診病例中,培養陽性僅有11%(3/28位),TB-PCR陽性高達54%(15/28位)。結核分枝桿菌培養陽性分佈的年齡層以64歲以上(4.6%)與24-33歲(4.5%)的陽性率最高。再就抗藥性而論,結核分枝桿菌對各種抗生素的抗性比例分別為ethambutol 10 (7.5%)、ethambutol 5.0 (13.2%)、isoniazid 0.2 (18.2%)、isoniazid 1.0 (14.1%)、pyrazinamide 25 (4.6%)、pyrazinamide 50 (4.6%)、rifampin 1.0 (9%)、rifampin 5.0 (7.8%)、streptomycin 10 (11.1%)、streptomycin 2.0 (12%)。 討論:若僅開立一套培養,其偽陰性比例將高達33%,應該儘量開立三套培養。約有85%結核病患無法由培養得知,有必要運用分子醫學方法增加篩檢率,多重抗性菌株(對isoniazid 0.2 與rifampin 1.0皆為抵抗性)約為4.7%,與疾病管制局於1997-2000年公佈的2.1%相當接近。

並列摘要


Backgrounds: From 1990 to 2000, tuberculosis caused an estimated 88 million new infections and 30 millions deaths worldwide. Methods: From January 2003 to December 2004, we surveyed the sputum or relative specimens of 3184 OPD patients to culture the Mycobacterium tuberculosis. The numbers of 9366 specimens from 3184 persons for TB were ordered for cultures. Results: 4.2% (132/3184) patients had positive culture results. Among the 132 positive persons, 19% (25/132) were arranged with more than 3 orders, 36% (47/132) with three orders, 31% (41/132) persons with two orders and still 14% (19/132) with only one order of TB culture. Among all the positive sets from 132 persons, 33% (43/132) got negative results in the first set. We found that the sensitivity, specificity, PPV, PNV of acid fast stain compared with cultures were 37%, 98%, 32% and 98%. The numbers of 603 specimens from 457 persons were ordered for TB-PCR. We also found that the sensitivity, specificity, PPV, PNV of molecular diagnosis compared with cultures were 31%, 83%, 10% and 95%. Among 28 well diagnosed TB patients by CDC with X-ray and C/T confirmation, only 11% (3/28) patients were positive for culture but 43% (12/28) patients were positive for molecular diagnosis. 4.6% of those ages above 64 and 4.5% of those ages from 24 to 33 were infected with high prevalence rates. Resistant rates were ethambutol 10 (7.5%), ethambutol 5.0 (13.2%), isoniazid 0.2 (18.2%), isoniazid 1.0 (14.1%), pyrazinamide 25 (4.6%), pyrazinamide 50 (4.6%), rifampin 1.0 (9%), rifampin 5.0 (7.8%), streptomycin 10 (11.1%), streptomycin 2.0 (12%). Discussions: There will be 33% false negative with only one order for positive patients. In order to reduce false negative rates, more sets should be order. On account of 85% TB patients being not able to be cultured, we are of the opinion that molecular diagnosis test should be order. Multiple drug resistance rates (resistant to both INH 0.2 and RP 1.0) were around 4.7%; which is near to 2.1% reported by CDC in 1997 to 2000.

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