進階搜尋


   電子論文尚未授權公開,紙本請查館藏目錄
(※如查詢不到或館藏狀況顯示「閉架不公開」,表示該本論文不在書庫,無法取用。)
系統識別號 U0026-1511201118002500
論文名稱(中文) 以DNA晶片鑑定陽性液態培養中之分枝桿菌
論文名稱(英文) Detection of Mycobacteria in Positive Broth Cultures by an Oligonucleotide Array
校院名稱 成功大學
系所名稱(中) 醫學檢驗生物技術學系碩博士班
系所名稱(英) Department of Medical Laboratory Science and Biotechnology
學年度 100
學期 1
出版年 100
研究生(中文) 林耀正
研究生(英文) Yao-Cheng Lin
學號 T36981029
學位類別 碩士
語文別 中文
論文頁數 84頁
口試委員 指導教授-張長泉
召集委員-吳俊忠
口試委員-周如文
口試委員-盧柏樑
口試委員-柯文謙
中文關鍵字 分枝桿菌 
英文關鍵字 mycobacteria 
學科別分類
中文摘要 結核病是由結核桿菌群(Mycobacterium tuberculosis complex, MTBC)感染所造成的傳染性疾病,該疾病是人類健康及公共衛生重要的問題。2009年世界衛生組織統計,全球每年約940萬人感染結核病並導致170萬人死亡。台灣的結核病盛行率,過去五年間介於58~75例/10萬人口,2009年肺結核新案總數為13336例。另外,非結核分枝桿菌(nontuberculous mycobacteria, NTM)的感染近年來有增加的趨勢,傳統上分枝桿菌的檢驗仰賴培養及生化反應法。本研究目的在利用本實驗室先前已建構之寡核苷酸晶片加以修改及最適化,以檢測BACTEC MGIT (Becton, Dickinson and Company)生長及抗酸性桿菌陽性培養管中(簡稱陽性MGIT培養)之MTBC及NTM。檢體由高雄醫學大學附設中和紀念醫院提供,共檢測286個陽性MGIT培養,這些陽性培養經次培養後則以傳統生化法或熱休克蛋白質基因限制法(二者均簡稱傳統方法)鑑定菌種。晶片檢測到163個檢體含MTBC,傳統方法則鑑定154個檢體含MTBC,10個晶片陽性但培養陰性檢體經由Cobas TaqMan MTB Assay (Roche), MGIT TBc identification test (Becton, Dickinson and Company), 或GenoType Mycobacterium CM (Hain Lifesience GmbH) 測試, 證明確有MTBC存在檢體中,故這10個晶片陽性檢體視為真陽性。有一個檢體為培養陽性但晶片陰性。晶片鑑定陽性MGIT培養中MTBC之靈敏度、特異性、陽性預測值及陰性預測值分別為99.4% (163/164),100% (121/121),100% (164/164),及99.2% (121/122)。另外由286個陽性MGIT培養中,晶片檢測到127個檢體含NTM,傳統方法則檢測到118個檢體含NTM,其中菌種鑑定結果相同的有113個(88.9%,112/127)。有14個檢體晶片和培養方法結果不一致,其中9個檢體傳統方法沒有培養出NTM,5個檢體則是二種方法鑑定結果不符合,這14個檢體以GenoType Mycobacterium CM, intergenic spacer (ITS)或16S rRNA基因定序、或ITS選殖及定序,均確認晶片鑑定的結果是正確的。若晶片對NTM的鑑定率為100%, 則培養法為92.9% (118/127)。晶片對MTBC的偵測極限為25 fg/test,約相當於6個MTBC細菌,檢測時間需約7小時。總之,本研究的晶片可以快速及正確鑑定陽性MGIT培養中之MTBC及NTM。
英文摘要 Tuberculosis remains one of the most threatening curable infectious diseases. It was estimated that there were 9.4 million new cases each year in the world, and approximately 1.7 million deaths per year were TB-related. In addition, infections caused by nontuberculous mycobacteria (NTM) are increasing worldwide. The aim of this study was to modify a previously developed oligonucleotide array and to evaluate it for detecting Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM) in growth and acid-fast bacilli (AFB) positive BACTEC MGIT cultures (in abbreviation, positive MGIT cultures) (Becton, Dickinson and Company). Diagnostic cultures performed with 7H11 agar and Löwenstein-Jensen medium, followed by biochemical tests or heat shock protein 65 restriction analysis, were primarily considered as the reference methods. A total of 286 positive MGIT cultures, obtained from Kaohsiung Medical University Hospital, were analyzed in this study. When discrepant identifications between the array and culture methods occurred, test results from the Cobas TaqMan MTB Assay (Roche), MGIT TBc identification test (Becton, Dickinson and Company), GenoType Mycobacterium CM (Hain Lifesience GmbH), ITS cloning and resequencing, or sequencing of the 16S rRNA gene or intergenic spacer region (ITS) of isolates were used to resolve discrepancies. A total of 163 samples were MTBC positive by the array, while only 154 samples were MTBC positive by culture. The 10 array-positive but culture-negative samples were considered to be true positives as confirmed by the above molecular methods. The array produced only one false negative. The sensitivity, specificity, positive and negative predictive values of the array for detection of MTBC in positive MGIT cultures were 99.4% (163/164), 100% (121/121), 100% (164/164), and 99.2% (121/122), respectively.
For NTM detection, 127 samples were positive by the array, while 118 samples were positive by culture. Concordant results for NTM identification between the two methods were obtained in 113 samples (88.9%). Among the 14 discordant samples, nine were negative by culture and 5 were discordant identifications. The identifications of the 14 discordant samples by the array were found to be correct as evidenced by other molecular methods. If the detection rate of NTM by the array was considered as 100%, the rate by culture was 92.9% (118/127). The detection limit of the array for MTBC was 25 fg per assay and this was equivalent to 6 cells of MTBC. In conclusion, the array method, with a turnaround time of about 7 h, provides a faster and more sensitive method for diagnosing MTBC and NTM in positive MGIT cultures.
論文目次 目錄
摘要----------I
Abstract----------III
緒論----------1
分枝桿菌屬 (Mycobacterium)----------1
結核桿菌群 (Mycobacterium tuberculosis complex, MTBC) ----------2
非結核分枝桿菌 (nontuberculous mycobacteria, NTM)----2
實驗室診斷 (laboratory diagnosis)及分生鑑定方法----------4
分枝桿菌流行病學----------6
研究目的----------8
研究架構----------8
材料與方法----------9
實驗用菌株、菌株的培養保存、及菌種DNA----------9
MGIT (Mycobacterial Growth Indicator Tube ) 培養------10
菌種DNA萃取----------11
陽性MGIT檢體核酸萃取----------11
熱休克蛋白65聚合酶連鎖反應及限制酶分析(hsp65 PCR-restriction analysis, PRA)----------12
BD TBc ID test----------13
ITS區域之擴增及定序----------14
特異性探針(specific probes)之設計與修改 ----------15
內部增幅對照組(internal control, IC) DNA的建構及其探針-15
分子選殖 (Molecular cloning)----------17
寡核苷酸晶片之配置及點製----------19
晶片雜合反應 (chip hybridization)----------20
晶片判讀器(reader)及閾值(cutoff value)設定----------22
晶片雜合反應結果之判讀 ----------22
ITS, 16S rRNA基因定序 (sequencing)---------- 23
靈敏度、特異性、陽性預測值 (positive predictive value, PPV)、陰性預測值 (negative predictive value, NPV)及偵測極限(detection limit)之定義----------24
GenoType® Mycobacterium CM (Hain Lifescience)套組--26
結果----------28
結核桿菌群 (MTBC) 參考菌株之鑑定----------28
非結核分枝桿菌 (NTM)參考菌株之鑑定----------28
MGIT生長陽性及抗酸性染色陽性[AFB(+)]檢體中MTBC之檢測 ----------29
MGIT生長陽性及抗酸性染色陽性[AFB(+)]檢體中NTM之檢測 ----------30
晶片靈敏度 (sensitivity)、特異性 (specificity)、陽性預測值 (PPV)及陰性預測值 (NPV)分析----------30
晶片之偵測極限(detection limit)----------30
鎖核酸探針之訊號提升(locked nucleic acid, LNA)-------31
討論----------32
晶片鑑定混合菌種(mixed cultures)之能力 ----------32
晶片和傳統方法鑑定NTM不一致結果之分析:----------32
晶片為NTM陽性但培養陰性檢體之分析----------33
傳統方法容易鑑定錯誤的NTM----------35
MGIT培養為陰性但固態培養為陽性之檢體----------35
晶片與傳統方法檢測MTBC的靈敏度----------36
結論----------37
參考文獻----------38

表目錄

Table 1. Comparison of several commercial kits for identification of mycobacteria.----------47
Table 2. Reference strains of MTBC and NTM for sensitivity testing of the array.----------51
Table 3. Nontraget mycobacteria used for specificity testing of the array.----------52
Table 4. Detection of mycobacteria in 286 positive MGIT cultures by the array, culture, and other molecular methods ----------53
Table 5. Probe codes and probe informations.----------69
Table 6. The sensitivity, specificity, PPV and NPV of the array for identification of MTBC in positive MGIT cultures.-----70
Table 7. Discrepant analysis of 11 positive MGIT cultures that were MTBC positive by the array but negative by culture. ----------71
Table 8. Nontuberculous mycobacteria detected in 286 positive MGIT cultures by the array and culture----------72
Table 9. Analysis of five discordant identifications of NTM between the array and culture.----------73
Table 10. Discrepant analysis of 16 positive MGIT cultures from which NTM was not identified or not isolated by culture. ----------74

圖目錄

FIG. 1. The diagnostic procedure of mycobacteria-------75
FIG. 2. Layout of oligonucleotide probes on the array.----76
FIG. 3. The depicted procedures for array hybridization.--77
FIG. 4. Depicted procedures for comparison of the signal intensitites of the two MTBC probes.----------78
FIG. 5. Hybridization results of 34 species of Mycobacterium by the array.----------80
FIG. 6. A selection of positive MGIT cultures with condordant identifications between the array and culture. ----------81
FIG. 7. A selection of positive MGIT cultures from which mixed mycobacteria were identified by the array.--------82
FIG. 8. Determination of the detection limits of probes MTBC1-1 and MTBC3-1 for identification of M. tuberculosiss H37Rv.----------83
FIG. 9. (1) Determination of the detection limits of probes for identification of M. abscessus and M. kansasii.--------84
參考文獻 陸坤泰, 江振源, 李仁智, 李秉穎, 林錫勳, 姜義新, 洪健清, 索任, 黃瑞明, 詹珮君, 劉永慶, 蘇維鈞. 2008. 結核病診治指引 (Taiwan Guidelines on TB Diagnosis & Treatmrnt), 第三版,行政院衛生署疾病管制局。
張義峰, 施文儀, 林項, 周志浩, 陳穎慧, 莊人祥, 楊靖慧. 2010. 台灣肺結核防治年報 (Taiwan Tuberculosis control Report 2010), 行政院衛生署疾病管制局。
鄭伊珊. 2010. 以DNA晶片鑑定結核桿菌及非結核分枝桿菌. 碩士論文. 國立成功大學, 台南, 台灣.
Alexander, K. A., P. N. Laver, A. L. Michel, M. Williams, P. D. van Helden, R. M. Warren, and N. C. Gey van Pittius. 2010. Novel Mycobacterium tuberculosis complex pathogen, M. mungi. Emerg Infect Dis 16:1296-1299.
Alvarez-Uria, G. 2010. Lung disease caused by nontuberculous mycobacteria. Curr Opin Pulm Med 16:251-256.
Barrett, A., J. G. Magee, and R. Freeman. 2002. An evaluation of the BD ProbeTec ET system for the direct detection of Mycobacterium tuberculosis in respiratory samples. J Med Microbiol 51:895-898.
Behr, M. A., S. A. Warren, H. Salamon, P. C. Hopewell, A. Ponce de Leon, C. L. Daley, and P. M. Small. 1999. Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli. Lancet 353:444-449.
Bergmann, J. S., and G. L. Woods. 1996. Clinical evaluation of the Roche AMPLICOR PCR Mycobacterium tuberculosis test for detection of M. tuberculosis in respiratory specimens. J Clin Microbiol 34:1083-1085.
Boehme, C. C., P. Nabeta, D. Hillemann, M. P. Nicol, S. Shenai, F. Krapp, J. Allen, R. Tahirli, R. Blakemore, R. Rustomjee, A. Milovic, M. Jones, S. M. O'Brien, D. H. Persing, S. Ruesch-Gerdes, E. Gotuzzo, C. Rodrigues, D. Alland, and M. D. Perkins. 2010. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med 363:1005-1015.
Brown, T. J., and R. M. Anthony. 2000. The addition of low numbers of 3' thymine bases can be used to improve the hybridization signal of oligonucleotides for use within arrays on nylon supports. J Microbiol Methods 42:203-207.
Brunello, F., M. Ligozzi, E. Cristelli, S. Bonora, E. Tortoli, and R. Fontana. 2001. Identification of 54 mycobacterial species by PCR-restriction fragment length polymorphism analysis of the hsp65 gene. J Clin Microbiol 39:2799-2806.
Bull, T. J., and D. C. Shanson. 1992. Evaluation of a commercial chemiluminescent gene probe system 'AccuProbe' for the rapid differentiation of mycobacteria, including 'MAIC X', isolated from blood and other sites, from patients with AIDS. J Hosp Infect 21:143-149.
Chedore, P., and F. B. Jamieson. 2002. Rapid molecular diagnosis of tuberculous meningitis using the Gen-probe Amplified Mycobacterium Tuberculosis direct test in a large Canadian public health laboratory. Int J Tuberc Lung Dis 6:913-919.
Chien, H. P., M. C. Yu, M. H. Wu, T. P. Lin, and K. T. Luh. 2000. Comparison of the BACTEC MGIT 960 with Lowenstein-Jensen medium for recovery of mycobacteria from clinical specimens. Int J Tuberc Lung Dis 4:866-870.
Cristea-Fernstrom, M., M. Olofsson, E. Chryssanthou, J. Jonasson, and B. Petrini. 2007. Pyrosequencing of a short hypervariable 16S rDNA fragment for the identification of nontuberculous mycobacteria-a comparison with conventional 16S rDNA sequencing and phenotyping. APMIS 115:1252-1259.
Djelouadji, Z., D. Raoult, M. Daffe, and M. Drancourt. 2008. A Single-step sequencing method for the identification of Mycobacterium tuberculosis complex species. PLoS Negl Trop Dis 2:e253.
Field, S. K., and R. L. Cowie. 2006. Lung disease due to the more common nontuberculous mycobacteria. Chest 129:1653-1672.
Foulds, J., and R. O'Brien. 1998. New tools for the diagnosis of tuberculosis: the perspective of developing countries. Int J Tuberc Lung Dis 2:778-783.
Griffith, D. E. 2007. Therapy of nontuberculous mycobacterial disease. Curr Opin Infect Dis 20:198-203.
Gurtler, V., C. Harford, J. Bywater, and B. C. Mayall. 2006. Direct identification of slowly growing Mycobacterium species by analysis of the intergenic 16S-23S rDNA spacer region (ISR) using a GelCompar II database containing sequence based optimization for restriction fragment site polymorphisms (RFLPs) for 12 enzymes. J Microbiol Methods 64:185-199.
Heller, L. C., M. Jones, and R. H. Widen. 2008. Comparison of DNA pyrosequencing with alternative methods for identification of mycobacteria. J Clin Microbiol 46:2092-2094.
Hocqueloux, L., P. Lesprit, J. L. Herrmann, A. de La Blanchardiere, A. M. Zagdanski, J. M. Decazes, and J. Modai. 1998. Pulmonary Mycobacterium avium complex disease without dissemination in HIV-infected patients. Chest 113:542-548.
Hsiao, C. R., L. Huang, J. P. Bouchara, R. Barton, H. C. Li, and T. C. Chang. 2005. Identification of medically important molds by an oligonucleotide array. J Clin Microbiol 43:3760-3768.
Katila, M. L., E. Iivanainen, P. Torkko, J. Kauppinen, P. Martikainen, and P. Vaananen. 1995. Isolation of potentially pathogenic mycobacteria in the Finnish environment. Scand J Infect Dis (Suppl.) 98:9-11.
Kirschner, P., M. Kiekenbeck, D. Meissner, J. Wolters, and E. C. Bottger. 1992. Genetic heterogeneity within Mycobacterium fortuitum complex species: genotypic criteria for identification. J Clin Microbiol 30:2772-2775.
Kubitschek, H. E., and M. L. Freedman. 1971. Chromosome replication and the division cycle of Escherichia coli B-r. J Bacteriol 107:95-99.
Lebrun, L., F. Espinasse, J. D. Poveda, and V. Vincent-Levy-Frebault. 1992. Evaluation of nonradioactive DNA probes for identification of mycobacteria. J Clin Microbiol 30:2476-2478.
Lee, J. J., J. Suo, C. B. Lin, J. D. Wang, T. Y. Lin, and Y. C. Tsai. 2003. Comparative evaluation of the BACTEC MGIT 960 system with solid medium for isolation of mycobacteria. Int J Tuberc Lung Dis V 7:569-574.
Lemaitre, N., S. Armand, A. Vachee, O. Capilliez, C. Dumoulin, and R. J. Courcol. 2004. Comparison of the real-time PCR method and the Gen-Probe amplified Mycobacterium tuberculosis direct test for detection of Mycobacterium tuberculosis in pulmonary and nonpulmonary specimens. J Clin Microbiol 42:4307-4309.
Lu, P. L., Y. C. Yang, S. C. Huang, Y. S. Jenh, Y. C. Lin, H. H. Huang, and T. C. Chang. 2011. Evaluation of the Bactec MGIT 960 System in combination with the MGIT TBc identification test for detection of Mycobacterium tuberculosis complex in respiratory specimens. J Clin Microbiol 49:2290-2292.
Makinen, J., M. Marjamaki, H. Marttila, and H. Soini. 2006. Evaluation of a novel strip test, GenoType Mycobacterium CM/AS, for species identification of mycobacterial cultures. Clin MicrobiolInf12:481-483.
Mase, S. R., A. Ramsay, V. Ng, M. Henry, P. C. Hopewell, J. Cunningham, R. Urbanczik, M. D. Perkins, M. A. Aziz, and M. Pai. 2007. Yield of serial sputum specimen examinations in the diagnosis of pulmonary tuberculosis: a systematic review. Int J Tuberc Lung Dis 11:485-495.
Michos, A. G., G. L. Daikos, K. Tzanetou, M. Theodoridou, M. Moschovi, P. Nicolaidou, G. Petrikkos, T. Syriopoulos, S. Kanavaki, and V. P. Syriopoulou. 2006. Detection of Mycobacterium tuberculosis DNA in respiratory and nonrespiratory specimens by the Amplicor MTB PCR. Diagn Microbiol Infect Dis 54:121-126.
Millar, B. C., X. Jiru, J. E. Moore, and J. A. Earle. 2000. A simple and sensitive method to extract bacterial, yeast and fungal DNA from blood culture material. JMicrobiol Methods 42:139-147.
Moore, D. F., and J. I. Curry. 1998. Detection and identification of Mycobacterium tuberculosis directly from sputum sediments by ligase chain reaction. J Clin Microbiol 36:1028-1031.
Barbara A. Brown-elliott, Richard J. Wallace, JR. 2007. Mycobacterium: Clinical and Laboratory Characteristics of Rapidly Growing, p. 589-600. In P. R. Murray, E. J. Baron, J. H. Jorgensen, M. L. Landry, and M. A. Pfaller (9 ed.) ,Manual of clinical microbiology volume 1. ASM Press, washington, D.C.
Neonakis, I. K., Z. Gitti, E. Krambovitis, and D. A. Spandidos. 2008. Molecular diagnostic tools in mycobacteriology. J Microbiol Methods 75:1-11.
Piersimoni, C., and C. Scarparo. 2003. Relevance of commercial amplification methods for direct detection of Mycobacterium tuberculosis complex in clinical samples. J Clin Microbiol 41:5355-5365.
Richter, E., S. Niemann, S. Rusch-Gerdes, and S. Hoffner. 1999. Identification of Mycobacterium kansasii by using a DNA probe (AccuProbe) and molecular techniques. J Clin Microbiol 37:964-970.
Rohner, P., E. I. Jahn, B. Ninet, C. Ionati, R. Weber, R. Auckenthaler, and G. E. Pfyffer. 1998. Rapid diagnosis of pulmonary tuberculosis with the LCx Mycobacterium tuberculosis assay and comparison with conventional diagnostic techniques. J Clin Microbiol 36:3046-3047.
Roth, A., U. Reischl, A. Streubel, L. Naumann, R. M. Kroppenstedt, M. Habicht, M. Fischer, and H. Mauch. 2000. Novel diagnostic algorithm for identification of mycobacteria using genus-specific amplification of the 16S-23S rRNA gene spacer and restriction endonucleases. J Clin Microbiol 38:1094-1104.
Russo, C., E. Tortoli, and D. Menichella. 2006. Evaluation of the new GenoType Mycobacterium assay for identification of mycobacterial species. JClin Microbiol 44:334-339.
Russo, C., E. Tortoli, and D. Menichella. 2006. Evaluation of the new GenoType Mycobacterium assay for identification of mycobacterial species. J Clin Microbiol 44:334-339.
Shen, G. H., C. H. Hung, S. T. Hu, B. D. Wu, C. F. Lin, C. H. Chen, K. M. Wu, and J. H. Chen. 2009. Combining polymerase chain reaction restriction enzyme analysis with phenotypic characters for mycobacteria identification in Taiwan. Int J Tuberc Lung Dis 13:472-479.
Shin, J. H., H. K. Lee, E. J. Cho, J. Y. Yu, and Y. H. Kang. 2008. Targeting the rpoB gene using nested PCR-restriction fragment length polymorphism for identification of nontuberculous mycobacteria in hospital tap water. J Microbiol 46:608-614.
Shrestha, N. K., M. J. Tuohy, G. S. Hall, U. Reischl, S. M. Gordon, and G. W. Procop. 2003. Detection and differentiation of Mycobacterium tuberculosis and nontuberculous mycobacterial isolates by real-time PCR. J Clin Microbiol 41:5121-5126.
Sloutsky, A., L. L. Han, and B. G. Werner. 2004. New method for detection of Mycobacterium tuberculosis direct test inhibitors in clinical specimens. Diagn Microbiol Infect Dis 50:109-111.
Suffys, P. N., A. da Silva Rocha, M. de Oliveira, C. E. Campos, A. M. Barreto, F. Portaels, L. Rigouts, G. Wouters, G. Jannes, G. van Reybroeck, W. Mijs, and B. Vanderborght. 2001. Rapid identification of mycobacteria to the species level using INNO-LiPA Mycobacteria, a reverse hybridization assay. J Clin Microbiol 39:4477-4482.
Sun, J. R., S. Y. Lee, C. L. Perng, and J. J. Lu. 2009. Detecting Mycobacterium tuberculosis in Bactec MGIT 960 cultures by inhouse IS6110-based PCR assay in routine clinical practice. JFormMed Asso 108:119-125.
Telenti, A., F. Marchesi, M. Balz, F. Bally, E. C. Bottger, and T. Bodmer. 1993. Rapid identification of mycobacteria to the species level by polymerase chain reaction and restriction enzyme analysis. J Clin Microbiol 31:175-178.
Timpe, A., and E. H. Runyon. 1954. The relationship of atypical acid-fast bacteria to human disease; a preliminary report. J Lab Clin Med 44:202-209.
Tortoli, E. 2003. Impact of genotypic studies on mycobacterial taxonomy: the new mycobacteria of the 1990s. Clin Microbiol Rev 16:319-354.
Tortoli, E., A. Mariottini, and G. Mazzarelli. 2003. Evaluation of INNO-LiPA MYCOBACTERIA v2: improved reverse hybridization multiple DNA probe assay for mycobacterial identification. J Clin Microbiol 41:4418-4420.
Tortoli, E., M. Pecorari, G. Fabio, M. Messino, and A. Fabio. 2010. Commercial DNA probes for mycobacteria incorrectly identify a number of less frequently encountered species. J Clin Microbiol 48:307-310.
von Reyn, C. F., R. D. Waddell, T. Eaton, R. D. Arbeit, J. N. Maslow, T. W. Barber, R. J. Brindle, C. F. Gilks, J. Lumio, J. Lahdevirta, and et al. 1993. Isolation of Mycobacterium avium complex from water in the United States, Finland, Zaire, and Kenya. J Clin Microbiol 31:3227-3230.
World Health Organization. 2010. World Health Organization Report 2010. Global tuberculosis control. World Health Organization. Geneva, Switzerland.
Wilson, M. L., B. L. Stone, M. V. Hildred, and R. R. Reves. 1995. Comparison of recovery rates for mycobacteria from BACTEC 12B vials, Middlebrook 7H11-selective 7H11 biplates, and Lowenstein Jensen slants in a public health mycobacteriology laboratory. J Clin Microbiol 33:2516-2518.
Woods, G. L. 2001. Molecular techniques in mycobacterial detection. Arch Pathol Lab Med 125:122-126.
Yang, Y. C., P. L. Lu, S. C. Huang, Y. S. Jenh, R. Jou, and T. C. Chang. 2011. Evaluation of the Cobas TaqMan MTB test for direct detection of Mycobacterium tuberculosis complex in respiratory specimens. J Clin Microbiol 49:797-801.
論文全文使用權限
  • 同意授權校內瀏覽/列印電子全文服務,於2021-12-31起公開。


  • 如您有疑問,請聯絡圖書館
    聯絡電話:(06)2757575#65773
    聯絡E-mail:etds@email.ncku.edu.tw