今日の臨床サポート

肺結核

著者: 原田壮平 東京大学医学部附属病院 感染制御部

監修: 具芳明 東京医科歯科大学大学院医歯学総合研究科 統合臨床感染症学分野

著者校正/監修レビュー済:2020/11/06
参考ガイドライン:
  1. 日本結核病学会(日本結核・非結核性抗酸菌症学会):結核診療ガイド 2018
  1. 米国胸部学会(ATS)/米国感染症学会(IDSA)/アメリカ疾病予防管理センター(CDC) Clinical Practice Guidelines:Diagnosis of Tuberculosis in Adults and Children. Clin Infect Dis. 2017;64(2):111-115.
  1. 米国胸部学会(ATS)/ アメリカ疾病予防管理センター(CDC)/米国感染症学会(IDSA) Clinical Practice Guidelines:Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016 Oct 1;63(7):e147-e195.
患者向け説明資料

概要・推奨   

  1. 標準的抗結核治療を受ける患者は、定期的にAST値、ALT値、総ビリルビン値などの肝機能検査を行い、薬剤性肝炎のスクリーニングを行うことが強く推奨される(推奨度1)
  1. 標準的な抗結核療法を受ける患者においてHBs-Ag検査によるHBV感染症スクリーニングを治療開始時に施行することは、治療中の肝障害発症の確率を予測するうえで、おそらく推奨される(推奨度2)
  1. 肺結核の診断を受けた患者に対してHIV感染症のカウンセリングを行い、感染危険因子がある場合にはHIV抗体検査によるスクリーニングを行うことが推奨される(推奨度2)
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧に
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約 が必要となりま す。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. イソニアジドを使用する患者で神経障害の副作用発現のリスクが高い患者ではビタミンB6の補充を行うことが推奨される(推奨度2)。
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
原田壮平 : 特に申告事項無し[2021年]
監修:具芳明 : 特に申告事項無し[2021年]

改訂のポイント:
  1. 定期レビューを行った(変更なし)

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 肺結核の診断は、喀痰培養検査によるMycobacterium tuberculosisの検出がゴールドスタンダードである。
  1. 喀痰抗酸菌染色が陽性であれば肺結核の診断が示唆されるが、非結核性抗酸菌なども染色されるため、確定には培養検査の結果を待つ必要がある。
  1. PCR法などの喀痰核酸増幅検査は抗酸菌染色陽性例の早期診断に有用であり、また、塗抹陰性例においても診断感度の向上に役立つ。
  1. 核酸増幅検査で診断がほぼ確定した例においても、喀痰培養検査は必ず施行して診断を確認する。また、培養検査を施行しなければ、起因菌の抗結核薬感受性を確認できない。
  1. 空洞形成、tree in bud sign(木の芽サイン)、肺S1・S2・S6の病変など典型的な画像所見を呈する例では鑑別診断の上位に挙げ、速やかな診断検査と感染対策をとることが重要である。
 
典型的な肺結核の画像所見

a:胸部X線では右肺上葉の空洞を伴う浸潤影を認める。
b:胸部CTにおいては、空洞の存在が胸部X線検査よりも明瞭に描出される。

 
  1. 慢性咳嗽、市中肺炎、不明熱などの病態においても、結核を鑑別診断の1つとして考慮することが重要である。抗酸菌検査が施行されなくては、決して診断は得られない。
問診・診察のポイント  
  1. HIV感染症、コルチコステロイドや、ほかの免疫抑制薬の投与、糖尿病、悪性腫瘍、低栄養、塵肺、腎不全などの患者では活動性肺結核発症のリスクが高まるので、これらについて病歴を聴取する。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

最新のエビデンスに基づいた二次文献データベース「今日の臨床サポート」。
常時アップデートされており、最新のエビデンスを各分野のエキスパートが豊富な図表や処方・検査例を交えて分かりやすく解説。日常臨床で遭遇するほぼ全ての症状・疾患から薬剤・検査情報まで瞬時に検索可能です。

まずは15日間無料トライアル
本サイトの知的財産権は全てエルゼビアまたはコンテンツのライセンサーに帰属します。私的利用及び別途規定されている場合を除き、本サイトの利用はいかなる許諾を与えるものでもありません。 本サイト、そのコンテンツ、製品およびサービスのご利用は、お客様ご自身の責任において行ってください。本サイトの利用に基づくいかなる損害についても、エルゼビアは一切の責任及び賠償義務を負いません。 また、本サイトの利用を以て、本サイト利用者は、本サイトの利用に基づき第三者に生じるいかなる損害についても、エルゼビアを免責することに合意したことになります。  本サイトを利用される医学・医療提供者は、独自の臨床的判断を行使するべきです。本サイト利用者の判断においてリスクを正当なものとして受け入れる用意がない限り、コンテンツにおいて提案されている検査または処置がなされるべきではありません。 医学の急速な進歩に鑑み、エルゼビアは、本サイト利用者が診断方法および投与量について、独自に検証を行うことを推奨いたします。

文献 

著者: Payam Nahid, Susan E Dorman, Narges Alipanah, Pennan M Barry, Jan L Brozek, Adithya Cattamanchi, Lelia H Chaisson, Richard E Chaisson, Charles L Daley, Malgosia Grzemska, Julie M Higashi, Christine S Ho, Philip C Hopewell, Salmaan A Keshavjee, Christian Lienhardt, Richard Menzies, Cynthia Merrifield, Masahiro Narita, Rick O'Brien, Charles A Peloquin, Ann Raftery, Jussi Saukkonen, H Simon Schaaf, Giovanni Sotgiu, Jeffrey R Starke, Giovanni Battista Migliori, Andrew Vernon
雑誌名: Clin Infect Dis. 2016 Oct 1;63(7):e147-95. doi: 10.1093/cid/ciw376. Epub 2016 Aug 10.
Abstract/Text The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.

© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
PMID 27516382  Clin Infect Dis. 2016 Oct 1;63(7):e147-95. doi: 10.1093・・・
著者: W M Wong, P C Wu, M F Yuen, C C Cheng, W W Yew, P C Wong, C M Tam, C C Leung, C L Lai
雑誌名: Hepatology. 2000 Jan;31(1):201-6. doi: 10.1002/hep.510310129.
Abstract/Text Liver toxicity is a common side effect of antituberculosis (anti-TB) drugs. We studied the differences in liver dysfunction observed during anti-TB treatment between hepatitis B virus carriers (HBV) and noncarriers. Three hundred twenty-four patients on anti-TB drugs were recruited and followed up for 1 year. Forty-three patients with HBV and 276 non-HBV patients were included for analysis. Liver function tests and viral markers were monitored monthly. Liver biopsy was requested whenever the alanine transaminase (ALT) was persistently abnormal. Eighty-six HBV carriers who were not given anti-TB drugs were chosen as a second control and evaluated prospectively. The incidence of liver dysfunction was significantly higher in HBV carriers given anti-TB drugs (34.9%) when compared to noncarriers (9.4%, P <.001) and with HBV carriers not given anti-TB drugs (8.1%, P <.001). For patients given anti-TB drugs, HBV carriers who developed liver dysfunction were younger (P =.011) and had more severe liver injury compared with noncarriers (P =.008). By multiple logistic regression analysis, age (P =.002) and hepatitis B infection (P <.001) were the only 2 significant risk factors for hepatotoxicity related to anti-TB therapy.

PMID 10613746  Hepatology. 2000 Jan;31(1):201-6. doi: 10.1002/hep.5103・・・
著者: Byoung Hoon Lee, Won-Jung Koh, Moon Seok Choi, Gee Young Suh, Man Pyo Chung, Hojoong Kim, O Jung Kwon
雑誌名: Chest. 2005 Apr;127(4):1304-11. doi: 10.1378/chest.127.4.1304.
Abstract/Text STUDY OBJECTIVES: To determine whether inactive hepatitis B surface antigen (HBsAg) carriers are at a higher risk of drug-induced hepatotoxicity than control subjects during antituberculosis treatment with standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide.
DESIGN: Retrospective case-control study.
SETTING: Tertiary university medical center.
PATIENTS: One hundred ten inactive HBsAg carriers with newly diagnosed active tuberculosis who had been treated with isoniazid, rifampin, ethambutol, and/or pyrazinamide were included in the study population. Inactive HBsAg carriers were defined as follows: (1) positive for HbsAg; (2) negative for hepatitis B e antigen (HBeAg), positive for antibody to HBeAg; (3) < 10(5) copies per mL of serum hepatitis B virus DNA; and (4) normal pretreatment aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels. Ninety-seven HBsAg-negative patients who received standard antituberculosis medication were selected as control subjects.
RESULTS: The baseline characteristics of the 110 inactive HBsAg carriers were similar to those of the 97 noncarriers. A total of 85% of persons in both groups had received an initial treatment regimen that included pyrazinamide. Thirty-eight inactive HBsAg carriers (35%) and 19 control subjects (20%) exhibited elevated liver enzyme levels during antituberculosis treatment (p = 0.016). Drug-induced hepatotoxicity, which was defined as a liver transaminase level of >/= 120 IU/L, occurred more frequently in HBsAg carriers (9 of 110 carriers; 8%) than in control subjects (4 of 97 control subjects; 4%), although this was not a statistically significant discrepancy (p = 0.230). More importantly, HBsAg carriers (n = 9; 8%) who received antituberculosis therapy evidenced a higher proportion of moderate-to-severe drug-induced hepatotoxicity when compared with the control subjects (n = 2; 2%; p = 0.05). Isoniazid and rifampin were reintroduced as therapy after AST/ALT levels returned to baseline values in 10 patients (6 HBsAg carriers and 4 control subjects) among the 13 patients exhibiting drug-induced hepatotoxicity, and these retrials proved to be successful in 7 patients (5 HBsAg carriers and 2 control subjects).
CONCLUSIONS: Tuberculosis treatment in HBsAg-positive and HBeAg-negative inactive carriers could be pursued in the usual manner, using standard short-course regimens of isoniazid, rifampin, ethambutol, and/or pyrazinamide, with the condition that monthly liver function tests are performed.

PMID 15821209  Chest. 2005 Apr;127(4):1304-11. doi: 10.1378/chest.127.・・・
著者: S J Hwang, J C Wu, C N Lee, F S Yen, C L Lu, T P Lin, S D Lee
雑誌名: J Gastroenterol Hepatol. 1997 Jan;12(1):87-91.
Abstract/Text In order to evaluate the incidence, predisposing factors and clinical course of antituberculous drug-induced liver injury in hepatitis B surface antigen (HBsAg)-positive carriers and non-carriers, in an area endemic for hepatitis B, we prospectively followed 240 patients (154 male, 86 female; mean age 40 years) who had received daily isoniazid, rifampicin, ethambutol and pyrazinamide for the treatment of pulmonary tuberculosis. Patients with heavy alcohol consumption, with pretreatment serum alanine aminotransferase (ALT) elevation and who had less than 3 months post-treatment follow-up were excluded from the study. Thirty-one (13%) patients were positive for serum HBsAg before treatment. Sixty-three (26%; 95% CI: 21-32%) patients developed antituberculous drug-induced liver injury. The incidence of drug-induced liver injury was significantly more frequent in patients > 35 years of age than in patients < or = 35 years of age (33 vs 17%; P < 0.05), but was not different between HBsAg carriers and non-carriers (29 vs 26%; P > 0.05). Using step-wise logistic regression analysis, patient age > 35 years was the only independent variable for predicting antituberculous drug-induced liver injury, while sex, acetylator phenotype, HBsAg carrier status and severity of tuberculosis were not. The peak serum ALT levels in antituberculous drug-induced liver injury were not significantly different between HBsAg carriers and non-carriers. Only one 61-year-old HBsAg carrier developed severe jaundice after 6 months antituberculous therapy; he subsequently died of hepatic failure. In conclusion, the incidence of antituberculous drug-induced liver injury was significantly higher in patients > 35 years of age than in patients < or = 35 years of age, but was not different between HBsAg carriers and non-carriers. Mortality occurred in an aged HBsAg carrier superimposed with antituberculous drug-induced liver injury.

PMID 9076631  J Gastroenterol Hepatol. 1997 Jan;12(1):87-91.
著者: Kathryn DeRiemer, L Masae Kawamura, Philip C Hopewell, Charles L Daley
雑誌名: Am J Respir Crit Care Med. 2007 Nov 1;176(9):936-44. doi: 10.1164/rccm.200603-440OC. Epub 2007 Aug 9.
Abstract/Text RATIONALE: Human immunodeficiency virus (HIV) infection has a major but unquantified impact on the risk of tuberculosis.
OBJECTIVES: To quantify the impact of HIV infection on the number of tuberculosis cases in San Francisco.
METHODS: We studied all patients reported with tuberculosis in San Francisco from 1991 to 2002. The initial isolates of Mycobacterium tuberculosis were genotyped using IS6110 restriction fragment-length polymorphism genotyping as the primary method, and clustered cases (identical genotype patterns) were identified.
MEASUREMENTS AND MAIN RESULTS: We determined the case number, case rate, and the fraction of tuberculosis attributable to HIV infection. Of 2,991 reported tuberculosis cases, 2,193 (73.3%) had a genotype pattern of M. tuberculosis available. Genotypic clusters with at least one HIV-positive person were larger, lasted longer, and had a shorter time between successive cases relative to clusters with only HIV-uninfected persons (P < 0.00005, P = 0.0009, P = 0.018, respectively). Overall, 13.7% of the tuberculosis cases were attributable to HIV infection and an estimated 405 excess tuberculosis cases occurred.
CONCLUSIONS: During a period encompassing the resurgence and decline of tuberculosis in San Francisco, a substantial number of the tuberculosis cases were attributable to HIV infection. Coinfection with HIV amplified the local tuberculosis epidemic.

PMID 17690336  Am J Respir Crit Care Med. 2007 Nov 1;176(9):936-44. do・・・
著者:
雑誌名: MMWR Recomm Rep. 1998 Oct 30;47(RR-20):1-58.
Abstract/Text These guidelines update previous CDC recommendations for the diagnosis, treatment, and prevention of tuberculosis (TB) among adults and children coinfected with human immunodeficiency virus (HIV) in the United States. The most notable changes in these guidelines reflect both the findings of clinical trials that evaluated new drug regimens for treating and preventing TB among HIV-infected persons and recent advances in the use of antiretroviral therapy. In September 1997, when CDC convened a meeting of expert consultants to discuss current information about HIV-related TB, special emphasis was given to issues related to coadministration of TB therapy and antiretroviral therapy and how to translate this information into management guidelines. Thus, these guidelines are based on the following scientific principles: * Early diagnosis and effective treatment of TB among HIV-infected patients are critical for curing TB, minimizing the negative effects of TB on the course of HIV, and interrupting the transmission of Mycobacterium tuberculosis to other persons in the community. * All HIV-infected persons at risk for infection with M. tubercu losis must be carefully evaluated and, if indicated, administered therapy to prevent the progression of latent infection to active TB disease and avoid the complications associated with HIV-related TB. * All HIV-infected patients undergoing treatment for TB should be evaluated for antiretroviral therapy, because most patients with HIV-related TB are candidates for concurrent administration of antituberculosis and antiretroviral drug therapies. However, the use of rifampin with protease inhibitors or nonnucleoside reverse transcriptase inhibitors is contraindicated. Ideally, the management of TB among HIV-infected patients taking antiretroviral drugs requires a) directly observed therapy, b) availability of experienced and coordinated TB/HIV care givers, and in most situations, c) use of a TB treatment regimen that includes rifabutin instead of rifampin. Because alternatives to the use of rifampin for antituberculosis treatment are now available, the previously recommended practice of stopping protease inhibitor therapy to allow the use of rifampin for TB treatment is no longer recommended for patients with HIV-related TB. The use of rifabutin-containing antituberculosis regimens should always include an assessment of the patient's response to treatment to decide the appropriate duration of therapy (i.e., 6 months or 9 months). Physicians and patients also should be aware that paradoxical reactions might occur during the course of TB treatment when antiretroviral therapy restores immune function. Adding to CDC's current recommendations for administering isoniazid preventive therapy to HIV-infected persons with positive tuberculin skin tests and to HIV-infected persons who were exposed to patients with infectious TB, this report also describes in detail the use of new shortcourse (i.e., 2 months) multidrug regimens (e.g., a rifamycin, such as rifampin or rifabutin, combined with pyrazinamide) to prevent TB in persons with HIV infection. A continuing education component for U.S. physicians and nurses is included.

PMID 9809743  MMWR Recomm Rep. 1998 Oct 30;47(RR-20):1-58.
著者: Michael Brown, Hansa Varia, Paul Bassett, Robert N Davidson, Robert Wall, Geoffrey Pasvol
雑誌名: Clin Infect Dis. 2007 Jun 1;44(11):1415-20. doi: 10.1086/516782. Epub 2007 Apr 20.
Abstract/Text BACKGROUND: Many adults with pulmonary tuberculosis are unable to expectorate. Gastric washing, sputum induction using nebulized hypertonic saline, and bronchoscopy with bronchoalveolar lavage have all been used to obtain specimens for diagnosis, but to our knowledge, the timing and volume of induced sputum have not been well studied, and these 3 methods have not been compared.
METHODS: The study recruited consecutive adult inpatients with chest radiography findings suggestive of tuberculosis who were unable to expectorate. Subjects provided 3 induced sputum samples for culture on day 1 and additional samples on days 2 and 3. In addition, gastric washing specimens were collected on days 1, 2, and 3. A proportion of subjects with negative smear results underwent bronchoalveolar lavage.
RESULTS: The study recruited 140 subjects. Among 107 subjects who provided 3 gastric washing specimens and at least 3 induced sputum specimens, 43% had cultures positive for Mycobacterium tuberculosis. Use of 3 induced sputum samples detected more cases than did use of 3 gastric washings (39% vs. 30%; P=.03). Among 79 subjects with culture results for all 5 induced sputum specimens, there was no difference in yield between samples obtained by induced sputum induction performed in a single day or that performed over 3 days (34% vs. 37%; P=.63). There was no association between sputum volume and positive culture results. No additional cases were diagnosed in the 21 patients who underwent bronchoscopy.
CONCLUSIONS: Use of 3 induced sputum samples was more sensitive than use of 3 gastric washings for diagnosis of tuberculosis in patients who could not expectorate spontaneously. Use of bronchoscopy with bronchoalveolar lavage did not increase diagnostic sensitivity. Samples could be collected in 1 day, allowing for faster diagnosis, faster initiation of treatment, and shorter hospital stay.

PMID 17479935  Clin Infect Dis. 2007 Jun 1;44(11):1415-20. doi: 10.108・・・
著者: H Kawada, N Suzuki, Y Takeda, E Toyoda, M Takahara, N Kobayashi, T Suzuki, K Kudo, J Kabe
雑誌名: Kekkaku. 1996 Nov;71(11):603-6.
Abstract/Text This study was designed to compare the results of culture for tubercle bacilli using induced sputum by an ultrasonic nebulizer and gastric aspirates from same patients who were suspected of having active tuberculosis with little or no sputum and had received no prior chemotherapy. 22 patients included in this series were either culture positive for tubercle bacilli or showed unequivocal radiographic improvement after three months of therapy with three anti-tuberculosis drugs. Induced sputum from 17 patients and gastric aspirates from seven patients were culture positive for M.tuberculosis. This difference is significant (p < 0.01). Paired induced sputum and gastric aspirates were both positive for tubercle bacilli in seven patients. The finding of acid-fast bacilli on microscopy or tubercle bacilli in culture in four of the seven patients were available much earlier with induced sputum than with gastric aspirates. Positive gastric aspirates and negative induced sputum for tubercle bacilli was not seen. These results suggest that induced sputum by an ultrasonic nebulizer is superior to gastric aspirates in terms of high sensitivity and early finding for tubercle bacilli and induced sputum and gastric aspirates do not supplement each other.

PMID 8958672  Kekkaku. 1996 Nov;71(11):603-6.
著者: Fabienne Laraque, Anne Griggs, Meredith Slopen, Sonal S Munsiff
雑誌名: Clin Infect Dis. 2009 Jul 1;49(1):46-54. doi: 10.1086/599037.
Abstract/Text BACKGROUND: A diagnosis of tuberculosis (TB) relies on acid-fast bacilli (AFB) smear and culture results. Two rapid tests that use nucleic acid amplification (NAA) have been approved by the US Food and Drug Administration for the diagnosis of TB based on detection of Mycobacterium tuberculosis from specimens obtained from the respiratory tract. We evaluated the performance of NAA testing under field conditions in a large urban setting with moderate TB prevalence.
METHODS: The medical records of patients with suspected TB during 2000-2004 were reviewed. Analysis was restricted to the performance of NAA on specimens collected within 7 days after the initiation of treatment for TB. The assay's sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively) were evaluated.
RESULTS: The proportion of patients with confirmed or suspected TB whose respiratory tract specimens were tested by use of NAA increased from 429 (12.9%) of 3334 patients in 2000 to 527 (15.6%) of 3386 patients in 2004; NAA testing among patients whose respiratory tract specimens tested positive for AFB increased from 415 (43.6%) of 952 patients in 2000 to 487 (55.5%) of 877 patients in 2004 (P < .001 for both trends). Of the 16,511 patients being evaluated for pulmonary TB, 4642 (28.1%) had specimens that tested positive for AFB on smear. Of those 4642 patients, 2241 (48.3%) had NAA performed on their specimens. Of those 2241 patients, 1279 (57.1%) had positive test results. Of those 1279 patients, 1262 (98.7%) were confirmed to have TB. For 1861 (40.1%) of the 4642 patients whose specimens tested positive for AFB on smear, the NAA test had a sensitivity of 96.0%, a specificity of 95.3%, a PPV of 98.0%, and an NPV of 90.9%. For 158 patients whose specimens tested negative for AFB on smear, the NAA test had a sensitivity of 79.3%, a specificity of 80.3%, a PPV of 83.1%, and an NPV of 76.0%, respectively. For the 215 specimens that tested positive for AFB by smear, we found a sensitivity, specificity, PPV, and NPV of 97.5%, 93.6%, 95.1%, and 96.8%, respectively. A high-grade smear was associated with a better test performance.
CONCLUSION: NAA testing was helpful for determining whether patients whose specimens tested positive for AFB on smear had TB or not. This conclusion supports the use of this test for early diagnosis of pulmonary and extrapulmonary TB.

PMID 19476429  Clin Infect Dis. 2009 Jul 1;49(1):46-54. doi: 10.1086/5・・・
著者: David M Lewinsohn, Michael K Leonard, Philip A LoBue, David L Cohn, Charles L Daley, Ed Desmond, Joseph Keane, Deborah A Lewinsohn, Ann M Loeffler, Gerald H Mazurek, Richard J O'Brien, Madhukar Pai, Luca Richeldi, Max Salfinger, Thomas M Shinnick, Timothy R Sterling, David M Warshauer, Gail L Woods
雑誌名: Clin Infect Dis. 2017 Jan 15;64(2):111-115. doi: 10.1093/cid/ciw778.
Abstract/Text BACKGROUND: Individuals infected with Mycobacterium tuberculosis (Mtb) may develop symptoms and signs of disease (tuberculosis disease) or may have no clinical evidence of disease (latent tuberculosis infection [LTBI]). Tuberculosis disease is a leading cause of infectious disease morbidity and mortality worldwide, yet many questions related to its diagnosis remain.
METHODS: A task force supported by the American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America searched, selected, and synthesized relevant evidence. The evidence was then used as the basis for recommendations about the diagnosis of tuberculosis disease and LTBI in adults and children. The recommendations were formulated, written, and graded using the Grading, Recommendations, Assessment, Development and Evaluation (GRADE) approach.
RESULTS: Twenty-three evidence-based recommendations about diagnostic testing for latent tuberculosis infection, pulmonary tuberculosis, and extrapulmonary tuberculosis are provided. Six of the recommendations are strong, whereas the remaining 17 are conditional.
CONCLUSIONS: These guidelines are not intended to impose a standard of care. They provide the basis for rational decisions in the diagnosis of tuberculosis in the context of the existing evidence. No guidelines can take into account all of the often compelling unique individual clinical circumstances.

© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.
PMID 28052967  Clin Infect Dis. 2017 Jan 15;64(2):111-115. doi: 10.109・・・
著者: Madhukar Pai, Alice Zwerling, Dick Menzies
雑誌名: Ann Intern Med. 2008 Aug 5;149(3):177-84. Epub 2008 Jun 30.
Abstract/Text BACKGROUND: Interferon-gamma-release assays (IGRAs) are alternatives to the tuberculin skin test (TST). A recent meta-analysis showed that IGRAs have high specificity, even among populations that have received bacille Calmette-Guérin (BCG) vaccination. Sensitivity was suboptimal for TST and IGRAs.
PURPOSE: To incorporate newly reported evidence from 20 studies into an updated meta-analysis on the sensitivity and specificity of IGRAs.
DATA SOURCES: PubMed was searched through 31 March 2008, and citations of all original articles, guidelines, and reviews for studies published in English were reviewed.
STUDY SELECTION: Studies that evaluated QuantiFERON-TB Gold, QuantiFERON-TB Gold In-Tube (both from Cellestis, Victoria, Australia), and T-SPOT.TB (Oxford Immunotec, Oxford, United Kingdom) or its precommercial ELISpot version, when data on the commercial version were lacking. For assessing sensitivity, the study sample had to have microbiologically confirmed active tuberculosis. For assessing specificity, the sample had to comprise healthy, low-risk individuals without known exposure to tuberculosis. Studies with fewer than 10 participants and those that included only immunocompromised participants were excluded.
DATA EXTRACTION: One reviewer abstracted data on participant characteristics, test characteristics, and test performance from 38 studies; these data were double-checked by a second reviewer. The original investigators were contacted for additional information when necessary.
DATA SYNTHESIS: A fixed-effects meta-analysis with correction for overdispersion was done to pool data within prespecified subgroups. The pooled sensitivity was 78% (95% CI, 73% to 82%) for QuantiFERON-TB Gold, 70% (CI, 63% to 78%) for QuantiFERON-TB Gold In-Tube, and 90% (CI, 86% to 93%) for T-SPOT.TB. The pooled specificity for both QuantiFERON tests was 99% among non-BCG-vaccinated participants (CI, 98% to 100%) and 96% (CI, 94% to 98%) among BCG-vaccinated participants. The pooled specificity of T-SPOT.TB (including its precommercial ELISpot version) was 93% (CI, 86% to 100%). Tuberculin skin test results were heterogeneous, but specificity in non-BCG-vaccinated participants was consistently high (97% [CI, 95% to 99%]).
LIMITATIONS: Most studies were small and had limitations, including no gold standard for diagnosing latent tuberculosis and variable TST methods and cutoff values. Data on the specificity of the commercial T-SPOT.TB assay were limited.
CONCLUSION: The IGRAs, especially QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube, have excellent specificity that is unaffected by BCG vaccination. Tuberculin skin test specificity is high in non-BCG-vaccinated populations but low and variable in BCG-vaccinated populations. Sensitivity of IGRAs and TST is not consistent across tests and populations, but T-SPOT.TB appears to be more sensitive than both QuantiFERON tests and TST.

PMID 18593687  Ann Intern Med. 2008 Aug 5;149(3):177-84. Epub 2008 Jun・・・
著者: M Sester, G Sotgiu, C Lange, C Giehl, E Girardi, G B Migliori, A Bossink, K Dheda, R Diel, J Dominguez, M Lipman, J Nemeth, P Ravn, S Winkler, E Huitric, A Sandgren, D Manissero
雑誌名: Eur Respir J. 2011 Jan;37(1):100-11. doi: 10.1183/09031936.00114810. Epub 2010 Sep 16.
Abstract/Text Interferon-γ release assays (IGRAs) are now established for the immunodiagnosis of latent infection with Mycobacterium tuberculosis in many countries. However, the role of IGRAs for the diagnosis of active tuberculosis (TB) remains unclear. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and quality assessment of diagnostic accuracy studies (QUADAS) guidelines, we searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-November 2009 that evaluated the evidence of using QuantiFERON-TB® Gold in-tube (QFT-G-IT) and T-SPOT.TB® directly on blood or extrasanguinous specimens for the diagnosis of active TB. The literature search yielded 844 studies and 27 met the inclusion criteria. In blood and extrasanguinous fluids, the pooled sensitivity for the diagnosis of active TB was 80% (95% CI 75-84%) and 48% (95% CI 39-58%) for QFT-G-IT, and 81% (95% CI 78-84%) and 88% (confirmed and unconfirmed cases) (95% CI 82-92%) for T-SPOT.TB®, respectively. In blood and extrasanguinous fluids, the pooled specificity was 79% (95% CI 75-82%) and 82% (95% CI 70-91%) for QFT-G-IT, and 59% (95% CI 56-62%) and 82% (95% CI 78-86%) for T-SPOT.TB®, respectively. Although the diagnostic sensitivities of both IGRAs were higher than that of tuberculin skin tests, it was still not high enough to use as a rule out test for TB. Positive evidence for the use of IGRAs in compartments other than blood will require more independent and carefully designed prospective studies.

PMID 20847080  Eur Respir J. 2011 Jan;37(1):100-11. doi: 10.1183/09031・・・
著者: D L Combs, R J O'Brien, L J Geiter
雑誌名: Ann Intern Med. 1990 Mar 15;112(6):397-406.
Abstract/Text STUDY OBJECTIVE: To determine the effectiveness, toxicity, and acceptability of a 6-month antituberculous regimen compared with a 9-month regimen.
DESIGN: A nonblinded, unbalanced, randomized, multicenter clinical trial.
SETTING: Twenty-two tuberculosis clinics in public health departments and hospitals in the United States.
PATIENTS: Patients were eligible if Mycobacterium tuberculosis, isolated from sputum cultures, was susceptible to study drugs. Of 1451 patients enrolled, 75% (617 of 823) assigned to the 6-month regimen and 71% (445 of 628) assigned to the 9-month regimen were eligible.
INTERVENTIONS: Patients took self-administered isoniazid and rifampin daily for 24 weeks (6-month regimen) or 36 weeks (9-month regimen). In addition, patients assigned to the 6-month regimen took self-administered pyrazinamide daily during the first 8 weeks.
RESULTS: Patients on the 6-month regimen converted more rapidly than patients on the 9-month regimen (94.6% compared with 89.9% after 16 weeks of therapy, with a difference of 4.7% [95% CI, 0.7% to 8.7%]); had similar rates of adverse drug reactions (7.7% compared with 6.4%, with a difference of 1.3% [95% CI, 0.0% to 4.6%]); had lower noncompliance rates (16.8% compared with 29.2%, with a difference of 12.4% [95% CI, 6.8% to 18.0%]); and had similar relapse rates 96 weeks after completing therapy (3.5% compared with 2.8%, with a difference of 0.7% [95% CI, 0.0% to 3.9%]). A significantly greater proportion of patients assigned to the 6-month regimen successfully completed therapy (61.4% compared with 50.6%; chi 2 = 11.976).
CONCLUSIONS: Our results suggest that this 6-month regimen is similar in effectiveness, toxicity, and acceptability to the 9-month regimen for treating pulmonary tuberculosis.

PMID 2155569  Ann Intern Med. 1990 Mar 15;112(6):397-406.
著者: Debra Benator, Mondira Bhattacharya, Lorna Bozeman, William Burman, Antonino Cantazaro, Richard Chaisson, Fred Gordin, C Robert Horsburgh, James Horton, Awal Khan, Christopher Lahart, Beverly Metchock, Constance Pachucki, Llewellyn Stanton, Andrew Vernon, M Elsa Villarino, Yong Chen Wang, Marc Weiner, Stephen Weis, Tuberculosis Trials Consortium
雑誌名: Lancet. 2002 Aug 17;360(9332):528-34.
Abstract/Text BACKGROUND: Rifapentine has a long half-life in serum, which suggests a possible treatment once a week for tuberculosis. We aimed to compare rifapentine and isoniazid once a week with rifampicin and isoniazid twice a week.
METHODS: We did a randomised, multicentre, open-label trial in the USA and Canada of HIV-negative people with drug-susceptible pulmonary tuberculosis who had completed 2 months of a 6-month treatment regimen. We randomly allocated patients directly observed treatment with either 600 mg rifapentine plus 900 mg isoniazid once a week or 600 mg rifampicin plus 900 mg isoniazid twice a week. Primary outcome was failure/relapse. Analysis was by intention to treat.
FINDINGS: 1004 patients were enrolled (502 per treatment group). 928 successfully completed treatment, and 803 completed the 2-year 4-month study. Crude rates of failure/relapse were 46/502 (9.2%) in those on rifapentine once a week, and 28/502 (5.6%) in those given rifampicin twice a week (relative risk 1.64, 95% CI 1.04-2.58, p=0.04). By proportional hazards regression, five characteristics were independently associated with increased risk of failure/relapse: sputum culture positive at 2 months (hazard ratio 2.8, 95% CI 1.7-4.6); cavitation on chest radiography (3.0, 1.6-5.9); being underweight (3.0, 1.8-4.9); bilateral pulmonary involvement (1.8, 1.0-3.1); and being a non-Hispanic white person (1.8, 1.1-3.0). Adjustment for imbalances in 2-month culture and cavitation diminished the association of treatment group with outcome (1.34; 0.83-2.18; p=0.23). Of participants without cavitation, rates of failure/relapse were 6/210 (2.9%) in the once a week group and 6/241 (2.5%) in the twice a week group (relative risk 1.15; 95% CI 0.38-3.50; p=0.81). Rates of adverse events and death were similar in the two treatment groups.
INTERPRETATION: Rifapentine once a week is safe and effective for treatment of pulmonary tuberculosis in HIV-negative people without cavitation on chest radiography. Clinical, radiographic, and microbiological data help to identify patients with tuberculosis who are at increased risk of failure or relapse when treated with either regimen.

PMID 12241657  Lancet. 2002 Aug 17;360(9332):528-34.
著者: D A Mitchison
雑誌名: Am Rev Respir Dis. 1993 Apr;147(4):1062-3. doi: 10.1164/ajrccm/147.4.1062.
Abstract/Text
PMID 8466107  Am Rev Respir Dis. 1993 Apr;147(4):1062-3. doi: 10.1164・・・
著者:
雑誌名: Am Rev Respir Dis. 1991 Feb;143(2):262-7. doi: 10.1164/ajrccm/143.2.262.
Abstract/Text Patients with silicotuberculosis have been reported to respond poorly to antituberculosis chemotherapy. Therefore, in a study in Hong Kong, 240 Chinese male patients with both silicosis and pulmonary tuberculosis were all prescribed treatment three times weekly with streptomycin, isoniazid, rifampin, and pyrazinamide, allocated at random to be given for a total duration of either 6 (M6 regimen) or 8 months (M8 regimen) in a concurrent comparison. Those with a history of previous antituberculosis chemotherapy received ethambutol as well for the first 3 months. The intake in the M6 regimen was terminated when preliminary results showed that it was inadequate, and a further 53 patients were assigned to the M8 series. Of 91 assessable patients in the concurrent comparison with susceptible strains pretreatment, 44% were culture negative at 1 month, 80% at 2 months, and 98% at 3 months, and 1 had an unfavorable bacteriologic response during chemotherapy. During 3 yr of assessment, bacteriologic relapse after chemotherapy occurred in 22% of the M6 compared with 7% of the M8 patients (p less than 0.025, log-rank test). Inadequate chemotherapy was received by 12% of the 240 patients in the concurrent comparison because of default and by 22% because of adverse effects, but by 3 yr 92% of patients with susceptible strains pretreatment in each series had a favorable status following retreatment for relapse or for initially inadequate chemotherapy when required. The results show that patients with silicosis require at least 8 months of treatment.

PMID 1990938  Am Rev Respir Dis. 1991 Feb;143(2):262-7. doi: 10.1164/・・・
著者: John L Johnson, David Jamil Hadad, Reynaldo Dietze, Ethel Leonor Noia Maciel, Barrett Sewali, Phineas Gitta, Alphonse Okwera, Roy D Mugerwa, Mary Rose Alcaneses, Maria Imelda Quelapio, Thelma E Tupasi, Libby Horter, Sara M Debanne, Kathleen D Eisenach, W Henry Boom
雑誌名: Am J Respir Crit Care Med. 2009 Sep 15;180(6):558-63. doi: 10.1164/rccm.200904-0536OC. Epub 2009 Jun 19.
Abstract/Text RATIONALE: Cavitary disease and delayed culture conversion have been associated with relapse. Combining patient characteristics and measures of bacteriologic response might allow treatment shortening with current drugs in some patients.
OBJECTIVES: To assess whether treatment could be shortened from 6 to 4 months in patients with noncavitary tuberculosis whose sputum cultures converted to negative after 2 months.
METHODS: This study was a randomized, open-label equivalence trial. HIV-uninfected adults with noncavitary tuberculosis were treated daily with isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by 2 months of isoniazid and rifampin. After 4 months, patients with drug-susceptible TB whose sputum cultures on solid media were negative after 8 weeks of treatment were randomly assigned to continue treatment for 2 more months or to stop treatment. Patients were followed for relapse for 30 months after beginning treatment.
MEASUREMENTS AND MAIN RESULTS: Enrollment was stopped by the safety monitoring committee after 394 patients were enrolled due to apparent increased risk for relapse in the 4-month arm. A total of 370 patients were eligible for per protocol analysis. Thirteen patients in the 4-month arm relapsed, compared with three subjects in the 6-month arm (7.0 vs. 1.6%; risk difference, 0.054; 95% confidence interval with Hauck-Anderson correction, 0.01-0.10).
CONCLUSION: Shortening treatment from 6 to 4 months in adults with noncavitary disease and culture conversion after 2 months using current drugs resulted in a greater relapse rate. The combination of noncavitary disease and 2-month culture conversion was insufficient to identify patients with decreased risk for relapse.

PMID 19542476  Am J Respir Crit Care Med. 2009 Sep 15;180(6):558-63. d・・・

ページ上部に戻る

戻る

さらなるご利用にはご登録が必要です。

こちらよりご契約または優待日間無料トライアルお申込みをお願いします。

(※トライアルご登録は1名様につき、一度となります)


ご契約の場合はご招待された方だけのご優待特典があります。

以下の優待コードを入力いただくと、

契約期間が通常12ヵ月のところ、14ヵ月ご利用いただけます。

優待コード: (利用期限:まで)

ご契約はこちらから