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結核 第92巻 第 8 号 2017年 8 月 518

Abstract [Purpose] There are no comparative studies of

treatment outcome of drug susceptible and isoniazid (INH) mono-resistant tuberculosis in Japan. We retrospectively investigated the clinical characteristics and time to sputum conversion of INH mono-resistant tuberculosis.

 [Methods] We reviewed the medical records of all patients with smear-positive tuberculosis admitted and treated in Kanagawa Cardiovascular and Respiratory Center between April 2010 and March 2015. Patients in whom negative cul- ture conversion were confirmed were included. The study compared patient characteristics, imaging findings, laboratory results, and time to sputum culture conversion between 20 patients with INH mono-resistance and 523 patients suscep- tible for all drugs used.

 [Results] INH mono-resistant patients were more likely to have a history of tuberculosis treatment, and tended to have more extended lesion. On the other hand, the sputum culture conversion time was not significantly different between two groups. Similarly, there was no significant difference between

low- and high-level of INH resistance in time to sputum culture and smear conversion.

 [Conclusion] INH mono-resistance did not affect early treatment outcomes, and initial treatment of standard regimen had validity even in INH mono-resistant tuberculosis.

Key words: Pulmonary tuberculosis, Drug resistance, Initial

treatment, Isoniazid, Negative conversion

1Department of Respiratory Medicine, Kanagawa Cardiovas- cular and Respiratory Center, 2Department of Respiratory Medicine, Tokyo Jikei University Hospital

Correspondence to : Yumie Yamanaka, Department of Respiratory Medicine, Kanagawa Cardiovascular and Respi- ratory Center, 6_16_1, Tomioka-higashi, Kanazawa-ku, Yokohama-shi, Kanagawa 236_0051 Japan.

(E-mail: y-miyakawa@jikei.ac.jp) −−−−−−−−Original Article−−−−−−−−

CLINICAL CHARACTERISTICS AND TIME TO SPUTUM CONVERSION OF

ISONIAZID MONO-RESISTANT PULMONARY TUBERCULOSIS

1, 2Yumie YAMANAKA, 1Eri HAGIWARA, 1, 2Hideaki YAMAKAWA, 1Akimasa SEKINE, 1Tomohisa BABA, 1Shigeru KOMATSU, and 1Takashi OGURA

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Pyrazinamide Susceptibility / S. Mitarai et al. 527

Abstract [Objective] Pyrazinamide (PZA) is one of the

major anti-tuberculosis drugs. The drug susceptibility testing (DST) method for PZA is unique and many false-resistant results are reported. To reveal the accuracy of DST for PZA in Japan, the external quality assessment (EQA) was implemented.

 [Method] A total of 10 Mycobacterium tuberculosis strains

of which the resistances are confirmed in the Supra-National Reference Laboratory Network of STOP TB partnership was used in this study. The major target of EQA in this study was PZA, but other six drugs, isoniazid (INH), rifampicin (RFP), streptomycin (SM), ethambutol (EB), kanamycin (KM) and levofloxacin (LVFX) could be included in the EQA. The participating facilities performed DST using their routine methods and the results were compared with the judicial diagnoses. The evaluation factors were sensitivity, specificity, efficiency and kappa coefficient.

 [Results] A total of 97 facilities (70 hospitals, 21 private commercial laboratories, and 6 public health laboratories) participated in this study, and the overall results became 105 because 8 laboratories submitted multiple results. The average turn-around time (TAT) was 65.4±20.7 (range: 21_109) days. A total of 60 facilities performed phenotypic PZA susceptibility testing, and resulted the sensitivity of 96.6% (95% CI: 87.4_99.4%) and specificity of 64.3% (95% CI: 50.8_76.0%). Forty-four facilities used Kyokuto PZA liquid medium (Kyokuto PZA; Kyokuto Pharmaceuticals) and 16 used MGIT series PZA (MGIT AST PZA; Becton Dickinson). The specificities of Kyokuto PZA and MGIT AST PZA were

69.5% (95% CI: 53.6_82.0%) and 48.8% (95% CI: 24.5_ 73.5%), respectively. There was a significant difference in specificity between two kits (p=0.0043).

 [Discussion] The specificity of current PZA DST kits was quite low. There already exist several reports that are showing the low specificity of MGIT AST PZA, the Kyokuto PZA test also showed less than 70% of specificity. Due to the relatively short TAT of liquid PZA DST, it will be happening that the doctor stops PZA in the standard regimen according to the wrong DST result. PZA also contributes deeply for the treatment of drug resistant tuberculosis, then the accuracy of DST results are surely important. It will be recommended to conduct appropriate training of DST for PZA, to revise the standard operational procedure, and to use alternative DST like line probe assay or pyrazinamidase testing to improve the performance of PZA DST.

Key words:Mycobacterium tuberculosis, Pyrazinamide, Drug

susceptibility testing, External quality assessment

1Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association (JATA), 2Basic Mycobacteriology, Graduate School of Biomedical Science, Nagasaki University, Japan Correspondence to: Satoshi Mitarai, Department of Myco- bacterium Reference and Research, Research Institute of Tuberculosis, JATA, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8533 Japan. (E-mail: mitarai@jata.or.jp)

−−−−−−−−Original Article−−−−−−−−

EXTERNAL QUALITY ASSESSMENT OF PYRAZINAMIDE SUSCEPTIBILITY

TESTING AGAINST

MYCOBACTERIUM TUBERCULOSIS

1Satoshi MITARAI, 1Hiroyuki YAMADA, 1Akio AONO, 1Kinuyo CHIKAMATSU, 1Yuriko IGARASHI, 1Yoshiro MURASE, 2Kentaro SAKASHITA, 2Takashi OHFUJI,

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534 結核 第92巻 第 8 号 2017年 8 月

Abstract [Objective] Treatment is basically done on out-

patient department (OPD) basis for sputum smear negative tuberculosis cases. We evaluated the treatment result of MDR-TB cases with emphasis on the admission or OPD treatment.  [Method] Retrospective review of medical record of MDR-TB cases that were treated at Fukujuji Hospital from January 1990 to November 2016.

 [Result] Among 46 cases, four cases defaulted including two cases that were culture positive at the time of default, twenty five cases completed medical treatment including surgical treatment for four cases, four cases were without treatment, eight cases were transfer out and two of them were culture positive at the time of transfer, no dead case and five cases were without information of treatment results. Multivariate analysis showed the risk factors of default with OPD cases, foreign born cases, cases that were treated in earlier years, cases that were treated with less drugs, and cavitary cases.

 [Discussion] OPD management of MDR-TB was safe but the risk of default was higher, especially among foreign born cases with less social contact with Japanese society. Considering the higher proportion of cases with loss to follow up, some sputum smear negative cases will need to be admitted for directly observed treatment.

Key words : Multi drug resistant tuberculosis (MDR-TB),

Outpatient clinic management (OPD management), Default, Sputum smear negative

Fukujuji Hospital, Japan Anti-Tuberculosis Association Correspondence to : Takashi Yoshiyama, Fukujuji Hospital, Japan Anti-Tuberculosis Association, 3_1_24, Matsuyama, Kiyose-shi, Tokyo 204_8522 Japan.

(E-mail: yoshiyama@jata.or.jp) −−−−−−−−Short Report−−−−−−−−

USEFULNESS AND LIMITATION OF OUTPATIENT DEPARTMENT MANAGEMENT

OF SPUTUM SMEAR NEGATIVE MDR-TB IN JAPAN

Takashi YOSHIYAMA, Hideo OGATA, Yuka SASAKI, Masao OKUMURA, Kozo MORIMOTO, Takashi OFUJI, and Hajime GOTO

力的な運用が必要である。  外来例の中には無治療例があり,2001年以降の例は 1 例で前医に戻った例であった。2000 年までの例は 3 例 あり,死亡の 1 例を除くとその後の 2 例の経過は不明で ある。無治療例はおそらく慢性排菌となっているが,こ のような例は年間 50 例以下となったがまだ存在し5),一 部外来症例も存在する。結核薬としてはまだ承認されて いないが 2010 年代にリネゾリドが多剤耐性結核にも使 用されるようになり,さらに,2014 年のデラマニド発 売,近々期待されるベダキリンの発売により,慢性排菌 例の治療が今後変わっていくと考えられる。ただこれら の薬は高価であり,高費用が外来治療の中断の危険を高 める要因にもなりかねず,今後の結核医療費の負担につ いての検討が必要となる。  著者の COI(conflicts of interest)開示:本論文発表内 容に関して特になし。 文   献 1 ) 厚生労働省健康局結核感染症課長:感染症の予防及び 感染症の患者に関する医療に関する法律における結核 患者の入退院及び就業制限の取扱いについて. 健感発 第 0907001号, 平成19年 9 月 7 日.

2 ) Suárez PG, Floyd K, Portocarrero J, et al. : Feasibility and cost-effectiveness of standardised second-line drug treat- ment for chronic tuberculosis patients : a national cohort study in Peru. Lancet. 2002 ; 359 : 1980 ‒ 9.

3 ) 厚生労働省告示平成 21 年 16 号 結核医療の基準改正. 2016/01/29 発行, 官報本紙 06704 号(3/0 頁) 4 ) 日本結核病学会治療委員会:「結核医療の基準」の見 直し― 2014年. 結核. 2014 ; 89 : 683‒690. 5 ) 結核予防会:「結核の統計 2015」. 結核予防会, 東京, 2015, 109.

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結核 第92巻 第 8 号 2017年 8 月 538

Abstract [Purpose] In populations with first QFT-3G

(QFT)-positive rate of ≧50% 2 to 3 months after the last contact with index cases (high-infection-rate populations), we conducted second QFT after 6 months, and analyzed/evaluated the results to improve future contact investigations.

 [Methods] Among contacts belonging to the high-infection-rate populations on a contact investigation between 2014 and 2015, the subjects were those for whom second QFT was conducted 6 months after the last contact with index cases with first QFT-negative or QFT-equivocal reactions.

 [Results] (1) First QFT (2 to 3 months after the last contact with index cases): The number of groups for contacts was 13. First QFT was performed for 108 contacts after 2 to 3 months. The QFT-positive rate was 59.3% (50.0_66.7%). (2) Second QFT (6 months after the last contact with index cases): After 6 months, second QFT was conducted for 27 contacts with QFT-negative reactions and 2 contacts with QFT-equivocal reactions on the first QFT. In 1 contact for whom evaluation was QFT-equivocal on the first QFT, evaluation was also QFT-equivocal, whereas the others showed QFT-negative reactions.

 [Conclusion] There was no QFT-positive patient after 6 months among those with QFT-negative reactions after 2 to 3 months in the high-infection-rate populations. In the present situation that the sensitivity of QFT in the diagnosis of tuber- culosis infection and the timing of positive conversion have not been sufficiently clarified, contacts of these groups should undergo not only the reexamination of QFT but also chest X-ray examinations and consult a hospital in the presence of symptoms for the early detection of tuberculosis.

Key words: Tuberculosis, Contact investigation, High-infec-

tion-rate populations, Second QFT-3G after 6 months, Tuber- culosis epidemic

1Osaka City Public Health Office, 2Nishinari Ward Office, Osaka City

Correspondence to : Kenji Matsumoto, Osaka City Public Health Office, 1_2_7_1000, Asahimachi, Abeno-ku, Osaka-shi, Osaka 545_0051 Japan.

(E-mail: ke-matsumoto@city.osaka.lg.jp) −−−−−−−−Short Report−−−−−−−−

EFFECTIVENESS OF SECOND QFT-3G FOR CONTACTS

6 MONTHS AFTER THE LAST CONTACT WITH INDEX CASES

IN THE HIGH-INFECTION-RATE POPULATIONS

1Kenji MATSUMOTO, 1Jun KOMUKAI, 1Yuko TSUDA, 1Hideya UEDA, 1Miho TAKEGAWA, 1Maiko ADACHI, 1Naoko SHIMIZU, 1Kazumi SAITO,

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Adrenal Crisis Induced by RFP / Y. Suwa et al. 543

Abstract A 66-year-old woman was diagnosed as having

pulmonary tuberculosis based on chest X-ray and TB positive bronchoalveolar lavage. Treatment with antituberculous drugs, including rifampicin (RFP), was started.

 However, one week later these drugs were discontinued, because of anorexia, nausea, general lassitude and liver dis- function. Restart of antituberculous treatment after recovery of symptoms and liver function, developed a state of shock with hypoglycemia. Computed tomography revealed swelling and calcification of the bilateral adrenal glands. In addition, skin pigmentations, the elevated serum level of ACTH and the decreased level of cortisol were also observed. Therefore, the patient was diagnosed as having adrenal insufficiency asso- ciated with adrenal crisis due to adrenal gland tuberculosis. The symptoms improved with cortisol supplementation.  RFP is known to induce CYP3A4 and enhance cortisol metabolism. In the current case, RFP administration might

decrease the serum level of cortisol through the induction of CYP3A4, causing adrenal crisis. When pulmonary tuberculosis is complicated by adrenal gland tuberculosis, RFP can cause adrenal crisis. So the caution should be paid when administer- ing RFP to a patient with these conditions.

Key words: Pulmonary tuberculosis, Adrenal tuberculosis,

Adrenal crisis, Rifampicin, CYP3A4

1Department of Internal Medicine, Tsubame Rosai Hospital ; 2Department of Respiratory Medicine, 3Department of Infec- tious Disease, Nagaoka Red Cross Hospital

Correspondence to : Yoko Suwa, Department of Internal Medicine, Tsubame Rosai Hospital, 633, Sawatari, Tsubame-shi, Niigata 959_1228 Japan. (E-mail: yokosuwa@tsrh.jp) −−−−−−−−Case Report−−−−−−−−

A CASE OF ADRENAL CRISIS INDUCED BY THE ADMINISTRATION

OF RIFAMPICIN FOR PULMONARY TUBERCULOSIS

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