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結核 第 93 巻 第 11_12号 2018年11_12月 560

10) Papaventsis D, Casali N, Kontsevaya I, et al.: Whole genome sequencing of Mycobacterium tuberculosis for detection of drug resistance: a systematic review. Clin Microbiol Infect. 2017 ; 23 : 61 68.

11) Coll F, Phelan J, Hill-Cawthorne GA, et al.: Genome-wide analysis of multi- and extensively drug-resistant Mycobac-terium tuberculosis. Nat Genet. 2018 ; 50 : 307 316. 12) WHO: WHO treatment guidelines for drug-resistant

tuber-culosis (2016 update). Geneva, 2016.

13) Van Deun A, Maug AK, Salim MA, et al.: Short, highly effective, and inexpensive standardized treatment of multi-drug-resistant tuberculosis. Am J Respir Crit Care Med. 2010 ; 182 : 684 92.

14) Diacon AH, Pym A, Grobusch M, et al.: The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N Engl J Med. 2009 ; 360 : 2397 405.

15) Diacon AH, Pym A, Grobusch MP, et al.: Multidrug-resistant tuberculosis and culture conversion with bedaquiline. N Engl J Med. 2014 ; 371 : 723 32.

16) Schnippel K, Ndjeka N, Maartens G, et al.: Effect of bedaquiline on mortality in South African patients with

drug-resistant tuberculosis: a retrospective cohort study. Lancet Respir Med. 2018 Jul 9.pii: S2213 2600 (18) 30235-2. doi: 10.1016/S2213 2600 (18) 30235-30235-2.

17) Lee M, Lee J, Carroll MW, et al.: Linezolid for treatment of chronic extensively drug-resistant tuberculosis. N Engl J Med. 2012 ; 367 : 1508 18.

18) 吉山 崇, 尾形英雄, 佐々木結花, 他:多剤耐性結核症 の外来治療の有効性と限界について. 結核. 2017 ; 92 : 529 534.

19) Tang S, Yao L, Hao X, et al.: Clofazimine for the treatment of multidrug-resistant tuberculosis: prospective, multicenter, randomized controlled study in China. Clin Infect Dis. 2015 ; 60 : 1361 7.

20) 小林弘美, 小柳孝太郎, 加藤 収, 他:血液透析施設に おける超多剤耐性結核の集団感染. 結核. 2013 ; 88 : 477 484.

21) Yoshiyama T: Low risk of hospital-acquired infection and reinfection of multidrug-resistant tuberculosis. Infect Dis (Lond). 2017 ; 49 : 158 160.

22) 伊藤邦彦, 高橋光良, 吉山 崇, 他:重感染による多剤 耐性肺結核. 結核. 2004 ; 79 : 387 390.

Abstract The proportion of multi drug resistant

tuberculo-sis (MDR-TB) among new TB cases is 0.5% in Japan and 3% overall the world and with the increasing trend of TB cases that were born in endemic countries of TB, the risk of MDR-TB is increasing in Japan. Drug susceptibility test has been done traditinoally with phenotypic method but the genotypic method is prevailing globally in 2010s and Xpert®

MTB/RIF has been introduced in Japan from 2016. When the case is detected as Rifampicin resistant, we need to start treatment with isoniazid, ethambutol, pyrazinamide, kanamy-cin, ethionamide, cycloserine and para-amino salycilic acid together with rifabutin until we know the drug susceptibility test result consideirng the risk of drug resistance and in order to avoid further acquisition of drug resistance. Globally, 9 months regimen including moxifl oxacin, clofazimine, pyrazin-amide, high dose isoniazid, ethambutol, ethionamide/proth-ionamide is used with good treatment result. In Japan, high cost of bedaquiline and delamanid, non-approval of

beda-quiline and delamanid for non-MDR-TB who cannot be treated with isoniazid and rifampicin with adverse drug reactions, and non-approval of linezolid, clofazimine and moxifl oxacin for tuberculosis are the barriers to the appro-priate prevention and treatment of MDR-TB. Drug resistance to new drugs is appearing globally and we need to consider these resistant cases and avoid further acquisition of drug resitance, and role of surgery will continue in this setting.

Key words : Multi drug resistant tuberculosis, Xpert®MTB/

RIF, Acquisition of drug resistance

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: yoshiyama1962@yahoo.co.jp) −−−−−−−−Review Article−−−−−−−−

MULTI DRUG RESISTANT TUBERCULOSIS

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結核 第 93 巻 第 11_12号 2018年11_12月 568

Abstract Treatment of tuberculosis is under control of

government in Japan by administrative standards for tuber-culosis care with public expenses payment system and DOT by public health center nurses. But the treatment success rate of initial treatment is lately around 50 percent which is substantially lower than recommended target level. Though high mortality in aged is the utmost cause and failure plus dropout is less than 5%, proportion of patients still on treat-ment at 12 months is around 10%. Long-term treattreat-ment of drug-susceptible tuberculosis may be caused by treatment without PZA, and/or inadequate cope with adverse reaction by general practitioner. Provision of information on standard treatment, more detailed guides of countermeasures to side effects and liaison between general practitioner and TB experts or Regional Tuberculosis Advisory Committees are required.

 Treatment of drug-resistant tuberculosis needs different viewpoint. Drug-resistant tuberculosis patients are treated by personalized regimen based on drug-resistant test, but molecular based drug sensitivity tests are not widely used despite being approved for RFP, INH and PZA. Several drugs including moxifl oxacin and linezolid recommended in WHO guidelines for drug-resistant tuberculosis are used by some experts but insuffi ciently because they are off-label. Consid-eration is necessary for these laboratory tests and off-label drugs to be available when needed. Delamanid and bedaqui-line are approved for pulmonary MDR-TB and under control of tuberculosis expert through responsible access program by the pharmaceutical company. From September 2014 to

February 2018, 135 cases were eligible to use delamanid and no acquisition of resistance is reported till June 2018. These new drugs are properly used under the control of experts, but its cost can be heavy burden on outpatient who must pay 5% of medical expenses. Abatement of economic burden for these patients is required.

 DOTS is widely and well done lately, but recent issue is the support for foreign born patients who now account for more than 50% in 20_29yr age group. Language barrier is common, and knowledge of patient’s religious constraints and customs are required. Tuberculosis treatment literacy materials in various languages are recently becoming avail-able but the need for medical interpreter is not fulfi lled.  Political will is required for implementation of adequate treatment in response to new technology and change of patient background.

Key words : Pyrazinamide, Treatment success rate, Adequate

treatment, Drug-resistant tuberculosis, Medical system for tuberculosis treatment

National Hospital Organization Higashihiroshima Medical Center

Correspondence to: Eriko Shigeto, National Hospital Orga-nization Higashihiroshima Medical Center, 513 Jike, Saijyo-cho, Higashihiroshima-shi, Hiroshima 739_0041 Japan. (E-mail: eshigetou@hiro-hosp.jp)

−−−−−−−−Review Article−−−−−−−−

ISSUES IN TREATMENT OF TUBERCULOSIS IN JAPAN

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Education for TB and NTB Diseases / J. Fujita 577

冨岡洋海編, 医学書院, 東京, 2006, 26 40.

3 ) 藤田次郎:患者さんの人生を理解した肺結核の画像診 断. 結核. 2013 ; 88 : 763 773.

4 ) Rothlin E, Undritz E: Beitrag zur Lokalisationsregel der Tuberkulose. Schweiz Z allg Path Bakt. 1952 ; 15 : 690 700. 5 ) 伊藤春海:肺結核の画像 ― 呼吸器画像診断学の貴重な

教育資源. 結核. 2010 ; 85 : 869 879.

6 ) 伊藤春海:肺結核の画像診断 ― Radiologic-Anatomic-Pathologic Correlation. 結核. 2016 ; 91 : 667 676. 7 ) Andersen P, Munk ME, Pollock JM, et al.: Specifi c

immune-based diagnosis of tuberculosis. Lancet. 2000 ; 356 (9235) : 1099 1104.

8 ) Nagano H, Kinjo T, Nei Y, et al.: Causative species of nontuberculous mycobacterial lung disease and compara-tive investigation on clinical features of Mycobacterium

ab-scessus complex disease: A retrospective analysis for two major hospitals in a subtropical region of Japan. PLoS One. 2017 ; 12 : e0186826.

9 ) Fujita J, Kishimoto T, Ohtsuki Y, et al.: Clinical features of eleven cases of Mycobacterium avium-intracellulare com-plex pulmonary disease associated with pneumoconiosis. Respir Med. 2004 ; 98 : 721 725.

10) 岩崎龍郎:「改訂 結核の病理」, 財団法人結核予防会, 東京, 1997.

11) Hibiya K, Shigeto E, Iida K, et al.: Distribution of myco-bacterial antigen based on differences of histological char-acteristics in pulmonary Mycobacterium avium infectious diseases―consideration of the extent of surgical resection from the pathological standpoint. Pathol Res Pract. 2012 ; 208 : 53 58.

Abstract The diagnosis of an acid-fast bacterial infection

should be performed comprehensively, using medical history, physical fi ndings, microbiological examination, and radio-logical fi ndings. However, the fi nal diagnosis of mycobac-terial diseases is traditionally based on a microbiological examination or pathological fi nding, but radiological fi ndings can assist this. In recent years, a pathologic-radiologic cor-relation has been established through the detailed analysis of chest high-resolution CT (HRCT); specifi cally, the radio-logical fi ndings of pulmonary tuberculosis patients compared with their pathological fi ndings. Now, it is possible to estimate pathological fi ndings from HRCT images. In other words, the radiological fi ndings of pulmonary tuberculosis contain fun-damentals of chest radiological diagnosis. Potentially, under-standing the radiological fi ndings of pulmonary tuberculosis will, in turn, deepen the entire understanding of chest imag-ing diagnoses. Indeed, to learn more about mycobacterial lung diseases, we should fi rst understand the clinical features of the non-tuberculous mycobacteria often experienced in general clinical practice. Then, the clinical experiences of the National Hospital Organization will be useful to examine

pulmonary tuberculosis cases, intensively. By strengthening the National Hospital Organization Hospitals function as training hospitals, our knowledge of tuberculosis and other mycobacterial lung diseases will deepen.

Key words : Pulomanry tuberculosis, Non-tuberculous

my-cobacteria, Education, Radiological fi ndings, Differential diagnosis

Department of Infectious, Respiratory, and Digestive Medi-cine, Control and Prevention of Infectious Diseases, Graduate School of Medicine, University of the Ryukyus; University of the Ryukyus Hospital

Correspondence to: Jiro Fujita, Department of Infectious, Respiratory, and Digestive Medicine, Control and Prevention of Infectious Diseases, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Nakagami-gun, Okinawa 903_0215 Japan.

(E-mail: fujita@med.u-ryukyu.ac.jp) −−−−−−−−Review Article−−−−−−−−

EDUCATION FOR TUBERCULOSIS AND NON-TUBERCULOUS

MYCOBACTERIAL DISEASES

― Comparison between Lung Tuberculosis and Non-Tuberculous Mycobacterial Lung Diseases ― Jiro FUJITA

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579

Abstract [Objective] The purpose of this study was to compare the negative conversion rate between

intraoperative specimens of spinal tuberculosis and sputum specimens of pulmonary tuberculosis after 1 month of treatment with a standard anti-tuberculosis drug regimen. [Patients and Methods] We retrospectively reviewed the records of 111 patients who underwent anterior spinal fusion for spinal tuberculosis. All patients received anti-tuberculosis drug using a standard regimen with either INH, RFP, PZA, EB or SM (Method A) or a standard regimen with INH, RFP, EB or SM (Method B). Overall, 76 patients were treated with Method A and 35 patients were treated with Method B. Forty-fi ve out of the 111 patients had intrathoracic lesions: 40 of these patients were smear-positive and 5 were smear-negative as well as PCR-positive. Nineteen patients were classifi ed as having extra-pulmonary lesions such as miliary tuberculosis or tuberculous pleuritis. Forty-seven out of the 111 patients did not have intrathoracic lesions. All the patients underwent surgery 1 month after the initiation of the anti-tuberculous treatment. The negative conversion rate was compared between the intraoperative specimens of spinal tuberculosis and sputum specimens of the 40 smear-positive patients with pulmonary tuberculosis. [Results] The negative conversion rate of intraoperative specimens after 1-month treatment for spinal tuberculosis was 7.2% (Method A: 10.5%, Method B: 0%). The negative conversion rates of the sputum specimens were 82.5% (Method A: 78.2%, Method B: 88.2%) at 1 month, 92.5% (Method A: 87.0%, Method B: 100%) at 2 months, and 97.5% (Method A: 95.7%, Method B: 100%) at 3 months after treatment initiation. A comparison of the negative conversion rates of the sputum specimen at 1 month and the intraoperative specimen at the same period showed a signifi cant difference (p<0.01). [Conclusion] The negative conversion rate for intraoperative specimen in patients with spinal tuberculosis after 1 month of standard treatment was less than that of pulmonary tuberculosis at that time period.

Key words: Spinal tuberculosis, Standard treatment, Intraoperative specimen

Department of Orthopaedic Surgery, National Hospital Organization Toneyama National Hospital

Correspondence to : Kazutaka Izawa, Department of Orthopaedic Surgery, National Hospital Organization Toneyama National Hospital, 5_1_1, Toneyama, Toyonaka-shi, Osaka 560_8552 Japan.

(E-mail: izawakaz@toneyama.go.jp)

(Received 14 May 2018/Accepted 15 Aug. 2018) Kekkaku Vol. 93, No. 11_12: 579_583, 2018

−−−−−−−−Original Article−−−−−−−−

MYCOBACTERIAL EXAMINATION OF INTRAOPERATIVE SPECIMENS

AFTER A 1-MONTH STANDARD TREATMENT REGIMEN

IN PATIENTS WITH SPINAL TUBERCULOSIS

Kazutaka IZAWA

INTRODUCTION

 Following the introduction of rifampicin (RFP), short-course chemotherapy was extensively developed in the 1970s.1) A

four-drug regimen including RFP and pyrazinamide (PZA) was found to be especially effective with considerably low relapse rates. Throughout the 1980s, the regimen was used worldwide (including Japan) and became standard chemo-therapy.2) 3) Currently, a standard four-drug regimen exists

and consists of RFP, PZA, isoniazid (INH), and ethambutol (EB) or streptomycin (SM). Patients take RFP, PZA, INH, and EB or SM in the fi rst 2 months followed by INH and RFP in the next 4 months (Method A). The standard three-drug regimen consists of INH, RFP and EB or SM, which are

taken in the fi rst 2 months followed by INH and RFP only in the next 7 months (Method B). Previous studies have shown satisfactory results in the use of these regimens in the treatment of spinal tuberculosis.4) 5) However, the duration of treatment

administration is still controversial since there is no clear defi nition of healing spinal tuberculosis.6) One of the diffi

cul-ties in assessing spinal tuberculosis activity may be due to issues related to mycobacterial assessment. Unless a spinal biopsy is performed while a patient is undergoing treatment, mycobacterial activity cannot be assessed. However, unlike the sputum test for pulmonary tuberculosis, the spinal biopsy is not a practical procedure to perform periodically. On the other hand, during surgical treatment for spinal tuberculosis for a patient who has initiated treatment, intraoperative

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Sever Liver Dysfunction after Treatment of LTBI / Ryoken 589

御手洗聡,分担研究者 永井英明)のもと行われた。  著者の COI(confl icts of interest)開示:本論文発表内 容に関して特になし。 文   献 1 ) 伊藤邦彦:イソニアジド単剤投与における重症肝障害 の発生頻度とリスク因子. 結核. 2016 ; 91 : 607 616. 2 ) 結核療法研究協議会内科会:日本における潜在性結核 感染症治療の状況. 結核. 2018 ; 93 : 447 457.

3 ) Centers for Disease Control and Prevention (CDC): Severe isoniazid-associated liver injuries among persons being treated for latent tuberculosis infection ― United States, 2004 2008. MMWR. 2010 Mar 5 ; 59 (8) : 224 9. 4 ) The competing risks of tuberculosis and hepatitis for

adult tuberculin reactors. American Review of Respiratory Diseases. 1975 ; 111 : 573 577. 5 ) 安田和雅, 佐藤篤彦, 千田金吾, 他:結核化学療法中に 発生した肝機能障害例の検討. 結核. 1990 ; 65 : 407 413. 6 ) 長山直弘, 益田公彦, 馬場基男, 他:INH, RFPを含む 結核化学療法における薬剤性肝炎出現率の経年上昇. 結 核. 2003 ; 78 : 339 346.

7 ) Guidelines on the management of latent tuberculosis infection WHO. WHO/HTM/TB/ 2015.01 ISBN 978 92 4 154890 8 Geneva 2015.

8 ) Ziakas PD, Mylonakis E: 4 Months of Rifampin Compared with 9 Months of Isoniazid for the Management of Latent Tuberculosis Infection: A Meta-analysis and Cost-Effec-tiveness Study That Focuses on Compliance and Liver Tox-icity. Clinical Infectious Diseases. 2009 ; 49 : 1883 1889. 9 ) 結核療法研究協議会内科会:80歳以上の結核標準治療

の検討. 結核. 2017 ; 92 : 485-491.

10) 日本結核病学会治療委員会:抗結核薬使用中の肝障害 への対応について. 結核. 2007 ; 82 : 115 118.

11) Azuma J, Ohno M, Kubota R, et al.: Pharmacogenetics-based tuberculosis therapy research group. NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: A randomized controlled trial for pharmacogenetics-based therapy. Eur J Clin Pharmacol. 2013 ; 69 : 1091 1101.

Abstract [Objective] Multi central retrospective analysis

was done for the treatment of latent tuberculosis infection (LTBI) in Japan. Severe liver dysfunction during Isoniazid treatment of LTBI was analyzed.

 [Target] Those who started isoniazid (INH) in 2014 and 2015 in the hospital belonging to Internal Medical Group of Ryoken was analyzed.

 [Result] The frequency of severe liver dysfunction with AST or ALT more than 500 IU/L was observed among 6% of persons aged 50_69 years old, among 4% of those aged 40_49 years old, and around 1% of those older than 70 years and those 30_39 years old, and no persons among younger than 30 years old. The frequency of severer liver dysfunction

with AST or ALT more than 1000 IU/L and total bilirubin more than 3 mg/dl was observed among 1.3% of persons aged 50_69 and more among females (1%) than males (0.1%). All cases recovered with conservative treatment although the maximum of total bilirubin was 17 mg/dl .

Key words: Latent tuberculosis infection, Isoniazid, Severe

liver dysfunction

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

(E-mail: yoshiyama1962@yahoo.co.jp) −−−−−−−−Original Article−−−−−−−−

RETROSPECTIVE ANALYSIS OF TREATMENT

OF LATENT TUBERCULOSIS INFECTION IN JAPAN,

SEVERE LIVER DYSFUNCTION DURING ISONIAZID TREATMENT

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591

Abstract [Objectives] Although the prevalence of tuberculosis has been decreasing in Japan, the prevalence

of miliary tuberculosis (TB) has been gradually increasing. Therefore, it would be important that we know prognostic factors for miliary TB to provide suitable treatment and general management. To identify prog-nostic factors, we retrospectively studied 106 cases of miliary TB in our hospital. [Methods] We reviewed the medical records of 106 patients who had been diagnosed with miliary TB and undergone in-hospital treat-ment at our medical institution between April 2004 and March 2013. We conducted retrospective compar-ative analyses of age, sex, smoking history, complications, history of immunosuppressant use, presence or absence of hypoxemia, Eastern Cooperative Oncology Group Performance Status (PS), blood cultures, blood tests, administration of rifampicin (RFP) and isoniazid (INH), and time delay from symptom presentation to diagnosis between the patients who survived and were discharged (survivor group) and those who died in hospital (non-survivor group). In addition, we examined factors which contributed to longer survival period. [Results] The patients in the non-survivor group (n=41) were older and less nourished and had poorer oxygenation, poorer PS, and smaller number of peripheral blood lymphocyte count than the patients in the survivor group (n=65). And the rate of administration of RFP in the non-survivor group was lower than that in the survivor group. Administration of RFP was related to the longer survival time in the non-survivor group. [Conclusions] Nutritional status, oxygenation, PS, peripheral blood lymphocyte count, and RFP administration were identifi ed as prognostic factors of miliary TB. Administration of RFP appeared to be most important for the survival.

Key words: Miliary tuberculosis, Prognostic factors, Rifampicin, Lymphocyte count

1Center for Pulmonary Diseases, 2Center for Asthma, Allergy, and Rheumatism, National Hospital Organization Tokyo National Hospital

Correspondence to : Eri Inoue, Center for Pulmonary Diseases, National Hospital Organization Tokyo National Hospital, 3_1_1, Takeoka, Kiyose-shi, Tokyo 204_8585 Japan.

(E-mail: inouee@tokyo-hosp.jp)

(Received 19 Jun. 2018/Accepted 24 Aug. 2018) Kekkaku Vol. 93, No. 11_12: 591_596, 2018

−−−−−−−−Original Article−−−−−−−−

INVESTIGATION OF POTENTIAL PROGNOSTIC FACTORS

FOR THE INCREASINGLY PREVALENT

MILIARY TUBERCULOSIS IN JAPAN

1

Eri INOUE,

2

Nobuharu OHSHIMA,

1

Miki IKEDA,

1

Masato WATANABE,

1

Masahiro KAWASHIMA,

1

Junko SUZUKI,

1

Kimihiko MASUDA,

1

Akira YAMANE,

1

Hirotoshi MATSUI, and

1

Hideaki NAGAI

INTRODUCTION

 Miliary tuberculosis is a hematogenously disseminated type of tuberculosis, which involves active tuberculosis lesions identifi ed bacteriologically or pathologically in at least two organs and diffuse nodular satellite lesions equivalent or close in size to grains of millet1). The most frequently affected

organs are the lung, liver, and spleen, but the kidney, bone marrow, brain, and other organs in any part of the body can be affected. Because the disease can affect multiple organs, delayed diagnosis can be fatal; thus, early detection is critical. However, early diagnosis is often diffi cult because symptoms vary considerably depending on the organs affected.

 Although the prevalence of tuberculosis has been decreasing

in Japan, the prevalence of miliary tuberculosis has been gradually increasing (Fig. 1). In the 2016 statistics, 633 cases of miliary tuberculosis were registered in Japan, which corresponds to 0.50 incidences per 100,000 people and accounts for 15.8% of extrapulmonary tuberculosis cases2).

In other countries, of all patients with tuberculosis, 1.5% and 2.7% were estimated to have miliary tuberculosis in the US and in the European Union/European Economic Area (EU/ EEA), respectively3) 4). It appears that miliary tuberculosis

may be found in a certain population at the present time when prevalence rate of tuberculosis is decreasing.

 In spite of the critical importance of identifying prognostic factors (factors related to in-hospital death) for providing appropriate treatment and general care to the patients with

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結核 第 93 巻 第 11_12号 2018年11_12月 602

Abstract [Objectives] The aim of this study was to identify

the erm genes conferring the resistance variation in clinical non-photochromogenic rapidly growing mycobacterium (NPRGM) isolates identifi ed Mycolicibacterium fortuitum by DDH myco-bacteria kit.

 [Material] All NPRGM isolates were collected from 14 consecutive bronchiectasis patients at the National Hospital Organization Kinki-chuo Chest Medical Center, Osaka, Japan, between 1 January 2016 and 31 December 2017.

 [Methods] All of isolates were confi rmed using rpoB,

hsp 65, and 16S_23S ITS region gene sequencing. Also, these isolates were evaluated the presence of erm genes and determined the minimum inhibitory concentration to clarith-romycin according to CLSI 2011 M24_A2.

 [Results] The presence of erm consensus regions among the 13 clinical isolates were determined, and heterogeneous

erm genes including erm (39) and erm (40) presented in them which belonged to fi ve species of NPRGM. However, the fi nding that the inducible resistance of NPRGM by erm methylases could not be confi rmed by conventional susceptible

testing.

 [Discussion] It therefore appears necessary to develop more proper inducible resistant evaluation to clarithromycin of NPRGM and accurate identifi cation for selecting appro-priate antimicrobial therapies.

Key words: Mycolicibacterium fortuitum,

Non-photochro-mogenic rapidly growing mycobacterium, Clarithromycin, Inducible resistance, erm gene, DDH mycobacteria

1Clinical Research Center, 2Department of Clinical

Labora-tory, 3Department of Respiratory Medicine, National Hospital

Organization Kinki-chuo Chest Medical Center

Correspondence to: Shiomi Yoshida, Clinical Research Center, National Hospital Organization Kinki-chuo Chest Medical Center, 1180 Nagasone-cho, Kita-ku, Sakai-shi, Osaka 591_8555 Japan.

(E-mail: yoshida.shiomi.vg@mail.hosp.go.jp) −−−−−−−−Original Article−−−−−−−−

CORRELATION BETWEEN GENOTYPIC ERM GENES AND

PHENOTYPIC INDUCIBLE CLARITHROMYCIN RESISTANCE OF CLINICAL

NON-PHOTOCHROMOGENIC RAPIDLY GROWING MYCOBACTERIUM

ISOLATES WHICH WERE IDENTIFIED

MYCOLICIBACTERIUM FORTUITUM

BY DDH MYCOBACTERIA

1Shiomi YOSHIDA, 1Kazunari TSUYUGUCHI, 2Mika KIHARA, 2Motohisa TOMITA, 1Yoshikazu INOUE, 3Seiji HAYASHI, and 3Katsuhiro SUZUKI

Agents Chemother. 2006 ; 50 : 3476 3478.

15) Nash KA, Zhang Y, Brown-Elliott BA, et al.: Molecular basis of intrinsic macrolide resistance in clinical isolates of Mycobacterium fortuitum. J Antimicrob Chemother. 2005 ; 55 : 170 177.

16) Wallace RJ Jr, Brown-Elliot B, Hall L, et al.: Clinical and laboratory features of Mycobacterium mageritense. J Clin Microbiol. 2002 ; 40 : 2930 2935.

17) Huth RG, Brown-Elliott BA, Wallace RJ Jr.: Mycobacte-rium mageritense pulmonary disease in patient with com-promised immune system. Emerg Infect Dis. 2011 ; 17 : 557 558.

18) Schinsky MF, McNeil MM, Whitney AM, et al.: Myco-bacterium septicum sp. nov., a new rapidly growing species associated with catheter-related bacteraemia. Int J Syst Evol Microbiol. 2000 ; 50 : 575 581. 19) 小林 治, 森田絹代, 鹿住祐子, 他:希少菌種 Myco-bacterium septicumを検出した市中肺炎の一例. 日本臨床 微生物学雑誌. 2016 ; 26 : 124 130. 20) 吉田志緒美, 露口一成, 鈴木克洋, 他:Mycobacterium fortuitumを対象とした Ziehl-Neelsen 染色法と蛍光染色法 における抗酸性の比較検討. 結核. 2013 ; 88 : 461 467. 21) Lévesque S, Dufresne PJ, Soualhine H, et al.: A Side by Side

Comparison of Bruker Biotyper and VITEK MS: Utility of MALDI-TOF MS Technology for Microorganism Identi-fi cation in a Public Health Reference Laboratory. PLoS ONE. 2015 ; 10 : e0144878.

22) 鈴木弘倫, 吉田 敦, 樽川友美, 他:比較的まれな非結 核性抗酸菌臨床株を対象としたMALDI-TOF MSによる 同定性能の評価. 日本臨床微生物雑誌. 2016 ; 26 : 105 111.

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結核 第 93 巻 第 11_12号 2018年11_12月 608

Abstract [Objective] We investigated the actual condition,

the effi cacy, and the safety of use of sitafl oxacin (STFX) for

Mycobacterium avium complex pulmonary disease (MAC-PD).

 [Materials and Methods] Eighty nine patients who were newly prescribed STFX for MAC-PD were retrospectively investigated about reasons for prescribing STFX, effi cacy as an alternative drug for standard therapeutic agents, effi cacy of add-on therapy for refractory cases, and adverse events.  [Results] STFX were the most frequently prescribed in 54 patients (61%) as an alternative drug for standard therapeutic agents. Of the 46 patients who were able to follow up, 21 patients completed treatment. In refractory cases, no cases achieve negative sputum conversion, although symptom improvement was observed in 4 cases and radiological improvement was confi rmed in 3 cases. Adverse events of STFX were seen in 50 (56%) of 89 patients. Diarrhea was the most common adverse event (22%). Twenty-three patients

were discontinued due to adverse events.

 [Conclusion] STFX for MAC-PD shows a certain effect as an alternative drug, and add-on therapy for refractory cases. However, there was a limit to the effi cacy, and many adverse events were seen.

Key words: Mycobacterium avium complex pulmonary

disease, Sitafl oxacin, Alternative medicine, Refractory case, Adverse events

Department of Respiratory Medicine, National Hospital Organization Higashinagoya National Hospital

Correspondence to: Mitsuaki Yagi, Department of Respiratory Medicine, National Hospital Organization Higashinagoya National Hospital, 5_101, Umemorizaka, Meito-ku, Nagoya-shi, Aichi 465_8620 Japan.

(E-mail: yagim@e-nagoya.hosp.go.jp) −−−−−−−−Original Article−−−−−−−−

EFFICACY AND SAFETY OF SITAFLOXACIN FOR

MYCOBACTERIUM AVIUM

COMPLEX PULMONARY DISEASE

Mitsuaki YAGI, Taku NAKAGAWA, Yuta HAYASHI, Noritaka YAMADA, Osamu TARUMI, Yasutaka FUKUI, and Kenji OGAWA

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609

Abstract An 82-year-old man was diagnosed with active pulmonary tuberculosis and tuberculous

lymph-adenitis because Mycobacterium tuberculosis was detected in both the sputum and pus collected from the incision site in the neck. He was treated with a combination of isoniazid, rifampicin, and ethambutol. How-ever, even after 2 months of treatment, the lymphadenopathy worsened with new lesions arising. The histo-pathological examination of cervical lymph nodes revealed T-cell non-Hodgkin lymphoma. He tested positive for anti-human T-lymphotropic virus type 1 (HTLV-1) antibody. The diagnosis of adult T-cell leukemia-lymphoma (ATL) lymphoma type was made. He was treated with supportive care alone because of his poor performance status. Approximately 2 months later he died. HTLV-1 infection, which underlies ATL, might have contributed to the development of tuberculosis in this case as HTLV-1 infection is associated with immunosuppression. When a patient does not improve after treatments, physicians should perform histological examination to avoid making a premature diagnosis and overlooking underlying serious diseases.

Key words: Adult T-cell leukemia-lymphoma, Tuberculous lymphadenitis, Human T-lymphotropic virus

type 1; HTLV-1

1Department of Internal Medicine, 2Department of Surgery, Osaka Anti-Tuberculosis Association Osaka Hospital

Correspondence to : Masayoshi Higashiguchi, Department of Internal Medicine, Osaka Anti-Tuberculosis Association Osaka Hospital, 2276_1, Neyagawakoen, Neyagawa-shi, Osaka 572_0854 Japan. (E-mail: dr-higashiguchi@osaka-hospital.jp)

(Received 25 Jun. 2018/Accepted 25 Aug. 2018) Kekkaku Vol. 93, No. 11_12: 609_614, 2018

−−−−−−−−Case Report−−−−−−−−

A CASE OF CONCOMITANT ADULT T-CELL LEUKEMIA-LYMPHOMA

LYMPHOMA TYPE AND TUBERCULOUS LYMPHADENITIS

1Masayoshi HIGASHIGUCHI, 2Shigeru NAKANE, 1Tomoshige MATSUMOTO, and 1Takashi FUJII

INTRODUCTION

 Tuberculosis is one of the most prevalent infectious diseases in the world causing substantial morbidity and mortality1).

It should be noted that tuberculosis can develop secondary to immunosuppression and human immunodefi ciency virus infection is one of the most important immunosuppressive diseases which can lead to the development of tuberculosis2).

In addition, human T-lymphotropic virus type 1 (HTLV-1) infection may be an underrated important condition which underlies tuberculosis3). Here, we present a patient who was

initially diagnosed with tuberculous lymphadenitis, but was revealed to concomitantly have adult T-cell leukemia-lymphoma (ATL). There may be a relationship between the two diseases, as HTLV-1 infection, which underlies ATL, is associated with immunosuppression3).

CASE REPORT

 An 82-year-old man was referred to our hospital owing to suspected active pulmonary tuberculosis. Approximately 4 months before the hospitalization, nurses in the day care center noticed the enlargement of his neck. One month later, the neck enlargement worsened. The neck lesion was incised

to drain pus for the preliminary diagnosis of purulent lymph-adenitis. However, his neck lesion did not improve after the incision and drainage, and neck computed tomography (CT) revealed multiple nodular opacifi cations in both the upper lungs in addition to multiple cervical lymphadenopathy. His medical history was remarkable for gastric cancer, which was treated by performing distal gastrectomy and cholecystectomy. In addition, he developed cerebral infarction that left him with permanent right hemiplegia and motor aphasia, and since then, he had been almost confi ned to bed. He had smoked 1 pack of cigarettes per day for approximately 30 years.

 On referral, CT revealed a large low-density mass measuring approximately 6×5×3 centimeters in the left neck (Fig. 1) and multiple nodular opacities in both upper lungs (Fig. 2). No signifi cant lymphadenopathy was detected elsewhere in the initial scan, which was not contrasted. Both the sputum and pus collected from the incision site in the neck were smear-positive for acid-fast bacilli and positive for the loop-mediated isothermal amplifi cation (LAMP) assay. The patient was immediately admitted in our hospital with the diagnosis of active pulmonary tuberculosis and tuberculous lymphadenitis. On admission, he was afebrile and appeared well. His blood pressure was 148/74 mmHg and pulse was

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620 結核 第 93 巻 第 11_12号 2018年11_12月 620

Abstract An initial aggravation after anti-tuberculosis

che-motherapy is characterized as a paradoxical reaction, and a progressive tuberculoma is recognized as one of the initial aggravations.

 A patient aged 37 years, female without history of tuber-culosis and immunosuppressive diseases visited our clinic due to persistent fever and non-productive coughing. She was admitted due to bilateral pleural effusions. There was no evidence of tuberculosis antigens from sputum and pleu-ral effusions. Bilatepleu-ral tuberculous pleurisy was suspected, because of high levels of adenosine deaminase of both pleural effusions (right 73.2 IU/L and left 77.5 IU/L) and positive results in QuantiFERON®-GIT (ESAT-6 : 1.03 IU/mL). She

was discharged after interventions of anti-tuberculosis che-motherapy with pyrazinamide, rifampicin, isoniazid and ethambutol.

 However, she was re-admitted due to new symptoms of right chest discomfort and abnormal shadows at right pleura on chest x-ray fi ndings one month after the interventions. Diagnosis of right progressive chest and abdominal tuber-culoma was made from the detections of tuberculosis DNA by polymerase chain reaction techniques from punctured fl

u-ids of the abdominal shadows. The tuberculoma disappeared 1 year and 4 months after consolidated anti-tuberculosis chemotherapy. This case was, here, presented as a diagnostic diffi culty that development to pleural and peritoneal tuber-culoma one month after initiation anti-tuberculosis chemo-therapy on bilateral tuberculous pleurisy might be considered as paradoxical reactions, which was different from progres-sive diseases.

Key words: Bilateral tuberculous pleurisy, Peritoneum

tuber-culoma, Pleural tubertuber-culoma, Paradoxical response

1Division of Respirology, Neurology, and Rheumatology,

Department of Medicine, Kurume University School of Medicine; 2National Hospital Organization Fukuoka-higashi

Medical Center

Correspondence to: Takashi Kinoshita, Division of Respi-rology, NeuRespi-rology, and Rheumatology, Department of Medi-cine, Kurume University School of MediMedi-cine, 67 Asahi-cho, Kurume-shi, Fukuoka 830_0011 Japan.

(E-mail: tkino@med.kurume-u.ac.jp) −−−−−−−−Case Report−−−−−−−−

A CASE OF BILATERAL TUBERCULOUS PLEURISY WITH

DEVELOPMENT TO PLEURAL AND PERITONEAL

TUBERCULOMA DURING ANTI-TUBERCULOSIS TREATMENT

1Yusuke OKAYAMA, 1Takashi KINOSHITA, 1Takayuki TOYAMA, 1Youhei IMAMURA, 1Masaki TOMINAGA, 2Shohei TAKATA, 1Tomoaki HOSHINO, and 1Tomotaka KAWAYAMA

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