Serum Procalcitonin Levels Predict Mortality Risk in Patients With Pulmonary Tuberculosis: A Single-Center Prospective Observational Study.

Globally, tuberculosis is the leading infectious cause of death; discovering biomarkers that predict a high mortality risk may improve treatment outcomes. We prospectively enrolled 252 pulmonary tuberculosis patients who were not coinfected with human immunodeficiency virus and initiated antituberculosis treatment, measured serum procalcitonin levels (PCT), and assessed mortality risk. PCT serum levels higher than 0.13 (day 0), 0.05 (day 7), 0.12 (day 14), or 0.06 (day 28) ng/mL predicted nonsurvivors with odds ratios of 7.9, 14.3, 20.0, and 7.3, respectively (P ≤ .005 for all), respectively. Therefore, serum PCT levels are a promising mortality risk indicator for patients with pulmonary tuberculosis. Main Point. For patients with pulmonary tuberculosis, a promising mortality risk indicator is the level of serum procalcitonin, which is weakly associated with sputum bacterial load and independent of radiographic findings.

Limited benefit of CT scans in tuberculosis contact tracing.

OBJECTIVE: The detection of abnormal findings on computed tomography (CT) scans of tuberculosis contacts combined with normal plain radiographs contributes to the early detection of tuberculosis. However, the benefit of the early detection of abnormalities for the prevention of active tuberculosis during follow-up requires evaluation. METHOD: We conducted retrospective comparison of the existence of CT scans of tuberculosis contacts without findings of active tuberculosis on plain radiographs at a hospital in Japan. RESULTS: Among 243 contacts without CT scans, five developed tuberculosis during follow-up. Among 229 contacts with CT scans, 24 were judged as targets of multi-drug therapy since their CT findings were suggestive of active tuberculosis at the time of the CT screening. Among 205 contacts judged as having latent tuberculous infection with CT screening, three developed tuberculosis diseases during follow-up. CONCLUSION: CT scans detected abnormal findings among contacts without abnormalities of plain radiographs but there were some contacts that developed tuberculosis diseases among those with contact investigation including CT scan. The value of CT is equivocal considering the balance of true treatment, overtreatment and harm of radiation.

[THE FREQUENCIES AND MANAGEMENT OF ADVERSE REACTIONS IN MULTI-DRUG RESISTANT TUBERCULOSIS TREATMENT].

[Objectives] To investigate the adverse reactions of antimicrobial drugs in multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR- TB) patients. [Results] Sixty-six patients with MDR-TB who have been treated from 2010 through 2014 were evaluated in the retro- spective analysis. Variety of adverse reactions including psychological reaction, central nervous system toxicity, ophthalmic toxicity, peripheral neurotoxicity, gastrointestinal reactions, hematologic abnormalities, musculoskeletal adverse effects, and endocrine disorder, were observed. However, there was no fatal case due to the adverse reactions of the anti-tubercu- losis drugs in this observation. [Conclusions] Drugs for MDR-TB and XDR-TB treatment are limited and the adverse reactions of drugs for MDR-TB and XDR-TB are not well-known. Therefore, the treatment may fail due to inappropriate management of adverse events. MDR-TB and XDR-TB should be treated by the experts of the adverse reactions of all anti-tuberculosis drugs.

Delamanid for multidrug-resistant pulmonary tuberculosis.

BACKGROUND: Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. METHODS: In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months. RESULTS: Among patients who received a background drug regimen plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo (P=0.008). Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%, P=0.04). The findings were similar with assessment of sputum-culture conversion in solid medium. Most adverse events were mild to moderate in severity and were evenly distributed across groups. Although no clinical events due to QT prolongation on electrocardiography were observed, QT prolongation was reported significantly more frequently in the groups that received delamanid. CONCLUSIONS: Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis. This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. (Funded by Otsuka Pharmaceutical Development and Commercialization; ClinicalTrials.gov number, NCT00685360.).

[CLINICO-MICROBIOLOGICAL CHARACTERISTICS OF MYCOBACTERIUM KANSASII PULMONARY DISEASE AT A SPECIALIZED MYCOBACTERIOSIS HOSPITAL IN TOKYO, JAPAN].

BACKGROUND: Mycobacterium kansasii is the second most common nontuberculous mycobacterial pulmonary disease pathogen in Japan. Fibrocavitary disease is characteristic of M. kansasii pulmonary disease in male patients. OBJECTIVE: To clarify the clinico-microbiological characteristics of M. kansasii pulmonary disease in recent years in a Tokyo hospital specializing in mycobacteriosis. METHODS: A retrospective chart review was performed on 77 M. kansasii culture-positive cases from January 2003 to December 2010. Sequence analysis of the hsp65 gene using PCR-restriction enzyme pattern analysis (hsp65-PRA) was used to identify bacterial genotypes. RESULTS: Seventy-four cases fulfilled the diagnostic criteria for inclusion. Female patients comprised 22% of cases (16 cases, 63.2 ± 24.6 years of age) and were older than male patients (58 cases, 55.5 ± 17.5 years of age). Although the peak distribution among men was patients in their 50s, female patients showed a bimodal distribution with increased occurrence in older women. Radiological examination showed that approximately 90% of male and younger female patients had fibrocavitary disease. However, elderly female patients tended to have nodular bronchiectatic disease. Genotype analysis revealed that all bacterial strains from both genders were subtype I. CONCLUSIONS: Compared to previous reports, the number of female patients with M. kansasii pulmonary disease had increased, with an unusual age distribution. These different age-related radiological findings might be due to host factors.

[CLINICAL EFFECTS OF TREATMENT FOR MYCOBACTERIUM TUBERCULOSIS INFECTION IN PATIENTS AT A SPECIALIZED HOSPITAL IN 2011].

OBJECTIVE AND METHODS: We analyzed the clinical effects of treatment for Mycobacterium tuberculosis infection for 1 year in our specialized hospital in 2011. Two hundred and ninety-six (296) patients were admitted and received treatment. RESULTS: Two hundred and fifty-six patients (86.5%) were started on the standard treatment with 3 drugs (isoniazid [INH, rifampicin [RFP], and ethambutol [EB] or streptomycin [SM]) or 4 drugs (INH, RFP, EB or SM, and pyrazinamide [PZA]). One hundred and seventy-one patients (66.8%) continued receiving the standard treatment during the admission period. Of 160 cases who could continue 4 drugs, under 80 year-old patients were 127 cases (76.0%), but over 80 year-old patients were 33 cases (49.3%). The mean duration for negative conversion of sputum culture was 40.6 days. Liver dysfunction due to 4 drugs (INH, RFP, EB, and PZA) was noted in 8.5% of patients. Eighteen of the 296 patients had multi-drug resistant tuberculosis (MDR-TB). Each MDR-TB patient received individualized treatment. Moreover, 7 of the MDR-TB cases were treated surgically. DISCUSSION: Treatment of TB had taken long time, and some patients could not continue the treatment owing to the adverse effects of drugs. Hence, it is important to monitor adverse effects of drugs in each patient.

MUTYH-associated colorectal cancer and adenomatous polyposis.

MUTYH-associated polyposis (MAP) was first described in 2002. MUTYH is a component of a base excision repair system that protects the genomic information from oxidative damage. When the MUTYH gene product is impaired by bi-allelic germline mutation, it leads to the mutation of cancer-related genes, such as the APC and/or the KRAS genes, via G to T transversion. MAP is a hereditary colorectal cancer syndrome inherited in an autosomal-recessive fashion. The clinical features of MAP include the presence of 10-100 adenomatous polyps in the colon, and early onset of colorectal cancer. Ethnic and geographical differences in the pattern of the MUTYH gene mutations have been suggested. In Caucasian patients, c.536A>G (Y179C) and c.1187G>A (G396D) mutations are frequently detected. In the Asian population, Y179C and G396D are uncommon, whereas other variants are suggested to be the major causes of MAP. We herein review the literature on MUTYH-associated colorectal cancer and adenomatous polyposis.

[Experience of rapid drug desensitization therapy in the treatment of mycobacterial disease].

BACKGROUND: Drugs for tuberculosis and non-tuberculosis mycobacterial diseases are limited. In particular, no new drugs for non-tuberculosis mycobacterial disease have been developed in recent years. Antimycobacterial drugs have many adverse reactions, for which drug desensitization therapy has been used. PURPOSE: Rapid drug desensitization (RDD) therapy, including antituberculosis drugs and clarithromycin, has been implemented in many regions in Europe and the United States. We investigated the validity of RDD therapy in Japan. PATIENTS AND METHOD: We report our experience with RDD therapy in 13 patients who developed severe drug allergy to antimycobacterial treatment. The desensitization protocol reported by Holland and Cernandas was adapted. RESULT: The underlying diseases were 7 cases of pulmonary Mycobacterium avium complex disease and 6 cases of pulmonary tuberculosis. Isoniazid was readministered in 2 (100%) of 2 patients; rifampicin, in 8 (67.7%) of 12 patients; ethambutol, in 4 (67.7%) of 6 patients; and clarithromycin, in 2 (100%) of 2 patients. CONCLUSION: In Japan, the desensitization therapy recommended by the Treatment Committee of the Japanese Society for Tuberculosis have been implemented generally. We think RDD therapy is effective and safe as the other desensitization therapy. We will continue to investigate the efficiency of RDD therapy in patients who had discontinued antimycobacterial treatment because of the drug allergic reaction.

Activities of Daily Living, Hypoxemia, and Lymphocytes Score for Predicting Mortality Risk in Patients With Pulmonary TB.

BACKGROUND: A clinically applicable mortality risk prediction system for pulmonary TB may improve treatment outcomes, but no easy-to-calculate and accurate score has yet been reported. The aim of this study was to construct a simple and objective disease severity score for patients with pulmonary TB. RESEARCH QUESTION: Does a clinical score consisting of simple objective factors predict the mortality risk of patients with pulmonary TB? STUDY DESIGN AND METHODS: The data set from our previous prospective study that recruited patients newly diagnosed with pulmonary TB was used for the development cohort. Patients for the validation cohort were prospectively recruited between March 2021 and September 2022. The primary end point was all-cause in-hospital mortality. Using Cox proportional hazards regression, a mortality risk prediction model was optimized in the development cohort. The disease severity score was developed by assigning integral points to each variate. RESULTS: The data from 252 patients in the development cohort and 165 patients in the validation cohort were analyzed, of whom 39 (15.5%) and 17 (10.3%), respectively, died in the hospital. The disease severity score (named the AHL score) included three clinical parameters: activities of daily living (semi-dependent, 1 point; totally dependent, 2 points); hypoxemia (1 point), and lymphocytes (< 720/µL, 1 point). This score showed good discrimination with a C statistic of 0.902 in the development cohort and 0.842 in the validation cohort. We stratified the score into three groups (scores of 0, 1-2, and 3-4), which clearly corresponded to low (0% and 1.3%), intermediate (13.5% and 8.9%), and high (55.8% and 39.3%) mortality risk in the development and validation cohorts. INTERPRETATION: The easy-to-calculate AHL disease severity score for patients with pulmonary TB was able to categorize patients into three mortality risk groups with great accuracy. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Center; No. UMIN000012727 and No. UMIN000043849; URL: www.umin.ac.jp.

CD24 expression is associated with progression of gastric cancer.

BACKGROUND/AIMS: Mortality rates due to gastric cancer are high in Japan. To improve patient prognosis, new biomarkers for diagnosis and treatment are urgently required. In this study we investigated the role of CD24, a cell adhesion glycoprotein implicated in tumor cell proliferation, which is used as a prognostic marker in various cancers. METHODOLOGY: We analyzed CD24 expression in 173 gastric adenocarcinomas by immunohistochemistry and compared the data with clinicopathological parameters and patient overall survival. Furthermore, we performed Western blotting analysis of CD24 in six human gastric adenocarcinoma cell lines, Kato III, MKN1, MKN28, MKN45, MKN74, and HGC-27. RESULTS: CD24 up-regulation was significantly correlated with depth of invasion (p=0.005) and pathological high stages (p=0.043). We observed a relationship between high CD24 expression and lymph node metastasis, venous invasion and lymphatic invasion. CD24 expression tended to be higher in cell lines derived from differentiated gastric carcinoma, including those derived from lymph node metastasis. CONCLUSIONS: Our study suggests that gastric cancer patients with high CD24 expression should be closely monitored for recurrence following resections. CD24 expression is a potential biomarker for gastric cancer prognosis and provides a new molecular target for therapeutic strategies.

[Estimating the prevalence of tuberculosis infection among healthcare workers in our hospital by repeat QFT-G testing].

OBJECTIVE: The QuantiFERON-TB (QFT) blood test is the major tool for the diagnosis of Mycobacterium tuberculosis (TB) infection among healthcare workers (HCWs). We used QFT tests to estimate the prevalence of TB infection among HCWs in our hospital. MATERIAL AND METHODS: Between 2003 and 2010, a total of 733 HCWs were enrolled in this study, and the prevalence of TB infection was analyzed according to the HCWs' jobs and work place. RESULTS: Among the 152 men and 581 women who were evaluated, 3 female HCWs had a history of TB. Fifty-eight HCWs (8 men and 50 women with a mean age of 56.3 years and 48.4 years, respectively) demonstrated positive QFT tests. The positive rate was 7.9% for all staff members throughout the study period. The QFT test was positive for 1 HCW who was treated for TB in 1998, and negative and inconclusive for 2 other HCWs treated for TB in 2002. The positive rate for QFT was 16.0% in the TB ward (12/75, 95% confidence interval [CI]: 7.7-24.3%), 9.9% in the other wards (22/222, 95% CI: 7.9-11.9), and 1.1% in the outpatient department (1/91, 95% CI: 0-2.2). According to the job category, the QFT positive rates were as follows: doctors, 4.3% (3/70, 95% CI: 1.9-6.7); nurses, 10.3 (4/35, 95% CI: 6.0-16.8). The positive rate among doctors working in the TB ward was 10.0%, and that for nurses was 24.3%. This indicates that the prevalence of infection among HCWs in the TB ward was significantly higher than that in other work places. A comparison of the results from 2003 through 2007 revealed that for a total of 307 workers, 90.6% and 5.2% remained negative and positive, respectively, while 1.6% converted from negative to positive, and 2.6% from positive to negative. CONCLUSION: The positive rate among HCWs in the TB ward was higher than that in other wards. This is especially remarkable for doctors and nurses working in the TB ward.

[Clinical factors of pulmonary tuberculosis in non-tuberculosis wards and its incidence among contact patients and healthcare workers in our hospital using QuantiFERON GOLD testing].

OBJECTIVE AND METHODS: In our hospital, we analyzed the clinical factors of pulmonary tuberculosis (TB) diagnosed in non-TB wards and the incidence of TB infection among contact patients and healthcare workers (HCWs) using QuantiFERON-TB GOLD (QFT) testing. MATERIAL: This study included 16 patients who were diagnosed with pulmonary TB in non-TB wards in our hospital from January 2008 to May 2011. Eight contact patients and 120 HCWs were also enrolled. RESULTS: The 16 TB patients comprised 11 men (77.7 years) and 5 women (74.4 years). Among them, only 9 patients exhibited positive results for Mycobacterium tuberculosis after the first acid-fast bacterial examination; the other 7 patients presented positive results only after the second or third examinations. Moreover, there were 3 cases of positive Mycobacterium avium samples in the first acid-fast bacterial examination. Among 16 pulmonary Mycobacterium tuberculosis cases, 8 were sputum smear and culture positive, 7 were sputum smear negative and culture positive, and 1 was sputum smear and culture negative. Moreover, 17 days had elapsed from the time of admission to the non-TB ward to diagnosis. TB contact examination revealed that QFT results for 2 HCWs changed from negative to positive. DISCUSSION: We suspected pulmonary aspergillosis or old TB when presented with cases with a history of TB. Moreover, we believe that the periods from admission to diagnosis were delayed when the first acid-fast bacterial sputum examination was negative or showed non-tuberculous mycobacteria.

[Clinical evaluation of a line probe assay kit for the identification of Mycobacterium species and detection of drug-resistant Mycobacterium tuberculosis].

BACKGROUND: Multidrug resistance (MDR) involves resistance to both isoniazid and rifampicin, which makes the treatment of tuberculosis very difficult. Extensive drug resistance (XDR) occurs when, in addition to isoniazid and rifampicin resistance, the microorganisms are resistant to a fluoroquinolone and an injectable agent (e.g., kanamycin, amikacin, or capreomycin). Generally, drug susceptibility testing takes more than 3-4 weeks after the initial cultivation. There is an urgent need to identify methods that can rapidly detect both the presence of Mycobacterium tuberculosis and the status of drug resistance. PURPOSE: This study was aimed at evaluating the line probe assay (LiPA; Nipro Co.), for the identification of Mycobacterium species and detection of mutations associated with antituberculous drugs. RESULTS: We found that LiPA enabled the rapid identification of M. tuberculosis, M. avium, M. intracellulare, and M. kansasii. When the results of the LiPA and conventional drug susceptibility tests were compared, there was no difference in the susceptibility to rifampicin, pyrazinamide, and levofloxacin; however, there was a difference in the susceptibility to isoniazid. CONCLUSION: Thus, LiPA can be used for the rapid identification of Mycobacterium species and the determination of susceptibility to drugs, which can help in the early initiation of appropriate treatment, leading to a reduction in infectiousness.

[Clinical experience using rifabutin for treating infection with Mycobacterium tuberculosis in elderly Japanese patients].

OBJECTIVES: To clarify whether rifabutin (RBT) can be used for treating tuberculosis in elderly Japanese patients in the clinical setting. METHOD: We performed a clinical chart review from Oct 2008 to Dec 2011, for patients who were diagnosed with tuberculosis and were prescribed rifabutin, at the Fukujuji Hospital (180 beds for respiratory medicine, including 60 for TB). Primarily, we focused on characteristics of patients, the cause for RBT indication, and success rate of treatment. RESULTS: During the study period, 1129 patients were diagnosed with tuberculosis, and among these, 42 (3.7%) patients were prescribed RBT. Of these, 39 patients were included in this study (3 were excluded because their prescription was terminated within 2 weeks because of reasons other than adverse effects). In all, 69% patients were male. Mean age was 69 years, and mean body mass index was 19.1 +/- 3.4 kg/m2. RFP-related adverse effects were observed in 28 patients (72%; age, 73 years); these included gastrointestinal complications in 16, liver dysfunction in 7, skin rashes in 6, and renal dysfunction and thrombocytopenia in 1 each). Additional medication was required in 6 patients, and RBT-resistant TB was noted in 5 patients (28%; age, 60 years). A success rate of 71.4% was observed in cases of RFP-related adverse effects, and that of 81.8% was observed in cases of other reasons. Except for the patient who experienced renal dysfunction, RBT could be used in all patients who experienced RFP-related adverse effects. CONCLUSION: RBT showed a relatively good success rate, even in patients who experienced RFP-related adverse effects. Thus, RBT could be an alternative in cases of RFP-related adverse effects, even in elderly patients.

Comprehensive multicenter evaluation of a new line probe assay kit for identification of Mycobacterium species and detection of drug-resistant Mycobacterium tuberculosis.

We evaluated a new line probe assay (LiPA) kit to identify Mycobacterium species and to detect mutations related to drug resistance in Mycobacterium tuberculosis. A total of 554 clinical isolates of Mycobacterium tuberculosis (n = 316), Mycobacterium avium (n = 71), Mycobacterium intracellulare (n = 51), Mycobacterium kansasii (n = 54), and other Mycobacterium species (n = 62) were tested with the LiPA kit in six hospitals. The LiPA kit was also used to directly test 163 sputum specimens. The results of LiPA identification of Mycobacterium species in clinical isolates were almost identical to those of conventional methods. Compared with standard drug susceptibility testing results for the clinical isolates, LiPA showed a sensitivity and specificity of 98.9% and 97.3%, respectively, for detecting rifampin (RIF)-resistant clinical isolates; 90.6% and 100%, respectively, for isoniazid (INH) resistance; 89.7% and 96.0%, respectively, for pyrazinamide (PZA) resistance; and 93.0% and 100%, respectively, for levofloxacin (LVX) resistance. The LiPA kit could detect target species directly in sputum specimens, with a sensitivity of 85.6%. Its sensitivity and specificity for detecting RIF-, PZA-, and LVX-resistant isolates in the sputum specimens were both 100%, and those for detecting INH-resistant isolates were 75.0% and 92.9%, respectively. The kit was able to identify mycobacterial bacilli at the species level, as well as drug-resistant phenotypes, with a high sensitivity and specificity.

[Can an individual with a positive baseline QuantiFERON test result develop active tuberculosis?].

OBJECTIVES: QuantiFERON-TB Gold (QFT-G) test has been recommended as a new tool for the diagnosis of latent tuberculosis (TB) infection. However, the risk of development of active TB in the future depends on the period after the infection. The aim of this study was to evaluate the risk of development of active TB in individuals who have been infected. METHODS: Clinical development of TB in subjects with positive baseline QFT test results was retrospectively analyzed. The subjects included healthcare workers, since 2003, at the Fukujuji Hospital who were examined at employment. RESULTS: In total, 667 subjects were examined using the QFT-2G test, and 62 subjects were QFT positive at the first examination. One was treated using isoniazid, and 61 subjects were followed up for an average of 4.7 years (286 person-years). None of the subjects developed active TB during the observation period, and the probability of clinical breakdown (95% confidence interval) was 0-0.0104/person-year. CONCLUSION: The risk of development of active TB among subjects with positive QFT-G test results at baseline was low. Treatment of latent TB infection is not recommended, unless an individual has been recently infected.

[Factors related to the occurrence of multi- (extensively-) drug resistant tuberculosis (M/XDR-TB) in our hospital].

OBJECTIVE: To analyze the clinical characteristics of multi- (extensively-) drug-resistant tuberculosis (M/XDR-TB) in our hospital. MATERIALS AND METHODS: One-hundred and forty-one cases diagnosed with MDR-TB and thirteen cases with XDR-TB admitted to our hospital over the last nine years were enrolled in this study. RESULTS: The gender distribution was: ninety-nine males and forty-two females in MDR-TB and nine males and four females in XDR-TB. The mean age was 52.0 years in males and 43.1 years in females in the MDR-TB patients, and 49.1 years in males and 42.0 years in females in the XDR-TB patients. There were 11 Chinese patients and 7 Koreans, as well as 8 patients from other countries abroad. Eighty-four (59.6%) MDR-TB patients and 9 (69.2%) XDR-TB patients had a smoking history. Diabetes mellitus was seen in 30 MDR-TB and 3 XDR-TB patients. The period from manifestation to the first visit to our hospital was 41.5 months on average in the MDR-TB patients, and 79.6 months in the XDR-TB patients. The average period from first diagnosis of TB to that of M/XDR-TB was 30.9 months in the MDR and 56.8 months in the XDR. Thirty (21.3%) MDR-TB patients and one (7.7%) XDR-TB patient were first diagnosed in our hospital. One-hundred and fifteen patients (81.6%) with MDR-TB and 6 (46.1%) with XDR-TB achieved negative sputum bacteriological conversion. Fifty-six cases (48.7%) of 115 MDR-TB and all (100%) of the XDR-TB patients underwent surgical treatment. Sixteen (11.3%) MDR-TB and 3 (23.1%) XDR-TB patients died. Thirty of the MDR-TB and 1 of the XDR-TB patients had never been previously treated for tuberculosis. Twelve (8.5%) MDR-TB and 5 (38.5%) XDR-TB patients had been treated with four drugs including isoniazid (INH), rifampicin (RFP), pyrazinamide (PZA), and either ethambutol (EB) or streptomycin (SM) in previous hospitals. Twenty-five (17.7%) MDR-TB and 5 (38.5%) XDR-TB patients had been treated with three drug regimens not including PZA in previous hospitals. CONCLUSION: M/XDR-TB is a man-made disease and can be infectious. Even the current standard regimens can produce M/ XDR-TB, if they are used improperly and carelessly. Great care should be taken to prevent XDR and MDR-TB.

[Nontuberculous mycobacteriosis mortality in Japan].

UNLABELLED: The aim of this research was to clarify epidemiological characteristics of nontuberculous mycobacteriosis deaths in Japan. We analyzed the frequency of deaths due to nontuberculous mycobacteriosis (NTM) and regional differences using the Vital Statistics of Japan, published by the Ministry of Health, Labour and Welfare. The crude death rate was calculated using the Population Census of Japan published every 5 years (Ministry of Internal Affairs and Communications). In addition, changes in the proportions of death cases due to NTM disease among total autopsies were calculated using the Annual of the Pathological Autopsy in Japan (The Japanese Society of Pathology). RESULTS: NTM disease deaths appeared for the first time in 1970, with a marked increase by 2007, when there were 912 certified deaths. The increase was more marked after the mid-1990s. The number of women's deaths exceeded 300 in 1999 and reached 570 in 2007, while that of men exceeded 300 in 2001 and remained at nearly the same level until 2007. The death rate increased in all eight regions of Japan. The highest single-year regional death rate was 212 in Kanto in 2005. However, correcting by population size, the crude death rate was higher in the western regions of Japan than in the eastern ones. The proportion of NTM among total autopsies also showed an increase from 0.066% in 1993 to 0.304% in 2007. Included in the report is a comparison of trends of NTM deaths with those of major respiratory diseases including tuberculosis, emphysema, bronchial asthma and airway cancers.

[A case of drug-induced pneumonitis caused by saikokeishikankyoto].

We report a case of drug-induced pneumonitis caused by saikokeishikankyoto. A 68-year-old woman was admitted to our hospital complaining of dry cough, fever, and dyspnea after taking saikokeishikankyoto for 16 days. A chest radiograph showed widespread ground-glass shadows in both lung fields. Chest CT showed ground-glass opacities and thickening of the interlobular septum in both lung fields. Bronchoalveolar lavage fluids and transbronchial lung biopsy specimen showed findings consistent with drug-induced pneumonitis, therefore we diagnosed drug-induced pneumonitis caused by saikokeishikankyoto. Three years previously she had suffered from a similar illness after taking hangeshashinto. Ougon is suspected to be a causative component for her saikokeishikankyoto-induced pneumonitis, because it has been reported to be as a main cause for kampo-induced pneumonitis.