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Our aim was to investigate the clini- cal effects of levofloxacin (LVFX) administered intravenously to patients with pulmonary tuberculosis.We studied 65 patients hospitalized at The National Hospital Organization Tokyo National Hospital between January 2010 and December 2012. The patients did not have human immunodeficiency virus (HIV) infection, and received anti-tuberculous drugs intravenously due to the inability to receive drugs orally.Twenty-seven patients were intravenously treated with isoniazid (INH), streptomycin (SM) and LVFX (HLS), and 38 patients were treated with INH and SM (HS). For both groups, mean age was very high (80.6±15.0 years, HLS group; 81.0± 12.1 years, HS group) and serum albumin levels were low (2.0 ± 0.62 mg/dl and 2.1 ± 0.42 mg/dl, respectively). Most patients were administered oxygen (81.5%, HLS; 78.9 %, HS). In radiological findings, most patients had bilateral (92.6%, HLS; 92.1%, HS) and widely spread (55.6%, HLS; 57.9%, HS) shadows. No significant differences were found between both groups in terms of the above data, except for sex. Almost 70% of all patients died; 51.9% of patients in the HLS group and 50.0% of those in the HS group died of tuberculosis, while 18.5% of patients in the HLS group and 18.4% of those in the HS group died of the other diseases. There were no significant differences in the causes of death and the survival rates of both groups.Patients with pulmonary tuberculosis who were administered intravenous drugs were elderly and in poor general health. As such, mortality of these patients was very high. In this study, no clinical effects were found in the patients administered intravenous LVFX with INH and SM compared with patients treated with INH and SM.

We encountered 2 patients with pulmonary Mycobacterium avium complex disease in whom resistance to clarithromycin (CAM) was confirmed after treatment with rifampicin, ethambutol, and CAM. We evaluated the disease course in both patients. The deterioration of radiological findings was preceded by the acquisition of resistance to CAM in both cases. When symptoms of pulmonary MAC disease exacerbate, and radiological findings deteriorate, we should reconsider the type of treatment after determination of the minimal inhibitory concentration (MIC) of CAM for culture positive MAC strains.

The aim of this study was to investigate the current status of doctor's delay in diagnosing endobronchial tuberculosis (EBTB) and to elucidate the risk factors contributing to the delay.Retrospective clinicopathological analysis.Sixty-two patients with EBTB were admitted at our hospital between 1999 and 2010. Their backgrounds, symptoms, diagnoses at initial consultation, delay in diagnosis, and clinical examination results were analyzed.Of the 62 patients, 59 had acid-fast, bacillipositive sputum smear test results at admission. Among the 40 patients with total diagnostic delay of more than 2 months, only 11 experienced long patient's delay exceeding 2 months. However, 22 patients experienced long doctor's delay of more than 2 months (28% vs. 55%, respectively, p0.05), suggesting that doctor's delay contributes more to total delay than patient's delay. Fever was less frequent in patients with long doctor's delays than in those without (0% vs. 18%, respectively), at the initial consultation. In addition, radiographs showed that patients with long doctor's delays more frequently presented with shadows in the lower lung field (50% vs. 23%, p0.05), and most of these patients had noncavitary shadows on admission. All 7 patients diagnosed with bronchial asthma at the initial consultation had long doctor's delays.These findings demonstrate that long doctor's delays in diagnosing EBTB remain an issue. The clinical features of EBTB with long doctor's delays were confirmed to be quite different from those of pulmonary tuberculosis.

The purpose of this study was to evaluate tuberculosis treatment including levofloxacin (LVFX) and to investigate the effectiveness of changing drug regimens at our hospital.A retrospective study was conducted on 331 patients with tuberculosis admitted to Tokyo National Hospital in 2005. Out of these 331 patients, LVFX was used in 48 (14.5%), 41 of which were initial-treatment cases. We studied why and how LVFX was used and compared bacteriological negative conversion rates between the initial-treatment cases in which the initial standard regimen was changed to regimens including LVFX, and those in which the initial standard regimen was either maintained throughout or modified with drugs other than LVFX. Sputum cultures were examined with Mycobacteria Growth Indicator Tube System (BACTEC MGIT 960).LVFX was used in 41 (13.6%) of 302 initial-treatment cases and in 7 (24.1%) of 29 retreatment cases. Out of the 269 initial-treatment cases starting with the standard regimen, LVFX was later used in 26 cases (9.7%). The reasons for using LVFX were adverse reaction to antituberculosis drugs in 23 cases (88.5%) and resistance to antituberculosis drugs in 3 cases (11.5%). We investigated the bacteriological conversion rate in 228 patients who could be followed up for more than five months. The conversion rates in 105 cases under the standard regimen including PZA (PZA+) were 92.4% in three months, 98.1% in four months, and 100% in five months. The rates in 56 cases under the standard regimen without PZA (PZA-) were 92.9 %, 98.2% and 100%,respectively. The rates of 22 cases under the initial regimen modified with LVFX (LVFX +) were 68.2 %, 95.5% and 100%, respectively. In 45 cases under the initial regimen modified with drugs other than LVFX (LVFX-), the rates were 80.0%, 97.8% and 100%, respectively.This study showed that LVFX was an effective drug in terms of the bacteriological conversion rate, without adverse reaction. LVFX is not approved as an antituberculosis drug in Japan, but it is often used in cases of MDR-TB or in situations in which the patients cannot continue treatment with the standard regimen. We hope that LVFX will be approved as an antituberculosis drug as soon as possible in Japan.

We discussed the factors which may confuse diagnosis and treatment of tuberculosis (TB) in elderly patients, in order to improve the situation.414 patients who were hospitalized for active tuberculosis in Tokyo National Hospital were divided into three groups according to their ages (in years): less than 65, 65 to 74, and greater than 75. The three groups were compared in terms of performance status (PS), serum albumin level (whether over 3 g/dl or not), underlying diseases, symptoms at onset, sputum smear findings for acid-fast bacilli, presence or absence of cavitary lesion, regimen of treatment, adverse reaction to medications, and treatment outcome.The older group had significantly poorer PS (3 or 4), lower albumin level, more complications, a larger proportion of non-respiratory to respiratory symptoms, less cavity formation, less likelihood of continuing to take drugs regularly and higher mortality. It is supposed that these characteristics are mostly due to the aging itself.Diagnosing and treating active tuberculosis among elderly people is difficult because of nonspecific and thus confusing findings due to other diseases or aging. Delay in diagnosis and start of treatment makes prognosis of their TB poorer. To improve this situation we should keep a high index to TB and make better use of novel diagnostic technologies. For satisfactory treatment that allows maintenance of a high level of activity of daily life, it is necessary to pay more attention to such aspects as nutrition and rehabilitation and to offer appropriate supports.

To investigate clinical features of patients with pulmonary Mycobacterium xenopi infection treated at our hospital.We diagnosed 11 cases of M. xenopi infection at Tokyo National Hospital between 2000 and 2008 and recorded the drug susceptibility, patient characteristics, radiographic findings, treatments given and clinical courses. Eighteen other Japanese cases from the literature were discussed along with our findings.The cases of M. xenopi infection at our hospital consisted of 10 men and 1 woman with a mean age (+/- SD) of 55.1 +/- 19.4 years. Among the patients, 10 were smokers, 4 were heavy drinkers, and 6 had sequelae of pulmonary tuberculosis as an underlying disorder. Four patients had chronic obstructive pulmonary disease and 2 had diabetes mellitus, while there were 2 patients who had no underlying disease. All cases had radiographic opacities, predominantly found in the upper lung region, and cavernous lesions. These findings were demonstrated in both lungs in 5 patients, in the right lung only in 5 patients and in the left lung only in 1 patient. Concurrent aspergillosis was observed in 8 patients. The bacterial isolates from 7 cases were tested for drug sensitivity to levofloxacin (LVFX) and were found to be susceptible. M. xenopi disease was treated in 5 cases with INH+RFP+EB, in 2 cases with INH+RFP+Clarithromycin (CAM), and in 1 case with RFP+EB+CAM. Concurrent aspergillosis was treated with itraconazole in 2 cases. One patient underwent surgery for lung cancer. The duration of treatment was 16.4 +/- 12.8 months (range, 4-36 months). The radiographic findings were improved in 4 cases, deteriorated in 2 and unchanged in 5. M. xenopi was eradicated bacteriologically in 6 cases. The combination of radiographic and bacteriological findings indicated improvement in 3 cases, no change in 6 and deterioration in 2.The review of our cases disclosed that medical treatment alone was not sufficient in most cases for the control of clinical M. xenopi infection as reported overseas. Although we did not use LVFX for treatment, LVFX might be recommended for the treatment since all isolates tested proved to be susceptible to LVFX.

Abdominal tuberculous lymphadenitis is very rare. We report a case of pulmonary tuberculosis showing marked abdominal lymphadenopathy and splenomegaly. A 95-year-old man was admitted to our hospital because of abnormal chest X-ray and body weight loss in last 6 months. He had low grade fever with no abdominal pain. He did not have past history of tuberculosis. Laboratory examination showed mild renal dysfunction and mild glucose intolerance. Soluble interleukin 2 recepter was highly elevated (3800 U/ml). Tumor markers, such as carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA), and progastrin-releasing peptide (Pro GRP) were all within normal limit. Chest X-ray showed multiple nodules in bilateral lung fields. Chest computed tomography showed multiple nodules in bilateral lungs, especially in upper part of lungs, right hilar lymphadenopathy and upper mediastinal lymphadenopathy. Abdominal and pelvic enhanced computed tomography showed marked abdominal lymphadenopathy and splenomegaly (67 x 49 mm). Abdominal lymph nodes were hepatoduodenal (50 x 50 mm), splenic hilar (40 x 25 mm), upper paraaortic (30 x 60 mm), and small superior mesenteric (10 x 10 mm) lymph nodes. FDG-PET showed accumulation in the nodules of right lung field, right hilar lymph nodes, upper mediastinal lymph nodes, and abdominal lymph nodes. Bronchial lavage fluid (BAL) smear for acid-fast bacilli was positive, polymerase chain reaction for Mycobacterium tuberculosis was positive and acid-fast bacilli was cultured. Transbronchial lung biopsy specimen demonstrated non-specific intraalveolar organization and alveolitis. The patient was diagnosed as pulmonary tuberculosis, but about abdominal lymphadenopathy and splenomegaly we had to differentiate malignant lymphoma, and for definite diagnosis, laparotomy was necessary. But considering his age and general condition, we followed up carefully with anti-tuberculosis therapy. Pulmonary tuberculosis, abdominal lymphadenopathy and splenomegaly all showed marked improvement 4 months after starting anti-tuberculosis therapy with isoniazid, rifampicin, and ethambutol, so we clinically diagnosed abdominal tuberculous lymphadenitis and splenic tuberculosis.

The aim of this study was to evaluate the usefulness of bronchofiberscopy (BFS) in the diagnosis of pulmonary non-tuberculous mycobacteriosis (PNTM).Among 909 PNTM patients admitted to our hospital during the period from 1995 to 2006, BFS was performed for the diagnosis of PNTM in 107 patients (12%) who had either a negative sputum-smear for acid-fast bacilli (AFB) (n = 100) or from whom it had been impossible to collect sputum (n =7). For these 107 cases, we retrospectively compared and analyzed the findings from specimens obtained by BFS, such as smears, cultures, polymerase-chain reaction (PCR), and transbronchial lung biopsy (TBLB), with clinical, radiological, and sputum examination disease, was also seen in the positive ratios of other nontuberculous mycobacteriosis cases. Type and/or spread of MAC disease on chest radiographs did not relate to positive ratios of BFS obtained specimens. Based on overall BFS findings, including the examination of sputum immediately after BFS, 68 of 92 (74%) patients met the diagnostic criteria of MAC disease. Furthermore, through a combination of positive-TBLB findings and positive-PCR findings of BFS specimens, we were able to obtain an early and strong indication of MAC disease in 17 of 36 (47%) patients.Using BFS to obtain various kinds of specimens is a useful tool for the early and definite diagnosis of PNTM/pulmonary MAC disease.

New blood test (QuantiFERON-TB-2G: QFT-2G), based on detection of IFN-gamma released by T cells in response to M. tuberculosis specific antigens, has the high sensitivity and specificity for diagnosis of tuberculosis. However, it is essential to evaluate this T cell-based approach in individuals with HIV-associated impairment in T cell immunity.We assessed the usefulness of QFT-2G on diagnosis of tuberculosis in 13 HIV-infected patients with tuberculosis and the performance of 25 HIV infected persons under highly active antiretroviral treatment (HAART). QFT-2G, CD4 counts, and tuberculosis skin test and so on were examined.The sensitivity of QFT-2G in HIV-infected patients with tuberculosis was 76.9%, which was significantly higher compared with tuberculin skin test, 15.4%. There was one indeterminate case of which CD4 count was 16/microl, the lowest count among the all patients. CD4 counts of 25 HIV infected persons under HAART were between 100 and 1157/microl. There were 3 QFT-2G positive cases among them, who had past history of tuberculosis.Although the very low CD4 counts in HIV-infected patients might adversely affect QFT-2G performance, the sensitivity of QFT-2G in the most of HIV-infected patients with tuberculosis was high, and it was thought that it was useful enough to diagnose tuberculosis infection. Careful observation is required in whether the recurrence of tuberculosis takes place among QFT-2G positive persons who have past history of tuberculosis.

The aim of this study is to clarify the features of bronchial tuberculosis.We analyzed the clinicopathological data from 103 out of 4467 (2.3%) cases of culture positive tuberculosis admitted to the National Hospital Organization Tokyo National Hospital in the period from 1993 to 2004 in which bronchial tuberculosis was confirmed by bronchofiberscopy.There were 62 women and 41 men, and 53 cases were less than 50 years old. The most common symptom, namely cough was observed in 70 cases, while 79 cases showed III1 to III2 on roentgenographic examination, and 81 cases were smear-positive for acid-fast bacilli in the sputum. Regarding the bronchofiberscopic findings, ulcers were detected in 60 cases, and the major site of bronchial tuberculosis was in the left main bronchus (35 cases). The number of the cases in which the time span from the onset of symptoms to diagnosis took over 3 months was 29, and 26 of them were "doctor's delay" cases which had a history of medical consultation resulting in diagnosis and treatment of other diseases, such as bronchial asthma (7 cases). There were 41 cases in which the second bronchofiberscopic findings have been reviewed, and regardless of the length of the span from the onset to diagnosis, the first bronchofiberscopy mostly revealed ulcer within 1 month after the start of treatment for tuberculosis, and 3 months after the start of treatment, many patients developed fibrous scars. Between 1999 to 2004, the first bronchofiberscopies were usually performed within 2 weeks to 1 month after the start of the treatment in contrast to the cases admitted between 1993 to 1998 in which bronchofribroscopy was mainly performed before the start of the treatment. However, there were no differences in the findings due to the timing of bronchofiberscopy.The clinical characteristics of bronchial tuberculosis have not changed, and the delay of diagnosis of bronchial tuberculosis due to doctor's delay also continues to be an important issue today. In patients showing positive sputum smear for mycobacteria, the timing of bronchofiberscopy, although required upon medical examination, is considered to be more appropriately performed from 2 weeks to 1 month after the start of treatment from the view point of nosocomial tuberculosis infection control strategy.

In the treatment of tuberculosis with rifampicin in patients treated with prednisolone and cyclosporine, we have to increase the dosage of these drugs. Although prednisolone dosage is recommended to be doubled, there is no established consensus about cyclosporine dosage. Our aim is to review the current situation at our institution regarding the dosage of cyclosporine administered to tuberculous patients after the addition of rifampicin to the treatment regimen.We reviewed patients' clinical status and how dosages of cyclosporine were altered during a course of tuberculosis treatment including rifampicin in 4 patients (2 interstitial pneumonitis, 2 collagen vascular disease) who were being treated with cyclosporine between 2001 and 2003. Prednisolone had been also administrated in all patients and the dosage was doubled from the beginning of the treatment. The appropriate dosage of cyclosporine was found to be 2.5-3.5 (average 3) times that of initial dosage, and it required 5-12 weeks (average 8.3) measurements of trough levels and 6-27 (average 12) weeks until appropriate trough levels were obtained.The appropriate dosage of cyclosporine was found to be approximately 3 times that of the initial dosage in all patients, but it required a long-term and frequent measurements of trough levels before reaching this goal. It seems that trebling the dosage of cyclosporine from the start of anti-tuberculosis chemotherapy will be an efficient way to achieve good clinical outcome.

To study the characteristics of bone or joint tuberculosis (TB) accompanied by TB in other organs (especially the lung), and to study patients' and doctors' delay in detecting bone or joint TB.A retrospective study was conducted on 33 patients with bone or joint TB concurrent with TB of other organs, especially the lung, who were admitted to our hospital between 1981 and 2005. The patients were divided into the following three groups according to the organ of concurrent TB : (1) miliary TB group (N = 10), (2) pulmonary TB group (N = 19), and (3) other TB site group (N = 4). The relationship between bone/joint TB and TB of other organs was studied by comparing the three groups with respect to the time of appearance of musculo-skeletal symptoms or signs such as swelling and pain and that of symptoms or signs originating from other organs, such as cough, sputum, miliary pattern on chest radiograph and superficial lymph node swelling.The mean age (SD) of patients was 50.5 (18.9) yr, and the male to female ratio was 23 : 10. Among 33 patients, bone TB (including 18 spinal TB) was detected in 24 patients, joint TB in 14, and abscess in 3 (concurrent lesions in some patients). The mean intervals from onset of symptoms to consultation (patients' delay), from consultation to diagnosis (doctors' delay) and from symptom onset to diagnosis (total delay) were 5.5 (13.9), 3.4 (5.2) and 8.9 (13.9) months, respectively. (1) Bone/joint TB concurrent with miliary TB (N = 10) In 8 patients with mean age of 61.0 (17.4) yr, musculo-skeletal symptoms/signs preceded respiratory symptoms or appearance of miliary pattern on chest radiograph by 7.8 (7.2) (range; 1-24) months. The patients', doctors' and total delays were 0.4 (0.5), 7.3 (7.8), and 7.7 (7.6) months, respectively. In most cases, bone/joint TB was diagnosed after the onset of miliary pattern on chest radiograph. In one patient with simultaneous onset of musculo-skeletal and respiratory symptoms/signs (age 21 yr), the interval of total delay was 1 month, and in one patient with musculoskeletal symptoms which appeared six months later than respiratory symptoms (age 28 yr), the interval of total delay was 2 months. (2) Bone/joint TB concurrent with active pulmonary TB (N = 19). In this group, the mean age was 52.2 (17.1) yr, and males were predominant (M/F = 15/4). Active pulmonary TB was diagnosed by positive sputum culture in 13 patients, by positive sputum smear or PCR results in 4 patients, and by the clinical course in 2 patients. Ten patients (53%) had a previous TB history. Cavitary lesion was observed in 15 patients, and the upper lobes were predominantly involved on chest radiograph in 19 patients, indicating that the pulmonary TB was probably post-primary (reactivation) in all patients. In 9 patients with mean age of 49.7 (15.7) yr, musculo-skeletal symptoms/signs preceded respiratory symptoms by 14.1 (14.0) (range; 4-48) months. The patients', doctors' and total delays were 13.3 (17.8), 3.8 (6.6), and 17.1 (16.1) months, respectively. On the other hand, in 10 patients with mean age of 54.5 (18.7) yr, musculo-skeletal symptoms/signs and respiratory symptoms/signs appeared simultaneously, and the total delay was 2.7 (1.9) months. Twelve of 19 patients (63%) had complications such as diabetes mellitus, steroid use, and liver diseases. In cases with miliary or pulmonary tuberculosis, the total delay in diagnosis (Y) correlates positively with the time lag from onset of musculo-skeletal symptoms to respiratory symptoms/signs (X), and the regression line (Y = 0.94X + 2.3, r = 0.98, p0.001) was almost linear (Y = X), indicating that the diagnosis of bone/joint TB was made just after the diagnosis of miliary or pulmonary TB. (3) Bone/joint TB concurrent with TB of other sites (N = 4) In 2 female cases (21 and 28 yrs) with cervical lymph node TB, musculo-skeletal symptoms/signs and cervical lymph node swelling appeared simultaneously. In a 54-yr male patient, musculo-skeletal symptoms/signs appeared 5 years after appearance of testicular enlargement, and testicular TB was diagnosed by biopsy simultaneously. In a 33 year-old male patient, musculo-skeletal symptoms/signs appeared 7 months after the drainage of pleural and pericardial effusions (TB was not diagnosed initially), and then the diagnosis of bone/joint, pleural, and pericardial tuberculosis was made for the first time.In middle-aged or elderly patients with active bone/joint TB, miliary TB is sometimes caused by bacillemia originating from the infected bone/joint lesions. In cases with bone/joint TB and concurrent pulmonary TB, bone/joint TB and pulmonary TB are probably reactivated independently as a result of decreased systemic immunocompetence.