[A DRG/PPS simulation in the medical care of tuberculosis].

PURPOSE: To study the expected usefulness of the introduction of the DRG-PPS (Diagnosis-Related Group/Prospective Payment System, in which an insurer pays a fixed medical fee per hospitalization) into the current medical care of tuberculosis (TB) in Japan. METHOD: The medical fees were reviewed for all TB inpatients at 19 hospitals under the National Hospital Organization who were discharged in either June 2007 or February 2008. The sum of the fixed fee by the DRG was assumed based on the bivariate regression analysis of each patient's hospital days and his or her total actual fees during the hospital stay under the current (fee for care) system, since it was difficult to directly calculate the daily fees for every patient that would be the basis of DRG-PPS. RESULTS: Linear regression analysis estimated that the medical fees (including fees for the medical examinations and the treatments) for a hospital stay of 60 days, which is the standard for TB treatment, was 1,192,470 yen (19,870 yen per person per day) in June 2007, and 1,167,600 yen (19,460 yen per person per day) in February 2008. DISCUSSION: If we assume an average medical fee of about Y1.1-1.2 million yen for the standard hospital care of TB, the economic balance of the hospitals is negative, with a deficit of 0.6-0.7 million yen, given the estimated expenses of 1.8 million yen (i.e., 30,000 yen per person per day x 60 days). CONCLUSION: If the DRG-PPS is to be implemented based on the current medical fee rating system, the hospital administrators could not accept its introduction to the TB medical care service as it is, because it may undermine the economic management of hospitals.

[Clinical analysis of drug interaction between rifampicin and clarithromycin which are used for treating pulmonary Mycobacterium avium complex infection].

PURPOSE: We reviewed the interaction between rifampicin (RFP) and clarithromycin (CAM) during treatment of pulmonary Mycobacterium avium complex infection. SUBJECTS AND METHODS: The subjects were patients with pulmonary non-tuberculous acid-fast bacillus infection during the period from September 2004 to January 2006 who consented to this study. Drug blood concentrations were compared with the minimum inhibitory concentrations for M. avium isolated from sputum and blood levels of CAM were assessed when the time of administration was changed for RFP. RESULTS: The blood concentration of CAM showed a marked decrease in all cases (n = 6) when administered together with RFP, but there was no significant difference in the blood concentration of 14-R-hydroxy-clarithromycin (M-5), the active metabolite of CAM. However, the total blood concentration of CAM and M-5 showed a significant fall, similar to the blood concentration of CAM alone. When the blood concentration and bacterial MIC were compared for RFP, the blood concentration exceeded five MIC(s) in six samples as did the CAM+M-5 level in four out of six samples. There was no significant difference in the blood concentration of CAM (n = 5) when the time of RFP administration was altered. CONCLUSION; Because the total blood concentration of CAM+M-5 fell markedly by co-administration of RFP, this might have an influence on the antibacterial effect of CAM. In addition, examination of the administration of RFP and CAM at different times showed that the blood concentration of CAM did not increase and the influence of induction of hepatic drug-metabolizing enzymes by RFP could not be avoided.

[Comparative study of bactec MGIT 960 AST and conventional proportion method using Ogawa medium for the drug susceptibility testing of Mycobacterium tuberculosis to isoniazid].

OBJECTIVE: To evaluate the accuracy of drug susceptibility testing to isoniazid with BACTEC MGIT 960 (MGIT AST) comparing with the standard proportion method using Ogawa medium. METHOD: A total of 1109 M. tuberculosis strains, which were selected from the collection of RYOKEN drug resistance survey in 2002, were selected and subjected to the susceptibility testing to isoniazid using MGIT AST and 1% Ogawa standard methods. The results from MGIT AST were compared with the judicial diagnosis by Ogawa. The sensitivity to detect drug resistance, the specificity for susceptible strain, the efficiency of overall agreement, and kappa coefficient were calculated to evaluate the performance. The treatment process, outcome and prognosis were analysed for the patients on whom the tests showed discrepant results. RESULTS: Compared with the judicial results, the sensitivity, specificity, efficiency, and kappa coefficient of MGIT AST were 100%, 97.1%, 97.3%, and 0.798, respectively. The strains, which showed discrepant results between MGIT AST and Ogawa, were all susceptible by Ogawa and resistant by MGIT AST. A total of 11 out of 30 discrepant cases were followed clinically and no relapse cases were identified, irrespective of the modification of the treatment regimen. As for the proportion of primary INH drug resistance in the present study, it was 5.3% with MGIT AST but was 2.7% with Ogawa, and the difference was statistically significant (p = 0.005). DISCUSSION: The discrepancies on the results of drug susceptibility testing of M. tuberculosis strains to isoniazid between MGIT AST and 1% Ogawa proportion method have been reported. In the present study, the sensitivity, specificity, and overall efficiency of MGIT AST on the prevalent strains in Japan were all beyond 95%, and considered sufficient as the anti-tuberculosis drug susceptibility testing (AST), though 2.7% of discrepancy was observed. Even for the discrepant cases, there was no difference in the treatment outcome and prognosis. Thus, MGIT AST was confirmed as a reliable AST method comparable to Ogawa standard. However, MGIT AST might increase the proportion of INH resistance if it was used as a major AST method, compared with Ogawa.

[The clinical study on efficacy of clarithromycin, levofloxacin, and streptomycin for pulmonary Mycobacterium avium-intracellulare complex infection].

OBJECTIVE: The purpose of this study was to elucidate retrospectively the clinical effects of using RFP, EB, CAM, LVFX, and SM for pulmonary Mycobacterium avium-intracellulare complex infection. MATERIALS AND METHODS: During 9-year (1995-2003) period, 72 patients diagnosed according to the criteria of the Japanese Society for Tuberculosis Guidelines and treated for at least 6 months were available for this study. RESULTS: The age averaged 68 (range, 32-92) years. The male to female ratio was approximately 2 : 3. The follow-up period averaged 344 (190-365) days. 59 of 72 patients were treated for the first time. 58 of 72 patients were diagnosed as primary infection type. Among them, 20, 38, and 14 patients were treated by RFP, EB, and CAM (REC group), RFP, EB, CAM and LVFX (LVFX group), and RFP, EB, CAM, and SM (SM group), respectively. Comparing the baseline patient characteristics among three groups, we found significant difference (measured by ANOVA) in gender (male/female, REC group: 8/12, LVFX group: 20/18, and SM group: 2/12, p < 0.05), age (REC group: 75.2 +/- 9.1, LVFX group : 66.5 +/- 12.5, and SM group: 63.9 +/- 11.9, p < 0.01) and body mass index (REC group: 17.2 +/- 2.9, LVFX group: 18.9 +/- 2.8, and SM group: 19.7 +/- 2.4, p < 0.05). However, we did not find any significant difference in the clinical outcomes (improving rate of the symptoms, change of the erythrocyte sedimentation rate, improving rate of the chest X-ray, and the results of follow-up on bacteriological effect). In the 60 of 72 patients treated for 1 year, the results were superior to those of some previous reports (1-year improving rate of the symptoms, 1-year improving rate of the chest X-ray, 1-year improving rate of the sputum conversion, and 1-year rate of the relapse were 54.3%, 65.0%, 60.0%, and 15.3%, respectively). CONCLUSION: Further study was warranted that no advantage was shown by an additional use of LVFX or SM on REC from the point of view of the clinical effects for pulmonary Mycobacterium avium-intracellulare complex infection, in spite of the higher age and deteriorated nutritional status of REC group.

[A case of pulmonary tuberculosis complicated with tuberculosis of bilateral cervical lymph nodes and exacerbated pericostal abscess].

A 23-year-old man was admitted to our hospital because of cough and sputum in April 2001. A chest roentgenogram revealed infiltrative shadow with cavity formation in the bilateral lung fields. He was treated with sensitive antituberculous drugs. After starting the antituberculous therapy with INH, RFP, EB and PZA, bilateral cervical lymphadenopathy developed. Three months later, pericostal abscess appeared in the left anterior chest wall. Microscopic examination of the specimen obtained by needle aspiration biopsy disclosed positive for acid-fast bacilli. Smears of the pus showed acidfast bacilli identified as Mycobacterium tuberculosis by DNA-DNA PCR method. He developed tuberculous bilateral cervical lymphadenopathy and pericostal abscess during the course of antituberculosis chemotherapy. Drug sensitivity test revealed that tubercle bacilli in this case were sensitive. One year after the administration of chemotherapy, cervical lymphadenopathy and pericostal abscess were improved. Both masses were discontinuous with pulmonary tuberculosis and the possibility of lymphogenous spread of organism was speculated as its etiology. We assumed that both masses were due to paradoxical response to the antituberculosis chemotherapy.

[A case of multidrug-resistant tuberculosis (MDR-TB) in young female complicated with acute respiratory distress syndrome and developing multiple giant cysts and pneumothorax in both lung].

A 20-year-old woman was admitted to our hospital because of cough and dyspnea in April 2001. On admission, laboratory data showed positive inflammatory signs. A chest roentogenogram revealed infiltrated shadow in the bilateral lung fields. Sputum smear examination showed acid-fast bacilli identified as Mycobacterium tuberculosis by DNA-DNA PCR method. Four days after admission, she had an acute respiratory distress syndrome (ARDS) and serious liver dysfunction. Moreover, drug sensitivity test revealed that this case was multidrug-resistant tuberculosis (MDR-TB), and she was treated with sensitive anti-tuberculous drugs (PZA, SM, LVFX). Three months later, her sputa converted to negative for tubercle bacillis, however, a chest computed tomogram (CT) revealed multiple giant cysts in the bilateral lung fields, which developed during treatment. Pneumothorax of both sides was repeatedly observed, and it was difficult to treat. At present (1 year after admission), multiple giant cysts stopped its progression and treatment for tuberculosis is being continued.

Evaluation of a commercially available serologic assay for antibodies against tuberculosis-associated glycolipid antigen.

A commercially available enzyme immunoassay developed to detect antibodies to a tuberculosis-associated glycolipid antigen was evaluated for serologic diagnosis of tuberculosis. This was a multicenter study comparing the assay with other methods in 78 patients with active pulmonary tuberculosis and in 54 controls with non-tuberculous lung diseases. Sensitivities were highest for sputum culture (91.0%), followed by immunoassay (79.5%), nucleic acid amplification (77.3%), and finally acid-fast staining of sputum smear (60.3%). Immunoassay and amplification, both rapid methods, had similarly high sensitivity in smear-positive subjects (89.4 and 88.9%, respectively); in smear-negative subjects these two techniques showed low sensitivity (64.5 and 60.0%, respectively). Concordance between the two methods was relatively low (72.0%). With regard to specificity, seven out of ten patients with old tuberculosis had positive result by immunoassay (30% specificity). In the control group, 10 out of 54 patients had positive immunoassay result (72.2% specificity), with notably limited specificity in the elderly. The tuberculous glycolipid assay is a rapid method sufficiently sensitive for detection of tuberculosis infection, even in smear-negative patients.