Negative Conversion Of Sputum Culture Research Articles

Treatment outcomes and relapse in patients with Mycobacterium avium-intracellulare complex pulmonary disease.

The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. This retrospective study was conducted in Taiwan between 2011 and 2020. A microbiological cure was defined as the requirement for a minimum of three consecutive negative cultures following culture conversion that continued until the completion of anti-MAC treatment. A total of 97 patients with MAC-PD were enrolled in this study. The sputum smear-negative conversion rate was 40% (19/47). Thirty (31%) patients achieved sputum culture-negative conversion rates within 3 years after treatment initiation. All patients with negative sputum culture conversion rates achieved microbiological cure. Patients treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than the other patients (39% vs 17%, P = 0.023). Patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate than those with negative sputum smears (6% vs 44%, P < 0.001). Among 30 patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 (0-483) days, and the 1-year relapse rate was 17%. Treatment with the M + R + EMB-based regimen was associated with a higher microbiological cure rate, and patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate. IMPORTANCE The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. In this study, patients with MAC-PD treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than those treated with other regimens. After 6 months of treatment, patients with persistently positive sputum smears had a lower microbiological cure rate than those with negative sputum smears. Among patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 days (range, 0-483), and the 1-year relapse rate was 17%.

Factors associated with adverse drug reactions or death in very elderly hospitalized patients with pulmonary tuberculosis

The aging of patients with tuberculosis and better therapeutic management for them are recent concerns. This study aimed to identify risk factors for adverse drug reactions (ADRs) or death in very elderly patients with pulmonary tuberculosis and to assess the association between the dosage of antituberculosis drugs and outcomes. We conducted a multicenter retrospective study at two hospitals. Hospitalized patients (≥ 80 years old) with pulmonary tuberculosis who were treated with antituberculosis drugs were enrolled. Multivariate analysis was performed to assess factors associated with ADRs or death within 60 days after treatment initiation. In total, 632 patients were included. The primary endpoint occurred in 268 patients (190 ADRs and 78 deaths). A serum albumin level < 2.5 g/dL, respiratory failure, and dependent activities of daily living were independent risk factors for ADRs or death. However, a low dosage (< 8 mg/kg/day) of rifampicin was associated with a lower risk of the primary outcomes. Delayed time to negative sputum culture conversion was not observed in the lower dosage of rifampicin group. Very elderly hospitalized tuberculosis patients with the aforementioned risk factors should be carefully monitored to receive safer treatment. Rifampicin dosage reduction may be considered for very elderly tuberculosis patients to prevent ADRs/death.

Treatment shortening of drug-sensitive pulmonary tuberculosis using high-dose rifampicin for 3 months after culture conversion (Hi-DoRi-3): a study protocol for an open-label randomized clinical trial

BackgroundThe standard treatment regimen for drug-sensitive tuberculosis (TB), comprising four companion drugs, requires a minimum duration of 6 months, and this lengthy treatment leads to poor adherence and increased toxicity. To improve rates of adherence, reduce adverse events, and lower costs, a simplified and shortened treatment regimen is warranted.MethodsThis study is a multicenter, open-label randomized clinical trial of non-inferiority design that compares a new regimen with the conventional regimen for drug-sensitive pulmonary TB. The investigational group will use a regimen of high-dose rifampicin (30 mg/kg/day) with isoniazid and pyrazinamide, and the treatment will be maintained for 12 weeks after the achievement of negative conversion of sputum culture. The control group will be treated for 6 months with a World Health Organization-endorsed regimen consisting of isoniazid, rifampicin (10 mg/kg/day), ethambutol, and pyrazinamide. The primary endpoint is the proportion of unfavorable outcomes at 18 months after randomization. Secondary outcomes include time to unfavorable treatment outcome, time to culture conversion on liquid medium, treatment success rate at the end of treatment, proportion of recurrence at 18 months after randomization, time to recurrence after treatment completion, and adverse events of grade 3 or higher during the treatment. We predict a 10% unfavorable outcome for the control group, and 0% difference from the investigational group. Based on 80% verification power and a 2.5% one-sided significance level for a non-inferiority margin of 6%, 393 participants per group are required. Considering the 15% dropout rate, a total of 926 participants (463 in each group) will be recruited.DiscussionThis study will inform on the feasibility of the treatment regimen using high-dose rifampicin with a shortened and individualized treatment duration for pulmonary TB.Trial registrationClinicalTrials.gov NCT04485156. Registered on July 24, 2020.

The New Frontier of Host-Directed Therapies for Mycobacterium avium Complex.

Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In order to address similar challenges facing the management of patients with tuberculosis, recent attention has focused on the development of novel adjunctive, host-directed therapies (HDTs), with the goal of accelerating the clearance of mycobacteria by immune defenses and reducing or reversing mycobacterial-induced lung damage. In this review, we will summarize the evidence supporting specific adjunctive, HDTs for MAC, with a focus on the repurposing of existing immune-modulatory agents targeting a variety of different cellular pathways. We also highlight areas meriting further investigation.

Resumption/efficacy and safety of an azithromycin-containing regimen against Mycobacterium avium complex lung disease in patients who experienced adverse effects with a clarithromycin-containing regimen.

Antibiotic therapy, including clarithromycin (CLR), has been widely used for the management of Mycobacterium avium complex (MAC) lung disease in clinical settings. When patients develop adverse events (AEs) during CLR-based treatment, the treatment regimen is modified or chemotherapy itself is discontinued. The need for alternative macrolide treatment strategies is emphasized due to the high rate of AEs possibly caused by CLR. Thus, the current study aimed to examine the efficacy and safety of azithromycin (AZM) in patients with MAC lung disease whose treatment was switched from CLR to AZM. We performed a retrospective study of patients with MAC lung disease. The inclusion criteria were as follows: (1) patients who experienced AEs during treatment with antibiotics, including CLR, between December 2012 and November 2017, and (2) those who had antimicrobial therapy that was switched from CLR to AZM. The efficacy and safety of AZM during the clinical course of the disease after switching the regimen from CLR to AZM were investigated. Antibiotic therapy was switched in 31 patients who presented with AEs including drug-induced fever, rash, dysgeusia, liver dysfunction, and neutropenia during treatment with CLR-containing regimens. After switching to AZM, the median duration of treatment was 1286 (364-4615) days. During follow-up, 13 patients had a negative conversion of sputum culture. AZM may be safe and effective for patients with MAC lung disease who have difficulty tolerating CLR. In patients who experienced AEs possibly caused by CLR, switching from CLR to AZM might be an appropriate strategy.

Minimal Inhibitory Concentration of Clofazimine Among Clinical Isolates of Nontuberculous Mycobacteria and Its Impact on Treatment Outcome

Clofazimine has been regarded as a promising agent for the treatment of nontuberculous mycobacteria pulmonary disease (NTM-PD). However, its overall effectiveness invitro and in the clinic remains unknown. What is the minimal inhibitory concentration (MIC) of clofazimine in clinical isolates and the association between MICs and treatment outcome? MICs for clofazimine were measured in clinical isolates from NTM-PD patients who participated in a prospective study at Seoul National University Hospital. The MIC was determined by using the broth microdilution concentration method. Correlation between MIC and conversion to negative of sputum culture with clofazimine was determined. Of a total 189 isolates, 133 strains were Mycobacterium avium complex (MAC) and 40 strains were M abscessus. Although the clofazimine MICs for MAC ranged from 0.031mg/L to 8mg/L, the values obtained for M abscessus ranged from 0.031mg/L to 16mg/L. Of 20 patients who were treated with a regimen including clofazimine, eight achieved negative conversion of sputum culture. All patients with isolates exhibiting clofazimine MIC values≤ 0.25mg/L achieved culture conversion. The likelihood of culture conversion in patients with MIC value≤ 0.25mg/L was much higher than that of patients with MIC value > 0.5mg/L (OR, 39.3; P= .021). The MICs of clofazimine varied widely in clinical isolates from patients with NTM-PD. Negative conversion of sputum culture with clofazimine use was associated with a lower MIC value. Clofazimine use could be considered in patients with NTM-PD when the MIC value is≤ 0.25mg/L. ClinicalTrials.gov; No.: NCT01616745; URL: www.clinicaltrials.gov.

Serum Krebs von den Lungen-6 level in the disease progression and treatment of Mycobacterium avium complex lung disease.

The lack of useful biomarkers reflecting the disease state limits the management of Mycobacterium avium complex lung disease (MAC-LD). We clarified the associations between serum KL-6 level, disease progression and treatment response. Resected lung tissues from MAC-LD patients were immunostained for KL-6. We compared serum KL-6 levels between MAC-LD and healthy control or bronchiectasis patients without nontuberculous mycobacterial lung disease (NTM-LD). Serum KL-6 level was assessed in a prospective observational study at Keio University Hospital between May 2012 and May 2016. We investigated associations between serum KL-6 level and disease progression and treatment response in patients untreated for MAC-LD on registration (n = 187). The KL-6+ alveolar type 2 cell population in the lung and serum KL-6 level were significantly higher in MAC-LD patients than in controls. Serum KL-6 level in bronchiectasis patients without NTM-LD showed no significant increase. Of the 187 patients who did not receive treatment on registration, 53 experienced disease progression requiring treatment. Multivariable Cox analysis revealed that the serum KL-6 level (aHR: 1.18, P = 0.005), positive acid-fast bacilli smear (aHR: 2.64, P = 0.001) and cavitary lesions (aHR: 3.01, P < 0.001) were significantly associated with disease progression. The change in serum KL-6 (ΔKL-6) was significantly higher in the disease progression group; it decreased post-treatment, reflecting the negative sputum culture conversion. Serum KL-6 level is associated with disease progression and treatment response. Longitudinal assessment combined with AFB smear status and presence of cavitary lesions may aid MAC-LD management.

The impact of adjuvant surgical treatment of nontuberculous mycobacterial pulmonary disease on prognosis and outcome

BackgroundLung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has been reported to be associated with favorable outcomes. However, little is known regarding the risk and prognostic factors for refractory and recurrent cases. We aimed to evaluate the overall impact and benefit of adjuvant lung surgery by comparing NTM-PD patients who underwent adjuvant lung resection with those treated exclusively with antibiotics. We also investigated the efficacy of serum IgA antibody against glycopeptidolipid (GPL) core antigen (GPL core antibody) to monitor disease activity and predict the recurrence of disease after adjuvant lung resection.MethodsWe retrospectively evaluated the clinical characteristics and surgical outcomes of 35 patients surgically treated for NTM-PD. Furthermore, we compared surgically treated patients and control patients treated exclusively with antibiotics who were matched statistically 1:1 using a propensity score calculated from age, sex, body mass index, and radiologic features of disease.ResultsIn the surgically treated patients, the median age was 58 (interquartile range, 47–65) years and 65.7% were female. Twenty-eight patients had Mycobacterium avium complex. Operations comprised four pneumonectomies, two bilobectomies, one bilobectomy plus segmentectomy, 17 lobectomies, two segmentectomies, and nine lobectomies plus segmentectomies. Postoperative complications occurred in seven patients (20%), there were no operative deaths, and 33 (94.3%) patients achieved negative sputum culture conversion. Refractory and recurrent cases were associated with remnant bronchiectasis, contralateral shadows, and positive acid-fast bacilli staining or culture. Of 28 statistically matched pairs, long-term sustained negative culture conversion was observed in 23 (82.2%) surgical group patients and in 14 (50.0%) non-surgical group patients (0.0438). The mortality rate was lower in the surgical group, but did not reach statistical significance (one in the surgical group and four in the non-surgical group, p = 0.3516). GPL core antibody was correlated with disease activity and recurrence.ConclusionsNTM-PD patients who underwent adjuvant lung resection experienced overall favorable outcomes and achieved sputum culture conversion more frequently. Long-term mortality may have been reduced by this procedure, and the level of GPL core antibody was shown to be a good clinical indicator of disease activity after surgery.

Early treatment outcome of bedaquiline plus optimised background regimen in drug resistant tuberculosis patients

AimsBedaquiline (BDQ) has been recently approved for drug resistant tuberculosis with active drug safety monitoring under programmatic condition. The present study was conducted to evaluate safety, tolerability and efficacy of bedaquiline plus optimised background regimen. MethodsA prospective study was conducted on cohort of pre-extensively drug resistant (XDR) and XDR pulmonary TB patients. Eligible patients were closely monitored for cardiac safety, adverse events (AEs), clinical and microbiological improvement during BDQ (6 months) and post BDQ phase for twelve months. ResultsOf 127 patients enrolled, a significant increase in mean QTc interval was observed on 13th day and 3rd week as compared to baseline (p < 0.0001). Mean maximum increase of QTc was 37.92ms (95% CI, 14.1–61.74ms). Concomitant anti-TB medications, age, gender, low body mass index (BMI) had significant effect on QTc prolongation (p < 0.0001, p < 0.05). However, none of the patient required discontinuation of BDQ. Majority of AEs (86.3%) were non-serious and not preventable 108 (87.1%). The median time for sputum-culture conversion was 40.89 ± 3.5 days (95% CI, 34–48 days) and the treatment outcome was successful in 102 (80.3%) patients with negative sputum culture conversion. ConclusionsBedaquiline containing regimen achieved favourable outcome. Although, bedaquiline along with concomitant anti-TB medications has the potential to prolong QTc interval, the benefit certainly outweighs the risk. This calls for a through pre-treatment cardiovascular and biochemical evaluation as a preventive measure and appropriate selection of patients for safe use of BDQ and successful outcome.

Multidrug-resistant tuberculosis in South Korea: a retrospective analysis of national registry data in 2011-2015.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) poses a threat to public health as a result of high treatment costs and unsatisfactory outcomes.OBJECTIVE: To elucidate trend, demographic and clinical characteristics and treatment outcomes of patients with MDR-TB between 2011 and 2015 in South Korea.METHOD: Data of patients with MDR-TB diagnosed between 1 January 2011 and 31 December 2015 were retrieved from the nationwide Internet-based TB notification system and analysed retrospectively.RESULTS: During the study period, 5192 MDR-TB patients were notified. We identified an increasing number of MDR-TB patients among foreign populations (from 1.3% to 7.7%), decreasing resistance rates to other anti-TB drugs (e.g., resistance to pyrazinamide, from 40.9% to 28.2%), a decreasing interval from treatment initiation to negative conversion of sputum culture (from 165.7 to 103.7 days) and shortening of treatment duration (719.7 to 613.2 days). However, treatment success rates did not change, and had an average of 65.7%.CONCLUSION: Despite decreasing resistance rates to other drugs and faster treatment responses, treatment outcomes did not improve during the study period. Strict management of MDR-TB patients on treatment should be adopted to improve treatment outcomes.

Sitafloxacin-Containing Regimen for the Treatment of Refractory Mycobacterium avium Complex Lung Disease.

BackgroundSitafloxacin (STFX) exhibits potent activity against Mycobacterium avium complex (MAC) in both in vitro and in vivo experiments. However, limited data are available for the clinical efficacy and adverse effects of STFX and the susceptibility of refractory MAC lung disease (MAC-LD) to the drug. Therefore, this study was aimed at evaluating the clinical efficacy and safety of an STFX-containing regimen for the treatment of refractory MAC-LD.MethodsWe retrospectively evaluated treatment outcomes of 31 patients with refractory MAC-LD, who received an STFX-containing regimen for ≥4 weeks between January 2010 and July 2017. Refractory MAC-LD was defined as persistent positive sputum cultures for >6 months of macrolide-based standard therapy.ResultsClarithromycin resistance (minimum inhibitory concentration [MIC] ≥32 μg/mL) was identified in 15 patients (48%). Twelve months after receiving the STFX-containing regimen, 26% and 19% of patients showed symptomatic and radiological responses, respectively. Although STFX-associated adverse effects were noted in 9 patients, their severity was grade 1 (National Cancer Institute Common Terminology Criteria); only 1 patient discontinued STFX because of suspected gastrointestinal disturbance. Negative sputum culture conversion was achieved in 7 patients (23%). Both univariate and multivariate logistic regression analyses revealed that surgery, low STFX MIC (≤1 μg/mL), and macrolide resistance were significant predictors of negative sputum culture conversion.ConclusionsOur results demonstrate that STFX may be effective in one-fourth of patients with refractory MAC-LD. Prospective larger studies that include the analyses of MAC are needed to determine the clinical efficacy of STFX against refractory MAC-LD.

Treatment of Mycobacterium avium Complex Pulmonary Disease.

The pathogen Mycobacterium avium complex (MAC) is the most common cause of nontuberculous mycobacterial pulmonary disease worldwide. The decision to initiate long-term antibiotic treatment is difficult for the physician due to inconsistent disease progression and adverse effects associated with the antibiotic treatment. The prognostic factors for the progression of MAC pulmonary disease are low body mass index, poor nutritional status, presence of cavitary lesion(s), extensive disease, and a positive acid-fast bacilli smear. A regimen consisting of macrolides (clarithromycin or azithromycin) with rifampin and ethambutol has been recommended; this regimen significantly improves the treatment of MAC pulmonary disease and should be maintained for at least 12 months after negative sputum culture conversion. However, the rates of default and disease recurrence after treatment completion are still high. Moreover, treatment failure or macrolide resistance can occur, although in some refractory cases, surgical lung resection can improve treatment outcomes. However, surgical resection should be carefully performed in a well-equipped center and be based on a rigorous risk-benefit analysis in a multidisciplinary setting. New therapies, including clofazimine, inhaled amikacin, and bedaquiline, have shown promising results for the treatment of MAC pulmonary disease, especially in patients with treatment failure or macrolide-resistant MAC pulmonary disease. However, further evidence of the efficacy and safety of these new treatment regimens is needed. Also, a new consensus is needed for treatment outcome definitions as widespread use of these definitions could increase the quality of evidence for the treatment of MAC pulmonary disease.

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Assessing Treatment Response of Pulmonary Multidrug-Resistant Tuberculosis.

Background: The purpose of this prospective study was to evaluate the role of 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) for assessing treatment response in patients with pulmonary multidrug-resistant tuberculosis (MDR-TB). Methods: The study subjects were four patients diagnosed with pulmonary MDR-TB who underwent MDR-TB treatment and serial 18F-FDG PET/CT at baseline and 6 and 12 months after treatment. The highest lung maximum standardized uptake value (SUVmax), average SUVmean (average of all hypermetabolic parenchymal lesions), total metabolic lung volume (TMLV, sum of metabolic volumes from the hypermetabolic parenchymal lesions), and total lung glycolysis (TLG, sum of lesion glycolysis from the hypermetabolic parenchymal lesions) were determined as representative quantitative PET parameters for each patient. Results: All patients except one had negative sputum culture conversion after one month of treatment and achieved successful treatment outcomes. Baseline TMLV and TLG PET parameters were much higher in the single patient with treatment failure than in the remaining three patients with treatment success. No other PET parameters at baseline or follow-up were associated with the treatment results. Conclusions: Pretreatment volume-based 18F-FDG PET/CT lung parameters were associated with the final therapeutic response in patients with pulmonary MDR-TB. Our preliminary results warrant a larger study.

Oral Macrolide Therapy Following Short-term Combination Antibiotic Treatment of Mycobacterium massiliense Lung Disease

Although Mycobacterium massiliense lung disease is increasing in patients with cystic fibrosis and non-cystic fibrosis bronchiectasis, optimal treatment regimens remain largely unknown. This study aimed to evaluate the efficacy of oral macrolide therapy after an initial 2-week course of combination antibiotics for the treatment of M massiliense lung disease. Seventy-one patients received oral macrolides, along with an initial 4-week (n=28) or 2-week (n= 43) IV amikacin and cefoxitin (or imipenem) treatment. These patients were treated for 24months (4-week IV group) or for at least 12months after negative sputum culture conversion (2-week IV group). Total treatment duration was longer in the 4-week IV group (median, 23.9months) than in the 2-week IV group (15.2months; P< .001). The response rates after 12months of treatment were 89%for symptoms, 79%for CT scanning, and 100%for negative sputum culture results in the 4-week IV group. In the 2-week IV group, these values were 100%(P=.057), 91%(P= .177), and 91%(P= .147), respectively. Acquired macrolide resistance developed in two patients in the 2-week IV group. Genotyping analyses of isolates from patients who did not achieve negative sputum culture conversion during treatment and from those with positive culture results after successful treatment completion revealed that most episodes were due to reinfection with different genotypes of M massiliense. Oral macrolide therapy after an initial 2-week course of combination antibiotics might be effective in most patients with M massiliense lung disease. ClinicalTrials.gov; No.: NCT00970801; URL: www.clinicaltrials.gov.

Effect of drug resistance on negative conversion of sputum culture in patients with pulmonary tuberculosis.

Negative conversion of sputum culture is a useful marker for predicting treatment outcome and relapse of pulmonary tuberculosis (TB). The effect of drug resistance on negative conversion of sputum culture with treatment was evaluated in this study. A total of 535 patients with culture-proven pulmonary TB were classified into three groups: drug-susceptible (DS), other drug-resistant (ODR), and multidrug-resistant/extensively drug-resistant (MDR/XDR). Rates of conversion of sputum culture at 4, 8, and 12 weeks were compared. At 4 weeks of treatment, the conversion rate in the DS group (52.7%) was higher than that in the ODR group (30.8%, p=0.003), but was not different compared with the MDR group (45.7%, p=0.427). At 8 weeks, the conversion rate in the DS group (76.3%) was higher than that in the ODR (63.5%, p=0.042) and MDR groups (60.0%, p=0.031). At 12 weeks, the conversion rate in the DS group (85.9%) tended to be higher than that in the MDR group (74.3%, p=0.062), but was not different from that in the ODR group (84.6%, p=0.796). The pattern of resistance to anti-TB drugs affects culture conversion rates in the early phase of treatment and also prolongs the time to culture conversion.

Mycobacterium abscessus Lung Disease in a Patient with Kartagener Syndrome.

Primary ciliary dyskinesia (PCD) is characterized by the congenital impairment of mucociliary clearance. When accompanied by situs inversus, chronic sinusitis and bronchiectasis, PCD is known as Kartagener syndrome. The main consequence of impaired ciliary function is a reduced mucus clearance from the lungs, and susceptibility to chronic respiratory infections due to opportunistic pathogens, including nontuberculous mycobacteria (NTM). There has been no report of NTM lung disease combined with Kartagener syndrome in Korea. Here, we report an adult patient with Kartagener syndrome complicated with Mycobacterium abscessus lung disease. A 37-year-old female presented to our hospital with chronic cough and sputum. She was ultimately diagnosed with M. abscessus lung disease and Kartagener syndrome. M. abscessus was repeatedly isolated from sputum specimens collected from the patient, despite prolonged antibiotic treatment. The patient's condition improved and negative sputum culture conversion was achieved after sequential bilateral pulmonary resection.

A study on pulmonary tuberculosis retreatment cases

To investigate the factors leading to the retreatment for tuberculosis. Forty-seven retreatment cases with pulmonary tuberculosis, who were discharged from the National Chiba Higashi Hospital from 2000 to 2002. Data on all retreatment cases were studied as to the condition of the original treatment and factors leading to the retreatment. Of the 47 cases, 33 cases received the original treatment in our hospital. Of the 33 cases, 24 cases were relapsed cases and 9 cases were defaulters. Most relapsed cases were male aged 50s and 12 cases (50%) were jobless. As the factors leading to retreatment, the delay in the negative conversion of sputum culture accounted for 11 cases (45.8%) out of 24 cases. No specific factors were found in three cases (12.5%). Among the defaulters, no bias was seen as to age and occupation of cases, but all the cases were male, and they defaulted during the maintenance phase of treatment at the out-patient department. CONSIDERATION: The delay in the negative conversion of sputum culture was the main factor relating to the relapse. Diabetes mellitus (DM) is one of the factors leading to the relapse, but many factors were observed in DM patients. Male cases aged 50s had many factors leading to the relapse. An intensive management for out-patients and involvement of welfare department aiming at the completion of treatment for the socially vulnerable groups might be necessary as the measure to prevent defaulting. The delay in the negative conversion of sputum culture was the main factor leading to relapse, and intensive management for out-patients aiming at the completion of treatment is necessary to prevent the defaulting.

Perspective of pulmonary MAC infection treatment

Chemotherapy of pulmonary MAC (Mycobacterium avium complex) infection has been almost universally agreed with the multidrugs regimen that contains Clarithromycin (CAM), Rifampin (RFP), Ethambtol (EB), and aminoglycoside in case of advanced stage. One of the reason for the multidrugs regimen which is similar to tuberculous chemotherapy is to inhibit the emersion of resistant MAC strain. The other reasons, enhancement of anti microbial activity and response to polyclonal infection are unique to the MAC chemotherapy. In the current MAC chemotherapy, both CAM and aminoglycoside are main axes because only they can suppress the growth of MAC alone respectively. Efficacy of CAM was revealed through the randomized controlled trials of disseminated MAC infection with HIV and that consequences applied to pulmonary MAC infection treatment. CAM is not effective unless exceed 2 microg/ml blood concentration. RFP decreases CAM blood concentration remarkably, but the regimens contained RFP and CAM are superior clinically to the regimens without RFP. There seemed to be unknown pharmacological mechanisms with RFP. Although the advantage of aminoglycosides is easily achieved high blood concentration, if aminoglycoside dosage is exceed 15 mg/kg, the possibility of auditory disturbance increase. About the duration of MAC chemotherapy, many guidelines recommended that one year continuation after the negative conversion of sputum culture. It is not the evidence but an expert opinion. We often experience recurrences several months later after the all drugs are ceased. The interval days to positive conversion of sputum culture from the day of completion of chemotherapy are randomly distributed with weibull's equation. It suggests that exogenous re-infection may cause the recurrence of pulmonary MAC infection as pointed out by Wallace Jr. Considering these issues, we have the conception of pulmonary MAC infection chemotherapy as follows. 1. Full dose induction chemotherapy (two years). 2. Maintenance chemotherapy (one year). 3. Preventive chemotherapy (one year). These conceptions have to be the problem validated. However, these current chemotherapies are not effective adequately, we need the combination treatment with surgical resection when indicated as a localized focus for example. Generally chemotherapy could not cured the destructed bronchial lesion due to MAC infection as like as local bronchiectasis or cavities. Consequently, the chemotherapy just after the surgical resection of destructed focus is most appropriate period.

Evaluation of care for elderly pulmonary tuberculosis patients

To examine the clinical problem of elderly pulmonary tuberculosis patients. Clinical findings of pulmonary tuberculosis in elderly patients, who admitted to our hospital from 2001 to 2003, were analyzed in their status, complication, treatment, and prognosis. There were 145 patients, and the early elders from 65 to 74 years old were 67, and the latter elders over 75 years old were 78. Most of the cases were treated by the standard tuberculosis treatment, but in the latter elders, less patients were treated by the short course treatment with PZA than the early elders. The rate of negative conversion of sputum culture was good in both the early and the latter elders who were able to continue treatment. But, the elderly pulmonary tuberculosis patients were severe status and their prognosis was in general not good. The elderly pulmonary tuberculosis patients needed frequent care continuously. Tuberculosis problem should be understood more correctly in the medical and the nursing facilities.

Surgical Treatment of Pulmonary Diseases Due to Nontuberculous Mycobacteria

Although the treatment of pulmonary diseases due to nontuberculous mycobacteria (NTM) requires the long-term use of antibiotics in combination, the treatment success rates are unsatisfactory. We evaluated the clinical characteristics and surgical outcomes of 23 patients with NTM lung diseases who had underwent pulmonary resection. The median age of the patients was 45 yr. Of the 23 patients, 10 had Mycobacterium avium-intracellulare complex infection, 12 had M. abscessus infection, and one had M. xenopi infection. The indications for surgery were antibiotic therapy failure (n=11), remnant cavitary lesion with high probability of relapse (n=8), and massive hemoptysis (n=4). The most common procedure was lobectomy (48%). Postoperative complications occurred in eight patients (35%), including postoperative pneumonia (n=3) and late bronchopleural fistula (n=2). Negative sputum culture conversion was achieved and maintained in all except two mortalities. Although it is associated with a relatively high complication rate, patients with NTM lung disease whose disease is localized to one lung and who can tolerate resectional surgery might be considered for surgery, if there has been poor response to drug therapy or if the patients develop significant disease-related complications such as hemoptysis.