Risk factors for 1-year relapse of pulmonary tuberculosis treated with a 6-month daily regimen

Jo, Kyung‐Wook; Yoo, Jung‐Wan; Hong, Yoonki; Lee, Jae Seung; Lee, Sang‐Do; Kim, Woo Sung; Kim, Dong Soon; Shim, Tae Sun

doi:10.1016/j.rmed.2014.01.010

Cited by 52 publications

(38 citation statements)

References 12 publications

(13 reference statements)

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“…In patients with pulmonary tuberculosis, the most consistent risk factors for recurrence within 2 years of treatment success were a positive acid-fast bacillus (AFB) culture after 2 months of treatment and cavitation on the initial chest X ray, probably because these two parameters are associated with a higher initial mycobacterial load (11)(12)(13). Despite our finding that approximately twothirds of recurrences of MAC lung disease occurred within 2 years, factors related to mycobacterial burden, including a positive AFB smear at treatment initiation and the fibrocavitary form of the disease, were not associated with disease recurrence.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Recurrence after Successful Treatment of Mycobacterium avium Complex Lung Disease

Lee

Kim

Hong

et al. 2015

Antimicrob Agents Chemother

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Section: Discussionmentioning

confidence: 99%

Risk Factors for Recurrence after Successful Treatment of Mycobacterium avium Complex Lung Disease

Lee

Kim

Hong

et al. 2015

Antimicrob Agents Chemother

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“…Unfortunately, there are no defined criteria for prolonging treatment to prevent a relapse of TB. In a recent study, the combination of cavitation on initial chest radiograph, and positive culture after 2 months, was associated with an increased risk of 1-year relapse, and the authors suggested an extension of treatment in these patients38. However, this study was a single center retrospective study that included only 6 patients with TB relapse, and there was no proven efficacy of prolonged TB treatment in these patients.…”

Section: Tuberculosismentioning

confidence: 89%

Respiratory Review of 2014: Tuberculosis and Nontuberculous Mycobacterial Pulmonary Disease

Park

Kwon

2014

Tuberc Respir Dis

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Since tuberculosis (TB) remains a major global health concern and the incidence of multi-drug resistant (MDR)-TB is increasing globally, new modalities for the detection of TB and drug resistant TB are needed to improve TB control. The Xpert MTB/RIF test can be a valuable new tool for early detection of TB and rifampicin resistance, with a high sensitivity and specificity. Late-generation fluoroquinolones, levofloxacin, and moxifloxacin, which are the principal drugs for the treatment of MDR-TB, show equally high efficacy and safety. Systemic steroids may reduce the overall TB mortality attributable to all forms of TB across all organ systems, although inhaled corticosteroids can increase the risk of TB development. Although fixed dose combinations were expected to reduce the risk of drug resistance and increase drug compliance, a recent meta-analysis found that they might actually increase the risk of relapse and treatment failure. Regarding treatment duration, patients with cavitation and culture positivity at 2 months of TB treatment may require more than 6 months of standard treatment. New anti-TB drugs, such as linezolid, bedaquiline, and delamanid, could improve the outcomes in drug-resistant TB. Nontuberculous mycobacterial lung disease has typical clinical and immunological phenotypes. Mycobacterial genotyping may predict disease progression, and whole genome sequencing may reveal the transmission of Mycobacterium abscessus. In refractory Mycobacterium avium complex lung disease, a moxifloxacin-containing regimen was expected to improve the treatment outcome.

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“…Nearly half of the cavities in HRZE-treated animals were sterile after 6 weeks of treatment compared to only 8% of cavities in animals treated with HS. This finding is critically important because cavities are an independent risk factor for relapse disease in large phase 3 studies (9,31), and the sterilization of cavities, therefore, may be the reason why HRZE cures patients better than HS. Other important risk factors include bilateral abnormalities and failure to convert sputum culture by 2 or 3 months.…”

Section: Discussionmentioning

confidence: 99%

A Sterilizing Tuberculosis Treatment Regimen Is Associated with Faster Clearance of Bacteria in Cavitary Lesions in Marmosets

Via

England

Weiner

et al. 2015

Antimicrob Agents Chemother

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g Shortening the lengthy treatment duration for tuberculosis patients is a major goal of current drug development efforts. The common marmoset develops human-like disease pathology and offers an attractive model to better understand the basis for relapse and test regimens for effective shorter duration therapy. We treated Mycobacterium tuberculosis-infected marmosets with two drug regimens known to differ in their relapse rates in human clinical trials: the standard four-drug combination of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) that has very low relapse rates and the combination of isoniazid and streptomycin that is associated with higher relapse rates. As early as 2 weeks, the more sterilizing regimen significantly reduced the volume of lung disease by computed tomography (P ‫؍‬ 0.035) and also significantly reduced uptake of [18 F]-2-fluoro-2-deoxyglucose by positron emission tomography (P ‫؍‬ 0.049). After 6 weeks of therapy, both treatments caused similar reductions in granuloma bacterial load, but the more sterilizing, four-drug regimen caused greater reduction in bacterial load in cavitary lesions (P ‫؍‬ 0.009). These findings, combined with the association in humans between cavitary disease and relapse, suggest that the basis for improved sterilizing activity of the four-drug combination is both its faster disease volume resolution and its stronger sterilizing effect on cavitary lesions. Definitive data from relapse experiments are needed to support this observation.T reatment of drug-sensitive tuberculosis (TB) requires 6 months of chemotherapy with a combination of four agents, isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB), to achieve a durable cure (1). The durability of a regimen is determined by carefully measuring the rate of disease recrudescence over 1 to 2 years in patients after completing chemotherapy. Under controlled conditions in the setting of a clinical trial, the rate of relapse with active disease using this fourdrug combination is typically 2 to 4% (2), while under more typical conditions in national TB control programs, this rate can be as high as 10 to 14% (3, 4). Shortening the duration of treatment would greatly simplify the management of this disease by improving adherence, reducing the rate of adverse events, and reducing costs (5-7).An inverse relationship between the risk of relapse and the killing of bacilli in the sputum of patients (culture conversion after 2 months of treatment) has been proposed. Although some risk of relapse is clearly related to culture positivity at 2 months, this association appears to be dependent on geography and extent of disease (8). An additional risk factor for relapse observed in larger phase 3 clinical trials is the presence of cavitary lesions at the time of initial diagnosis of disease (9). However, a clinical trial to shorten therapy to 4 months for patients who did not have cavitary disease by chest X-ray and were culture negative at 2 months was stopped early because of unacceptably high rates ...

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Risk factors for 1-year relapse of pulmonary tuberculosis treated with a 6-month daily regimen

Cited by 52 publications

References 12 publications

Risk Factors for Recurrence after Successful Treatment of Mycobacterium avium Complex Lung Disease

Risk Factors for Recurrence after Successful Treatment of Mycobacterium avium Complex Lung Disease

Respiratory Review of 2014: Tuberculosis and Nontuberculous Mycobacterial Pulmonary Disease

A Sterilizing Tuberculosis Treatment Regimen Is Associated with Faster Clearance of Bacteria in Cavitary Lesions in Marmosets

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