Efficacy of Extended Treatment in Drug-Susceptible Pulmonary Tuberculosis with Cavitary Lesions or Positive Culture at 2 Months

Efficacy of Extended Treatment in Drug-Susceptible Pulmonary Tuberculosis with Cavitary Lesions or Positive Culture at 2 Months | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Efficacy of Extended Treatment in Drug-Susceptible Pulmonary Tuberculosis with Cavitary Lesions or Positive Culture at 2 Months Chang-Seok Yoon, Tae-Ok Kim, Hong-Joon Shin, Hyung Woo Kim, Eung Gu Lee, and 17 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6349890/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Extended treatment is recommended for patients with pulmonary tuberculosis (TB) and cavitary lesions or positive culture at 2 months, but evidence remains limited. A retrospective analysis across 18 Korean institutions compared recurrence between standard (≤ 200 days) and extended treatment (> 200 days) in patients with drug-susceptible TB and cavitary lesions on chest radiography or positive sputum cultures at 2 months. Among 173 patients, 65 (37.6%) received standard and 108 (62.4%) extended treatment. Recurrence rates were similar (3.1% vs. 1.9%, p = 0.60), even after propensity score matching (4.7% vs. 2.3%, p = 0.56). Logistic regression analysis of all 854 patients with drug-susceptible TB with treatment success revealed chronic lung disease (OR 6.49, CI: 2.21–19.10, p < 0.01) and medication interruption exceeding 7 days (OR 4.43, CI: 1.63–12.03, p < 0.01) as significant predictors of recurrence. Positive culture at 2 months (OR 0.85, CI: 0.11–6.87, p = 0.88), cavitary lesions (OR 0.94, CI: 0.31–2.83, p = 0.91), either factors (OR 0.98, CI: 0.39–2.47, p = 0.99), and extended treatment (OR 1.17, CI: 0.49–2.81, p = 0.72) were not significant. Extended treatment did not reduce recurrence in patients with drug-susceptible TB and cavitary lesion or positive culture at 2 months. Health sciences/Diseases Health sciences/Medical research Health sciences/Risk factors Extended treatment cavitary lesions 2 months positive culture pulmonary tuberculosis recurrence Figures Figure 1 INTRODUCTION Pulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis and transmitted through respiratory droplets, is a preventable and treatable infectious disease. Standard six-month treatment achieves nearly 95% success in drug-susceptible TB 1 , 2 . However, advanced TB can result in severe lung damage and cavitary lesion formation. The prevalence of cavitary TB is reported to range from 29–87% 3 . Patients with pulmonary cavities can have severe disease, including a higher bacterial load in the sputum, and might be related to a higher treatment recurrence rate 4 – 9 . A key predictor of recurrence is a positive culture 2 months after treatment initiation 7 , 8 , 10 . Recurrence could increase the risk of mortality and development of drug-resistant TB 1 , highlighting the need for effective prevention strategies. The 2016 guidelines from the American Thoracic Society (ATS), Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) recommend extending the continuation phase by 3 months. This applies to patients with cavitation on chest radiographs and positive cultures at 2 months. These factors are linked to an increased risk of recurrence 8 . However, this recommendation is based on expert opinion, and the supporting evidence remains limited. Extended exposure to TB medication, on the other hand, has been shown to cause various side effects and higher costs. Additionally, it facilitates M. tuberculosis resistance through mutations, increasing the risk of drug-resistant TB 11 . Therefore, optimizing treatment duration and tailoring therapy to individual patients is crucial. This study aims to investigate whether 2-month positive cultures or cavitary lesions predict recurrence and evaluates the effect of extended treatment in these patients. RESULTS Overall, 173 patients with cavitary lesions on chest radiography or culture-positive results at 2 months of treatment were included. Among them, 65 (37.6%) received standard treatment, while 108 (67.4%) received extended treatment. The extended treatment group had higher AFB smear positivity than the standard treatment group (57.4% vs. 32.3%, p < 0.01). However, no significant differences were observed in demographic characteristics, comorbidities, or laboratory findings (Table 1 ). Table 1 Baseline characteristics of patients with pulmonary TB and cavitary lesions or positive cultures at 2 months of treatment All patients Propensity score matching Characteristics Total, n = 173 Standard, n = 65 Extended, n = 108 P value Total, n = 86 Standard, n = 43 Extended, n = 43 P value Age ≥ 65, n (%) 44(25.4) 18(27.7) 26(24.1) 0.60 27(31.4) 15(34.9) 12(27.9) 0.64 Males, n (%) 138(79.8) 52(80.0) 86(79.6) 0.95 71(82.6) 36(83.7) 35(81.4) 0.78 BMI < 18.5 kg/m 2 , n/N (%) 29/150(19.3) 7/51(13.7) 22/99(22.2) 0.21 19/74(25.7) 7/33(21.2) 12/41(29.3) 0.60 Ever smoker, n/N (%) 124/172(72.1) 47/65(72.3) 77/107(72.0) 0.96 67(77.9) 34(79.1) 33(76.7) 0.80 Comorbid conditions Hypertension, n/N (%) 36/172(20.9) 16/65(24.6) 20/107(18.7) 0.35 23(26.7) 11(25.6) 12(27.9) 0.81 Diabetes mellitus, n/N (%) 51/172(29.7) 16/65(24.6) 35/107(32.7) 0.26 23(26.7) 13(30.2) 10(23.3) 0.63 Cardiovascular, n (%) 2(1.2) 1(1.5) 1(0.9) 0.72 2(2.3) 1(2.3) 1(2.3) 1.00 Chronic lung disease, n/N (%) 8/172(4.7) 4/65(6.2) 4/107(3.7) 0.47 4(4.7) 2(4.7) 2(4.7) 1.00 Chronic liver disease, n/N (%) 5/172(2.9) 1/65(1.5) 4/107(3.7) 0.41 2(2.3) 1(2.3) 1(2.3) 1.00 Cerebrovascular, n/N (%) 2/172(1.2) 1/65(1.5) 1/107(0.9) 0.72 0(0.0) 0(0.0) 0(0.0) 1.00 Malignancy, n/N (%) 3/172(1.7) 1/65(1.5) 2/107(1.9) 0.87 2(2.3) 1(2.3) 1(2.3) 1.00 Previous TB treatment history, n/N (%) 31/172(18.0) 9/64(14.1) 22/108(20.4) 0.30 13(15.1) 7(16.3) 6(14.0) 0.76 Extrapulmonary TB, n (%) 11(6.4) 4(6.2) 7(6.5) 0.93 5(5.8) 2(4.7) 3(7.0) 0.65 Multilobe infiltration, n (%) 73(42.2) 26(40.0) 47(43.5) 0.65 39(45.3) 19(44.2) 20(46.5) 0.83 AFB Smear positive, n (%) 83(48.0) 21(32.3) 62(57.4) < 0.01 43(50.0) 20(46.5) 23(53.5) 0.67 Laboratory findings Anemia a , n/N (%) 69/155(44.5) 24/54(44.4) 45/101(44.6) 0.99 35/75(46.7) 17/34(50.0) 18/41(43.9) 0.60 Thrombocytopenia b , n/N (%) 7/155(4.5) 4/54(7.4) 3/101(3.0) 0.21 3/75(4.0) 2/34(5.9) 1/41(2.4) 0.45 LFT abnormalities c , n/N (%) 22/152(14.5) 6/53(11.3) 16/99(16.2) 0.42 8/73(11.0) 2/33(6.1) 6/40(15.0) 0.22 Hypoalbuminemia d , n/N (%) 18/142(12.7) 3/47(6.4) 15/95(15.8) 0.11 18/67(26.9) 7/29(24.1) 11/38(28.9) 0.66 Hyperbilirubinemia e , n/N (%) 2/145(1.4) 2/51(3.9) 0/94(0.0) 0.05 0/70(0.0) 0/31(0.0) 0/39(0.0) 1.00 RFT abnormalities f , n/N (%) 15/155(9.7) 8/54(14.8) 7/101(6.9) 0.11 7/74(9.5) 4/33(12.1) 3/41(7.3) 0.48 CRP elevation g , n/N (%) 96/128 (75.0) 27/40(67.5) 69/88(78.4) 0.19 44/61(72.1) 17/26(65.4) 27/35(77.1) 0.47 Abbreviation: BMI, body mass index; TB, Tuberculosis; AFB, acid-fast bacilli; LFT, liver function test; RFT, renal function test; CRP, C-reactive protein a: hemoglobin level below 13.0 g/dL in males and 12.0 g/dL in females b: platelet count below 150,000/µL c: defined as AST > 40 U/L or ALT > 40 U/L d: blood albumin level below 3.5 g/dL e: total serum bilirubin level exceeding 1.3 mg/dL f: defined as BUN > 20 mg/dL and creatinine > 1.2 mg/dL in females or > 1.3 mg/dL in males g: C-reactive protein level above 10 mg/L The recurrence rate did not differ between both groups, in the overall cohort (3.1% in the standard group vs. 1.9% in the extended group, p = 0.60) and in propensity score-matched patients (4.7% in the standard group vs. 2.3% in extended group, p = 0.56) (Table S1). Medication interruption owing to adverse drug events was more frequent in the extended group both before and after matching. However, no significant difference was observed in the overall incidence of adverse events (Table S2). Logistic regression analysis of the primary outcome using PSM data showed no significant factor linked to recurrence, including extended treatment (OR 0.49, CI: 0.04–5.59, p = 0.56) (Table 2 ). Table 2 Risk factors for the primary outcome in patients with pulmonary TB and cavitary lesions or positive cultures at 2 months of treatment after PSM Variables Univariate Multivariate OR 95% CI P value OR 95% CI P value Age ≥ 65 1.10 0.10–12.64 0.94 Ever smoker 0.55 0.05–6.46 0.64 Diabetes mellitus 5.91 0.51–68.49 0.16 Chronic lung disease 13.33 0.93–191.16 0.06 Previous TB treatment history 2.96 0.25–35.23 0.39 Multilobe infiltration 1.69 0.15–19.36 0.67 AFB smear positivity 2.05 0.18–23.48 0.56 Hepatotoxicity 1.58 0.14–18.30 0.72 Leukopenia a 7.80 0.60–101.42 0.12 20.00 0.65–613.18 0.09 Neuropathy or arthropathy 1.94 0.17–22.70 0.60 General weakness 6.74 0.58–78.42 0.13 Infection 7.80 0.60–101.42 0.12 Extended treatment 0.49 0.04–5.59 0.56 Abbreviation: OR, odds ratio; CI, confidence interval; TB, tuberculosis; AFB, acid-fast bacilli; PSM, propensity score matching a: low white blood cell (WBC) count, below 4,000 cells/µL To further investigate whether a positive culture at 2 months or cavitary lesions predict recurrence, a logistic regression analysis was performed on the primary outcome. The analysis included all 854 patients with drug-susceptible TB who achieved treatment success with the standard HREZ regimen. The univariable analysis revealed chronic lung disease, medication interruption exceeding 7 days for any reason, and generalized weakness owing to anti-TB medication as statistically significant factors. However, cavitary lesions, positive culture at 2 months, the presence of both factor and extended treatment were not significant predictors. In the multivariable analysis, chronic lung disease (OR: 6.49, CI: 2.21–19.10, p < 0.01) and medication interruption exceeding 7 days for any reason (OR 4.43, CI: 1.63–12.03, P < 0.01) were identified as statistically significant factors (Table 3 ). Table 3 Risk factors for the primary outcome in 854 patients with drug-susceptible pulmonary TB with treatment success using the standard HREZ regimen Variables Univariate Multivariate OR 95% CI P value OR 95% CI P value Age ≥ 65 1.74 0.73–4.14 0.21 Males 1.73 0.63–4.76 0.29 Ever smoker 0.68 0.28–1.61 0.38 BMI < 18.5 1.42 0.47–4.32 0.54 Hypertension 0.72 0.26–1.98 0.52 Diabetes mellitus 1.78 0.72–4.35 0.21 Chronic lung disease 6.72 2.34–19.35 < 0.01 6.49 2.21–19.10 < 0.01 Chronic liver disease 1.49 0.19–11.53 0.70 Cerebrovascular 2.72 0.61–12.21 0.19 Previous TB treatment history 1.35 0.45–4.07 0.60 Extrapulmonary TB 2.41 0.79–7.36 0.12 Multilobe infiltration 1.16 0.48–2.79 0.74 AFB Smear positive 0.75 0.25–2.24 0.60 Cavitary lesion 0.94 0.31–2.83 0.91 2 months culture-positive 0.85 0.11–6.87 0.88 Cavitary lesion or 2 months culture-positive 0.98 0.39–2.47 0.99 Medication interruption > 7 days for any reasons 4.57 1.72–12.17 < 0.01 4.43 1.63–12.03 < 0.01 Gastrointestinal adverse reaction 2.04 0.84–4.98 0.12 Hepatotoxicity 1.64 0.67–4.02 0.28 Cutaneous adverse reaction 1.21 0.50–2.95 0.68 Leukopenia a 1.61 0.53–4.89 0.40 Neuropathy or arthropathy 1.17 0.39–3.51 0.79 Generalized weakness 2.54 1.01–6.41 < 0.05 Ototoxicity 0.54 0.07–4.06 0.55 Nephrotoxicity 2.72 0.61–12.21 0.19 Infection 1.62 0.21–12.52 0.65 Medication interruption owing to AE 1.41 0.32–6.19 0.65 Extended treatment 1.17 0.49–2.81 0.72 Abbreviation: HREZ, H, isoniazid; E, ethambutol; R, rifampin; Z, pyrazinadmide; OR, odds ratio; CI, confidence interval; BMI, body mass index; TB, tuberculosis; AFB, acid-fast bacilli; AE, adverse events a: low white blood cell (WBC) count, below 4,000 cells/µL DISCUSSION This prospective cohort study reports that extended treatment did not significantly reduce recurrence among patients with drug-susceptible pulmonary TB. These patients had cavitary lesions on chest radiography or positive sputum cultures at 2 months, despite initial treatment success. Furthermore, neither cavitary lesions nor positive sputum cultures at 2 months were significant predictors of recurrence. However, underlying chronic lung disease and medication interruptions exceeding 7 days, regardless of cause, were identified as significant predictors of recurrence. This study has several clinical implications. First, extended treatment has minimal effect on preventing recurrence in high-risk patients, defined by positive cultures at 2 months or cavitary lesions on chest radiography. Prolonged exposure to anti-TB medication provides no clear clinical benefit and may increase the risk of drug-related adverse effects. Although statistical significance was not observed between both groups, medication interruptions owing to adverse drug events were more frequent in the extended treatment group (Table S2). The relationship between prolonged drug exposure and increased adverse effects is well-documented in the literature 12 – 14 . Moreover, drug-related adverse events frequently disrupt TB treatment, potentially increasing the risk of developing drug-resistant TB 15 . Therefore, the balance between clinical benefits and risks warrants careful reassessment of any significant advantage extending TB treatment offers. Second, cavitary lesions on chest radiography and positive cultures at 2 months were not significant predictors of recurrence. In contrast, studies report that these factors increase the risk of treatment failure or recurrence 4 – 9 . A Korean study reports cavitation with positive sputum culture at 2 months as a significant predictor of recurrence within a year 7 . However, the finding was limited by its single-center retrospective design and the absence of extended treatment data Differences in patient characteristics and treatment environments may account for varying results across studies. Patients in previous studies may have had more severe TB or comorbidities affecting prognosis. Additionally, differences in healthcare settings and treatment regimens, such as intermittent therapy administered twice weekly vs. daily therapy in Korea, may contribute to these inconsistencies. The nationwide public-private mix program in Korea has recently improved treatment outcomes 16 . These contextual differences may have influenced treatment outcomes. Additionally, bacterial burden may vary significantly based on observed cavity size and number 3 . For instance, a patient with multiple large cavities potentially has a significantly higher bacterial load than those with a single small cavity despite both being classified as having cavitary disease. Similarly, when assessing culture positivity, relying solely on a binary classification of 2-month culture results may not accurately represent TB burden. Instead, a more precise evaluation of TB burden and monitoring biomarkers that can predict recurrence are needed. Third, chronic lung diseases were significant risk factors for recurrence. Conditions such as chronic obstructive pulmonary disease, asthma, and silicosis are established risk factors for TB development 17 – 21 . However, their role as specific risk factors for TB recurrence remains unclear, as does whether recurrence primarily represents reinfection or relapse. A study conducted in a low-incidence setting—where relapse occurred more frequently than reinfection—shows that chronic lung disease independently increased recurrence risk 22 . These findings are consistent with those of our study, further supporting the hypothesis that chronic lung disease may be a significant risk factor for TB relapse. Lastly, treatment-related factors—particularly medication interruptions exceeding 7 days for any reason—were identified as significant risk factors for TB recurrence. Such interruptions can disrupt therapeutic drug levels, resulting in suboptimal treatment outcomes, a finding consistent with those of previous studies 23 – 25 . These findings highlight the critical importance of adherence to treatment for achieving favorable clinical outcomes. Enhancing adherence requires minimizing medication-related side effects and optimizing treatment duration through individualized monitoring and tailored therapeutic strategies within a well-structured national TB control program. This study has several limitations. First, as this is not a randomized prospective study, the decision to extend treatment was made by attending physicians rather than a predefined protocol. Additionally, factors were not adequately controlled, which may have influenced the results. Although PSM was used to address this limitation, it reduced the sample size, potentially weakening the strength of the findings. Furthermore, PSM carries a risk of selection bias during variable selection, which might have led to the exclusion of significant factors or the overestimation of selected variables. Second, patients with TB who had both 2-month culture positivity and cavities on chest radiographs, for whom extended treatment is recommended by ATS/CDC/IDSA guidelines, were not analyzed. This is because few patients met these criteria, limiting statistical analysis. However, studies show that these two factors are independent predictors of poor outcomes. Despite the limitation, this study provides valuable insights into the effects of extended treatment, contributing to its clinical significance. Third, data on potential factors influencing recurrence, including nutritional status, poor glycemic control in patients with diabetes, human immunodeficiency virus infection, and immunosuppressive therapy, were incomplete. This potentially affected the accuracy of the analysis. In conclusion, extended treatment for patients with positive sputum cultures at 2 months or cavitary lesions did not reduce recurrence risk. However, chronic lung disease and treatment interruption emerged as significant risk factors, highlighting the need for individualized treatment strategies based on patient-specific risk profiles. METHODS Population In this study, a prospective cohort of 1,204 patients with pulmonary TB recruited from 18 centers in South Korea between July 2019 and June 2023 was used. To evaluate the efficacy and safety of extended treatment in patients at high risk of recurrence, those with cavitation on chest radiography or culture positivity at 2 months into treatment were included. Exclusion criteria comprised confirmed or prior multidrug-resistant or rifampin-resistant TB (MDR/RR TB) (n = 135), isoniazid mono-resistant TB (n = 49), or other forms of mono-resistant TB (n = 13). Among patients with drug-susceptible TB, only those who achieved treatment success with the standard isoniazid, rifampin, ethambutol, and pyrazinamide (HREZ) regimen were included. Therefore, patients were further excluded if they did not receive the HREZ regimen (n = 36) or experienced treatment failure (n = 4). Those who died (n = 53) or transferred to other clinics (n = 41) were also excluded. Additionally, those lost to follow-up (n = 8) or who discontinued treatment owing to consent withdrawal or changes in diagnosis (n = 11) were excluded. Ultimately, 854 patients with drug-susceptible TB who achieved treatment success with a standard HRZE regimen were selected. Those at high recurrence risk—defined by cavitation on chest radiography or culture positivity at 2 months—were included for final analysis (n = 173) (Fig. 1 ). Data collection Baseline demographic data, such as age, sex, and comorbidities, were recorded at diagnosis for selected patients. Initial clinical data, including vital signs, biochemical tests, and microbiological results, were also documented. Biochemical tests, including complete blood count, liver and renal function test, and inflammation markers, were conducted through blood sampling. Chest radiography was used to assess cavitation or multilobe infiltration, while microbiological evaluation included acid-fast bacilli (AFB) smear and culture from sputum samples. Throughout follow-up, participants underwent regular biochemical evaluations and close monitoring for adverse drug reactions at predefined intervals (14 days, 28 days, 2 months, and monthly thereafter). Follow-up continued until treatment completion or discontinuation, death, or the final hospital visit 26 , 27 . Group classification and study outcome Patients were categorized into two groups based on treatment duration. Those treated for more than 200 days were defined as the extended treatment group, while those treated for less than 200 days were classified as the standard treatment group. A two-week threshold was chosen, as interruptions of at least 2 weeks during the intensive phase require treatment restart, thereby extending the overall treatment duration 28 . The primary outcome of this study was recurrence, defined as bacteriologically confirmed positivity within one year after treatment completion in patients previously classified as cured or having successfully completed treatment. Propensity score matching Propensity score matching (PSM) was applied in the comparative analysis to adjust for confounders and rigorously evaluate the effect of treatment duration on outcomes. Matching variables included demographic factors—age, sex, and comorbidities. TB-specific indicators include AFB smear positivity at diagnosis, multilobar infiltration on chest imaging, extrapulmonary TB, and prior TB treatment history. These microbiological factors reflecting TB burden and treatment discontinuation were matched to evaluate the effect of treatment duration on outcomes. Statistical analysis Continuous variables were expressed as means ± standard deviations, while categorical variables were presented as count (%). Group comparisons were conducted using t-tests for the means of continuous variables and Pearson’s chi-square or Fisher’s exact test for categorical variable analysis. Logistic regression analysis was performed to identify factors influencing the primary outcome. Univariable logistic regression tests were conducted using demographic characteristics, comorbidities, radiologic findings, and microbiologic results. Variables with a p-value < 0.2 in the univariable analysis were then included in the multivariable logistic regression model using the backward selection method. A p-value of < 0.05 was considered statistically significant. PSM was performed using the nearest-neighbor approach to achieve a 1:1 matching between both groups, with a caliper set at 0.1. To ensure matching quality, matched variables between both groups were compared using a t-test or chi-square test. Additionally, factors potentially influencing outcomes within the propensity score-matched cohort were analyzed using binary logistic regression. All analyses were performed using IBM SPSS Statistics version 25 (SPSS Inc., Chicago, IL, USA). Declarations Ethics declarations This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board and Ethics Committee of Chonnam National University Hospital (IRB No. CNUH-2022-122). Written informed consent was obtained from all adult participants in the pulmonary TB cohort study. Author contributions: Conceptualization: C.S.Y., Y.S.K. Data curation: All authors. Formal analysis: C.S.Y., T.O.K. Methodology: C.S.Y., T.O.K., Y.S.K. Software: C.S.Y., T.O.K. Validation: J.M., Y.S.K. Investigation: C.S.Y., T.O.K. Writing - original draft: C.S.Y. Writing - review & editing: C.S.Y., T.O.K., J.M., Y.S.K. All authors revied the manuscript. Competing interests: The authors declare no competing interest Funding This work was supported by the Research Program funded by the Korea National Institute of Health (grant number 2022E200100) and by a grant (BCRI24033) from Chonnam National University Hospital Biomedical Research Institute. The funders had no role in study design, data collection, analysis, the decision to publish, or preparation of the manuscript. 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Impact of pyrazinamide usage on serious adverse events in elderly tuberculosis patients: A multicenter cohort study. PLOS ONE . 19 , e0309902. 10.1371/journal.pone.0309902 (2024). Kim, K. H. et al. Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis. Respirology 29 , 624–632. 10.1111/resp.14714 (2024). van’t Boveneind-Vrubleuskaya, N. et al. Predictors of Prolonged TB Treatment in a Dutch Outpatient Setting. PLOS ONE . 11 , e0166030. 10.1371/journal.pone.0166030 (2016). Additional Declarations No competing interests reported. Supplementary Files TableS1andS2.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6349890","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":444644639,"identity":"8a0da77c-b47c-4a2d-a409-2bff3b0abef6","order_by":0,"name":"Chang-Seok Yoon","email":"","orcid":"","institution":"Chonnam National University Hospital, Chonnam National University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Chang-Seok","middleName":"","lastName":"Yoon","suffix":""},{"id":444644641,"identity":"f8382533-2fe5-43d3-ad92-be091daef44f","order_by":1,"name":"Tae-Ok Kim","email":"","orcid":"","institution":"Chonnam National University Hospital, Chonnam National University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Tae-Ok","middleName":"","lastName":"Kim","suffix":""},{"id":444644643,"identity":"cf420149-9975-47a5-8283-c07c337a6aab","order_by":2,"name":"Hong-Joon Shin","email":"","orcid":"","institution":"Chonnam National University Hospital, Chonnam National University Medical School","correspondingAuthor":false,"prefix":"","firstName":"Hong-Joon","middleName":"","lastName":"Shin","suffix":""},{"id":444644646,"identity":"a5467e46-a0b5-4e36-828c-f73b3f3b5468","order_by":3,"name":"Hyung Woo Kim","email":"","orcid":"","institution":"The Catholic University of Korea","correspondingAuthor":false,"prefix":"","firstName":"Hyung","middleName":"Woo","lastName":"Kim","suffix":""},{"id":444644648,"identity":"8191842b-60f0-45e2-a950-05cc744a8218","order_by":4,"name":"Eung Gu Lee","email":"","orcid":"","institution":"The Catholic University of 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Korea","correspondingAuthor":false,"prefix":"","firstName":"Jin","middleName":"Woo","lastName":"Kim","suffix":""},{"id":444644652,"identity":"51255886-5fa2-4705-bd18-5071c0909a00","order_by":8,"name":"Jee Youn Oh","email":"","orcid":"","institution":"Korea University Guro Hospital, Korea University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jee","middleName":"Youn","lastName":"Oh","suffix":""},{"id":444644653,"identity":"8b4988e1-ecf3-445e-b651-dfc7657a0d57","order_by":9,"name":"Heayon Lee","email":"","orcid":"","institution":"The Catholic University of Korea","correspondingAuthor":false,"prefix":"","firstName":"Heayon","middleName":"","lastName":"Lee","suffix":""},{"id":444644654,"identity":"ffa233e7-e9b5-49dd-96f2-83d7a61ded6f","order_by":10,"name":"Seung Hoon Kim","email":"","orcid":"","institution":"St. Vincent’s Hospital, The Catholic University of Korea","correspondingAuthor":false,"prefix":"","firstName":"Seung","middleName":"Hoon","lastName":"Kim","suffix":""},{"id":444644655,"identity":"3f8076ba-e81b-43d1-b373-ea9ac9ea752b","order_by":11,"name":"Sun-Hyung Kim","email":"","orcid":"","institution":"Chungbuk National University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sun-Hyung","middleName":"","lastName":"Kim","suffix":""},{"id":444644656,"identity":"a0574b3c-9730-43bc-b29b-0e62dd966346","order_by":12,"name":"Jiwon Lyu","email":"","orcid":"","institution":"Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jiwon","middleName":"","lastName":"Lyu","suffix":""},{"id":444644657,"identity":"cf9a36a5-6194-443d-a6a6-d2148d018a42","order_by":13,"name":"Sun Jung Kwon","email":"","orcid":"","institution":"Konyang University Hospital, Konyang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sun","middleName":"Jung","lastName":"Kwon","suffix":""},{"id":444644658,"identity":"9c478c56-d3e6-4646-b28a-3db32ed030a3","order_by":14,"name":"Yun-Jeong Jeong","email":"","orcid":"","institution":"Dongguk University Ilsan Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yun-Jeong","middleName":"","lastName":"Jeong","suffix":""},{"id":444644659,"identity":"07dadcfb-2376-4b50-92c7-c9f91dfc3e2e","order_by":15,"name":"Do Jin Kim","email":"","orcid":"","institution":"Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Do","middleName":"Jin","lastName":"Kim","suffix":""},{"id":444644660,"identity":"ed77565c-c894-4a96-ba97-cd638e7170bc","order_by":16,"name":"Hyeon-Kyoung Koo","email":"","orcid":"","institution":"Inje University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hyeon-Kyoung","middleName":"","lastName":"Koo","suffix":""},{"id":444644661,"identity":"e16f88c2-cd18-459d-ac17-ad59c80d5f0a","order_by":17,"name":"Ganghee Chae","email":"","orcid":"","institution":"Ulsan University Hospital, Ulsan University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ganghee","middleName":"","lastName":"Chae","suffix":""},{"id":444644662,"identity":"e9c3193a-81c7-4da9-96ea-193fdcd55811","order_by":18,"name":"Sun Young Kyoung","email":"","orcid":"","institution":"Gachon University Gil Hospital","correspondingAuthor":false,"prefix":"","firstName":"Sun","middleName":"Young","lastName":"Kyoung","suffix":""},{"id":444644663,"identity":"48d394a6-d2ca-4e8d-bf52-fcb72abc4fe3","order_by":19,"name":"Ju Sang Kim","email":"","orcid":"","institution":"The Catholic University of Korea","correspondingAuthor":false,"prefix":"","firstName":"Ju","middleName":"Sang","lastName":"Kim","suffix":""},{"id":444644664,"identity":"c1708096-ab3b-4c43-9634-eeeebea2e377","order_by":20,"name":"Jinsoo Min","email":"","orcid":"","institution":"The Catholic University of Korea","correspondingAuthor":false,"prefix":"","firstName":"Jinsoo","middleName":"","lastName":"Min","suffix":""},{"id":444644665,"identity":"2441d7ef-8e0c-4751-9653-0d97a8b52890","order_by":21,"name":"Yong-Soo Kwon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYFACNhBhwwzlJRCtJY10LYdhPCK0GJw/libxccd5dnOJBMYPPxjS8glruZF2THLmmdvMljMSmCV7GHIsGwhrYW+7zdt2m9ngRgKDNANDhQERDjsO0nIOpIX5N3FaDqQdA2o5ANLCBrQlh7AWyRtp6T9ntiUzG5x52GbZY5BGWAvf+WPGBh/b7JINjicfvvGjIpmwFoUDEDqZgYGxAehOghoYGOQbILQdEWpHwSgYBaNgpAIAdh46g4waPgIAAAAASUVORK5CYII=","orcid":"","institution":"Chonnam National University Hospital, Chonnam National University Medical School","correspondingAuthor":true,"prefix":"","firstName":"Yong-Soo","middleName":"","lastName":"Kwon","suffix":""}],"badges":[],"createdAt":"2025-04-01 06:08:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6349890/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6349890/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82081477,"identity":"a60032f3-facb-4003-bc6c-70084c0be6b2","added_by":"auto","created_at":"2025-05-06 14:31:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":61850,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of participant enrollment. Abbreviation: TB, tuberculosis; MDR/RR, multi-drug resistance/rifampin-resistance; CXR, chest x-ray\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6349890/v1/b181957864e7b750d50c6181.png"},{"id":90698182,"identity":"be888eef-a75d-431c-9379-3f051d287c53","added_by":"auto","created_at":"2025-09-05 21:16:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1028114,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6349890/v1/6eb3152a-c758-490a-a2a1-3334efc6022a.pdf"},{"id":82081476,"identity":"b88bad46-5704-46f5-88ff-7f853ab14f14","added_by":"auto","created_at":"2025-05-06 14:31:04","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17788,"visible":true,"origin":"","legend":"","description":"","filename":"TableS1andS2.docx","url":"https://assets-eu.researchsquare.com/files/rs-6349890/v1/7c4435b286f6d8f6f487f86d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy of Extended Treatment in Drug-Susceptible Pulmonary Tuberculosis with Cavitary Lesions or Positive Culture at 2 Months","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePulmonary tuberculosis (TB), caused by \u003cem\u003eMycobacterium tuberculosis\u003c/em\u003e and transmitted through respiratory droplets, is a preventable and treatable infectious disease. Standard six-month treatment achieves nearly 95% success in drug-susceptible TB \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. However, advanced TB can result in severe lung damage and cavitary lesion formation. The prevalence of cavitary TB is reported to range from 29\u0026ndash;87% \u003csup\u003e3\u003c/sup\u003e. Patients with pulmonary cavities can have severe disease, including a higher bacterial load in the sputum, and might be related to a higher treatment recurrence rate \u003csup\u003e\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. A key predictor of recurrence is a positive culture 2 months after treatment initiation \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Recurrence could increase the risk of mortality and development of drug-resistant TB \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e, highlighting the need for effective prevention strategies. The 2016 guidelines from the American Thoracic Society (ATS), Centers for Disease Control and Prevention (CDC), and Infectious Diseases Society of America (IDSA) recommend extending the continuation phase by 3 months. This applies to patients with cavitation on chest radiographs and positive cultures at 2 months. These factors are linked to an increased risk of recurrence \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. However, this recommendation is based on expert opinion, and the supporting evidence remains limited.\u003c/p\u003e \u003cp\u003eExtended exposure to TB medication, on the other hand, has been shown to cause various side effects and higher costs. Additionally, it facilitates \u003cem\u003eM. tuberculosis\u003c/em\u003e resistance through mutations, increasing the risk of drug-resistant TB \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eTherefore, optimizing treatment duration and tailoring therapy to individual patients is crucial. This study aims to investigate whether 2-month positive cultures or cavitary lesions predict recurrence and evaluates the effect of extended treatment in these patients.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eOverall, 173 patients with cavitary lesions on chest radiography or culture-positive results at 2 months of treatment were included. Among them, 65 (37.6%) received standard treatment, while 108 (67.4%) received extended treatment. The extended treatment group had higher AFB smear positivity than the standard treatment group (57.4% vs. 32.3%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). However, no significant differences were observed in demographic characteristics, comorbidities, or laboratory findings (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics of patients with pulmonary TB and cavitary lesions or positive cultures at 2 months of treatment\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAll patients\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePropensity score matching\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal,\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;173\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStandard,\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtended,\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;108\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal,\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eStandard,\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtended,\u003c/p\u003e\n \u003cp\u003en\u0026thinsp;=\u0026thinsp;43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;65, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44(25.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(27.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(31.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(34.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(27.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMales, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e138(79.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52(80.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86(79.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e71(82.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(83.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35(81.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u0026thinsp;\u0026lt;\u0026thinsp;18.5 kg/m\u003csup\u003e2\u003c/sup\u003e, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29/150(19.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7/51(13.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22/99(22.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19/74(25.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7/33(21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12/41(29.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEver smoker, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e124/172(72.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47/65(72.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77/107(72.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67(77.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(79.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33(76.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComorbid conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36/172(20.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16/65(24.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20/107(18.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(25.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(27.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.81\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51/172(29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16/65(24.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35/107(32.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(26.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(30.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCardiovascular, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic lung disease, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8/172(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/65(6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/107(3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic liver disease, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5/172(2.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/65(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/107(3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCerebrovascular, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/172(1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/65(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/107(0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMalignancy, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/172(1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/65(1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/107(1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious TB treatment history, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31/172(18.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9/64(14.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22/108(20.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(15.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.76\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtrapulmonary TB, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(5.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMultilobe infiltration, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e73(42.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(40.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47(43.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(45.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(44.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(46.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.83\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAFB Smear positive, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83(48.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(32.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62(57.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43(50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(46.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(53.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLaboratory findings\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnemia\u003csup\u003ea\u003c/sup\u003e, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69/155(44.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24/54(44.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45/101(44.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35/75(46.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17/34(50.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18/41(43.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThrombocytopenia\u003csup\u003eb\u003c/sup\u003e, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7/155(4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/54(7.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/101(3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/75(4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/34(5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1/41(2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLFT abnormalities\u003csup\u003ec\u003c/sup\u003e, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22/152(14.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/53(11.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16/99(16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8/73(11.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/33(6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6/40(15.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypoalbuminemia\u003csup\u003ed\u003c/sup\u003e, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18/142(12.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/47(6.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15/95(15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18/67(26.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7/29(24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11/38(28.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHyperbilirubinemia\u003csup\u003ee\u003c/sup\u003e, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/145(1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2/51(3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/94(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/70(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/31(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0/39(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRFT abnormalities\u003csup\u003ef\u003c/sup\u003e, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15/155(9.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8/54(14.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7/101(6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7/74(9.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4/33(12.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3/41(7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRP elevation\u003csup\u003eg\u003c/sup\u003e, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96/128 (75.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27/40(67.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69/88(78.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44/61(72.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17/26(65.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27/35(77.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003eAbbreviation: BMI, body mass index; TB, Tuberculosis; AFB, acid-fast bacilli; LFT, liver function test; RFT, renal function test; CRP, C-reactive protein\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003ea: hemoglobin level below 13.0 g/dL in males and 12.0 g/dL in females\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003eb: platelet count below 150,000/\u0026micro;L\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003ec: defined as AST\u0026thinsp;\u0026gt;\u0026thinsp;40 U/L or ALT\u0026thinsp;\u0026gt;\u0026thinsp;40 U/L\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003ed: blood albumin level below 3.5 g/dL\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003ee: total serum bilirubin level exceeding 1.3 mg/dL\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003ef: defined as BUN\u0026thinsp;\u0026gt;\u0026thinsp;20 mg/dL and creatinine\u0026thinsp;\u0026gt;\u0026thinsp;1.2 mg/dL in females or \u0026gt;\u0026thinsp;1.3 mg/dL in males\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\"\u003eg: C-reactive protein level above 10 mg/L\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eThe recurrence rate did not differ between both groups, in the overall cohort (3.1% in the standard group vs. 1.9% in the extended group, p\u0026thinsp;=\u0026thinsp;0.60) and in propensity score-matched patients (4.7% in the standard group vs. 2.3% in extended group, p\u0026thinsp;=\u0026thinsp;0.56) (Table S1).\u003c/p\u003e\n\u003cp\u003eMedication interruption owing to adverse drug events was more frequent in the extended group both before and after matching. However, no significant difference was observed in the overall incidence of adverse events (Table S2).\u003c/p\u003e\n\u003cp\u003eLogistic regression analysis of the primary outcome using PSM data showed no significant factor linked to recurrence, including extended treatment (OR 0.49, CI: 0.04\u0026ndash;5.59, p\u0026thinsp;=\u0026thinsp;0.56) (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eRisk factors for the primary outcome in patients with pulmonary TB and cavitary lesions or positive cultures at 2 months of treatment after PSM\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eUnivariate\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eMultivariate\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.10\u0026ndash;12.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEver smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.05\u0026ndash;6.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.51\u0026ndash;68.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic lung disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.93\u0026ndash;191.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious TB treatment history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.25\u0026ndash;35.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMultilobe infiltration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.15\u0026ndash;19.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAFB smear positivity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.18\u0026ndash;23.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHepatotoxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.14\u0026ndash;18.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLeukopenia\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.60\u0026ndash;101.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.65\u0026ndash;613.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeuropathy or arthropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.17\u0026ndash;22.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGeneral weakness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.58\u0026ndash;78.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.60\u0026ndash;101.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtended treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.04\u0026ndash;5.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eAbbreviation: OR, odds ratio; CI, confidence interval; TB, tuberculosis; AFB, acid-fast bacilli; PSM, propensity score matching\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003ea: low white blood cell (WBC) count, below 4,000 cells/\u0026micro;L\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTo further investigate whether a positive culture at 2 months or cavitary lesions predict recurrence, a logistic regression analysis was performed on the primary outcome. The analysis included all 854 patients with drug-susceptible TB who achieved treatment success with the standard HREZ regimen. The univariable analysis revealed chronic lung disease, medication interruption exceeding 7 days for any reason, and generalized weakness owing to anti-TB medication as statistically significant factors. However, cavitary lesions, positive culture at 2 months, the presence of both factor and extended treatment were not significant predictors. In the multivariable analysis, chronic lung disease (OR: 6.49, CI: 2.21\u0026ndash;19.10, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and medication interruption exceeding 7 days for any reason (OR 4.43, CI: 1.63\u0026ndash;12.03, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) were identified as statistically significant factors (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eRisk factors for the primary outcome in 854 patients with drug-susceptible pulmonary TB with treatment success using the standard HREZ regimen\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eUnivariate\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eMultivariate\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u0026thinsp;\u0026ge;\u0026thinsp;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.73\u0026ndash;4.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMales\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.63\u0026ndash;4.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEver smoker\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.28\u0026ndash;1.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u0026thinsp;\u0026lt;\u0026thinsp;18.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.47\u0026ndash;4.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.26\u0026ndash;1.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.72\u0026ndash;4.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic lung disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.34\u0026ndash;19.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.21\u0026ndash;19.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChronic liver disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u0026ndash;11.53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCerebrovascular\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.61\u0026ndash;12.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePrevious TB treatment history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.45\u0026ndash;4.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtrapulmonary TB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.79\u0026ndash;7.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMultilobe infiltration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.48\u0026ndash;2.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAFB Smear positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.25\u0026ndash;2.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCavitary lesion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.31\u0026ndash;2.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 months culture-positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.11\u0026ndash;6.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCavitary lesion or 2 months culture-positive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.39\u0026ndash;2.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedication interruption\u0026thinsp;\u0026gt;\u0026thinsp;7 days for any reasons\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.72\u0026ndash;12.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.63\u0026ndash;12.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGastrointestinal adverse reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.84\u0026ndash;4.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHepatotoxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.67\u0026ndash;4.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCutaneous adverse reaction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.50\u0026ndash;2.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLeukopenia\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.53\u0026ndash;4.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNeuropathy or arthropathy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.39\u0026ndash;3.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGeneralized weakness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.01\u0026ndash;6.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOtotoxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.07\u0026ndash;4.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNephrotoxicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.61\u0026ndash;12.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInfection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.21\u0026ndash;12.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedication interruption owing to AE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.32\u0026ndash;6.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtended treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.49\u0026ndash;2.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003eAbbreviation: HREZ, H, isoniazid; E, ethambutol; R, rifampin; Z, pyrazinadmide; OR, odds ratio; CI, confidence interval; BMI, body mass index; TB, tuberculosis; AFB, acid-fast bacilli; AE, adverse events\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003ea: low white blood cell (WBC) count, below 4,000 cells/\u0026micro;L\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis prospective cohort study reports that extended treatment did not significantly reduce recurrence among patients with drug-susceptible pulmonary TB. These patients had cavitary lesions on chest radiography or positive sputum cultures at 2 months, despite initial treatment success. Furthermore, neither cavitary lesions nor positive sputum cultures at 2 months were significant predictors of recurrence. However, underlying chronic lung disease and medication interruptions exceeding 7 days, regardless of cause, were identified as significant predictors of recurrence.\u003c/p\u003e \u003cp\u003eThis study has several clinical implications. First, extended treatment has minimal effect on preventing recurrence in high-risk patients, defined by positive cultures at 2 months or cavitary lesions on chest radiography. Prolonged exposure to anti-TB medication provides no clear clinical benefit and may increase the risk of drug-related adverse effects. Although statistical significance was not observed between both groups, medication interruptions owing to adverse drug events were more frequent in the extended treatment group (Table S2). The relationship between prolonged drug exposure and increased adverse effects is well-documented in the literature \u003csup\u003e\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Moreover, drug-related adverse events frequently disrupt TB treatment, potentially increasing the risk of developing drug-resistant TB \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. Therefore, the balance between clinical benefits and risks warrants careful reassessment of any significant advantage extending TB treatment offers.\u003c/p\u003e \u003cp\u003eSecond, cavitary lesions on chest radiography and positive cultures at 2 months were not significant predictors of recurrence. In contrast, studies report that these factors increase the risk of treatment failure or recurrence \u003csup\u003e\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. A Korean study reports cavitation with positive sputum culture at 2 months as a significant predictor of recurrence within a year \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. However, the finding was limited by its single-center retrospective design and the absence of extended treatment data Differences in patient characteristics and treatment environments may account for varying results across studies. Patients in previous studies may have had more severe TB or comorbidities affecting prognosis. Additionally, differences in healthcare settings and treatment regimens, such as intermittent therapy administered twice weekly vs. daily therapy in Korea, may contribute to these inconsistencies. The nationwide public-private mix program in Korea has recently improved treatment outcomes \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. These contextual differences may have influenced treatment outcomes. Additionally, bacterial burden may vary significantly based on observed cavity size and number \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. For instance, a patient with multiple large cavities potentially has a significantly higher bacterial load than those with a single small cavity despite both being classified as having cavitary disease. Similarly, when assessing culture positivity, relying solely on a binary classification of 2-month culture results may not accurately represent TB burden. Instead, a more precise evaluation of TB burden and monitoring biomarkers that can predict recurrence are needed.\u003c/p\u003e \u003cp\u003eThird, chronic lung diseases were significant risk factors for recurrence. Conditions such as chronic obstructive pulmonary disease, asthma, and silicosis are established risk factors for TB development \u003csup\u003e\u003cspan additionalcitationids=\"CR18 CR19 CR20\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. However, their role as specific risk factors for TB recurrence remains unclear, as does whether recurrence primarily represents reinfection or relapse. A study conducted in a low-incidence setting\u0026mdash;where relapse occurred more frequently than reinfection\u0026mdash;shows that chronic lung disease independently increased recurrence risk \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. These findings are consistent with those of our study, further supporting the hypothesis that chronic lung disease may be a significant risk factor for TB relapse.\u003c/p\u003e \u003cp\u003eLastly, treatment-related factors\u0026mdash;particularly medication interruptions exceeding 7 days for any reason\u0026mdash;were identified as significant risk factors for TB recurrence. Such interruptions can disrupt therapeutic drug levels, resulting in suboptimal treatment outcomes, a finding consistent with those of previous studies \u003csup\u003e\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. These findings highlight the critical importance of adherence to treatment for achieving favorable clinical outcomes. Enhancing adherence requires minimizing medication-related side effects and optimizing treatment duration through individualized monitoring and tailored therapeutic strategies within a well-structured national TB control program.\u003c/p\u003e \u003cp\u003eThis study has several limitations. First, as this is not a randomized prospective study, the decision to extend treatment was made by attending physicians rather than a predefined protocol. Additionally, factors were not adequately controlled, which may have influenced the results. Although PSM was used to address this limitation, it reduced the sample size, potentially weakening the strength of the findings. Furthermore, PSM carries a risk of selection bias during variable selection, which might have led to the exclusion of significant factors or the overestimation of selected variables.\u003c/p\u003e \u003cp\u003e Second, patients with TB who had both 2-month culture positivity and cavities on chest radiographs, for whom extended treatment is recommended by ATS/CDC/IDSA guidelines, were not analyzed. This is because few patients met these criteria, limiting statistical analysis. However, studies show that these two factors are independent predictors of poor outcomes. Despite the limitation, this study provides valuable insights into the effects of extended treatment, contributing to its clinical significance.\u003c/p\u003e \u003cp\u003eThird, data on potential factors influencing recurrence, including nutritional status, poor glycemic control in patients with diabetes, human immunodeficiency virus infection, and immunosuppressive therapy, were incomplete. This potentially affected the accuracy of the analysis.\u003c/p\u003e \u003cp\u003eIn conclusion, extended treatment for patients with positive sputum cultures at 2 months or cavitary lesions did not reduce recurrence risk. However, chronic lung disease and treatment interruption emerged as significant risk factors, highlighting the need for individualized treatment strategies based on patient-specific risk profiles.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003ePopulation\u003c/h2\u003e \u003cp\u003eIn this study, a prospective cohort of 1,204 patients with pulmonary TB recruited from 18 centers in South Korea between July 2019 and June 2023 was used. To evaluate the efficacy and safety of extended treatment in patients at high risk of recurrence, those with cavitation on chest radiography or culture positivity at 2 months into treatment were included. Exclusion criteria comprised confirmed or prior multidrug-resistant or rifampin-resistant TB (MDR/RR TB) (n\u0026thinsp;=\u0026thinsp;135), isoniazid mono-resistant TB (n\u0026thinsp;=\u0026thinsp;49), or other forms of mono-resistant TB (n\u0026thinsp;=\u0026thinsp;13). Among patients with drug-susceptible TB, only those who achieved treatment success with the standard isoniazid, rifampin, ethambutol, and pyrazinamide (HREZ) regimen were included. Therefore, patients were further excluded if they did not receive the HREZ regimen (n\u0026thinsp;=\u0026thinsp;36) or experienced treatment failure (n\u0026thinsp;=\u0026thinsp;4). Those who died (n\u0026thinsp;=\u0026thinsp;53) or transferred to other clinics (n\u0026thinsp;=\u0026thinsp;41) were also excluded. Additionally, those lost to follow-up (n\u0026thinsp;=\u0026thinsp;8) or who discontinued treatment owing to consent withdrawal or changes in diagnosis (n\u0026thinsp;=\u0026thinsp;11) were excluded. Ultimately, 854 patients with drug-susceptible TB who achieved treatment success with a standard HRZE regimen were selected. Those at high recurrence risk\u0026mdash;defined by cavitation on chest radiography or culture positivity at 2 months\u0026mdash;were included for final analysis (n\u0026thinsp;=\u0026thinsp;173) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eBaseline demographic data, such as age, sex, and comorbidities, were recorded at diagnosis for selected patients. Initial clinical data, including vital signs, biochemical tests, and microbiological results, were also documented. Biochemical tests, including complete blood count, liver and renal function test, and inflammation markers, were conducted through blood sampling. Chest radiography was used to assess cavitation or multilobe infiltration, while microbiological evaluation included acid-fast bacilli (AFB) smear and culture from sputum samples.\u003c/p\u003e \u003cp\u003eThroughout follow-up, participants underwent regular biochemical evaluations and close monitoring for adverse drug reactions at predefined intervals (14 days, 28 days, 2 months, and monthly thereafter). Follow-up continued until treatment completion or discontinuation, death, or the final hospital visit \u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e,\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\n\u003ch3\u003eGroup classification and study outcome\u003c/h3\u003e\n\u003cp\u003ePatients were categorized into two groups based on treatment duration. Those treated for more than 200 days were defined as the extended treatment group, while those treated for less than 200 days were classified as the standard treatment group. A two-week threshold was chosen, as interruptions of at least 2 weeks during the intensive phase require treatment restart, thereby extending the overall treatment duration \u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe primary outcome of this study was recurrence, defined as bacteriologically confirmed positivity within one year after treatment completion in patients previously classified as cured or having successfully completed treatment.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePropensity score matching\u003c/h2\u003e \u003cp\u003ePropensity score matching (PSM) was applied in the comparative analysis to adjust for confounders and rigorously evaluate the effect of treatment duration on outcomes. Matching variables included demographic factors\u0026mdash;age, sex, and comorbidities. TB-specific indicators include AFB smear positivity at diagnosis, multilobar infiltration on chest imaging, extrapulmonary TB, and prior TB treatment history. These microbiological factors reflecting TB burden and treatment discontinuation were matched to evaluate the effect of treatment duration on outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations, while categorical variables were presented as count (%). Group comparisons were conducted using t-tests for the means of continuous variables and Pearson\u0026rsquo;s chi-square or Fisher\u0026rsquo;s exact test for categorical variable analysis. Logistic regression analysis was performed to identify factors influencing the primary outcome. Univariable logistic regression tests were conducted using demographic characteristics, comorbidities, radiologic findings, and microbiologic results. Variables with a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.2 in the univariable analysis were then included in the multivariable logistic regression model using the backward selection method. A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003cp\u003ePSM was performed using the nearest-neighbor approach to achieve a 1:1 matching between both groups, with a caliper set at 0.1. To ensure matching quality, matched variables between both groups were compared using a t-test or chi-square test. Additionally, factors potentially influencing outcomes within the propensity score-matched cohort were analyzed using binary logistic regression. All analyses were performed using IBM SPSS Statistics version 25 (SPSS Inc., Chicago, IL, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board and Ethics Committee of Chonnam National University Hospital (IRB No. CNUH-2022-122). Written informed consent was obtained from all adult participants in the pulmonary TB cohort study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization:\u0026nbsp;C.S.Y., Y.S.K.\u0026nbsp;Data curation:\u0026nbsp;All authors.\u0026nbsp;Formal analysis:\u0026nbsp;C.S.Y.,\u0026nbsp;T.O.K. Methodology:\u0026nbsp;C.S.Y., T.O.K.,\u0026nbsp;Y.S.K.\u0026nbsp;Software:\u0026nbsp;C.S.Y.,\u0026nbsp;T.O.K.\u0026nbsp;Validation:\u0026nbsp;J.M.,\u0026nbsp;Y.S.K.\u0026nbsp;Investigation:\u0026nbsp;C.S.Y.,\u0026nbsp;T.O.K. Writing - original draft:\u0026nbsp;C.S.Y.\u0026nbsp;Writing - review \u0026amp; editing:\u0026nbsp;C.S.Y.,\u0026nbsp;T.O.K., J.M., Y.S.K. All authors revied the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interest\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Research Program funded by the Korea National Institute of Health (grant number 2022E200100) and by a grant (BCRI24033) from Chonnam National University Hospital Biomedical Research Institute. The funders had no role in study design, data collection, analysis, the decision to publish, or preparation of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from Korea Disease Control and Prevention Agency, however, restrictions apply. Data will be provided by the Korea Disease Control and Prevention Agency (Tae-hyoun Kim, D.V.M., Ph.D. [email protected], Division of Bacterial Disease Research, Center for Infectious Disease Research, National Institute of Health, Korea Disease Control and Prevention Agency, Cheongju, South Korea) and one of the authors (Prof. Jinsoo Min, [email protected]) upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZumla, A., Raviglione, M., Hafner, R., von Reyn, C. F. \u0026amp; Tuberculosis \u003cem\u003eN Engl. J. 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Predictors of Prolonged TB Treatment in a Dutch Outpatient Setting. \u003cem\u003ePLOS ONE\u003c/em\u003e. \u003cb\u003e11\u003c/b\u003e, e0166030. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0166030\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0166030\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2016).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Extended treatment, cavitary lesions, 2 months positive culture, pulmonary tuberculosis, recurrence","lastPublishedDoi":"10.21203/rs.3.rs-6349890/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6349890/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eExtended treatment is recommended for patients with pulmonary tuberculosis (TB) and cavitary lesions or positive culture at 2 months, but evidence remains limited. A retrospective analysis across 18 Korean institutions compared recurrence between standard (\u0026le;\u0026thinsp;200 days) and extended treatment (\u0026gt;\u0026thinsp;200 days) in patients with drug-susceptible TB and cavitary lesions on chest radiography or positive sputum cultures at 2 months. Among 173 patients, 65 (37.6%) received standard and 108 (62.4%) extended treatment. Recurrence rates were similar (3.1% vs. 1.9%, p\u0026thinsp;=\u0026thinsp;0.60), even after propensity score matching (4.7% vs. 2.3%, p\u0026thinsp;=\u0026thinsp;0.56). Logistic regression analysis of all 854 patients with drug-susceptible TB with treatment success revealed chronic lung disease (OR 6.49, CI: 2.21\u0026ndash;19.10, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and medication interruption exceeding 7 days (OR 4.43, CI: 1.63\u0026ndash;12.03, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) as significant predictors of recurrence. Positive culture at 2 months (OR 0.85, CI: 0.11\u0026ndash;6.87, p\u0026thinsp;=\u0026thinsp;0.88), cavitary lesions (OR 0.94, CI: 0.31\u0026ndash;2.83, p\u0026thinsp;=\u0026thinsp;0.91), either factors (OR 0.98, CI: 0.39\u0026ndash;2.47, p\u0026thinsp;=\u0026thinsp;0.99), and extended treatment (OR 1.17, CI: 0.49\u0026ndash;2.81, p\u0026thinsp;=\u0026thinsp;0.72) were not significant. Extended treatment did not reduce recurrence in patients with drug-susceptible TB and cavitary lesion or positive culture at 2 months.\u003c/p\u003e","manuscriptTitle":"Efficacy of Extended Treatment in Drug-Susceptible Pulmonary Tuberculosis with Cavitary Lesions or Positive Culture at 2 Months","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-06 14:31:00","doi":"10.21203/rs.3.rs-6349890/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b230db4a-6dc5-4f8e-984b-5071529e6915","owner":[],"postedDate":"May 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":47341239,"name":"Health sciences/Diseases"},{"id":47341240,"name":"Health sciences/Medical research"},{"id":47341241,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2025-09-05T21:08:20+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-06 14:31:00","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6349890","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6349890","identity":"rs-6349890","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}