---
title: "Extended Treatment Duration and Recurrence in Cavitary Drug-Susceptible Pulmonary Tuberculosis"
id: "plos-one-11-extended-treatment-duration-and-recurrence-in-successfully-treated-drug"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-11-extended-treatment-duration-and-recurrence-in-successfully-treated-drug"
content_type: "clinical_feed_article"
specialty: "Pulmonology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357772"
published_at: "2026-09-10T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Extended Treatment Duration and Recurrence in Cavitary Drug-Susceptible Pulmonary Tuberculosis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-11-extended-treatment-duration-and-recurrence-in-successfully-treated-drug
- **Specialty:** [Pulmonology](https://medichelpline.com/clinical-feed/pulmonology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0357772)
- **Published At:** 2026-09-10T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This multicenter analysis evaluated whether extending treatment beyond 200 days reduces bacteriologically confirmed **recurrence** among patients with drug-susceptible pulmonary tuberculosis (DS-TB) who had a **cavity on chest radiograph**. - From a prospective Korean cohort of 1,204 pulmonary TB patients, 159 pan-susceptible patients with cavitary disease who achieved treatment success and completed follow-up were analyzed; 58 received standard treatment (≤200 days) and 101 received extended treatment (>200 days). - Baseline AFB smear positivity was higher in the extended-treatment group (56.4% vs. 29.3%, p = 0.002), but 2-month culture positivity and time to culture conversion were similar between groups. - Four recurrence events (2.5%) occurred during follow-up: two in the standard group and two in the extended group; timing suggested earlier events were more compatible with relapse but molecular typing to distinguish relapse vs reinfection was not available. - Overall recurrence rates did not differ significantly between groups (3.4% vs. 2.0%, p = 0.966). Adverse event rates were similar, though treatment interruption due to adverse drug reactions was more frequent numerically in the extended group. - A fixed-time (200-day) exploratory analysis using **Firth’s penalized logistic regression** produced an adjusted odds ratio favoring extended treatment (aOR 0.07; 95% CI 0.01–1.06; p = 0.056), but this did not reach statistical significance and is imprecise given only four events. - Low body mass index (<18.5 kg/m²) was associated with recurrence in multivariable analysis, but the estimate was highly imprecise and should be interpreted cautiously. - Authors conclude that **cavity on chest radiograph alone** may not justify routine extension beyond 200 days; larger prospective studies with systematic microbiologic and radiologic data are needed to identify which cavitary patients might benefit from individualized extension.
## Clinical Analysis & Structured Key Points
Extended treatment duration and recurrence in successfully treated drug-susceptible pulmonary tuberculosis with cavity on chest radiograph | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Peer Review Reader Comments Figures Figures Abstract Background Cavity on chest radiograph is recognized as an independent risk factor for recurrence in pulmonary tuberculosis (TB), but evidence supporting extended treatment in these patients remains limited, particularly in real-world data from Korea. Methods We performed a retrospective analysis using data from a multicenter prospective cohort of patients with pulmonary tuberculosis enrolled at 18 Korean institutions, comparing recurrence rates between standard treatment (≤200 days) and extended treatment (>200 days) among drug-susceptible pulmonary TB patients with cavity on chest radiograph. Results Among 159 patients, 58 (36.5%) received standard treatment and 101 (63.5%) received extended treatment. Baseline sputum smear positivity was higher in the extended group (29.3% vs. 56.4%, p = 0.002), but 2-month culture positivity (6.3% vs. 4.4%, p > 0.999) and time to culture conversion (8.00 ± 3.91 vs. 7.45 ± 3.73 weeks, p = 0.454) were similar. Recurrence during post-treatment follow-up occurred in 4 patients (2.5%) and did not differ between groups (3.4% vs. 2.0%, p = 0.966). Treatment interruption due to adverse drug reactions was more frequent with extended treatment (1.7% vs. 7.9%, p = 0.204), while overall adverse event rates were comparable. In a fixed-time analysis using Firth’s penalized logistic regression, extended treatment showed a numerically lower risk of recurrence, although statistical significance was not reached (adjusted odds ratio [aOR], 0.07; 95% confidence interval [CI], 0.01–1.06; p = 0.056). Among covariates, low body mass index was associated with recurrence, but this estimate was very imprecise and should be interpreted with caution. Conclusion Cavity on chest radiograph alone may not be sufficient to justify routine extension of treatment beyond 200 days. Because only four recurrence events were observed, the adjusted association favoring extended treatment was imprecise and should be interpreted as exploratory rather than definitive. Larger prospective studies that systematically capture microbiologic response and detailed radiologic disease burden are needed to identify which patients with cavitary disease may benefit from individualized treatment extension. Citation: Yoon C-S, Kim T-O, Shin H-J, Kim JS, Kim HW, Lee EG, et al. (2026) Extended treatment duration and recurrence in successfully treated drug-susceptible pulmonary tuberculosis with cavity on chest radiograph. PLoS One 21(9): e0357772. https://doi.org/10.1371/journal.pone.0357772 Editor: Jung Yeon Heo, Ajou University School of Medicine, KOREA, REPUBLIC OF Received: February 11, 2026; Accepted: August 22, 2026; Published: September 10, 2026 Copyright: © 2026 Yoon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: The ownership of the primary datasets lies with the Korea Disease Control and Prevention Agency (KDCA) and the Korea National Institute of Health (KNIH). The de-identified datasets generated and/or analysed during the current study can be made available for replication purposes upon reasonable request. Interested researchers should first contact the corresponding author, who will provide detailed instructions for submitting a request to the KDCA/KNIH ( https://www.kdca.go.kr/kdca/index.do) , including required documents such as a brief study proposal, institutional review board (IRB) approval, and a data use agreement. Access will be granted only with permission from the KDCA/KNIH and will be limited to the scope of the approved research. Funding: This work was supported by the Research Program funded by a grant (BCRI24033) from Chonnam National University Hospital Biomedical Research Institute. The funders had no role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Introduction Pulmonary tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and transmitted via inhalation of airborne droplet nuclei generated by patients with infectious pulmonary TB. It is a preventable and treatable disease, with treatment success rates approach 95% in drug-susceptible (DS) TB when managed with the standard 6-month regimen [ 1 , 2 ]. However, advanced TB can lead to significant lung destruction and the development of cavitary lesions. The prevalence of cavitary TB has been reported to range from 29% to 87% [ 3 ]. Cavitary lesions in the lungs are associated with severe disease, including higher bacterial loads in sputum, and have been linked to an increased risk of post-treatment recurrence [ 4 – 10 ]. Recurrence is clinically important because it is associated with morbidity and mortality and may contribute to the development of drug-resistant TB [ 1 ]. To reduce recurrence risk in higher-risk phenotypes, 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, based largely on historical trial evidence and expert opinion, for patients with cavity on chest radiograph, particularly when cultures remain positive at 2 months [ 8 ]. However, contemporary evidence supporting routine treatment extension in cavitary TB remains limited. Treatment extension increases cumulative drug exposure and may increase the risk of adverse drug reactions, treatment interruptions, and additional costs. Drug resistance in M. tuberculosis arises through selection of spontaneous mutations under drug pressure, and inadequate or interrupted therapy can facilitate acquired resistance [ 11 ]. Therefore, optimizing treatment duration requires balancing potential benefits against the burden of longer therapy. We aimed to evaluate whether extending treatment beyond 200 days is associated with a reduced risk of bacteriologically confirmed recurrence during the post-treatment follow-up period among patients with DS pulmonary TB who had cavity on baseline chest radiograph. Methods Population A prospective cohort of 1,204 pulmonary TB patients who were recruited from 18 centers in South Korea between July 2019 and June 2023 was analyzed. Details of the cohort protocol have been described previously [ 12 ]. The data for this study were accessed on 30 June 2024. To evaluate the efficacy and safety of extended treatment in patients at high risk of recurrence, those with cavity on chest radiograph were included. Patients with any evidence or history of drug-resistant TB were excluded, including multidrug-resistant or rifampin-resistant TB, isoniazid mono-resistant TB, and other forms of mono-resistant TB. Accordingly, the analytic population was restricted to patients with pan-susceptible TB, defined as susceptibility to all standard HRZE components. Among these patients, only those who received the standard isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) regimen and achieved treatment success were included. Therefore, patients who did not receive the HRZE regimen, experienced treatment failure, died, transferred to other clinics, were lost to follow-up, or discontinued treatment for reasons such as consent withdrawal or changes in diagnosis were excluded. The final analytic cohort consisted of patients with cavity on chest radiograph who completed post-treatment follow-up ( Fig 1 ). Download: PNG larger image TIFF original image Fig 1. Flow chart of participant enrollment. Abbreviations: TB: tuberculosis; MDR/RR: multi-drug resistance/rifampin-resistance; HRZE: H: isoniazid; R: rifampin; Z: pyrazinamide; E: ethambutol. https://doi.org/10.1371/journal.pone.0357772.g001 Data collection For the selected patients, baseline demographic data such as age, sex, and comorbidities were recorded at the time of diagnosis. Comorbidities were defined based on documented diagnoses, relevant medication use, or available clinical information in the medical records. Diabetes mellitus and hypertension were defined by documented diagnoses or use of glucose-lowering or antihypertensive medications, respectively. Chronic pulmonary disease included asthma, chronic bronchitis, emphysema, or other chronic pulmonary diseases with ongoing respiratory symptoms. Chronic kidney disease and chronic liver disease were defined as documented chronic renal or hepatic disease. Cardiovascular disease included chronic cardiac conditions such as ischemic heart disease, heart failure, or arrhythmia; neurologic disease included chronic neurologic disorders such as stroke, dementia, or Parkinson’s disease; and malignancy included active or previous cancer. Additionally, initial clinical data, including vital signs, biochemical tests, and microbiological results, were documented. Biochemical tests, including complete blood count, liver function tests, renal function tests, and inflammation markers, were conducted through blood sampling. To evaluate cavity or multilobe infiltration, chest radiographs were assessed, and for microbiological evaluation, acid-fast bacilli (AFB) smear and culture were evaluated through sputum tests. Throughout the follow-up period, participants received regular biochemical evaluations and were closely monitored for adverse drug reactions at predefined intervals (14 days, 28 days, 2 months, and monthly thereafter). Adverse drug reactions were identified from the cohort medical records and categorized using operational definitions adapted from CTCAE version 5.0 where applicable. Although information on clinical severity was available in some medical records, formal CTCAE severity grades were not uniformly recorded in the cohort database. Therefore, adverse drug reactions were analyzed as binary outcomes based on their presence or absence rather than by severity grade. All patients were followed for a minimum of one year after treatment completion through regular outpatient visits, linkage with the national tuberculosis surveillance system, and telephone follow-up when necessary to ensure complete ascertainment of recurrence [ 12 – 14 ]. Group and study outcome The enrolled patients were categorized according to total treatment duration. Because the standard 6-month regimen corresponds to approximately 180 days, extended treatment was defined as treatment lasting >200 days, allowing an additional 2 weeks beyond the expected standard duration. This 2-week allowance was based on a previous study of prolonged TB treatment [ 15 ], which considered that treatment interruptions of ≥2 weeks during the intensive phase may require reintroduction of intensive-phase treatment and thereby prolong total treatment duration. Thus, the 200-day cutoff was selected to distinguish meaningful treatment extension from minor variations around the standard 6-month course. The primary outcome was recurrence, defined as bacteriologically confirmed tuberculosis occurring within the follow-up period after treatment completion in patients previously classified as cured or having successfully completed treatment. Statistical analysis Continuous variables are presented as means ± standard deviations, and categorical variables are presented as counts (%). When comparing the two groups, t-tests were used to compare the means of continuous variables, while Pearson’s chi-square test or Fisher’s exact test were used to analyze the associations between categorical variables. To identify factors associated with recurrence, logistic regression analyses were conducted. Because extended treatment was defined as a total treatment duration of >200 days, a fixed-time analysis at 200 days was used to ensure consistent exposure classification. Cox proportional hazards modeling was not used as the main analytic approach because total treatment duration was determined during treatment and was fully known only after treatment completion; therefore, treating it as a baseline exposure could introduce immortal-time bias. Time-dependent Cox modeling or modeling treatment duration as a continuous variable was also not applied as the main analytic approach because only four recurrence events were observed, making more complex models highly unstable. Given the small number of recurrence events and the presence of separation, both univariable and multivariable analyses were conducted using Firth’s penalized logistic regression. Univariable analyses were first performed using demographic characteristics, comorbidities, radiologic findings, and microbiologic results. Given the very small number of recurrence events, we sought to minimize overfitting by restricting the number of variables included in the multivariable model. Extended treatment was included as the main exposure of interest. Age and sex were included a priori as clinically important covariates, and variables with p 0.999). In addition, no significant difference was observed in the time to culture conversion between the groups (8.00 ± 3.91 weeks vs. 7.45 ± 3.73 weeks, respectively, p = 0.454) ( Table 2 ). Download: PNG larger image TIFF original image Table 2. Comparison of treatment outcomes between standard and extended treatment in pulmonary tuberculosis with cavity on chest radiograph. https://doi.org/10.1371/journal.pone.0357772.t002 Among the four patients with bacteriologically confirmed recurrence, two were in the standard-treatment group and two were in the extended-treatment group. In the standard-treatment group, recurrence was detected 197 days (6.5 months) and 414 days (13.6 months) after treatment completion. In the extended-treatment group, recurrence was detected 295 days (9.7 months) and 378 days (12.4 months) after treatment completion. Because molecular typing was not available, relapse and reinfection could not be definitively distinguished. Based on timing alone, the earlier recurrences were clinically more compatible with relapse, whereas the later recurrences could represent either late relapse or reinfection ( S2 Table ). Medication interruption due to adverse drug events tended to be more frequent in the extended group. However, there was no significant difference in the overall incidence of adverse events ( Table 3 ). Download: PNG larger image TIFF original image Table 3. Adverse drug reactions according to treatment duration in pulmonary tuberculosis patients with cavity on chest radiograph. https://doi.org/10.1371/journal.pone.0357772.t003 In univariable analyses using logistic regression, no baseline demographic, clinical, radiologic, or microbiologic variables were significantly associated with recurrence. Diabetes mellitus, chronic pulmonary disease, and thrombocytopenia showed nonsignificant trends toward higher recurrence, but confidence intervals were wide due to the small number of events ( S3 Table ). However, in Firth’s penalized logistic regression analysis for recurrence using a 200-day fixed-time approach, the exploratory adjusted analysis yielded an adjusted odds ratio of 0.07 for extended treatment, but this association did not reach statistical significance (95% CI, 0.01–1.06; p = 0.056). In contrast, low body mass index (BMI) (<18.5 kg/m²) was associated with recurrence in the multivariable Firth's penalized logistic regression model (OR, 81.92; 95% CI, 4.95–21,694.24; p < 0.001), although this estimate was highly imprecise due to sparse data ( Table 4 ). Download: PNG larger image TIFF original image Table 4. Firth's penalized logistic regression analysis of factors associated with recurrence in pulmonary tuberculosis patients with cavity on chest radiograph using a 200-day fixed-time approach. https://doi.org/10.1371/
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