Baseline Chest X-Ray and Sputum Predict MDR-TB Treatment Outcomes

Lesotho Clinical Cohort Study Identifies Baseline Predictors of Treatment Outcomes in Shortened MDR/RR-TB Regimens

The Tech TL;DR:
• A prospective cohort study evaluated 238 adults with bacteriologically-confirmed pulmonary MDR/RR-TB in Lesotho under NCT05871489, examining baseline microbiologic and radiographic features.
• Results showed 142 of 148 participants with positive baseline cultures achieved conversion within four months, while 27 experienced unfavorable outcomes including 20 deaths.
• Specific structural lung damage, such as severe fibrocavitary disease and multi-lobar fibrosis, negatively impacted final treatment success, pointing toward necessary risk-adapted clinical strategies.

World Health Organization-endorsed shortened, all-oral regimens have improved tolerability and outcomes for multidrug- or rifampicin-resistant tuberculosis treatment, but predictors of poor outcomes remain incompletely characterized. To address this data gap, researchers conducted a prospective cohort study (NCT05871489) of adults with bacteriologically-confirmed pulmonary multidrug-resistant or rifampicin-resistant tuberculosis treated with a shortened, all-oral regimen in Lesotho.

Radiographic Markers and Microbiologic Features in Cohort Analysis

Researchers analyzed how initial radiographic and microbiologic characteristics related to final post-treatment results, end-of-treatment success, and the duration required for culture conversion. Among 238 participants with a median age of 41 and an interquartile range from 31 to 56 years, 29 percent were female and 62 percent were living with HIV. Across this cohort, researchers recorded 27 unfavorable outcomes, which comprised 20 deaths, 3 treatment failures, and 4 recurrences.

Microbiologic conversion rates remained high among those evaluable. Specifically, 142 of 148 participants with positive baseline cultures experienced conversion within four months. However, specific structural and bacterial markers altered the trajectory of recovery. Slower culture conversion and diminished likelihood of treatment success correlated with bilateral disease, high smear grades, cavitation, and fibrosis.

Differential Impacts Across HIV Status and Cavitary Disease Severity

The statistical associations between baseline lesions and unfavorable outcomes shifted depending on patient HIV status. Bilateral disease was more strongly associated with unfavorable outcomes in participants without HIV, whereas fibrosis and high smear grade showed stronger associations among those living with HIV.

Combined structural indicators further isolated high-risk profiles. Cavitation with high smear grade demonstrated a negative association with favorable final outcomes, yielding an unadjusted odds ratio of 0.29 with a 95 percent confidence interval from 0.11 to 0.78, and an adjusted odds ratio of 0.39 with a confidence interval from 0.14 to 1.14. Severe fibrocavitary disease, defined as multi-lobar fibrosis and at least one cavity measuring 5 centimeters or larger, showed an unadjusted odds ratio of 0.20 with a 95 percent confidence interval from 0.07 to 0.64, and an adjusted odds ratio of 0.26 with a confidence interval from 0.07 to 0.94.

Implications for Risk-Adapted Treatment Strategies

These findings suggest that baseline sputum and chest radiographic features—particularly when evaluated in combination—identify higher-risk patients. Recognizing these structural and bacterial markers early may inform risk-adapted clinical strategies for shortened all-oral multidrug-resistant and rifampicin-resistant tuberculosis regimens going forward.