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Peer-reviewedCC BYJournal of Infection

Early sputum bacterial load dynamics predict treatment response in multidrug-resistant/rifampicin-resistant tuberculosis: A multicenter prospective cohort study

  • Fuzhen Zhang1
  • Zilong Yang2
  • Min Jiang2
  • Xiaomeng Hu3
  • Jun Li3
  • Kewei Liu4
  • Yilin Wang5
  • Yan Hu3
  • Yu Dong5
  • Mingyang Qin5
  • Qiang Li4
  • Liang Li6
1 more authors
  • Yu Pang6
6 affiliations
  1. 1Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing 101149, PR China; School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafety, Shenzhen Campus of Sun Yat-sen University, Sun Yat-sen University, Guangdong 518107, PR China
  2. 2Department of Tuberculosis, Guangzhou Chest Hospital/ Guangzhou Key Laboratory of Tuberculosis Research/ State Key Laboratory of Respiratory Disease, Guangzhou 510095, PR China
  3. 3Wuhan Pulmonary Hospital, Wuhan Institute for Tuberculosis Control, Wuhan, Hubei Province 430030, PR China
  4. 4Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, PR China
  5. 5Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing 101149, PR China
  6. 6Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing 101149, PR China; Corresponding author.
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Abstract

Objectives: Early assessment of treatment response is critical for optimizing the management of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). We aimed to establish a molecular bacterial load assay (MBLA) and evaluate early bacterial load dynamics for predicting 6-month treatment response. Methods: A multicenter prospective cohort study enrolled patients with MDR/RR-TB in China. MBLA was established and validated against conventional culture methods. Generalized linear mixed models (GLMM) and artificial neural network (ANN) models were constructed by integrating 14-day and 2-month bacterial load changes, and evaluated using area under the curve (AUC), accuracy, sensitivity, specificity, and F1 score. Results: MBLA enabled quantification within 24 h and strongly correlated with conventional culture (r = 0.792, −0.790; both P < 0.001). Patients with 6-month sputum culture conversion showed a rapid decline in sputum bacterial load, especially within the first 14 days after treatment initiation. Sputum bacterial load changes over the first 14 days of treatment yielded acceptable prognostic performance for predicting 6-month treatment response, albeit inferior to those obtained at 2 months. The ANN model outperformed the GLMM, with testing set AUCs of 0.91 (14-day) and 0.98 (2-month). Conclusions: MBLA enables rapid quantification of viable sputum bacterial load. The ANN model incorporating 14-day bacterial load dynamics achieves a favorable AUC for predicting 6-month sputum culture conversion. It may only serve as an auxiliary early-warning indicator to supplement routine clinical assessment for MDR/RR-TB patients. Prospective interventional trials and independent external validation are required before any consideration of its use to inform personalized anti-tuberculosis treatment decisions.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026early,
  title = {{Early sputum bacterial load dynamics predict treatment response in multidrug-resistant/rifampicin-resistant tuberculosis: A multicenter prospective cohort study}},
  author = {Fuzhen Zhang and Zilong Yang and Min Jiang and Xiaomeng Hu and Jun Li and Kewei Liu and Yilin Wang and Yan Hu and Yu Dong and Mingyang Qin and Qiang Li and Liang Li and Yu Pang},
  journal = {Journal of Infection},
  year = {2026},
  month = oct,
  doi = {10.1016/j.jinf.2026.106838},
  url = {https://doi.org/10.1016/j.jinf.2026.106838},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Early sputum bacterial load dynamics predict treatment response in multidrug-resistant/rifampicin-resistant tuberculosis: A multicenter prospective cohort study
AU  - Fuzhen Zhang
AU  - Zilong Yang
AU  - Min Jiang
AU  - Xiaomeng Hu
AU  - Jun Li
AU  - Kewei Liu
AU  - Yilin Wang
AU  - Yan Hu
AU  - Yu Dong
AU  - Mingyang Qin
AU  - Qiang Li
AU  - Liang Li
AU  - Yu Pang
PY  - 2026
DA  - 2026/10/23
JO  - Journal of Infection
DO  - 10.1016/j.jinf.2026.106838
UR  - https://doi.org/10.1016/j.jinf.2026.106838
AB  - Objectives: Early assessment of treatment response is critical for optimizing the management of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB). We aimed to establish a molecular bacterial load assay (MBLA) and evaluate early bacterial load dynamics for predicting 6-month treatment response. Methods: A multicenter prospective cohort study enrolled patients with MDR/RR-TB in China. MBLA was established and validated against conventional culture methods. Generalized linear mixed models (GLMM) and artificial neural network (ANN) models were constructed by integrating 14-day and 2-month bacterial load changes, and evaluated using area under the curve (AUC), accuracy, sensitivity, specificity, and F1 score. Results: MBLA enabled quantification within 24 h and strongly correlated with conventional culture (r = 0.792, −0.790; both P < 0.001). Patients with 6-month sputum culture conversion showed a rapid decline in sputum bacterial load, especially within the first 14 days after treatment initiation. Sputum bacterial load changes over the first 14 days of treatment yielded acceptable prognostic performance for predicting 6-month treatment response, albeit inferior to those obtained at 2 months. The ANN model outperformed the GLMM, with testing set AUCs of 0.91 (14-day) and 0.98 (2-month). Conclusions: MBLA enables rapid quantification of viable sputum bacterial load. The ANN model incorporating 14-day bacterial load dynamics achieves a favorable AUC for predicting 6-month sputum culture conversion. It may only serve as an auxiliary early-warning indicator to supplement routine clinical assessment for MDR/RR-TB patients. Prospective interventional trials and independent external validation are required before any consideration of its use to inform personalized anti-tuberculosis treatment decisions.
SN  - 1532-2742
ER  -