Drug Exposure and Susceptibility of Pyrazinamide Correlate with Treatment Response in Pyrazinamide-Susceptible Patients with Multidrug-Resistant Tuberculosis
Shulan Dong,
Ge Shao,
Lina Davies Forsman,
Sainan Wang,
Shanshan Wang,
Jiayi Cao,
Ziwei Bao,
Judith Bruchfeld,
Jan-Willem C. Alffenaar,
Jia Liu,
Yi Hu,
Meiying Wu
Affiliations
Shulan Dong
Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai 201203, China
Ge Shao
Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai 201203, China
Lina Davies Forsman
Department of Medicine, Division of Infectious Diseases, Karolinska Institutet Solna, 171 77 Stockholm, Sweden
Sainan Wang
Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai 201203, China
Shanshan Wang
Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai 201203, China
Jiayi Cao
Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai 201203, China
Ziwei Bao
Department of Infectious Diseases, The Fifth People’s Hospital of Suzhou, Suzhou 215007, China
Judith Bruchfeld
Department of Medicine, Division of Infectious Diseases, Karolinska Institutet Solna, 171 77 Stockholm, Sweden
Jan-Willem C. Alffenaar
School of Pharmacy, Faculty of Medicine and Health, University of Sydney, Sydney 2006, Australia
Jia Liu
Department of Infectious Diseases, The Fifth People’s Hospital of Suzhou, Suzhou 215007, China
Yi Hu
Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai 201203, China
Meiying Wu
Department of Infectious Diseases, The Fifth People’s Hospital of Suzhou, Suzhou 215007, China
Exploring the influence of pyrazinamide exposure and susceptibility on treatment response is crucial for optimizing the management of multidrug-resistant tuberculosis (MDR-TB). This study aimed to investigate the association between pyrazinamide exposure, susceptibility, and response to MDR-TB treatment, as well as find clinical thresholds for pyrazinamide. A prospective multi-center cohort study of participants with MDR-TB using pyrazinamide was conducted in three TB-designated hospitals in China. Univariate and multivariate analyses were applied to investigate the associations. Classification and Regression Tree (CART) analysis was used to identify clinical thresholds, which were further evaluated by multivariate analysis and receiver operating characteristic (ROC) curves. The study included 143 patients with MDR-TB. The exposure/susceptibility ratio of pyrazinamide was associated with two-month culture conversion (adjusted risk ratio (aRR), 1.1; 95% confidence interval (CI), 1.07–1.20), six-month culture conversion (aRR, 1.1; 95% CI, 1.06–1.16), treatment success (aRR, 1.07; 95% CI, 1.03–1.10), as well as culture conversion time (adjusted hazard ratio (aHR) 1.18; 95% CI,1.14–1.23). The threshold for optimal improvement in sputum culture results at the sixth month of treatment was determined to be a pyrazinamide AUC0–24h/MIC ratio of 7.8. In conclusion, the exposure/susceptibility ratio of pyrazinamide is associated with the treatment response of MDR-TB, which may change in different Group A drug-based regimens.
