Association between pre-diagnostic fluoroquinolone exposure and possible acquired fluoroquinolone resistance in Mycobacterium tuberculosis in Shanghai: An EHR-based case-control study using whole-genome sequencing

Yangyi Zhang; Danni Li; Jiazhen Liu; Yuan Jiang; Xin Shen; Biao Xu

doi:10.1016/j.jinf.2025.106648

Association between pre-diagnostic fluoroquinolone exposure and possible acquired fluoroquinolone resistance in Mycobacterium tuberculosis in Shanghai: An EHR-based case-control study using whole-genome sequencing

J Infect. 2025 Nov;91(5):106648. doi: 10.1016/j.jinf.2025.106648. Epub 2025 Oct 31.

Authors

Yangyi Zhang¹, Danni Li², Jiazhen Liu³, Yuan Jiang⁴, Xin Shen⁵, Biao Xu⁶

Affiliations

¹ Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, PR China; Division of TB and HIV/AIDS Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, PR China.
² Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, PR China.
³ Shanghai Health Statistics Center, Shanghai, PR China.
⁴ Division of TB and HIV/AIDS Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, PR China.
⁵ Division of TB and HIV/AIDS Prevention, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, PR China. Electronic address: shenxin@scdc.sh.cn.
⁶ Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety, Fudan University, Shanghai, PR China. Electronic address: bxu@shmu.edu.cn.

PMID: 41177177
DOI: 10.1016/j.jinf.2025.106648

Abstract

Objectives: Fluoroquinolones (FQ) are one of the most prescribed broad-spectrum antibiotics and a cornerstone of tuberculosis (TB) treatment. TB patients may have had FQ resistance before treatment initiation. However, the association between pre-diagnostic FQ exposure and acquired FQ-resistant TB remains unclear.

Methods: A case-control study was conducted among all pulmonary TB patients in Shanghai during 2022-2023. Cases were TB patients who had possible acquired FQ resistance identified through whole-genome sequencing (WGS), while controls were FQ susceptible patients. Pre-diagnostic FQ prescriptions were extracted from the Shanghai Electronic Health Record (EHR) platform.

Results: Among 3496 patients, 7.4% had FQ-resistant TB, with 93.5% (243/260) phylogenetically inferred as possible acquired resistance. Multivariate analysis revealed FQ exposure was the strongest predictor of possible acquired FQ resistance with an aOR of 4.31 for a single prescription and 13.18 for multiple prescriptions. A nonlinear dose-response relationship between resistance probability and prescription number was found. Most prescriptions to cases were from non-TB-designated tertiary hospitals for non-TB respiratory diseases, with an exposure interval of ≥61 days prior to TB diagnosis.

Conclusion: Acquired resistance dominates FQ resistance in Shanghai TB patients. The dose-response relationship between pre-diagnostic FQ exposure and possible acquired resistance underscores the need for judicious FQ use.

Keywords: Electronic health records; Fluoroquinolones resistance; Tuberculosis; Whole-genome sequencing.

MeSH terms

Adult
Aged
Anti-Bacterial Agents* / therapeutic use
Antitubercular Agents* / pharmacology
Antitubercular Agents* / therapeutic use
Case-Control Studies
China / epidemiology
Drug Resistance, Bacterial*
Electronic Health Records
Female
Fluoroquinolones* / pharmacology
Fluoroquinolones* / therapeutic use
Humans
Male
Middle Aged
Mycobacterium tuberculosis* / drug effects
Mycobacterium tuberculosis* / genetics
Tuberculosis, Multidrug-Resistant / drug therapy
Tuberculosis, Multidrug-Resistant / epidemiology
Tuberculosis, Multidrug-Resistant / microbiology
Tuberculosis, Pulmonary* / drug therapy
Tuberculosis, Pulmonary* / microbiology
Whole Genome Sequencing
Young Adult

Substances

Fluoroquinolones
Antitubercular Agents
Anti-Bacterial Agents