Abstract
Antibiotic therapy failure in scrub typhus (ST) has raised concerns about first-line antibiotic efficacy, necessitating reevaluation of recommended antibiotic therapies. A multicenter retrospective analysis included 2029 non-severe ST patients hospitalized in Guangzhou from 2012 to 2018. Antibiotic therapy failure was defined as needing to switch initial antibiotics due to persistent fever, clinical deterioration, or clinician-assessed need. The clinical outcomes of three antibiotic therapies were compared. Antibiotic therapy failure led to significantly greater medical needs, as evidenced by prolonged hospital stays (8 vs. 7 days, P < 0.001), longer antibiotic courses (7 vs. 5 days, P < 0.001), increased incidence of fever lasting over 5 days(19.7% [200/1821] vs. 11.0% [41/208], P < 0.001), and increased hepatic complication rates (29.8% [62/208] vs. 20.3% [370/1821], P = 0.002). Therapy failure rates varied substantially among antibiotics, being highest for chloramphenicol (32.4%, 99/306), intermediate for azithromycin (20.5%, 53/258), and lowest for doxycycline (3.8%, 56/1465). Furthermore, failure manifestations was antibiotic-specific. Azithromycin failure was associated with cardiovascular-type severe ST (RR: 3.87, P = 0.026), whereas chloramphenicol failure was correlated with hepatic-type severe ST (RR: 2.37, P = 0.008). Antibiotic therapy failure adversely affected ST outcomes with distinct, antibiotic-specific clinical patterns. Tailored monitoring and timely antibiotic switching are essential to reduce treatment failure burden and improve patient prognosis.
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Acknowledgements
We thank healthcare workers in Guangzhou City for their efforts in disease reporting and data collection.
Funding
This work was supported by the Guangzhou Health Science and Technology Project [grant number 20221A011066]; the Key Project of Medicine Discipline of Guangzhou [grant number 2025–2027-11]; the Guangzhou Science and Technology Planning Project [grant number 2023A03J0454]; and the Guangzhou Science and Technology Innovation Commission project [grant number 202102080035].
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JLL participated in study conception and design, statistical analysis, and manuscript writing. YCH contributed to data organization and methodology. KBL and XWW participated in literature search, manuscript editing and reviewing. ZBZ and YHW contributed to data acquisition, manuscript reviewing, and project supervision.
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Our study was reviewed and approved by the Guangzhou Center for Disease Control and Prevention Ethics Committee (Number: GZCDC-ER[A]2017009). We conducted the project in line with the declaration of Helsinki. All participants were fully informed of their rights and the potential risks associated with our study and signed an informed consent form on site. Privacy and confidentiality of patient identity were maintained. All patient identification numbers and information were stripped and replaced by anonymous numbers.
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Long, J., He, Y., Li, K. et al. Antibiotic therapy failure and clinical outcomes in scrub typhus patients from Guangzhou city, southern China. Sci Rep (2026). https://doi.org/10.1038/s41598-026-38264-6
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DOI: https://doi.org/10.1038/s41598-026-38264-6
