Antibiotic therapy failure and clinical outcomes in scrub typhus patients from Guangzhou city, southern China

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.