Objective: The clinical impact of antibiotic resistance on treating scrub typhus remains unclear. This systematic review and meta-analysis aims to assess the effectiveness of azithromycin compared to doxycycline in treating scrub typhus.

Materials and Methods: We searched Pubmed, Embase, and Directory of Open Access Journals from database inception to 31^st March 2022. Articles were eligible for inclusion if they compared azithromycin vs. doxycycline in scrub typhus patients of all age groups with respect to defervescence within 48 hours and treatment failure after 5 days in the two groups. The dichotomous outcomes were analyzed using Mantel-Haenszel random-effects meta-analysis for odds ratio (OR) with their 95% confidence intervals (CI).

Results: From the 156 records identified, 7 full-text articles were eligible for inclusion, all having a low to moderate risk of bias. The meta-analysis of five studies, including 1,051 patients, showed that the rate of defervescence within 48 hours was lower with azithromycin (n=512) compared to doxycycline (n=539) (OR: 0.46, 95% CI: 0.28 to 0.76, p=0.002, I²: 35%). Pooled analysis of seven studies, including 1,346 patients, did not show a significant difference between the rates of treatment failure at 5 days in the two groups receiving azithromycin (n=641) vs. doxycycline (n=705) (OR: 1.51, 95% CI: 0.51 to 4.45, p=0.45, I²: 45%).

Conclusions: The findings of this meta-analysis suggest that while scrub typhus patients treated with azithromycin or doxycycline have similarly low rates of treatment failure, the use of doxycycline results in more rapid resolution of fever compared to azithromycin.