Abstract: Objective To evaluate the efficacy, symptom improvement, and the impact on liver function of doxycycline versus azithromycin in patients with scrub typhus and hepatic impairment, and to analyze the safety of both drugs. Methods A total of 90 patients diagnosed with scrub typhus and hepatic impairment treated from January 2019 to December 2023 at the First People's Hospital of Suqian City were included in the study. Stratified random sampling was used to divide the patients into a trial group (45 patients) and a control group (45 patients). Patients in the control group received azithromycin, while those in the trial group were treated with doxycycline. The two groups were compared in terms of efficacy, symptom improvement, liver function, serum cytokine levels, and adverse reactions. Results The total effective rate of clinical treatment was 95.55% in the experimental group and 91.11% in the control group. Although the experimental group showed slightly better results, the difference was not statistically significant (χ²=0.714, P=0.398). After 7 days of treatment, the experimental group showed significantly shorter durations for fever resolution, headache relief, scab disappearance, reduction of lymph node swelling, rash disappearance, and liver damage recovery, with times of (2.22 ± 1.13) d, (3.22 ± 1.12) d, (3.69 ± 0.47) d, (6.46 ± 1.35) d, (6.23 ± 1.35) d, and (3.75 ± 1.03) d respectively, compared to the control group (4.22 ± 2.13) d, (5.56 ± 2.91) d, (5.82 ± 0.99) d, (9.21 ± 2.94) d, (9.20 ± 2.93) d, and (6.86 ± 1.27) d; all differences were statistically significant (t=5.466, 4.715, 12.283, 5.527, 5.566, 12.184, all P<0.05). Both groups showed a reduction in ALT and AST levels post-trearment, but there was no significant difference between groups (P>0.05). Post-treatment TNF-α, IL-6, and INF-γ levels were significantly lower in the experimental group at (32.59 ± 10.61) ng/L, (52.31 ± 16.31) ng/L, and (1.14 ± 0.52) ng/mL compared to the control group (58.39 ± 11.79) ng/L, (88.57 ± 20.46) ng/L, and (2.48 ± 0.72) ng/mL, respectively (t=10.912, 9.296, 10.561, all P<0.05). The total incidence of adverse reactions such as abdominal pain, diarrhea, nausea, vomiting, headache, somnolence, and dizziness was 4.44% in the experimental group, lower than 15.55% in the control group, although this difference was not statistically significant (χ²=3.086, P=0.079). Conclusion Doxycycline shows rapid improvement in symptoms and decreases in inflammatory markers in patients with scrub typhus and hepatic impairment. Although the overall efficacy is similar to azithromycin, doxycycline shows slight advantages in speeding symptom resolution and safety, making it an effective and safe treatment option.

Key words: Doxycycline, Azithromycin, Scrub typhus, Liver damage, Serum cytokines, Efficacy, Safety