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Meta-Analysis
. 2023 Dec 18;23(1):884.
doi: 10.1186/s12879-023-08893-7.

Doxycycline vs azithromycin in patients with scrub typhus: a systematic review of literature and meta-analysis

Nitin Gupta  1   2 , Carl Boodman  2   3 , Christelle Genevieve Jouego  2   4 , Steven Van Den Broucke  5
Affiliations
Meta-Analysis

Doxycycline vs azithromycin in patients with scrub typhus: a systematic review of literature and meta-analysis

Nitin Gupta et al. BMC Infect Dis. .

Abstract

Introduction: Scrub typhus is a bacterial mite-borne disease associated with poor clinical outcomes if not treated adequately. The study aimed to compare the time to defervescence, clinical failure, mortality and treatment-related adverse effects of two common drugs (doxycycline and azithromycin) used for its treatment.

Methodology: This was a systematic review and meta-analysis. All studies up to 20.03.2023 were screened for eligibility in Pubmed and Embase using a search string containing terms related to scrub typhus, doxycycline and azithromycin. After two phases of screening, all comparative studies where doxycycline and azithromycin were used to treat scrub typhus were included. The studies were critically appraised using standardised tools, and a meta-analysis was performed for time to defervescence (primary outcome), clinical failure, mortality and treatment-related adverse effects.

Results: Of 744 articles from two databases, ten were included in the meta-analysis. All but two studies had a high risk of bias. The meta-analysis for time to defervescence had a high heterogeneity and did not show any significant difference between doxycycline and azithromycin arms [Mean difference of -3.37 hours (95%CI: -10.31 to 3.57), p=0.34]. When the analysis was restricted to studies that included only severe scrub typhus, doxycycline was found to have a shorter time to defervescence [mean difference of -10.15 (95%CI: -19.83 to -0.46) hours, p=0.04]. Additionally, there was no difference between the two arms concerning clinical failure, mortality and treatment-related adverse effects.

Conclusion: The current data from studies with a high risk of bias did not find statistically significant differences in clinical outcomes between doxycycline and azithromycin for scrub typhus.

Keywords: Defervescence; Fever; Mortality; Orientia tsutsugamushi.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
PRISMA diagram showing the two screening phases and the number of included and excluded articles
Fig. 2
Fig. 2
Risk of bias analysis using (A) Cochrane Risk of Bias tool for randomised controlled trials and (B) ROBINS-1 tool for non-randomised clinical trials (including observational studies). Abbreviation: RCT- Randomised controlled trials, nRCTs- non-Randomised controlled trials, D- Domains of bias. *Colour grading- Red- High risk of bias, Yellow- Moderate risk of bias and Green- Low risk of bias. D1 to D7 stands for the various domains of critical appraisal
Fig. 3
Fig. 3
Meta-analysis of doxycycline vs. azithromycin for mean time to defervescence classified according to study type
Fig. 4
Fig. 4
Meta-analysis for time to defervescence with studies stratified according to severity
Fig. 5
Fig. 5
Meta-analysis of doxycycline vs. azithromycin showing clinical failure rates on Days 2 to 3
Fig. 6
Fig. 6
Meta-analysis of doxycycline vs. azithromycin for mortality
See this image and copyright information in PMC

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