A meta-analysis comparing the safety and efficacy of azithromycin over the alternate drugs used for treatment of uncomplicated enteric fever.

TLDR: Azithromycin can be recommended as a second-line drug in MDR typhoid fever, however, large trials involving pediatric age group patients are recommended to arrive at a definite conclusion.

Abstract: Background: Drug-resistant typhoid fever is a major clinical problem globally. Emergence of multidrug-resistant (MDR) S. Typhi has complicated therapy by limiting treatment options. Objectives: A meta-analysis was planned to determine the strength of evidence supporting use of azithromycin over the alternate drugs available for treatment of uncomplicated typhoid fever. Materials and Methods: Studies were identified using electronic database such as MEDLINE and other data at the National Library of Medicine assessed using PUBMED search engine as well as Cochrane Clinical Trial Register. Randomized control trials (RCTs) comparing azithromycin with chloramphenicol, fluoroquinolones and cephalosporins in culture-proven enteric fever were included. Data was extracted and methodological quality was assessed. Risk ratio (RR) with 95% confidence intervals was estimated for the dichotomous outcomes and mean difference (MD) with 95% confidence was estimated for continuous data. Primary outcomes studied were clinical failure (CF), microbiological failure, and relapse. Results: A total of seven RCTs involving 773 patients met with our inclusion criteria. In comparison to older fluoroquinolones, azithromycin is marginally better in reducing the chance of CF with RR 0.46 (95% CI 0.25-0.82), while in comparison to ceftriaxone, it significantly reduced the chance of relapse with RR 0.1 (95% CI 0.01- 0.76). There were no serious adverse events reported in any of the trials. Conclusion: Azithromycin can be recommended as a second-line drug in MDR typhoid fever, however, large trials involving pediatric age group patients are recommended to arrive at a definite conclusion.