Azithromycin resistance in Salmonella Typhi: navigating diagnostic uncertainties and clinical decision-making

Abstract

Background: Azithromycin susceptibility testing using disc diffusion (DD) and Etests has shown discrepancies with the broth microdilution (BMD) method. In this study, we assessed the association between azithromycin MIC distribution and disc inhibition zone size in Salmonella Typhi isolates. Methods: Non-duplicate S. Typhi isolates (n=353) were tested for azithromycin susceptibility as part of the Surveillance of Enteric Fever in India (SEFI), and a time–kill assay was performed using the measured MIC to assess the killing effect of azithromycin against S. Typhi isolates. Results: In DD testing, false-resistance/major error was noted in 1.9% of isolates. Time–kill assay revealed slow bacteriostatic activity of azithromycin against S. Typhi isolates. Conclusions: The findings of the present study advocate for careful interpretation of susceptibility results and support the continued use of azithromycin in uncomplicated cases and the recommendation of combination therapy to prevent relapses.