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BackgroundThe emergence and spread of antimicrobial resistance (AMR) pose a major threat to the effective treatment and control of typhoid fever. The ongoing outbreak of extensively drug-resistant Salmonella Typhi (S. Typhi) in Pakistan has left azithromycin as the only remaining broadly efficacious oral antimicrobial for typhoid in South Asia. Ominously, azithromycin-resistant S. Typhi organisms have been subsequently reported in Bangladesh, Pakistan, and Nepal.MethodsHere, we aimed to understand the molecular basis of AMR in 66 S. Typhi organisms isolated in a cross-sectional study performed in a suburb of Chandigarh in Northern India using whole-genome sequencing and phylogenetic analysis.ResultsWe identified 7 S. Typhi organisms with the R717Q mutation in the acrB gene that was recently found to confer resistance to azithromycin in Bangladesh. Six out of the seven azithromycin-resistant S. Typhi isolates also exhibited triple mutations in gyrA (S83F and D87N) and parC (S80I) genes and were resistant to ciprofloxacin. These contemporary ciprofloxacin/azithromycin-resistant isolates were phylogenetically distinct from each other and from those reported from Bangladesh, Pakistan, and Nepal.ConclusionsThe independent emergence of azithromycin-resistant typhoid in Northern India reflects an emerging broader problem across South Asia and illustrates the urgent need for the introduction of typhoid conjugate vaccines in the region.

Original publication

DOI

10.1093/cid/ciaa1773

Type

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Publication Date

03/2021

Volume

72

Pages

e120 - e127

Addresses

Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, United Kingdom.

Keywords

Humans, Salmonella typhi, Typhoid Fever, Azithromycin, Anti-Bacterial Agents, Microbial Sensitivity Tests, Cross-Sectional Studies, Phylogeny, Drug Resistance, Bacterial, Genotype, Bangladesh, India, Nepal, Pakistan