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The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31; 9.7%) than gatifloxacin (15/34; 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(pS. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure.

Original publication

DOI

10.7554/eLife.14003

Type

Journal article

Journal

Elife

Publication Date

11/03/2016

Volume

5

Keywords

<i>s. enterica</i> serovar typhi, H58, epidemiology, fluoroquinolones, global health, human, infectious disease, microbiology, nepal, randomised controlled trial, treatment failure, typhoid fever, Anti-Bacterial Agents, Bacterial Typing Techniques, Ceftriaxone, Ciprofloxacin, Fluoroquinolones, Gatifloxacin, Genotype, Humans, Nepal, Salmonella typhi, Sequence Analysis, DNA, Treatment Failure, Typhoid Fever