A novel ciprofloxacin resistant subclade of H58 Salmonella Typhi is associated with fluoroquinolone treatment failure
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)(p<0.001) H58 is the dominant S. 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. Clinical trial registration: ISRCTN63006567. DOI: http:/dx.doi.org/10.7554/eLife.14003.001
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