A novel ciprofloxacin-resistant subclade of H58 Salmonella Typhi is associated with fluoroquinolone treatment failure
- Duy, PT
- Karkey, A
- Dongol, S
- Nhan, HT
- Thompson, CN
- Rabaa, MA
- Arjyal, A
- Holt, KE
- Wong, V
- Nga, TVT
- Phat, VV
- Tuyen, HT
- Pradhan, A
- Shrestha, SK
- Gajurel, D
- Pickard, D
- Parry, CM
- Dougan, G
- Wolbers, M
- Dolecek, C
- Thwaites, GE
- Basnyat, B
- Baker, S
DOIAbstract
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 fluo...
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