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A novel ciprofloxacin-resistant subclade of H58 Salmonella Typhi is associated with fluoroquinolone treatment failure.

Duy Pham Thanh | Abhilasha Karkey | Sabina Dongol | Nhan Ho Thi | Corinne N Thompson | Maia A Rabaa | Amit Arjyal | Kathryn E Holt | Vanessa Wong | Nga Tran Vu Thieu | Phat Voong Vinh | Tuyen Ha Thanh | Ashish Pradhan | Saroj Kumar Shrestha | Damoder Gajurel | Derek Pickard | Christopher M Parry | Gordon Dougan | Marcel Wolbers | Christiane Dolecek | Guy E Thwaites | Buddha Basnyat | Stephen Baker
eLife | 2016

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.

Pubmed ID: 26974227

Research resources used in this publication

None found

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Antibodies used in this publication

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Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 100087
  • Agency: Medical Research Council, United Kingdom
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Wellcome Trust, United Kingdom
    Id: 106158/Z/14/Z
  • Agency: Wellcome Trust, United Kingdom
    Id: 100087/Z/12/Z

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This is a list of tools and resources that we have found mentioned in this publication.


SAMTOOLS (tool)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

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SMALT (tool)

RRID:SCR_005498

Software that aligns DNA sequencing reads with a reference genome. Reads from a wide range of sequencing platforms, for example Illumina, Roche-454, Ion Torrent, PacBio or ABI-Sanger, can be processed including paired reads.

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RAxML (tool)

RRID:SCR_006086

Software program for phylogenetic analyses of large datasets under maximum likelihood.

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