Emergence of Resistance to Fluoroquinolones and Third-Generation Cephalosporins in Salmonella Typhi in Lahore, Pakistan

Rasheed, Farhan; Saeed, Muhammad; Alikhan, Nabil-Fareed; Baker, David; Khurshid, Mohsin; Ainsworth, Emma V.; Turner, A. Keith; Imran, Ambereen Anwar; Rasool, Muhammad Hidayat; Saqalein, Muhammad; Nisar, Muhammad Atif; Rehman, Muhammad Fayyaz ur; Wain, John; Yasir, Muhammad; Langridge, Gemma C.; Ikram, Aamer

doi:10.3390/microorganisms8091336

Cited by 40 publications

(42 citation statements)

References 37 publications

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“…XDR S. Typhi shows emergence over recent years, with the first imported case identified in 2017, but 12 % of cases linked to Pakistan showing this phenotype in 2019. Imported infections caused by the XDR S. Typhi strain from Pakistan reflect the ongoing outbreak which was first reported in 2017, and has expanded since to include several regions within the country [26]. One isolate of S. Paratyphi A also showed extended resistance to beta-lactam antibiotics including ceftriaxone [27].…”

Section: Discussionmentioning

confidence: 98%

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Increasingly limited options for the treatment of enteric fever in travellers returning to England, 2014–2019: a cross-sectional analytical study

Herdman

Karo

Dave

et al. 2021

Journal of Medical Microbiology

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Introduction. Enteric fever (caused by Salmonella enterica serovars Typhi and Paratyphi) frequently presents as an acute, undifferentiated febrile illness in returning travellers, requiring timely empirical antibiotics. Gap Statement. Determining which empirical antibiotics to prescribe for enteric fever requires up-to-date knowledge of susceptibility patterns. Aim. By characterising factors associated with antimicrobial resistance in cases of S. Typhi and S. Paratyphi imported to England, we aim to guide effective empirical treatment. Methodology. All English isolates of S. Typhi and S. Paratyphi 2014–2019 underwent antimicrobial susceptibility testing; results were compared to a previous survey in London 2005–2012. Risk factors for antimicrobial resistance were analysed with logistic regression models to predict adjusted odds ratios (aOR) for resistance to individual antibiotics and multi-drug resistance. Results. We identified 1088 cases of S. Typhi, 729 S. Paratyphi A, 93 S. Paratyphi B, and one S. Paratyphi C. In total, 93 % were imported. Overall, 90 % of S. Typhi and 97 % of S. Paratyphi A isolates were resistant to ciprofloxacin; 26 % of S. Typhi were multidrug resistant to ciprofloxacin, amoxicillin, co-trimoxazole, and chloramphenicol (MDR+FQ). Of the isolates, 4 % of S. Typhi showed an extended drug resistance (XDR) phenotype of MDR+FQ plus resistance to third-generation cephalosporins, with cases of XDR rising sharply in recent years (none before 2017, one in 2017, six in 2018, 32 in 2019). For S. Typhi isolates, resistance to ciprofloxacin was associated with travel to Pakistan (aOR=32.0, 95 % CI: 15.4–66.4), India (aOR=21.8, 95 % CI: 11.6–41.2), and Bangladesh (aOR=6.2, 95 % CI: 2.8–13.6) compared to travel elsewhere, after adjusting for rising prevalence of resistance over time. MDR+FQ resistance in S. Typhi isolates was associated with travel to Pakistan (aOR=3.5, 95 % CI: 2.4–5.2) and less likely with travel to India (aOR=0.07, 95 % CI 0.04–0.15) compared to travel elsewhere. All XDR cases were imported from Pakistan. No isolate was resistant to azithromycin. Comparison with the 2005–2012 London survey indicates substantial increases in the prevalence of resistance of S. Typhi isolates to ciprofloxacin associated with travel to Pakistan (from 79–98 %) and Africa (from 12–60 %). Conclusion. Third-generation cephalosporins and azithromycin remain appropriate choices for empirical treatment of enteric fever in most returning travellers to the UK from endemic countries, except from Pakistan, where XDR represents a significant risk.

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Section: Discussionmentioning

confidence: 98%

“…Imported infections caused by the XDR S . Typhi strain from Pakistan reflect the ongoing outbreak which was first reported in 2017, and has expanded since to include several regions within the country [26]. One isolate of S .…”

Section: Discussionmentioning

confidence: 99%

Increasingly limited options for the treatment of enteric fever in travellers returning to England, 2014–2019: a cross-sectional analytical study

Herdman

Karo

Dave

et al. 2021

Journal of Medical Microbiology

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“…In 2016, outbreaks of the first widespread extensively drug resistant (XDR) clone occurred in Pakistan. This monophyletic outbreak cluster of genotype 4.3.1.1, resistant to chloramphenicol, ampicillin, and co-trimoxazole, fluroquinolones and third generation cephalosporins 7,14 , was designated genotype 4.3.1.1.P1 to aid its identification.…”

Section: Resultsmentioning

confidence: 99%

Five years of GenoTyphi: updates to the global Salmonella Typhi genotyping framework

Dyson

Holt

2021

Preprint

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In 2016 a whole genome sequence (WGS) based genotyping framework (GenoTyphi) was developed providing a phylogenetically informative nomenclature for lineages of Salmonella Typhi, the aetiological agent of typhoid fever. Subsequent surveillance studies have revealed additional epidemiologically important subpopulations, necessitating the definition of new genotypes and extension of associated software to facilitate the detection of antimicrobial resistance (AMR) mutations. Analysis of 4,632 WGS provide an updated overview of the global S. Typhi population structure and genotyping framework, revealing the widespread nature of H58 (4.3.1) genotypes and the diverse range of genotypes carrying AMR mutations.

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“…In addition to GyrA Ser83Phe , resistance to second-line antibiotics among XDR S. Typhi in Pakistan has been associated with an IncY region carrying the quinolone resistance gene qnrS (Figure 3A) and extended-spectrum -lactamase resistance gene blaCTX-M-15 (9,38).…”

Section: Molecular Basis Of Third-generation Cephalosporin-resistance Among Xdr S Typhi Isolatesmentioning

confidence: 99%

The molecular basis of extensively drug-resistant Salmonella Typhi isolates from pediatric septicemia patients

Kim

Latif

Neupane

et al. 2021

Preprint

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Sepsis is a syndromic response to infections and is becoming an emerging threat to the public health sector, particularly in developing countries. Salmonella Typhi (S. Typhi), the cause of typhoid fever, is one primary cause of pediatric sepsis in typhoid endemic areas. Extensively drug-resistant (XDR) S. Typhi is more common among pediatric patients, which is responsible for over 90% of the reported XDR typhoid cases, but the majority of antibiotic resistance studies available have been carried out using S. Typhi isolates from adult patients. Here, we characterized XDR S. Typhi isolates from a medium size cohort of pediatric typhoid patients to determine their antibiotic-resistance-related gene signatures associated with common treatment options to typhoid fever patients. This study informs the molecular basis of antibiotic-resistance among recent S. Typhi isolates from pediatric septicemia patients, therefore providing insights into the development of molecular detection methods and control strategies for XDR S. Typhi.

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Emergence of Resistance to Fluoroquinolones and Third-Generation Cephalosporins in Salmonella Typhi in Lahore, Pakistan

Cited by 40 publications

References 37 publications

Increasingly limited options for the treatment of enteric fever in travellers returning to England, 2014–2019: a cross-sectional analytical study

Increasingly limited options for the treatment of enteric fever in travellers returning to England, 2014–2019: a cross-sectional analytical study

Five years of GenoTyphi: updates to the global Salmonella Typhi genotyping framework

The molecular basis of extensively drug-resistant Salmonella Typhi isolates from pediatric septicemia patients

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