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

Abstract

<b>Introduction.</b> Enteric fever (caused by <i>Salmonella enterica</i> serovars Typhi and Paratyphi) frequently presents as an acute, undifferentiated febrile illness in returning travellers, requiring timely empirical antibiotics.<b>Gap Statement.</b> Determining which empirical antibiotics to prescribe for enteric fever requires up-to-date knowledge of susceptibility patterns.<b>Aim.</b> By characterising factors associated with antimicrobial resistance in cases of <i>S</i>. Typhi and <i>S</i>. Paratyphi imported to England, we aim to guide effective empirical treatment.<b>Methodology.</b> All English isolates of <i>S</i>. Typhi and <i>S</i>. 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.<b>Results.</b> We identified 1088 cases of <i>S</i>. Typhi, 729 <i>S</i>. Paratyphi A, 93 <i>S</i>. Paratyphi B, and one <i>S</i>. Paratyphi C. In total, 93 % were imported. Overall, 90 % of <i>S</i>. Typhi and 97 % of <i>S</i>. Paratyphi A isolates were resistant to ciprofloxacin; 26 % of <i>S</i>. Typhi were multidrug resistant to ciprofloxacin, amoxicillin, co-trimoxazole, and chloramphenicol (MDR+FQ). Of the isolates, 4 % of <i>S</i>. 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 <i>S</i>. 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 <i>S</i>. 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 <i>S</i>. Typhi isolates to ciprofloxacin associated with travel to Pakistan (from 79-98 %) and Africa (from 12-60 %).<b>Conclusion.</b> 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.