A systematic review of antimicrobial resistance in Salmonella enterica serovar Typhi, the etiological agent of typhoid.

Carl D Britto,Gordan Dougan,Vanessa K Wong,Andrew J Pollard,Gagandeep Kang

doi:10.1371/journal.pntd.0006779

Abstract

BackgroundThe temporal and spatial change in trends of antimicrobial resistance (AMR) in typhoid have not been systematically studied, and such information will be critical for defining intervention, as well as planning sustainable prevention strategies.Methodology and findingsTo identify the phenotypic trends in AMR, 13,833 individual S. Typhi isolates, reported from 1973 to 2018 in 62 publications, were analysed to determine the AMR preponderance over time. Separate analyses of molecular resistance determinants present in over 4,000 isolates reported in 61 publications were also conducted. Multi-drug resistant (MDR) typhoid is in decline in Asia in a setting of high fluoroquinolone resistance while it is on the increase in Africa. Mutations in QRDRs in gyrA (S83F, D87N) and parC (S80I) are the most common mechanisms responsible for fluoroquinolone resistance. Cephalosporin resistant S. Typhi, dubbed extensively drug-resistant (XDR) is a real threat and underscores the urgency in deploying the Vi-conjugate vaccines.ConclusionFrom these observations, it appears that AMR in S. Typhi will continue to emerge leading to treatment failure, changes in antimicrobial policy and further resistance developing in S. Typhi isolates and other Gram-negative bacteria in endemic regions. The deployment of typhoid conjugate vaccines to control the disease in endemic regions may be the best defence.

Highlights

Enteric fever is a systemic infection, caused by the Gram-negative bacteria Salmonella enterica subspecies enterica serovars Typhi and Paratyphi A, that continues to be a significant cause of morbidity and mortality in endemic regions
Typhi lineages spreading from South Asia to Africa, with resistance to first line antibiotics, and fluoroquinolones and, of concern, cephalosporins which contribute to treatment failure
The significance of this study revolves around identifying the different trends and mechanisms of antimicrobial resistance (AMR) and planning interventional strategies in light of the Viconjugate vaccine candidate which recently received Strategic Group of Experts (SAGE) recommendation and WHO pre-qualification

Summary

Introduction

Enteric fever is a systemic infection, caused by the Gram-negative bacteria Salmonella enterica subspecies enterica serovars Typhi and Paratyphi A, that continues to be a significant cause of morbidity and mortality in endemic regions. Typhi/ Paratyphi[1], and a significant proportion of isolates are resistant to multiple antimicrobials[2]. South and South-East Asia, continue to be critical hubs for enteric fever, dominated by the H58 haplotype of S. Fluoroquinolone resistance is widely prevalent across Asia, in part because of the widespread use of this class of antimicrobials. The temporal and spatial change in trends of antimicrobial resistance (AMR) in typhoid have not been systematically studied, and such information will be critical for defining intervention, as well as planning sustainable prevention strategies

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