Drug-resistant enteric fever worldwide, 1990 to 2018: a systematic review and meta-analysis

Abstract

BackgroundAntimicrobial resistance (AMR) is an increasing threat to global health. There are > 14 million cases of enteric fever every year and > 135,000 deaths. The disease is primarily controlled by antimicrobial treatment, but this is becoming increasingly difficult due to AMR. Our objectives were to assess the prevalence and geographic distribution of AMR in Salmonella enterica serovars Typhi and Paratyphi A infections globally, to evaluate the extent of the problem, and to facilitate the creation of geospatial maps of AMR prevalence to help targeted public health intervention.MethodsWe performed a systematic review of the literature by searching seven databases for studies published between 1990 and 2018. We recategorised isolates to allow the analysis of fluoroquinolone resistance trends over the study period. The prevalence of multidrug resistance (MDR) and fluoroquinolone non-susceptibility (FQNS) in individual studies was illustrated by forest plots, and a random effects meta-analysis was performed, stratified by Global Burden of Disease (GBD) region and 5-year time period. Heterogeneity was assessed using the I2 statistics. We present a descriptive analysis of ceftriaxone and azithromycin resistance.FindingsWe identified 4557 articles, of which 384, comprising 124,347 isolates (94,616 S. Typhi and 29,731 S. Paratyphi A) met the pre-specified inclusion criteria. The majority (276/384; 72%) of studies were from South Asia; 40 (10%) articles were identified from Sub-Saharan Africa. With the exception of MDR S. Typhi in South Asia, which declined between 1990 and 2018, and MDR S. Paratyphi A, which remained at low levels, resistance trends worsened for all antimicrobials in all regions. We identified several data gaps in Africa and the Middle East. Incomplete reporting of antimicrobial susceptibility testing (AST) and lack of quality assurance were identified.InterpretationDrug-resistant enteric fever is widespread in low- and middle-income countries, and the situation is worsening. It is essential that public health and clinical measures, which include improvements in water quality and sanitation, the deployment of S. Typhi vaccination, and an informed choice of treatment are implemented. However, there is no licenced vaccine for S. Paratyphi A. The standardised reporting of AST data and rollout of external quality control assessment are urgently needed to facilitate evidence-based policy and practice.Trial registrationPROSPERO CRD42018029432.

First Case of Typhoid Fever due to Extensively Drug-resistant Salmonella enterica serovar Typhi in Italy

“…The case described here is the first case of typhoid fever due to XDR S. Typhi detected in Italy and one of the first paediatric cases reported outside of Pakistan. As previously described in North America, Australia and some European countries [8][9][10], globalization is one of the main causes of the diffusion of microbial resistance to currently used antibiotics and can cause relevant treatment problems for diseases for which a previous therapeutic approach did not require careful handling [4][5][6].…”

“…Drug-resistant S. Typhi emerged in the late 1970s to early 1980s and led to the use of fluoroquinolones as a major treatment option for S. Typhi cases [1]. However, studies have identified S. Typhi isolates resistant to fluoroquinolones, with the first case being reported in 1992 [3,6]. After that, treatment of typhoid fever was based on third-generation cephalosporins, ceftriaxone for parenteral therapy and cefixime for oral therapy [3,6].…”

“…However, studies have identified S. Typhi isolates resistant to fluoroquinolones, with the first case being reported in 1992 [3,6]. After that, treatment of typhoid fever was based on third-generation cephalosporins, ceftriaxone for parenteral therapy and cefixime for oral therapy [3,6]. Resistance of S. Typhi to ceftriaxone remained rare until 2016, when a large outbreak of ceftriaxone-resistant cases was reported in Pakistan [7].…”

“…However, in recent years, two problems have raised new interest in the disease: evidence that a sudden increase in the number of typhoid fever diagnoses had occurred in some, if not all, industrialized countries and the demonstration that most of the unexpected cases were due to a S. Typhi strain with extensive drug resistance. An increase in typhoid fever cases was evidenced in Australia, Canada, Denmark, Taiwan, Ireland, the United Kingdom and the United States [4][5][6]. In most of these cases, diagnosis was made in subjects with a history of travel from Pakistan, where an outbreak of extensively drug resistant (XDR) S. Typhi cases began in November 2016 [7].…”

Prevalence and antibiotic resistance of <Salmonella> spp. in South Punjab-Pakistan

“…For example more than 14 million cases of enteric fever are reported annually resulting in 135,000 deaths. S. typhi and S. paratyphi infections have been shown to be more prevalent in South Asian regions where excessive use of antibiotic has been exacerbating the emergence of multidrug resistance in these strains [14,15]. Multi-drug resistance (MDR) Salmonella serotypes have become widespread in developed economies as well including USA.…”