A Systematic Review on Antimicrobial Resistance among Salmonella Typhi Worldwide

Abstract

Understanding patterns and trends of antimicrobial resistance (AMR) in Salmonella Typhi can guide empiric treatment recommendations and contribute to country decisions about typhoid conjugate vaccine (TCV) introduction. We systematically reviewed PubMed and Web of Science for articles reporting the proportion of Salmonella Typhi isolates resistant to individual antimicrobials worldwide from any time period. Isolates resistant to chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole were classified as multidrug resistant (MDR), and isolates that were MDR plus resistant to a fluoroquinolone and a third-generation cephalosporin were extensively drug resistant (XDR). Among the 198 articles eligible for analysis, a total of 55,459 Salmonella Typhi isolates were tested for AMR (median 80; range 2-5,191 per study). Of isolates from 2015 through 2018 in Asia, 1,638 (32.6%) of 5,032 were MDR, 167 (5.7%) of 2,914 were resistant to third-generation cephalosporins, and 148 (8.3%) of 1,777 were resistant to azithromycin. Two studies from Pakistan reported 14 (2.6%) of 546 isolates were XDR. In Africa, the median proportion of Salmonella Typhi isolates that were MDR increased each consecutive decade from 1990 to 1999 through 2010 to 2018. Salmonella Typhi has developed resistance to an increasing number of antimicrobial classes in Asia, where XDR Salmonella Typhi is now a major threat, whereas MDR has expanded in Africa. We suggest continued and increased surveillance is warranted to inform empiric treatment decisions and that AMR data be incorporated into country decisions on TCV introduction.

Figure 1.

Preferred reporting items for systematic reviews and meta-analyses flow diagram of search strategy and selection of articles for antimicrobial resistance in Salmonella Typhi, 1972–2018. Some articles met the multiple exclusion criteria, and thus the sum of exclusion reasons is greater than the number of articles excluded.

Figure 2.

(A) Number of study sites and isolates tested by country in the Asia region, 1972–2018 (created with MapChart). Number for each country denotes the number of study sites that reported data for Salmonella Typhi resistance. (B) Number of study sites and isolates tested by country in the Africa region, 1972–2018 (created with MapChart). Number for each country denotes the number of study sites that reported data for Salmonella Typhi resistance.

Figure 3.

(A) Antimicrobial resistant Salmonella Typhi isolates worldwide, 1972–2018. (B) Antimicrobial resistant Salmonella Typhi isolates in Asia, 1972–2018. (C) Antimicrobial resistant Salmonella Typhi isolates in Africa, 1972–2018. Full data provided in Supplement Table S4. *Ordered chronologically by antimicrobial agent introduction and grouped by color by multidrug resistant and extensively drug resistant phenotypes. †Fluoroquinolone includes ciprofloxacin and ofloxacin. ‡Third-generation cephalosporin includes ceftriaxone and cefotaxime.