A Systematic Review on Antimicrobial Resistance among Typhi Worldwide.

Understanding patterns and trends of antimicrobial resistance (AMR) in 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 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 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 Typhi isolates that were MDR increased each consecutive decade from 1990 to 1999 through 2010 to 2018. Typhi has developed resistance to an increasing number of antimicrobial classes in Asia, where XDR 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.