The molecular basis of extensively drug-resistant Salmonella Typhi isolates from pediatric septicemia patients

Sepsis is a syndromic response to infections and is becoming an emerging threat to the public health sector, particularly in developing countries. Salmonella Typhi ( S . Typhi), the cause of typhoid fever, is one primary cause of pediatric sepsis in typhoid endemic areas. Extensively drug-resistant (XDR) S . Typhi is more common among pediatric patients, which is responsible for over 90% of the reported XDR typhoid cases, but the majority of antibiotic resistance studies available have been carried out using S . Typhi isolates from adult patients. Here, we characterized antibiotic-resistance profiles of XDR S . Typhi isolates from a medium size cohort of pediatric typhoid patients (n = 45, 68.89% male and 31.11% female) and determined antibiotic-resistance-related gene signatures associated with common treatment options to typhoid fever patients of 18 XDR S . Typhi representing all 45 isolates. Their ages were 1–13 years old: toddlers aging 1–2 years old (n = 9, 20%), pre-schoolers aging 3–5 years old (n = 17, 37.78%), school-age children aging 6–12 years old (n = 17, 37.78%), and adolescents aging 13–18 years old (n = 2, 4.44%). Through analyzing bla TEM1 , dhfR7 , sul1 , and catA1 genes for multidrug-resistance, qnrS , gyrA , gyrB , parC , and parE for fluoroquinolone-resistance, bla CTX-M-15 for XDR, and macAB and acrAB efflux pump system-associated genes, we showed the phenotype of the XDR S . Typhi isolates matches with their genotypes featured by the acquisitions of the genes bla TEM1 , dhfR7 , sul1 , catA1 , qnrS , and bla CTX-M-15 and a point mutation on gyrA . This study informs the molecular basis of antibiotic-resistance among recent S . Typhi isolates from pediatric septicemia patients, therefore providing insights into the development of molecular detection methods and treatment strategies for XDR S . Typhi.