Epidemiology of Multidrug Resistance among Salmonella enterica serovars typhi and paratyphi A at a Tertiary Pediatric Hospital in India Over a Decade; In-silico Approach to Elucidate the Molecular Mechanism of Quinolone Resistance

Abstract

Background: Enteric fever caused by Salmonella enterica serovar typhi and Salmonella enterica serovar paratyphi A remains one of the most common causes of community-acquired bloodstream infection among children in India. Multidrug resistance is emerging and is a cause of concern as it affects the choice of treatment in enteric fever. Method: In this study, a 10-year analysis of resistance patterns was done along with in-silico homology modeling and molecular docking to understand the commonly occurring quinolone resistance. Results: A total of 1010 cases of blood culture–confirmed enteric fevers (S. typhi n=849; S. paratyphi A n=161) were recorded at the study hospital during the period from 2011-2020. Multidrug resistance among cases of S. typhi was 2.12 %, whereas it was completely absent among cases of S. paratyphi A. Fluoroquinolone resistance was high (>95%) throughout the study period. Resistance to ampicillin, chloramphenicol and co-trimoxacole was low (<3%) among S. typhi cases. No deaths were observed among study participants. Molecular docking analysis showed that quinolone had less binding affinity to mutated gyrase A than to its wild type for both S. typhi and S. paratyphi A. Conclusion: Quinolone resistance was high among cases of enteric fever, whereas no resistance was observed among third-generation cephalosporins. In-silico studies indicated that a mutation in gyrase A might be the cause of the gradual increase in ciprofloxacin resistance over the study period.

Keywords

• Enteric fever
• S. typhi
• S. paratyphi A
• Molecular docking
• Gyrase A
• Fluoroquinolone