Characteristics of Resistance Mechanisms and Molecular Epidemiology of Fluoroquinolone-Nonsusceptible Serovar Typhi and Paratyphi A Isolates from a Tertiary Hospital in Dhaka, Bangladesh.

The aim of this study was to characterize the fluoroquinolone (FQ) resistance mechanism of serovar Typhi and Paratyphi A in Bangladesh. Typhi isolates were classified into sequence type (ST) 1, ST2, and ST2209 and Paratyphi A isolates were classified into ST85 and ST129. The most common STs of the FQ-nonsusceptible strain were ST1 (44.4%) and ST129 (66.6%). Thirty-nine percent of Typhi isolates were multidrug resistant, and these were all ST1, which is the type prevalent in the Indian subcontinent. Although plasmid-mediated quinolone resistance genes were not detected in any of the tested strains, single and double mutations were identified in the quinolone resistance-determining region (QRDR). The most common QRDR mutation was GyrA_Ser83Phe (66.7% for Typhi and 100% for Paratyphi A). Treatment with an efflux pump inhibitor resulted in susceptibility of the strains to levofloxacin. All isolates demonstrated 100% susceptibility to ceftriaxone, azithromycin, and carbapenem. Our results suggest that mutations in gyrase A and enhancement of efflux pump activity are responsible for the resistance to FQs; in particular, the AcrAB-TolC efflux pump may be an important resistance factor for levofloxacin. To control the spread of FQ-nonsusceptible Typhi, intensive surveillance in endemic areas, including Bangladesh, and effective infection control are necessary.