Evaluation of Antimicrobial Susceptibility Profile inSalmonellaTyphi andSalmonellaParatyphi A: Presenting the Current Scenario in India and Strategy for Future Management

Abstract

Background Systematic studies to estimate the disease burden of typhoid and paratyphoid in India are limited. Therefore, a multicenter study on the Surveillance of Enteric Fever in India was carried out to estimate the incidence, clinical presentation, and antimicrobial resistance (AMR) trend. The data presented here represent the national burden of AMR in Salmonella Typhi and Salmonella Paratyphi A. Methods Antimicrobial susceptibility testing was performed for S. Typhi and S. Paratyphi A (n = 2373) isolates collected prospectively during a 2-year period from November 2017 to January 2020. Results Of 2373 Salmonella isolates, 2032 (85.6%) were identified as S. Typhi and 341 (14.4%) were S. Paratyphi A. Approximately 2% of S. Typhi were multidrug-resistant (MDR), whereas all 341 (100%) of S. Paratyphi A isolates were sensitive to the first-line antimicrobials. Among 98% of ciprofloxacin nonsusceptible isolates, resistance (minimum inhibitory concentration [MIC] >0.5 µg/mL) was higher in S. Typhi (37%) compared with S. Paratyphi A (20%). Azithromycin susceptibility was 99.9% and 100% with a mean MIC of 4.98 μg/mL for S. Typhi and 7.39 μg/mL for S. Paratyphi A respectively. Ceftriaxone was the only agent that retained 100% susceptibility. Moreover, beta-lactam/beta-lactamase inhibitors showed potent in vitro activity against the study isolates. Conclusions Data obtained from this systematic surveillance study confirms the declining trend of MDR Salmonella isolates from India. The higher prevalence of ciprofloxacin nonsusceptibility enforces to limit its use and adhere to the judicious usage of azithromycin and ceftriaxone for enteric fever management.

23-year trends indicate low rates of antimicrobial resistance inSalmonellaParatyphi A

“…In contrast, more than 98% of the Salmonella Paratyphi A isolates were nonsusceptible to fluoroquinolone. This was likely driven by overtreatment and irrational use of quinolones to treat enteric fever all over South Asia and is often mediated by single point mutations in quinolone-resistance determining region (QRDR) [33][34][35][36][37].…”

“…To date, there is only one published report of a ceftriaxone resistant Paratyphi A isolate and that was detected in the UK from a Bangladeshi traveler [38]. Other studies also found no ceftriaxone resistance in Salmonella Paratyphi A [29,32,34,36]. Examination of minimum inhibitory concentration depicted a slightly increasing trend, but the average MIC is still 32 folds lower than the MIC required to render it completely resistant to ceftriaxone.…”

Genomic analysis unveils the role of genome degradation events and gene flux in the emergence and persistence ofS. Paratyphi A lineages

“…On the contrary, fluoroquinolone non-susceptibility (FQNS) was high amongst S . Paratyphi A in South Asia, with FQNS strains from the SEFI collection accounting for 98% of all isolates [20].…”

“…Though MDR phenotypes were observed in a few S. Paratyphi A strains from the global collection, the plasmid was eventually lost during the evolution due to the greater fitness of antibioticsensitive strains [12]. On the contrary, fluoroquinolone non-susceptibility (FQNS) was high amongst S. Paratyphi A in South Asia, with FQNS strains from the SEFI collection accounting for 98% of all isolates [20]. The FQNS S. Paratyphi A were predominantly single QRDR mutant (gyrA-S83F) and distributed across the dominant phylogenetic lineages (A, C and F).…”

Unmet needs for management of drug-resistant infections: low- and middle-income countries’ viewpoint

“…Enteric fever and especially typhoidal Salmonella endemic to South and Southeast Asia and sub-Saharan Africa require continuous monitoring where changing resistance trends have been reported due to fluoroquinolones and cephalosporins ( 16 , 17 ). Drug-resistant bacteria such as third-generation cephalosporin-resistant E. coli , carbapenem-resistant A. baumannii , fluoroquinolone-resistant E. coli , carbapenem-resistant K. pneumoniae , and third-generation cephalosporin-resistant K. pneumoniae represent serious challenges in patient management, especially in critically ill patient with comorbidities ( 3 , 4 , 7 , 11 , 14 ).…”