A new article published in mBio discussed that the rising prevalence of antimicrobial resistance in Salmonella enterica serovars – Typhi and Paratyphi A—causative agents of typhoid and paratyphoid, have led to threats of untreatable infections. In particular, these species pose risk for emerging resistance against azithromycin – the only remaining oral drug to treat extensively drug resistant (XDR) typhoid. 

The genetic basis of this resistance is a single point mutation in the efflux pump AcrB (R717Q/L). This article reported 38 additional cases of azithromycin-resistant (AzmR) Salmonella Typhi and Paratyphi A isolated in Bangladesh, from 2016-2018. The authors confirmed that through genomic analysis that this mutation has spontaneously emerged in different Salmonella Typhi and Paratyphi A genotypes. The largest cluster of AzmR Typhi belonged to genotype 4.3.1.1 – the mutation was predicted to have emerged sometime in 2010. 

For real-time detection of AcrB-R717Q/L, an extraction-free, rapid and low-cost mismatch amplification mutation assay (MAMA) was developed. Validation of MAMA using 113 AzmR and non-AzmR isolates yielded > 98% specificity and sensitivity versus phenotypic and whole-genome sequencing assays—currently used for azithromycin resistance detection. 

It was stated that with increasing azithromycin use, AcrB-R717Q/L is likely to be acquired by XDR strains. Emergence of pan-oral drug resistant Salmonella Typhi is imminent. Here, a low-cost, rapid PCR tool was developed to facilitate real-time detection and prevention policies.

Source: mBio. 2021 Feb 16;12(1):e03481-20. doi: 10.1128/mBio.03481-20.