The emergence of azithromycin-resistant Salmonella Typhi in Nepal

Abstract

AbstractTyphoid fever remains a significant cause of morbidity and mortality in Asia and Africa. The emergence of azithromycin resistance in South Asia is concerning, as azithromycin is one of the last effective oral drugs for treating typhoid. In mid-2019, three azithromycin-resistant (AzithR) S. Typhi isolates were isolated from typhoid fever patients attending Patan Hospital, Kathmandu, Nepal. These organisms were whole genome sequenced and compared with a global collection. We found that the three AzithR isolates belonged to the H58 lineage and were genetically identical; they were distantly related to contemporaneous S. Typhi from Nepal and AzithRS. Typhi recently described in Bangladesh. Azithromycin resistance was mediated by nonsynonymous mutation in the acrB gene (R717L). Clinical information from one patient suggested non-response to azithromycin treatment. Further investigations are needed to evaluate treatment responses to azithromycin, predict AzithRS. Typhi’s evolutionary trajectories, and track the transmission of these organisms.