Ceftriaxone resistant Salmonella Typhi carries an IncI1-ST31 plasmid encoding CTXM-15

Purpose: Ceftriaxone is the drug of choice for typhoid fever and the emergence of resistant Salmonella Typhi raises major concerns for treatment. There are an increasing number of sporadic reports of ceftriaxone resistant S. Typhi and limiting the risk of treatment failure in the patient and outbreaks in the community must be prioritised. This study describes the use of whole genome sequencing to guide outbreak identification and case management. Methodology: An isolate of ceftriaxone resistant S. Typhi from the blood of a child taken in 2011 at the Popular Diagnostic Center, Dhaka, Bangladesh was subjected to whole genome sequencing, using an Illumina NextSeq 500 and analysis using Geneious software. Results: Comparison with other ceftriaxone resistant S. Typhi revealed an isolate from the Democratic Republic of the Congo in 2015 as the closest relative but no evidence of an outbreak. A plasmid belonging to incompatibility group I1 (IncI1-ST31) which included blaCTX-M-15 (ceftriaxone resistance) associated with ISEcp-1 was identified. High similarity (90%) was seen with pS115, an IncI1 plasmid from S. Enteritidis, and with pESBL- EA11, an incI1 plasmid from E. coli (99%) showing that S. Typhi has access to ceftriaxone resistance through the acquisition of common plasmids. Conclusions: The transmission of ceftriaxone resistance from E. coli to S. Typhi is of concern because of clinical resistance to ceftriaxone, the main stay of typhoid treatment. Whole genome sequencing, albeit several years after the isolation, demonstrated the success of containment but clinical trials with alternative agents are urgently required.