Introduction: Typhoid fever is a severe and potentially life-threatening bacteraemic disease caused by Salmonella enterica serovar Typhi (S. Typhi). In November 2016 an outbreak of extensively drug-resistant (XDR) S. Typhi was described originating in Pakistan. XDR Salmonella Typhi isolates are characterized by their resistance to first-line antimicrobials, fluoroquinolones, and third-generation cephalosporins. Since then, the emergence and spread of these isolates has been documented in different regions of the world, posinge significant challenges to public health, surveillance, antimicrobial resistance monitoring, and the development of alternative treatment strategies.

Objectives: Monitoring S. Typhi cases and isolate cluster occurring in Germany, especially to monitor the spread of resistant isolates.

Methods: Therefor, we sequenced all S. Typhi isolates submitted to the NRC from 2015 to 2023 and established cgMLST as routine typing method for cluster detection using an ad hoc scheme based on the reference strain CT18 comprising 3.687 loci and the EnteroBase wgMLST scheme in SeqSphere+ . Furthermore, we used the NGS data to identify and compare isolates of lineage H58 and XDR, that are characterized by 44 SNPs and multiple antibiotic resistances.

Results: In total we sequenced 408 S. Typhi isolates and were able to identify the XDR specific SNPs in 18 XDR isolates. In all cases these isolates were associated with travel to Pakistan. Our analysis showed an increase in multidrug-resistant S. Typhi isolates in Germany, especially since the emergence of the first XDR isolates.

Summary: We present the sequence-based surveillance of S. Typhi isolated in Germany to identify potential NGS clusters and the emergence of multidrug-resistant pathogens that represent an increasing challenge in the treatment of S. Typhi infections.