Common Determinants Of Antimicrobial Resistance In Sequential Episodes Of Sexually Transmitted Shigellosis In Men Who Have Sex With Men: A Cross-Sectional Study

Abstract Background In high-income nations, men who have sex with men (MSM) are at increased risk of shigellosis. A sublineage of Shigella flexneri serotype 3a was recently shown to have spread worldwide in MSM, driven by mobilisable azithromycin resistance. Since then, the serotype 2a and the species S sonnei have become epidemic in the UK. We aimed to determine whether these subsequent outbreaks were also attributable to epidemic sublineages in MSM and mobilisable antimicrobial resistance. Methods We applied whole-genome sequencing to a random cross-section of S flexneri 2a (n=176) and S sonnei (n=188) isolates submitted to the UK national reference laboratory between 2004 and 2014 (10% and 2% of travel-associated and 20% and 10% of domestically acquired cases, respectively). Phylogenetic analysis and patient data (date of illness, age, sex, travel history) were combined to identify potential MSM-associated sublineages, and antimicrobial resistance determinants were compared among S sonnei , S flexneri 2a, and pandemic S flexneri 3a. Findings Shorter phylogenetic distances (more closely related isolates) were statistically associated with male–male patient pairs for both S sonnei and S flexneri 2a. For S flexneri 2a, this association manifested as a single low-diversity sublineage containing 47 of 176 isolates collected over the epidemic window (2012–2014) mainly (43 of the 47 isolates) from 16–60-year-old male patients without recent travel. This lineage was associated with azithromycin resistance (odds ratio 25·8, p S flexneri 3a sublineage. For S sonnei there were multiple low-diversity sublineages with similar patient profiles, some of which were associated with this azithromycin resistance determinant. Interpretation These results suggest that outbreaks of S flexneri 2a and S sonnei were associated with MSM. The mobilisation of azithromycin resistance between S flexneri 3a, S flexneri 2a, and S sonnei indicates that antimicrobial resistance has a role in driving these epidemic waves. The presence of a single resistance determinant associated with all three epidemics suggests that future antimicrobial resistance surveillance might be enhanced by focusing at the level of genetic determinants rather than pathogens. Funding Wellcome Trust, Public Health England.