Mecillinam activity against multidrug-resistant Shigella sonnei and Shigella flexneri

We performed phenotypic susceptibility testing and whole-genome sequencing to investigate in vitro mecillinam activity against multidrug-resistant (MDR) Shigella. Ninety-five isolates (53 [56%] Shigella sonnei and 42 [44%] Shigella flexneri) were included. The MIC₅₀ and MIC₉₀ were 1 and 2 µg/mL, respectively, by agar dilution, and all zone diameters were ≥15 mm by disc diffusion testing. No known clinically relevant mecillinam resistance mutations (including cysB) were detected. The favorable MIC profile and absence of resistance markers make pivmecillinam an agent worth considering for the treatment of infections caused by MDR Shigella. Clinically feasible susceptibility testing methods and standardized interpretations for mecillinam and Shigella spp. are needed to guide therapy.

Rapidly emerging resistance in Shigella species leaves few antibiotic treatment options. The World Health Organization recommends pivmecillinam, a prodrug of mecillinam, for the treatment of Shigella infections. However, little is known about the susceptibility of Shigella spp. to mecillinam in North America. We performed mecillinam susceptibility testing on our collection of resistant Shigella isolates and investigated genetic mechanisms of resistance using whole-genome sequencing. We observed a favorable mecillinam susceptibility profile and a lack of known genetic mechanisms of resistance. However, in the absence of standardized laboratory guidelines for mecillinam susceptibility testing, interpreting susceptibility test results is challenging. We propose that further studies are needed to correlate susceptibility testing data with clinical outcomes, with the aim of establishing standardized clinical breakpoints for Shigella spp. and mecillinam.