Mecillinam activity against multidrug-resistant <i>Shigella sonnei</i> and <i>Shigella flexneri</i>

Rapidly emerging resistance in <i>Shigella</i> species leaves few antibiotic treatment options. The World Health Organization recommends pivmecillinam, a prodrug of mecillinam, for the treatment of <i>Shigella</i> infections. However, little is known about the susceptibility of <i>Shigella</i> spp. to mecillinam in North America. We performed mecillinam susceptibility testing on our collection of resistant <i>Shigella</i> 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 <i>Shigella</i> spp. and mecillinam.