New Perspectives on Antimicrobial Agents: Pivmecillinam.

Pivmecillinam is a prodrug of mecillinam, a semi-synthetic penicillin, that has recently been U.S. Food and Drug Administration approved for the treatment of uncomplicated urinary tract infections (UTIs) in the United States. Mecillinam demonstrates activity against a variety of common uropathogens, including Enterobacterales such as Escherichia coli and Klebsiella pneumoniae. Despite being available internationally for more than four decades, mecillinam retains high susceptibility rates against a variety of Enterobacterales, including some that produce extended-spectrum-β-lactamases (ESBL) and carbapenemases. Given extensive clinical experience and history with this agent outside the United States, this review highlights the available literature on pivmecillinam regarding susceptibility testing and implementation, empiric antibacterial activity with a focus on ESBL-producing isolates, optimal treatment dose, and duration, as well as adverse effects and tolerability. In the United States, the current lack of approved susceptibility tests will limit pivmecillinam use to empiric therapy. There is significant heterogeneity among clinical studies, limiting the ability to identify an optimal treatment regimen for most pathogens with certainty. Comparative data regarding pivmecillinam against other agents used for UTI treatment are similarly limited but do not suggest it is significantly different in terms of clinical outcomes when considering specific treatment regimens. Clinical data regarding pivmecillinam's use in UTI due to ESBL-producing Enterobacterales are less robust but appear supportive if used at higher doses and for longer durations. Pivmecillinam is generally well tolerated, with gastrointestinal-related complaints being the most common. In the future, the availability of susceptibility testing and clinical data for pivmecillinam against OXA-48-like-producing Enterobacterales could expand its therapeutic utility for UTI treatment.