Pharmacokinetic/Pharmacodynamic Determination of Systemic MIC Breakpoints for Intermittent, Extended, and Continuous...

Intravenous mecillinam has been used for the treatment of urosepsis at several dosing regimens, including a dose of 1,000 mg three times a day (TID). In the current pharmacokinetic/pharmacodynamic (PK/PD) study, we analyzed intermittent, extended, and continuous infusion regimens of mecillinam to provide dosage recommendations to treat infections caused by Enterobacterales exhibiting relatively higher mecillinam MICs than the wild-type strains. Monte Carlo simulation studies indicated that regimens of 1,000 mg TID and 1,000 to 1,200 mg four times a day (QID) are efficacious against wild-type and extended-spectrum β-lactamase-producing Enterobacterales, respectively. Prolonged infusion regimens (extended and continuous) could cover carbapenemase producers with a higher range of MICs (2 to 8 mg/L). IMPORTANCE Previous studies have shown that intravenous mecillinam might be suitable for treatment of urosepsis. Since multidrug-resistant Enterobacterales are common pathogens in such infections, an effort was made to delineate intermittent, extended, and continuous infusion regimens that could cover pathogens exhibiting relatively higher mecillinam MICs than the wild-type strains. Our PK/PD analysis has shown that mecillinam might be considered a valuable therapeutic option for the treatment of systemic infections caused by extended-spectrum β-lactamase- and carbapenemase-producing Enterobacterales exhibiting mecillinam MICs up to 8 mg/L.