A novel meropenem dosing strategy for Outpatient Parenteral Antimicrobial Therapy (OPAT): a pilot pharmacokinetic/pharmacodynamic study in non-critically ill patients

ABSTRACT Meropenem is a valuable option for outpatient parenteral antimicrobial therapy (OPAT) due to its broad-spectrum activity, including multidrug-resistant Gram-negative bacteria, particularly when no oral alternatives exist. However, its conventional thrice-daily dosing poses logistical challenges for home administration, as the third dose typically falls during nighttime. This prospective pharmacokinetic study evaluated the adequacy of a novel daytime-only meropenem regimen adapted for OPAT in non-critically ill hospitalized patients. Twenty-two patients receiving meropenem 2 g every 8 h were switched, once clinically stable, to a thrice-daily, 6-hourly regimen compatible with daytime administration only. Meropenem was infused over 20 min. At steady state, unbound meropenem concentrations were measured for both regimens. These data informed a population pharmacokinetic model and Monte Carlo simulations to compare the probability of achieving predefined PK/PD targets. Both the conventional and OPAT-adapted regimens achieved a probability of target attainment (PTA) >90% for 40% f T >MIC at MIC ≤4 mg/L, exceeding the EUCAST/IDSA susceptibility breakpoint of 2 mg/L. Extending the infusion duration to 3 or 5 h with the OPAT-adapted schedule restored PTA >90% for MIC ≤8 mg/L. However, trough concentrations after the evening dose were lower with the OPAT-adapted regimen than with the standard regimen (1–2 vs 3–5 mg/L, depending on infusion duration). This may increase the risk of resistance selection despite the post-antibiotic effect of meropenem. With this caveat, OPAT regimens, with infusion duration adapted to MIC, may enable practical daytime-only meropenem administration, avoiding the need for overnight nursing visits.