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.
Related
- Population Pharmacokinetics and Model-Informed Precision Dosing of Colistin Sulfate in Critically Ill Patients with Carbapenem-Resistant Gram-Negative Infections: A Prospective Pharmacokinetic-Pharmacodynamic Study.
- Outpatient parenteral antimicrobial therapy (OPAT) guidelines: A systematic review
- Optimizing intravenous amoxicillin for outpatient parenteral antimicrobial therapy
- Development of a national outpatient parenteral antimicrobial therapy (OPAT) pathway for skin and soft tissue infections in Scotland
- Caenorhabditis elegans as a Model to Dissect Pharmacokinetic and Pharmacodynamic Relationships of Gabapentinoids
BibTeX
@article{briquet2026novel,
title = {{A novel meropenem dosing strategy for Outpatient Parenteral Antimicrobial Therapy (OPAT): a pilot pharmacokinetic/pharmacodynamic study in non-critically ill patients}},
author = {Caroline Briquet and Perrin Ngougni Pokem and Xin Liu and Gert-Jan Wijnant and Olivier Cornu and Halil Yildiz and Alexia Verroken and Jason A. Roberts and Jean Cyr Yombi and Françoise van Bambeke},
journal = {Antimicrobial Agents and Chemotherapy},
year = {2026},
month = jun,
doi = {10.1128/aac.00372-26},
url = {https://hal.science/hal-05799941v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A novel meropenem dosing strategy for Outpatient Parenteral Antimicrobial Therapy (OPAT): a pilot pharmacokinetic/pharmacodynamic study in non-critically ill patients
AU - Caroline Briquet
AU - Perrin Ngougni Pokem
AU - Xin Liu
AU - Gert-Jan Wijnant
AU - Olivier Cornu
AU - Halil Yildiz
AU - Alexia Verroken
AU - Jason A. Roberts
AU - Jean Cyr Yombi
AU - Françoise van Bambeke
PY - 2026
DA - 2026/06/12
JO - Antimicrobial Agents and Chemotherapy
DO - 10.1128/aac.00372-26
UR - https://hal.science/hal-05799941v1
AB - 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.
SN - 0066-4804
SN - 1098-6596
ER -