Meropenem plasma concentration above a pathogen’s MIC over the whole dosing interval (100% ƒT_>MIC) is a determinant of outcome in severe infections. Significant variability of meropenem pharmacokinetics is reported in ICU patients.

To characterize meropenem pharmacokinetics in variable CL_CR or renal replacement therapy and assess the appropriateness of recommended regimens for MIC coverage.

A pharmacokinetic analysis (NONMEM) was conducted with external model validation. Patient characteristics were tested on meropenem clearance estimates, differentiated according to the presence/absence of continuous renal replacement therapy (CRRT, CL_CRRT or CL_no-CRRT). Simulations evaluated the appropriateness of recommended dosing for achieving 100% fT_>MIC in 90% of patients.

A total of 101 patients were studied: median 63 years (range 49–70), 56% male, SAPS II 38 (27–48). 32% had a CL_CR >60 mL/min, 49% underwent CRRT and 32% presented severe sepsis or septic shock. A total of 127 pathogens were documented: 76% Gram-negatives, 24% Gram-positives (meropenem MIC₉₀ 2 mg/L, corresponding to EUCAST susceptibility breakpoint). Three hundred and eighty plasma and 129 filtrate–dialysate meropenem concentrations were analysed: two-compartment modelling best described the data. Predicted meropenem CL_no-CRRT was 59% lower in impaired (CL_CR 30 mL/min) compared to normal (CL_CR 100 mL/min) renal function. Simulations showed that recommended regimens appropriately cover MIC₉₀ in patients with CL_CR <60 mL/min. Patients with CL_CR of 60 to <90 mL/min need 6 g/day to achieve appropriate coverage. In patients with CL_CR ≥90 mL/min, appropriate exposure is achieved with increased dose, frequency of administration and infusion duration, or continuous infusion.

Recommended meropenem regimens are suboptimal in ICU patients with normal or augmented renal clearance. Modified dosing or infusion modalities achieve appropriate MIC coverage for optimized antibacterial efficacy in meropenem-susceptible life-threatening infections.