Poor correlation between meropenem and piperacillin plasma concentrations and delivered dose of continuous renal replacement therapy.

There is insufficient data on the relationship between antibiotic dosing and plasma concentrations in patients treated with continuous renal replacement therapy (CRRT). In this prospective observational study, we explored the variability in plasma concentrations of meropenem and piperacillin in critically ill patients treated with CRRT and the correlation between concentrations and CRRT intensity. Antibiotic concentrations were measured at the mid and end of the dosing interval and repeated after 2-3 days when feasible. Measured concentrations were compared to the clinical susceptible breakpoints for Pseudomonas aeruginosa, 16 and 2 mg/L for piperacillin and meropenem respectively. CRRT intensity was estimated by delivered, time-averaged, total effluent flow (Qeff), corrected for predilution. Concentrations were also compared between patients with different residual diuresis. We included 140 meropenem concentrations from 98 patients and 47 piperacillin concentrations from 37 patients. Concentrations at the mid of the dosing interval were above target at all occasions for both antibiotics. For meropenem, 6.5% of trough concentrations were below target, for piperacillin 22%. Correlations between Qeff and antibiotic concentrations or concentration T½ were either statistically not significant or weak. Meropenem concentrations and T½ differed between patients with different residual diuresis. Thus, when treating ICU patients with CRRT and recommended doses of meropenem or piperacillin, both low, suboptimal, and unnecessary high, potentially toxic, plasma concentrations are common. Plasma concentrations cannot be predicted from CRRT intensity. Residual diuresis is associated with lower meropenem concentrations, but the correlation is weak. Concentration measurements is likely the most useful approach to avoid suboptimal treatment.