Adequate posology of antimicrobial therapy in the septic critically ill in continuous veno-venous hemofiltration: a single centre prospective observational study

Background Determining the optimal antibiotic (ATB) dosage in septic critically ill patients on continuous renal replacement therapy (CRRT) is still challenging. CRRT further disrupts antibiotic PK, already altered by sepsis-induced fluid shifts, volume of distribution (VD) changes and half-life modifications.Materials and methods Our multi-disciplinary team-comprising an intensivist, nephrologist and clinical pharmacologist-conducted a prospective observational cohort study to evaluate the extent of ATB removal by CRRT and to assess the pharmacokinetic/pharmacodynamic (PK/PD) parameters of the most commonly used antibiotics for treating severe infections.Results A total of 135 ATB therapeutic drug monitoring (TDM) assessments were conducted, measuring total drug concentrations (C) in both plasma (P) and ultrafiltrate in 85 septic patients undergoing CRRT. A high sieving coefficient (similar to 75%) was recorded for all antibiotics, with CRRT-related drug loss described by the following equations: (i) [CUF-ATB](trough level) = 0.77 x [CP-ATB](trough level) + 0.93 ng/mL; (ii) [CUF-ATB](peak) = 0.77 x [CP-ATB](peak) + 3.1 ng/mL. The VD exhibited wide variability, with values exceeding those reported in the literature. Lower ATB molecular weight and steric hindrance were associated with a higher elimination rate constant (Kemin(-)(1)). ATB TDM consistently correlated with AUC and AUC/MIC, ensuring effective bactericidal activity.Conclusions Despite its limitations, our study suggests to carry out a loading dose for the main antibiotics and consider the daily drug loss, as identified by the linear regression equation, along with daily TDM to guide further dosing adjustments.