Antimicrobial Dose Reduction in Continuous Renal Replacement Therapy: Myth or Real Need? A Practical Approach for Guiding Dose Optimization of Novel Antibiotics.

Acute kidney injury represents a common complication in critically ill patients affected by septic shock and in many cases continuous renal replacement therapy (CRRT) may be required. In this scenario, antimicrobial dose optimization is highly challenging as the extracorporeal circuit may cause several pharmacokinetic alterations, which add up to volume of distribution and clearance variations resulting from sepsis. Variations in CRRT settings (i.e. modality of solute removal, type of filter material, blood flow rate and effluent flow rate), coupled with the presence of residual and/or recovering renal function, may cause dynamic variations in the clearance of hydrophilic antimicrobials. This means that dose reduction may not always be needed. Nowadays, the lack of pharmacokinetic data for novel antimicrobials during CRRT limits evidence-based dose recommendations for critically ill patients in this setting, thus making available evidence hardly applicable in real-world scenarios. This review aims to summarize the major determinants involved in antimicrobial clearance, and the available pharmacokinetic studies performed during CRRT involving novel antibiotics used for the management of multidrug-resistant Gram-positive and Gram-negative infections (namely ceftolozane-tazobactam, ceftazidime-avibactam, cefiderocol, imipenem-relebactam, meropenem-vaborbactam, ceftaroline, ceftobiprole, dalbavancin, and fosfomycin), providing a practical approach in guiding dose optimization in this special population.