Basic Principles of Antibiotics Dosing in Patients with Sepsis and Acute Kidney Damage Treated with Continuous Venovenous Hemodiafiltration

Sepsis is the leading cause of acute kidney damage in patients in intensive care units. Pathophysiological mechanisms of the development of acute kidney damage in patients with sepsis may be hemodynamic and non-hemodynamic. Patients with severe sepsis, septic shock and acute kidney damage are treated with continuous venovenous hemodiafiltration. Sepsis, acute kidney damage, and continuous venovenous hemodiafiltration have a significant effect on the pharmacokinetics and pharmacodynamics of antibiotics. The impact dose of antibiotics is increased due to the increased volume of distribution (increased administration of crystalloids, hypoalbuminemia, increased capillary permeability syndrome toproteins). The dose of antibiotic maintenance depends on renal, non-renal and extracorporeal clearance. In the early stage of sepsis, there is an increased renal clearance of antibiotics, caused by glomerular hyperfiltration, while in the late stage of sepsis, as the consequence of the development of acute renal damage, renal clearance of antibiotics is reduced. The extracorporeal clearance of antibiotics depends on the hydrosolubility and pharmacokinetic characteristics of the antibiotic, but also on the type of continuous dialysis modality, dialysis dose, membrane type, blood flow rate, dialysis flow rate, net filtration rate, and effluent flow rate. Early detection of sepsis and acute kidney damage, early target therapy, early administration of antibiotics at an appropriate dose, and early extracorporeal therapy for kidney replacement and removal of the inflammatory mediators can improve the outcome of patients with sepsis in intensive care units.