[Adequate anti-infective treatment : Importance of individual dosing and application]. / Adäquate Antiinfektivatherapie : Bedeutung der individuellen Dosierung und Applikation.

Sepsis-induced changes in pharmacokinetic parameters are a well-known problem in intensive care medicine. Dosing of antibiotics in this setting is therefore challenging. Alterations to the substance-specific kinetics of anti-infective substances have an effect on the distribution and excretion processes in the body. Increased clearance and an increased distribution volume (Vd) and particularly compromized organ function with reduced antibiotic elimination are often encountered in patients with sepsis. Renal replacement treatment, which is frequently used in intensive care medicine, represents a substantial intervention in this system. Current international guidelines recommend individualized dosing strategies and adaptation of doses according to measured serum levels and pharmacokinetic/pharmacodynamic (PK/PD) parameters as concepts to optimize anti-infective therapy in the critically ill. Likewise, the recommendation to adjust the administration form of beta-lactam antibiotics to prolonged or continuous infusion can be found increasingly more often in the literature. This article reviews the background of the individual dosing in intensive care patients and their applicability to the clinical routine.

[Therapeutic drug monitoring and individual dosing of antibiotics during sepsis : Modern or just "trendy"?] / Therapeutisches Drug Monitoring und individualisierte Dosierung von Antibiotika bei der Sepsis : Modern oder nur "modisch"?

Pharmacokinetic variability of anti-infective drugs due to pathophysiological changes by severe sepsis and septic shock is a well-known problem for critically ill patients resulting in suboptimal serum and most likely tissue concentrations of these agents.To cover a wide range of potential pathogens, high concentrations of broad spectrum anti-infectives have to reach the site of infection. Microbiological susceptibility testing (susceptible, intermediate, resistant) don't take the pharmacokinetic variability into account and are based on data generated by non-critically ill patients. But inter-patient variability in distribution and elimination of anti-infective drugs in ICU patients is extremely high and also highly unpredictable. Drug clearance of mainly renally eliminated drugs and thus the required dose can differ up to 10-fold due to the variability in renal function in patients with severe infections. To assure a timely and adequate anti-infective regime, individual dosing and therapeutic drug monitoring (TDM) seem to be appropriate tools in the setting of pathophysiological changes in pharmacokinetics (PK) and pharmakodynamics (PD) due to severe sepsis. In the case of known minimal inhibitory concentration, PK/PD indices (time or peak concentration dependent activity) and measured serum level can provide an optimal target concentration for the individual drug and patient.Modern anti-infective management for ICU patients includes more than the choice of drug and prompt application. Individual dosing, optimized prolonged infusion time and TDM give way to new and promising opportunities in infection control.