Antiinfective therapy in ICU patients

Infections are of great importance in the intensive care unit, both as admission diagnosis (e.g. community-acquired pneumonia) and as complication (e.g. catheter-associated bloodstream infection). Antiinfective agents are a causative treatment and an essential part of the care for critically ill patients. The spread of resistant pathogens and thus difficult-to-treat infections are opposed by a scarce number of new antiinfective drugs. Additionally, the patients we treat tend to be more susceptible to infections because of advanced age, chronic diseases and extensive surgery.

Optimal use of the available antiinfective agents is therefore an important task, i.e. to give the right dose of the right drug to the right patient for the right duration. Dosing recommendations which were established in non-critically ill patients are likely to be suboptimal for ICU patients, in whom distribution and elimination of drugs (“pharmacokinetics“) can be massively altered, both by pathologic conditions (e.g. renal failure) and by the treatment (e.g. renal replacement therapy). Verification of the actual drug concentrations in clinical routine is available for few substances only. A better comprehension of the likely alterations of pharmacokinetics in ICU patients would allow for individualised dosing, which could contribute to a more successful therapy.

In our ICU, we investigate the pharmacokinetics of several antiinfective agents in critically ill patients. For analysis and interpretation of the data, we cooperate with the Department of Pharmacology and Toxicology of the University of Regensburg, where most drug concentrations are determined via HPLC, and the Department of Clinical Pharmacy and Biochemistry of the Institute of Pharmacy, Freie Universität Berlin. Based on the data from our own patients and from those of further clinical partners, we develop pharmacokinetic models and adapted dosing recommendations.

 

 

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Bibliography (excerpt)

Kees MG, Hilpert JW, Gnewuch C, Kees F, Voegeler S.
Clearance of vancomycin during continuous infusion in Intensive Care Unit patients: correlation with measured and estimated creatinine clearance and serum cystatin C.
Int J Antimicrob Agents 2010; 36(6):545–8.
Kees MG, Wicha SG, Seefeld A, Kees F, Kloft C.
Unbound fraction of vancomycin in intensive care unit patients.
J Clin Pharmacol 2014; 54(3):318-23.
Liebchen U, Kratzer A, Wicha SG, Kees F, Kloft C, Kees MG
Unbound fraction of ertapenem in intensive care unit patients.
J Antimicrob Chemother 2014;