Problems in the treatment of infectious diseases and the need for individualization
Critically ill patients with life threatening infections often experience multi-organ failure. These patients who are frequently hemodynamic unstable, require aggressive therapeutic interventions that will impact the pharmacokinetics of antifungal drugs. Vice versa, antifungal drugs are not without side-effects likely causing a further deterioration of specific organ functions. Applying effective (and safe) drug regimens for these patients with the selection of the most appropriate drug and to optimize the exposure of these drug, requires understanding of the pharmacokinetics.
In the treatment of infections in hematology and ICU patients, the heterogeneous nature of patients combined with limited evidence on how to manage these patients often leads to a high variability of applied drug regimens and regular off-label drug use. Failure to anticipate and monitor for changes in the pharmacokinetics of a drug can contribute to clinical failures or adverse drug events.
In this session I will discuss the general principles of PK of antimicrobial drugs and how critical illness can influence the specific pharmacokinetic phases (absorption, distribution, metabolism and elimination).
For the purpose of this section, we will highlight relevant literature and characterize the impact of above mentioned factors on the PK profile and, where appropriate, provide general suggestions on how to adapt drug regimens to manage specific challenges. Finally recommendations will be made on the role of therapeutic drug monitoring to guide dosing in the setting of critical illness.
In short, the following will be addressed: (i) potential impact of critical illness on the pharmacokinetic (implications for absorption, distribution, metabolism and elimination; including hepatic and renal dysfunction, extracorporeal elimination techniques etc; (ii) choice of drug in the setting of critical illness and specific organ dysfunction (including safety related aspects); and (iii) the role of TDM for dosage adjustment to achieve optimal drug exposure for individual patients in the setting of organ dysfunction.
1) Refresh knowledge on pharmacokinetics of antifective drugs in the setting of critical illness.
2) Is there a role for Therapeutic Drug Monitoring in the critical ill patient?
3) Identify research questions that to need be addressed for optimal deployment of TDM.