WeP1 - Problems in the Treatment of Infectious Diseases and the Need for Individualization
Roger Brüggemann

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.

WeP2 - A Survey on Laboratory Practice Around the World
Uwe Christians

Reliable, accurate and precise test methods for the clinical therapeutic drug monitoring (TDM) of small molecule immunosuppressants such as tacrolimus, cyclosporine, sirolimus and everolimus are essential in order to effectively monitor levels and to make proper dose adjustments. Data from proficiency testing programs have shown substantial inter-laboratory variability. The aim of this study was to systematically document current practices utilized for immunosuppressant drug TDM in clinical laboratories and to identify methodological and practice differences which may cause the variability observed among laboratories. Data collection was conducted via a structured web-based survey distributed by IATDMCT. Surveys were completed by 76 laboratories in 14 countries. The results of our survey suggested that inter-laboratory variability is a multifactorial problem and that there are three main reasons:

1. lack of standardization of laboratory procedures and workflows starting with sample collection and handling,
2. lack of use of appropriate reference materials (e.g. isotope-labeled internal standards for LC/MS-MS), and
3. poor compliance with internationally accepted good laboratory practice guidelines.

Technical level consensus and guidance on laboratory operational procedures, quality systems, and personnel training will be of great importance to improve quality and inter-laboratory comparability.

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