Bacterial and fungal infections

Progresses of modern medicine have made it possible to cure severe diseases for which, until recently, no efficacious therapeutic option was available. However, bacterial and fungal infections are frequent life threatening complications of invasive diagnostic procedures and therapeutic interventions, as well as immunosuppressive treatments. Information on the epidemiology of the pathogens, their early identification, appropriate treatment and targeted prevention are the cornerstones for an effective management of these complications and contribute to improve the chances of healing serious underlying conditions.

Fungal infections

Fungi, especially Candida and Aspergillus, are frequent causes of opportunistic infections in immunocompromised patients with cancer or chronic debilitating diseases, in solid organ or hematopoietic transplant recipients, and in critically ill patients with a prolonged stay in the intensive care unit or undergoing complex surgery. These infections, which that typically occur when the immune defenses and/or the physiological barriers are damaged, are difficult to diagnose at an early stage and are associated with high morbidity and mortality. This research topic, aiming at the improvement of the rapidity and efficiency in clinical management of patients at risk, has the following study objectives:

• Epidemiology of fungal infections
• Improvement of the efficiency and the timing of diagnosis by new microbiological tools (blood markers, molecular techniques) and by combining clinical, radiological and laboratory criteria
• New antifungal drugs and innovative therapeutic and preventive strategies.

Bacterial infections

Bacterial infections are a frequent cause of hospitalization and of nosocomial complications. The multiple invasive procedures in critically ill patients and surgical patients, and the neutropenia and mucositis resulting from cytotoxic chemotherapy in cancer patients are associated with a high risk of bacterial infections. The following subjects are investigated in this research topic:

• Epidemiology of bacterial infections
• Identification of risk factors predicting the occurrence and the severity of these complications
• Documentation of the etiology of infection with traditional diagnostic tools (cultures) and new tools (blood markers, molecular techniques)
• Efficacy and safety of new antibacterial agents and definition of new management strategies.

Individualized dosing of antibacterial and antifungal agents

Therapy with antibacterial and antifungal agents in patients with severe infections follows standard dosing schedules. However, these do not take into account the large inter- and intra-individual variability of drug blood concentrations resulting from the particular situation of each patient (e.g. renal and/or liver failure, shock, capillary leak syndrome, and accumulation of liquids in the extracellular space). This pharmacokinetic variability is unpredictable and may influence the efficacy (in case of insufficient blood concentrations) or safety (in case of toxic blood concentrations) of these lifesaving treatments. Measuring drug blood concentrations may help to optimize the management of these patients (reduced morbidity and mortality) by individualized dose adjustment aiming at maximizing efficacy, while avoiding severe side effects. Key elements of this research topic are:

• Development and validation of analytical methods for measurement of blood concentrations of antibacterial and antifungal agents
• Clinical studies on pharmacokinetics/-dynamics and "therapeutic drug monitoring" to define therapeutic ranges and appropriate dosing regimens as well as individualized dose adjustments.