Target-FN

Therapeutic drug monitoring (TDM) for personalized antibiotic treatment with piperacillin-tazobactam (PipTaz) in patients with febrile neutropenia

Febrile neutropenia (FN) occurs in 80% of patients with myelosuppressive chemotherapy and is usually the first sign of a systemic infection, the leading cause of treatment-related mortality in cancer patients. Most episodes are assumed to be due to bacterial infections in this immunosuppressed patient population. Thus, febrile neutropenia is always treated empirically with broad-spectrum antibiotics. The most widely used antibiotic agent in this setting is piperacillin-tazobactam (PipTaz), which leads to resolution of fever in approximately 50% of cases. The remaining 50% of patients with FN require salvage treatment with antibiotics of the last resort, leading to increased toxicity and high risk of multi-drug resistance. Preliminary data indicate that subtherapeutic drug levels may in part be responsible for therapy failure.

The clinical trial Target-FN assesses feasibility and efficacy of personalized application of PipTaz using therapeutic drug-monitoring (TDM) in patients with hematological malignancies and FN. The study aims to raise the response rate from 50% following standard therapy to 70% using TDM. Target-FN is a prospective, monocentric, randomized clinical trial. PipTaz is administered in conventional dosage to the control group and TDM samples are used for diagnostic evaluation only. In contrast, PipTaz dosage in the intervention group is adjusted according to TDM results.

The response rate is recorded as stable defervescence, i.e. 5 consecutive afebrile days. In addition, length of treatment and of hospital stay as well as survival is recorded. Target-FN is the first clinical trial on TDM in FN. If successful, a direct impact on clinical practice and guidelines is foreseeable.