Therapeutic drug monitoring (TDM) for personalized antibiotic treatment with piperacillin-tazobactam (PipTaz) in patients with febrile neutropenia after myelo-suppressive cytostatic chemotherapy

INTERVENTION: Product Name: Piperacillin/Tazobactam Product Code: Pip/Taz Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: Piperacillin CAS Number: 59703‐84‐3 Other descriptive name: PIPERACILLIN SODIUM Concentration unit: g gram(s) Concentration type: equal Concentration number: 4‐ INN or Proposed INN: Tazobactam CAS Number: 89785‐84‐2 Other descriptive name: TAZOBACTAM SODIUM Concentration unit: g gram(s) Concentration type: equal Concentration number: 0,5‐ CONDITION: Patients with febrile neutropenia after myelo‐suppressive chemotherapy treated with piperacillin/tazobactam Therapeutic area: Diseases [C] ‐ Bacterial Infections and Mycoses [C01] PRIMARY OUTCOME: Main Objective: The primary goal of the study is to examine if and in which extent the effect of a dose adjusted administration of piperacillin/tazobactam after therapeutic drug monitoring has a benefit on a stable fever recovery without changing the anti infective therapy in patients with neutropenia after myelo‐suppressive cytostatic chemotherapy Primary end point(s): stable fever recovery (yes/no) defined as 5 consecutive days without fever without any changes in the antibacterial therapy. This proportion of patients without fever under TDM will be compared according to the proportion of the control group. Secondary Objective: ‐ 30 day mortality; ‐ Infect associated 30 days mortality; ‐ Duration and cumulative doses of antibiotic therapy of the current fever episode; ‐ Number of dose adjustments/therapy cycle; ‐ Duration of combination therapy with anti‐infective in the current fever episode; ‐ Days without antibiotics at hospital stay; ‐ Need of intensive care unit; ‐ Time spent in hospital; ‐ Antibiotic therapy costs; ‐ Occurrence of antibiotic resistant bacteria; ‐ Pharmacokinetic / pharmacodynamic indices ; ‐ Days without antibiotics at stage of neutropenia; ‐ Recovery of the infection; ‐ Progression to SIRS/Sepsis; ‐ Rate of superinfection with another pathogen; ‐ Security (Side effects); Timepoint(s) of evaluation of this end point: Until the end of the therapy in accordance with the instructions of the treating physician or until 5 consecutive days without fever. SECONDARY OUTCOME: Secondary end point(s): ‐ 30 day mortality ; ‐ Infect associated 30 days mortality ; ‐ Duration and cumulative doses of antibiotic therapy of the current fever episode ; ‐ Number of dose adjustments/therapy cycle ; ‐ Duration of combination therapy with anti‐infective in the current fever episode ; ‐ Days without antibiotics at hospital stay ; ‐ Need of intensive care unit ; ‐ Time spent in hospital ; ‐ Antibiotic therapy costs ; ‐ Occurrence of antibiotic resistant bacteria ; ‐ Pharmacokinetic / pharmacodynamic indices ; ‐ Days without antibiotics at stage of neutropenia ; ‐ Recovery of the infection ; ‐ Progression to SIRS/Sepsis ; ‐ Rate of superinfection with another pathogen ; ‐ Security (Side effects) ; Timepoint(s) of evaluation of this end point: During course of treatment with Pip / Taz and until day 30 or until discharge with a follow‐up on day 30 INCLUSION CRITERIA: ‐ Fever (temperature >38.3°C at one time or temperature >38.0°C twice in 2 hours) and existing neutropenia after myelo‐suppressive cytostatic chemotherapy (leucocytes <1,0Gpt/l or netrophile granulocytes <0,5Gpt/l) ‐ Planned or started therapy with the antibiotic Piperacillin‐Tazobactam ‐ Written consent of the Patient Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 104 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 104