Piperacillin/tazobactam monotherapy versus combination ceftazidime plus amikacin for the treatment of febrile neutropenia in patients with cancer: A Hellenic Co-Operative Oncology Group Study

18590 Background: Combinations of β-lactam antibiotics and aminoglycosides are considered standard therapy for febrile neutropenia. Monotherapies have been proposed as standard treatments, demonstrating equal efficacy and better safety. Methods: This is a prospective, multi-centre, randomized clinical trial. Cancer patients with absolute neutrophil count (ANC) <1,000/mm3 and fever >38oC for ≥ 2 hours were randomized to either piperacillin/tazobactam 4.5 g every 8 h i.v. (group A) or ceftazidime 2 g every 8 h plus amikacin 15 mg/kg i.v. per day (group B). In case of fever >38oC 48 h after initiation of the therapy, vancomycin 500 mg every 6 h i.v. was added. Minimal duration of treatment was 72 hours. Treatment was continued for 7 days in case of improvement, otherwise vancomycin was added or the study therapy was discontinued. Early efficacy was assessed on day 3 and overall response 4 days after the end of treatment. Complete success was defined the patient to become afebrile and no other antibiotics to be added. Treatment failures were classified in two categories, those in which vancomycin was added to the study regimen, and those in which other antibiotics were used. Categorical variables were compared between treatment groups with the use of Fisher’s exact test, while for continuous Wilcoxon’s rank sum test was used. Results: One hundred twenty-seven febrile episodes were treated (group A: 66, group B: 61). Patient characteristics were well balanced in terms of age, underlying malignancies, ANC, and granulocyte-colony stimulating factor (G-CSF) support. Both treatments were well tolerated. No significant differences were seen in terms of success to treatment. Complete success was achieved in 45 (68%) of patients in group A and 40 (66%) in group B, while another 8 patients in group A (12%) and 6 in group B (10%) required addition of pre-defined anti-staphyloccocci antibiotic. Conclusions: Empirical treatment of febrile neutropenic episodes with piperacillin/tazobactam monotherapy appears to be as effective as the “standard” ceftazidime/amikacin combination. No significant financial relationships to disclose.