Imipenem/cilastatin versus piperacillin/tazobactam plus amikacin for empirical therapy in febrile neutropenic patients: results of the COSTINE study

• Published in: Current medical research and opinion 2005-05, Vol.21 (5), p.645-655
• Main Authors: Sanz, Miguel A., Bermúdez, Arancha, Rovira, Montserrat, Besalduch, Juan, Pascual, Maria-Jesus, Nocea, Gonzalo, Sanz-Rodríguez, César
• Format: Article
• Language: English
• Subjects: Adult; Amikacin; Amikacin - economics; Amikacin - therapeutic use; Anti-Bacterial Agents - economics; Anti-Bacterial Agents - therapeutic use; Cilastatin - economics; Cilastatin - therapeutic use; Cost-Benefit Analysis; Drug Therapy, Combination; Enzyme Inhibitors - economics; Enzyme Inhibitors - therapeutic use; Female; Fever; Fever - drug therapy; Fever - etiology; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Imipenem; Imipenem - economics; Imipenem - therapeutic use; Male; Middle Aged; Neoplasms - complications; Neoplasms - drug therapy; Neutropenia; Neutropenia - drug therapy; Neutropenia - physiopathology; Penicillanic Acid - analogs & derivatives; Penicillanic Acid - economics; Penicillanic Acid - therapeutic use; Piperacillin - economics; Piperacillin - therapeutic use; Piperacillin/tazobactam; Prospective Studies; Protease Inhibitors - economics; Protease Inhibitors - therapeutic use; Spain; Treatment Outcome
• ISSN: 0300-7995; 1473-4877
• DOI: 10.1185/030079905X43631

Background: Combinations of beta-lactams plus aminoglycosides have become standard therapy for suspected infections in patients with profound neutropenia. However, it is not clear whether such combinations are advantageous over therapy with a broad-spectrum antibiotic. Objective: To assess the clinical effectiveness and the cost-effectiveness ratio of empirical therapy of febrile neutropenia with imipenem/cilastatin (I/C) versus piperacillin/tazobactam plus amikacin (P/T+A). Research design and methods: Prospective, multicenter observational study with 2 matched parallel cohorts treated with I/C (500 mg/6 h iv) or P/T+A (P/T: 4 g/6 h iv; A: 20 mg/kg/day iv). Main outcome measures: Therapeutic success was defined as the resolution of fever following ≥ 7 days of unchanged antibiotic treatment. An economic comparison was conducted focusing on the daily treatment costs, and the management of its toxicity. Results: There were 343 eligible patients (180 I/C, 163 P/T+A), of whom 290 were evaluable for the primary clinical effectiveness analysis. Follow-up information beyond 7 days of study inclusion was only available for 52% of all evaluable patients. Treatment success was observed in 42% of I/C patients compared with 31% of P/T+A patients (95% CI: -0.01, 21.4). The incidence of drug-related adverse experiences was 13% for I/C and 6% for P/T+A, with no differences in moderate or severe adverse experiences nor in those causing discontinuation of antibiotic therapy. Treatment costs were 189.55 euros (95% CI: 127.46-251.46) lower per episode of febrile neutropenia for patients treated with I/C. Conclusions: The clinical effectiveness of I/C was similar to that of P/T+A. In both treatment groups toxicity was low and did not limit antibiotic therapy. Resource consumption was lower with I/C.