title: Imipenem/cilastatin versus piperacillin/tazobactam plus amikacin for empirical therapy in febrile neutropenic patients: results of the COSTINE study.
abstract: 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).
  
  
  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).
  
  
  METHODS
  Therapeutic success was defined as the resolution of fever following > or = 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.
authors.affiliation: Servicio de Hematología, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sanz
authors.forename: Arancha
authors.initials: A
authors.lastname: Bermúdez
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rovira
authors.forename: Juan
authors.initials: J
authors.lastname: Besalduch
authors.forename: Maria-Jesus
authors.initials: MJ
authors.lastname: Pascual
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Nocea
authors.forename: César
authors.initials: C
authors.lastname: Sanz-Rodríguez
mesh_terms: D000328:Adult; D000583:Amikacin / Q000191:economics / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000191:economics / Q000627:therapeutic use*; D015377:Cilastatin / Q000191:economics / Q000627:therapeutic use*; D003362:Cost-Benefit Analysis; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000191:economics / Q000627:therapeutic use*; D005260:Female; D005334:Fever / Q000188:drug therapy* / Q000209:etiology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D015378:Imipenem / Q000191:economics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy; D009503:Neutropenia / Q000188:drug therapy* / Q000503:physiopathology; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000191:economics / Q000627:therapeutic use*; D010878:Piperacillin / Q000191:economics / Q000627:therapeutic use*; D011446:Prospective Studies; D011480:Protease Inhibitors / Q000191:economics / Q000627:therapeutic use*; D013030:Spain; D000078142:Tazobactam; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011480:Protease Inhibitors; D015377:Cilastatin; D015378:Imipenem; D000583:Amikacin; D010397:Penicillanic Acid; D000078142:Tazobactam; D010878:Piperacillin