title: Comparison of antipseudomonal β-lactams for febrile neutropenia empiric therapy: systematic review and network meta-analysis.
abstract: OBJECTIVE
  To compare the effectiveness and safety of antipseudomonal β-lactam empiric monotherapy for febrile neutropenia by network meta-analysis.
  
  
  METHODS
  Searches using Pubmed, Cochrane CENTRAL, EMBASE and Web of Science Core Collection were carried out in June 2016. English articles, non-English articles, full-length articles, short articles and conference abstracts were allowed. Eligible trial design was a parallel-group individual randomization. We included febrile neutropenia adult and paediatric patients undergoing chemotherapy for either solid tumours or haematological malignancies and treated with intravenous antipseudomonal β-lactams for initial empiric therapy. Protocol was registered with PROSPERO ID 42016043377.
  
  
  RESULTS
  Of 1275 articles detected by the search, 50 studies with 10 872 patients were finally included. Among the guideline-recommended cefepime, meropenem, imipenem/cilastatin, piperacillin/tazobactam and ceftazidime; imipenem/cilastatin showed the highest odds of treatment success without modification, which was the primary endpoint, based on the random-effect model network analysis. Ceftazidime was related to lower treatment success rate without modification compared with imipenem/cilastatin with OR of 0.71 (95% CI 0.57-0.89, p 0.006). Imipenem/cilastatin showed the lowest odds of all-cause death. Patients treated with cefepime had higher risk for all-cause death compared with those treated with imipenem/cilastatin (OR 2.05, 95% CI 1.11-3.78, p 0.029). Any adverse event was significantly more prevalent in the imipenem/cilastatin arm; however, there was no difference concerning adverse events leading to discontinuation.
  
  
  CONCLUSIONS
  Imipenem/cilastatin, piperacillin/tazobactam and meropenem may be reasonable first-choice medications for empiric therapy of febrile neutropenia.
authors.affiliation: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address: horitano@yokohama-cu.ac.jp.
authors.forename: N
authors.initials: N
authors.lastname: Horita
authors.affiliation: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Shibata
authors.affiliation: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Watanabe
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Namkoong
authors.affiliation: Department of Pulmonology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kaneko
mesh_terms: D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D064147:Febrile Neutropenia / Q000188:drug therapy*; D006801:Humans; D009369:Neoplasms / Q000150:complications; D016019:Survival Analysis; D016896:Treatment Outcome; D047090:beta-Lactams / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams
keywords: Anti-bacterial agents; Drug therapy; Drug-related side effects and adverse reactions; Leukopenia; Neoplasms; Review literature as topic