title: Empirical antibiotics against Gram-positive infections for febrile neutropenia: systematic review and meta-analysis of randomized controlled trials.
abstract: OBJECTIVE
  To assess the value of empirical anti-Gram-positive antibiotics for the treatment of febrile neutropenia.
  
  
  METHODS
  Systematic review and meta-analysis of randomized controlled trials comparing antibiotics with anti-Gram-positive spectrum to control or placebo, in addition to the same baseline antibiotic regimen in both arms. We searched MEDLINE, EMBASE, LILACS, the Cochrane Library, conference proceedings, and references. No restrictions on inclusion were imposed. Two reviewers independently applied selection criteria, carried out quality assessment, and extracted the data. Relative risks with 95% confidence intervals were pooled using the fixed effect model. The primary outcome assessed was all-cause mortality.
  
  
  RESULTS
  Thirteen studies met inclusion criteria, including 2392 participants. Glycopeptides were assessed in nine trials. Empirical anti-Gram-positive antibiotics were assessed for the initial treatment in 11 studies, and for persistent fever in two. No significant difference in all-cause mortality was seen [RR 0.86 (0.58-1.26), seven studies, 852 participants]. Overall failure at end of therapy occurred equally [RR 1.00 (0.79-1.27), six studies, 943 participants]. Failure associated with treatment modifications was more frequent in the control arm when empirical initial glycopeptides were assessed [RR 0.70 (0.61-0.80), five studies, 1178 participants]. Bacterial superinfections, mainly Gram-positive, were detected less frequently in the intervention arm. Adverse events were significantly more common with the additional antibiotic, and nephrotoxicity was significantly more common with additional glycopeptides [RR 1.88 (1.10-3.22), six studies, 1282 participants]. No significant heterogeneity was present in these comparisons.
  
  
  CONCLUSIONS
  The use of glycopeptides can be safely deferred until the documentation of a resistant Gram-positive infection.
authors.affiliation: Department of Medicine E, Rabin Medical Center, Beilinson Campus, 49100 Petah-Tiqva. pil1pel@zahav.net.il
authors.forename: Mical
authors.initials: M
authors.lastname: Paul
authors.forename: Sara
authors.initials: S
authors.lastname: Borok
authors.forename: Abigail
authors.initials: A
authors.lastname: Fraser
authors.forename: Liat
authors.initials: L
authors.lastname: Vidal
authors.forename: Leonard
authors.initials: L
authors.lastname: Leibovici
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D005334:Fever; D006020:Glycopeptides / Q000627:therapeutic use; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006801:Humans; D009503:Neutropenia / Q000150:complications*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000900:Anti-Bacterial Agents; D006020:Glycopeptides