title: Appropriate initial antibiotic therapy in hospitalized patients with gram-negative infections: systematic review and meta-analysis.
abstract: BACKGROUND
  The rapid global spread of multi-resistant bacteria and loss of antibiotic effectiveness increases the risk of initial inappropriate antibiotic therapy (IAT) and poses a serious threat to patient safety. We conducted a systematic review and meta-analysis of published studies to summarize the effect of appropriate antibiotic therapy (AAT) or IAT against gram-negative bacterial infections in the hospital setting.
  
  
  METHODS
  MEDLINE, EMBASE, and Cochrane CENTRAL databases were searched until May 2014 to identify English-language studies examining use of AAT or IAT in hospitalized patients with Gram-negative pathogens. Outcomes of interest included mortality, clinical cure, cost, and length of stay. Citations and eligible full-text articles were screened in duplicate. Random effect models meta-analysis was used.
  
  
  RESULTS
  Fifty-seven studies in 60 publications were eligible. AAT was associated with lower risk of mortality (unadjusted summary odds ratio [OR] 0.38, 95 % confidence interval [CI] 0.30-0.47, 39 studies, 5809 patients) and treatment failure (OR 0.22, 95 % CI 0.14-0.35; 3 studies, 283 patients). Conversely, IAT increased risk of mortality (unadjusted summary OR 2.66, 95 % CI 2.12-3.35; 39 studies, 5809 patients). In meta-analyses of adjusted data, AAT was associated with lower risk of mortality (adjusted summary OR 0.43, 95 % CI 0.23-0.83; 6 studies, 1409 patients). Conversely, IAT increased risk of mortality (adjusted summary OR 3.30, 95 % CI 2.42-4.49; 16 studies, 2493 patients). A limited number of studies suggested higher cost and longer hospital stay with IAT. There was considerable heterogeneity in the definition of AAT or IAT, pathogens studied, and outcomes assessed.
  
  
  CONCLUSIONS
  Using a large set of studies we found that IAT is associated with a number of serious consequences,including an increased risk of hospital mortality. Infections caused by drug-resistant, Gram-negative organisms represent a considerable financial burden to healthcare systems due to the increased costs associated with the resources required to manage the infection, particularly longer hospital stays. However, there were insufficient data that evaluated AAT for the outcome of costs among patients with nosocomialGram-negative infections.
  
  
  CONCLUSIONS
  IAT in hospitalized patients with Gram-negative infections is associated with adverse outcomes. Technological advances for rapid diagnostics to facilitate AAT along with antimicrobial stewardship, surveillance, infection control, and prevention is needed.
authors.affiliation: Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Box 63, 800 Washington Street, Boston, MA, 02111, USA. graman@tuftsmedicalcenter.org.|Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA, 02111, USA. graman@tuftsmedicalcenter.org.
authors.forename: Gowri
authors.initials: G
authors.lastname: Raman
authors.affiliation: Center for Clinical Evidence Synthesis, Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Box 63, 800 Washington Street, Boston, MA, 02111, USA. eavendano@tuftsmedicalcenter.org.
authors.forename: Esther
authors.initials: E
authors.lastname: Avendano
authors.affiliation: Tufts University Friedman School of Nutrition Science and Policy, 150 Harrison Avenue, Boston, MA, 02111, USA. samantha.berger@tufts.edu.
authors.forename: Samantha
authors.initials: S
authors.lastname: Berger
authors.affiliation: Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA, 02111, USA. vandana.menon@gmail.com.|Currently employed at Baxalta and a former employee of Cubist Pharmaceuticals, 65 Hayden Avenue, Lexington, MA, 02421, USA. vandana.menon@gmail.com.
authors.forename: Vandana
authors.initials: V
authors.lastname: Menon
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016208:Databases, Factual; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006760:Hospitalization; D006801:Humans; D007902:Length of Stay; D016017:Odds Ratio; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents