title: Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused by Enterobacter, Citrobacter or Serratia species: a systematic review with meta-analysis.
abstract: OBJECTIVE
  This systematic review and meta-analysis compared effects of different antibiotics on mortality in patients with bloodstream infections caused by Enterobacteriaceae with chromosomal AmpC β-lactamase.
  
  
  METHODS
  Databases were systematically searched for studies reporting mortality in patients with bloodstream infections caused by AmpC producers treated with carbapenems, broad-spectrum β-lactam/β-lactamase inhibitors (BLBLIs), quinolones or cefepime. Pooled ORs for mortality were calculated for cases that received monotherapy with these agents versus carbapenems.
  
  
  BACKGROUND
  PROSPERO international prospective register of systematic reviews (CRD42014014992; 18 November 2014).
  
  
  RESULTS
  Eleven observational studies were included. Random-effects meta-analysis was performed on studies reporting empirical and definitive monotherapy. In unadjusted analyses, no significant difference in mortality was found between BLBLIs versus carbapenems used for definitive therapy (OR 0.87, 95% CI 0.32-2.36) or empirical therapy (OR 0.48; 95% CI 0.14-1.60) or cefepime versus carbapenems as definitive therapy (OR 0.61; 95% CI 0.27-1.38) or empirical therapy (0.60; 95% CI 0.17-2.20). Use of a fluoroquinolone as definitive therapy was associated with a lower risk of mortality compared with carbapenems (OR 0.39; 95% CI 0.19-0.78). Three studies with patient-level data were used to adjust for potential confounders. The non-significant trends favouring non-carbapenem options in these studies were diminished after adjustment for age, sex and illness severity scores, suggestive of residual confounding.
  
  
  CONCLUSIONS
  Despite limitations of available data, there was no strong evidence to suggest that BLBLIs, quinolones or cefepime were inferior to carbapenems. The reduced risk of mortality observed with quinolone use may reflect less serious illness in patients, rather than superiority over carbapenems.
authors.affiliation: University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia p.harris@uq.edu.au.
authors.forename: Patrick N A
authors.initials: PN
authors.lastname: Harris
authors.affiliation: School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Wei
authors.affiliation: School of Medicine, University of Queensland, Brisbane, Australia.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Shen
authors.affiliation: School of Medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Abdile
authors.affiliation: School of Public Health, University of Queensland, Brisbane, Australia.
authors.forename: Stuart
authors.initials: S
authors.lastname: Paynter
authors.affiliation: School of Public Health, University of Queensland, Brisbane, Australia.
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Huxley
authors.affiliation: School of Public Health, University of Queensland, Brisbane, Australia.
authors.forename: Nirmala
authors.initials: N
authors.lastname: Pandeya
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Doi
authors.affiliation: Division of Infectious Diseases, Armed Forces Capital Hospital, Seongnam, Republic of Korea.
authors.forename: Kyungmin
authors.initials: K
authors.lastname: Huh
authors.affiliation: Infectious Diseases, Louisiana State University Health Sciences Center, New Orleans, LA, USA.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: O'Neal
authors.affiliation: Departments of Medicine and Health Policy, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Talbot
authors.affiliation: University of Queensland, UQ Centre for Clinical Research, Brisbane, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000401:mortality; D015780:Carbapenems / Q000627:therapeutic use*; D000077723:Cefepime; D002511:Cephalosporins / Q000627:therapeutic use; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D015363:Quinolones / Q000627:therapeutic use; D016868:Serratia Infections / Q000188:drug therapy* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome; D065093:beta-Lactamase Inhibitors / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D002511:Cephalosporins; D015363:Quinolones; D065093:beta-Lactamase Inhibitors; D000077723:Cefepime