title: Risk factors for relapse or persistence of bacteraemia caused byEnterobacterspp.: a case-control study.
abstract: BACKGROUND
  Enterobacterspp. possess chromosomal AmpC beta-lactamases that may be expressed at high levels. Previous studies have demonstrated a risk of relapsed bacteraemia following therapy with third generation cephalosporins (3GCs). What additional factors predict microbiological failure inEnterobacterbacteraemia is unclear. We aimed to determine factors associated with microbiological failure inEnterobacterbacteraemia.
  
  
  METHODS
  We retrospectively identified cases of bacteraemia caused byEnterobacterspp. occurring in four hospitals. Using a case-control design, we determined clinical risk factors for persistence or relapse defined as repeated positive blood cultures collected between 72 hours and up to 28 days post initial positive blood culture.
  
  
  RESULTS
  During the study period a total of 922 bacteraemia events caused byEnterobacterspp. in adults were identified. The overall risk of relapsed or persisting bacteraemia at 28 days was low (31 of 922, 3.4%), with only 2 patients experiencing emergent resistance to 3GCs. A total of 159 patients were included in the case-control study. Using multivariate logistic regression, independent predictors for relapse were a line-associated source of infection (OR 3.87; 95% CI 1.56-9.60,p= 0.004) and the presence of immunosuppression (OR 2.70; 95% CI 1.14-6.44,p= 0.02). On univariate analysis definitive therapy with a broad-spectrum beta-lactam-beta-lactamase inhibitor (BLBLI, e.g. piperacillin-tazobactam) was not associated with relapse (OR 1.83; 95% CI 0.64-5.21,p= 0.26) although the proportion of patients receiving a BLBLI as definitive therapy was relatively small (21/159, 13.2%).
  
  
  CONCLUSIONS
  The risk of relapsed or persistentEnterobacterbacteraemia appears to be low in Australia. A line-associated source of infection and immunocompromise were significant independent predictors for relapse. Larger, preferably randomized, studies are needed to address whether BLBLIs represent an effective carbapenem-sparing option forEnterobacterbacteraemia.
authors.affiliation: University of Queensland, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Building 71/918 Royal Brisbane & Women's Hospital Campus, 4029 Herston, QLD Australia.
authors.forename: Patrick N A
authors.initials: PNA
authors.lastname: Harris
authors.affiliation: Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, Milan, Italy.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Peri
authors.affiliation: QIMR Berghofer Medical Research Institute, Herston, QLD Australia.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Pelecanos
authors.affiliation: Pathology North - Hunter, John Hunter Hospital, Newcastle, NSW Australia.
authors.forename: Carly M
authors.initials: CM
authors.lastname: Hughes
authors.affiliation: UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, QLD, Australia & Wesley Medical Research, University of Queensland, Toowong, QLD Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW Australia.|School of Rural Medicine, University of New England, Armidale, NSW Australia.|Pathology North - Hunter, John Hunter Hospital, Newcastle, NSW Australia.
authors.forename: John K
authors.initials: JK
authors.lastname: Ferguson
keywords: AmpC; Bacteraemia; Beta-lactamase; Enterobacter aerogenes; Enterobacter cloacae; Outcomes; Relapse; Treatment