title: Blood stream infections due to OXA-48-like carbapenemase-producing Enterobacteriaceae: treatment and survival.
abstract: BACKGROUND
  Blood stream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) are associated with high hospital mortality rates and present a tremendous challenge to clinicians. The optimal treatment remains undefined. We aimed to investigate the risk factors for mortality and the correlation between different treatment modalities and outcomes.
  
  
  METHODS
  The clinical characteristics and treatment outcomes of a cohort of 36 patients with BSIs due to CRE were investigated and a retrospective nested case-control study of surviving and non-surviving patients was conducted.
  
  
  RESULTS
  Fifty percent of the cases were male and the mean patient age was 54.9 ± 15.8 years. Klebsiella pneumoniae was the etiological agent in 26 cases (72.2%), Escherichia coli in eight (22.2%), and Enterobacter aerogenes in two (5.5%). All strains were phenotypically positive for carbapenemase activity and all except two (one E. coli and one K. pneumoniae) yielded both blaOXA-48 carbapenemases and blaCTX-M-type extended-spectrum beta-lactamases (ESBLs) in PCR products. The 14-day, 28-day, and all-cause in-hospital mortality rates were 41.6%, 50%, and 58.3%, respectively. The median time to death was 8 days (range 2-52 days). No significant differences were observed between survivors and non-survivors in terms of baseline characteristics, comorbid conditions, etiologies, or sources of bacteremia, however hematological malignancies (p=0.015) and prolonged neutropenia (p=0.044) were more common in non-survivors. Microbiological eradication and clinical response within 7 days were two major determinants of 28-day attributable mortality (p=0.001 and p=0.001, adjusted r(2)=0.845). Colistin-based dual combinations, and preferably triple combinations, were associated with significantly better outcomes when compared to non-colistin-based regimens (p<0.001). Time to active treatment had a significant effect on the course of infection (p=0.014).
  
  
  CONCLUSIONS
  Earlier active treatment with colistin based regimens and microbiological and clinical response within 7 days are major predictors of survival in cases of BSIs due to CRE. Rectal screening offers the advantage of earlier recognition and prompt empirical treatment.
authors.affiliation: Department of Infectious Diseases, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul 34098, Turkey. Electronic address: ilkerinancbalkan@hotmail.com.
authors.forename: Ilker Inanç
authors.initials: II
authors.lastname: Balkan
authors.affiliation: Department of Clinical Microbiology, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Aygün
authors.affiliation: Department of Infectious Diseases, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul 34098, Turkey.
authors.forename: Selda
authors.initials: S
authors.lastname: Aydın
authors.affiliation: Department of Infectious Diseases, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul 34098, Turkey.
authors.forename: Sibel Islak
authors.initials: SI
authors.lastname: Mutcalı
authors.affiliation: Department of Internal Medicine, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Kara
authors.affiliation: Department of Clinical Microbiology, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Mert
authors.initials: M
authors.lastname: Kuşkucu
authors.affiliation: Department of Clinical Microbiology, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Kenan
authors.initials: K
authors.lastname: Midilli
authors.affiliation: Department of Clinical Microbiology, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Vicdan
authors.initials: V
authors.lastname: Şemen
authors.affiliation: Section of Biochemistry and Biostatistics, Ahenk Diagnostics, Istanbul, Turkey.
authors.forename: Sükrü
authors.initials: S
authors.lastname: Aras
authors.affiliation: Department of Infectious Diseases, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul 34098, Turkey.
authors.forename: Mücahit
authors.initials: M
authors.lastname: Yemişen
authors.affiliation: Department of Infectious Diseases, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul 34098, Turkey.
authors.forename: Bilgül
authors.initials: B
authors.lastname: Mete
authors.affiliation: Department of Infectious Diseases, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul 34098, Turkey.
authors.forename: Reşat
authors.initials: R
authors.lastname: Özaras
authors.affiliation: Department of Infectious Diseases, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul 34098, Turkey.
authors.forename: Neşe
authors.initials: N
authors.lastname: Saltoğlu
authors.affiliation: Department of Infectious Diseases, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul 34098, Turkey.
authors.forename: Fehmi
authors.initials: F
authors.lastname: Tabak
authors.affiliation: Department of Infectious Diseases, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul 34098, Turkey.
authors.forename: Recep
authors.initials: R
authors.lastname: Öztürk
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016470:Bacteremia / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality*; D001426:Bacterial Proteins / Q000378:metabolism*; D015780:Carbapenems / Q000627:therapeutic use; D016022:Case-Control Studies; D003091:Colistin / Q000627:therapeutic use; D004755:Enterobacteriaceae / Q000201:enzymology* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality*; D004926:Escherichia coli / Q000302:isolation & purification; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007711:Klebsiella pneumoniae / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D001618:beta-Lactamases; C063912:carbapenemase; D003091:Colistin
keywords: Blood stream infection; Carbapenemase; Enterobacteriaceae; OXA-48; Survival; Treatment