title: Mortality burden related to infection with carbapenem-resistant Gram-negative bacteria among haematological cancer patients: a retrospective cohort study.
abstract: OBJECTIVE
  Carbapenem-resistant Gram-negative bacteria (CRGNB) pose a clinical challenge. We attempted to estimate the mortality burden of CRGNB among haematological cancer patients.
  
  
  METHODS
  This was a retrospective cohort study. We included adult patients hospitalized in the haemato-oncological/bone marrow transplantation departments for chemotherapy, between 2008 and 2014, with Gram-negative aerobic bacteraemia. We compared patients with CRGNB and carbapenem-susceptible Gram-negative bacteraemia (CSGNB). The primary outcome was 14 day all-cause mortality. In addition, we assessed 1 year survival. Multivariable logistics regression analysis and adjusted Cox regression analysis were conducted. Analyses were adjusted to the propensity for CRGNB bacteraemia.
  
  
  RESULTS
  The cohort included mostly young patients (mean age 50.1 years) with acute leukaemia (264/423, 62.4%) and the median absolute neutrophil count at bacteraemia onset was 0 × 10(9)/L. The unadjusted 14 day mortality rate was higher for patients with CRGNB compared with CSGNB [45.6% (47/103) versus 15% (48/320), respectively (P < 0.001)]. Adjusting to baseline prognostic factors, infection characteristics and the propensity score retained a significant association between CRGNB and 14 day mortality (OR 5.14, 95% CI 2.32-11.38). Including only the first bacteraemic episode per patient, 1 year mortality was 74.7% (68/91) for patients with CRGNB versus 49.8% (119/239) for patients with CSGNB (P < 0.001). Adjusting for risk factors associated with 1 year mortality, the HR for mortality with CRGNB was 1.48 (95% CI 1-2.2). CRGNB bacteraemia was associated with several risk factors for mortality, including inappropriate empirical antibiotic treatment and less effective definitive antibiotics.
  
  
  CONCLUSIONS
  This study demonstrated a significant adjusted association between CRGNB and mortality up to 1 year among haemato-oncological patients receiving chemotherapy.
authors.affiliation: Medicine B, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Nizar
authors.initials: N
authors.lastname: Andria
authors.affiliation: Unit of Infectious Diseases, Carmel Medical Center, Haifa, Israel.
authors.forename: Oryan
authors.initials: O
authors.lastname: Henig
authors.affiliation: The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Offer
authors.initials: O
authors.lastname: Kotler
authors.affiliation: The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Domchenko
authors.affiliation: The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Division of Infectious Diseases, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Oren
authors.affiliation: The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Tsila
authors.initials: T
authors.lastname: Zuckerman
authors.affiliation: The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Yishai
authors.initials: Y
authors.lastname: Ofran
authors.affiliation: Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheba, Israel.
authors.forename: Drora
authors.initials: D
authors.lastname: Fraser
authors.affiliation: The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel Division of Infectious Diseases, Rambam Health Care Campus, Haifa, Israel paulm@post.tau.ac.il.
authors.forename: Mical
authors.initials: M
authors.lastname: Paul
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology / Q000401:mortality*; D015780:Carbapenems / Q000494:pharmacology*; D015331:Cohort Studies; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology / Q000401:mortality*; D019337:Hematologic Neoplasms / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems