title: Administration of proton pump inhibitors in critically ill medical patients is associated with increased risk of developing Clostridium difficile-associated diarrhea.
abstract: OBJECTIVE
  Proton pump inhibitors (PPIs) effectively prevent gastrointestinal bleedings in critically ill patients at the intensive care unit (ICU). In non-ICU hospitalized patients, PPI administration increases the risk of infectious complications, especially Clostridium difficile-associated diarrhea (CDAD); but no such data are available for the ICU setting.
  
  
  METHODS
  This is a retrospective, observational, single-center analysis (1999-2010) including 3286 critically ill patients.
  
  
  RESULTS
  A total of 91.3% of patients received stress ulcer prophylaxis by PPI (55.6%), histamine 2 receptor antagonists (5.8%), sucralfate (10.1%), or combinations (19.8%). Only 29 (0.9%) of 3286 patients developed gastrointestinal bleedings during the course of ICU treatment, independent from the type of prophylaxis. The PPIs were not an independent risk factor for nosocomial pneumonia. One hundred and ten (3.3%) patients developed CDAD during the course of ICU treatment, which was associated with prolonged ICU stay and increased ICU mortality (odds ratio, 1.59). Similar to fluoroquinolones and cephalosporins, PPI was identified as an independent risk factor (odds ratio, 3.11) for developing CDAD at the ICU by multivariate analysis.
  
  
  CONCLUSIONS
  Proton pump inhibitor therapy was an independent risk factor for CDAD in medical ICU patients. Instead of routine PPI use for bleeding prophylaxis, further trials should investigate risk-adjusted algorithms, balancing benefits, and threats of PPI medication.
authors.affiliation: Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Lukas
authors.initials: L
authors.lastname: Buendgens
authors.affiliation: Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Bruensing
authors.affiliation: Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Matthes
authors.affiliation: Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Dückers
authors.affiliation: Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Luedde
authors.affiliation: Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.affiliation: Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany. Electronic address: frank.tacke@gmx.net.
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
authors.affiliation: Department of Medicine III, RWTH-University Hospital Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016360:Clostridioides difficile; D016638:Critical Illness; D003967:Diarrhea / Q000139:chemically induced* / Q000382:microbiology; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000517:prevention & control; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D013276:Stomach Ulcer / Q000517:prevention & control; D013392:Sucralfate / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors; D013392:Sucralfate
keywords: CDAD; Gastrointestinal bleeding; Nosocomial pneumonia; PPI; Sepsis; Stress ulcer