title: The Addition of Intravenous Metronidazole to Oral Vancomycin is Associated With Improved Mortality in Critically Ill Patients With Clostridium difficile Infection.
abstract: BACKGROUND
  The optimal therapy for critically ill patients with Clostridium difficile infection (CDI) is not known. We aimed to evaluate mortality among critically ill patients with CDI who received oral vancomycin (monotherapy) vs oral vancomycin with intravenous (IV) metronidazole (combination therapy).
  
  
  METHODS
  A single-center, retrospective, observational, comparative study was performed. Patients with a positive C. difficile assay who received oral vancomycin while bedded in an intensive care unit (ICU) between June 2007 and September 2012 were evaluated. Patients meeting ≥3 of the following criteria were included: albumin <2.5 g/dL, heart rate >90 bpm, mean arterial pressure <60 mmHg, white blood cell count ≥15 000 cells/mL, age >60 years, serum creatinine ≥1.5 times baseline, or temperature ≥100.4°F. Patients in the combination therapy group received IV metronidazole within 48 hours after initiating vancomycin. Patients <18 years or with unrelated gastrointestinal disease were excluded. The primary outcome was in-hospital mortality. Patients were matched using Acute Physiology and Chronic Health Evaluation II scores.
  
  
  RESULTS
  Eighty-eight patients were included, 44 in each group. Patient characteristics were similar although more patients in the combination group had renal disease. Mortality was 36.4% and 15.9% in the monotherapy and combination therapy groups, respectively (P = .03). Secondary outcomes of clinical success, length of stay, and length of ICU stay did not differ between groups.
  
  
  CONCLUSIONS
  Our data are supportive of the use of combination therapy with oral vancomycin and IV metronidazole in critically ill patients with CDI. However, prospective, randomized studies are required to define optimal treatment regimens in this limited population of CDI patients.
authors.affiliation: Department of Pharmacy, Wake Forest Baptist Medical Center.
authors.forename: Kristina E E
authors.initials: KE
authors.lastname: Rokas
authors.affiliation: Department of Pharmacy, Wake Forest Baptist Medical Center.
authors.forename: James W
authors.initials: JW
authors.lastname: Johnson
authors.affiliation: Department of Pharmacy, Wake Forest Baptist Medical Center.
authors.forename: James R
authors.initials: JR
authors.lastname: Beardsley
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ohl
authors.affiliation: Wake Forest University School of Medicine, Winston-Salem, North Carolina.
authors.forename: Vera P
authors.initials: VP
authors.lastname: Luther
authors.affiliation: Department of Pharmacy, Wake Forest Baptist Medical Center.
authors.forename: John C
authors.initials: JC
authors.lastname: Williamson
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D016360:Clostridioides difficile / Q000302:isolation & purification*; D016638:Critical Illness; D004359:Drug Therapy, Combination / Q000379:methods; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality*; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage*; D008875:Middle Aged; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D014640:Vancomycin / Q000008:administration & dosage*
chemical_list: D000890:Anti-Infective Agents; D008795:Metronidazole; D014640:Vancomycin
keywords: Clostridium difficile infection; metronidazole; mortality; sepsis; vancomycin