title: Antibiotic prophylaxis in variceal hemorrhage: timing, effectiveness and Clostridium difficile rates.
abstract: OBJECTIVE
  To investigate if antibiotics administered within 8 h of endoscopy reduce mortality or increase the incidence of Clostridium difficile infection (CDI).
  
  
  METHODS
  A 2-year retrospective analysis of all patients who presented with first variceal hemorrhage was undertaken. The primary outcome measure was 28-d mortality. Secondary outcome measures were 28-d rebleeding rates and 28-d incidence of CDI. All patients were admitted to a tertiary liver unit with a consultant-led, 24-h endoscopy service. Patients received standard care including terlipressin therapy. Data collection included: primary and secondary outcome measures, timing of first administration of intravenous antibiotics, etiology of liver disease, demographics, endoscopy details and complications. A prospective study was undertaken to determine the incidence of CDI in the study population and general medical inpatients admitted for antibiotic therapy of at least 5 d duration. Statistical analysis was undertaken using univariate, non-parametric tests and multivariate logistic regression analysis.
  
  
  RESULTS
  There were 70 first presentations of variceal hemorrhage during the study period. Seventy percent of cases were male and 65.7% were due to chronic alcoholic liver disease. In total, 64/70 (91.4%) patients received antibiotics as prophylaxis during their admission. Specifically, 53/70 (75.7%) received antibiotics either before endoscopy or within 8 h of endoscopy [peri-endoscopy (8 h) group], whereas 17/70 (24.3%) received antibiotics at > 8 h after endoscopy or not at all (non peri-endoscopy group). Overall mortality and rebleeding rates were 13/70 (18.6%) and 14/70 (20%), respectively. The peri-endoscopy (8 h) group was significantly less likely to die compared with the non peri-endoscopy group [13.2% vs 35.3%, P = 0.04, odds ratio (OR) = 0.28 (0.078-0.997)] and showed a trend towards reduced rebleeding [17.0% vs 29.4%, P = 0.27, OR = 0.49 (0.14-1.74)]. On univariate analysis, the non peri-endoscopy group [P = 0.02, OR = 3.58 (1.00-12.81)], higher model for end-stage liver disease (MELD) score (P = 0.02), presence of hepatorenal syndrome [P < 0.01, OR = 11.25 (2.24-56.42)] and suffering a clinical episode of sepsis [P = 0.03, OR = 4.03 (1.11-14.58)] were significant predictors of death at 28 d. On multivariate logistic regression analysis, lower MELD score [P = 0.01, OR = 1.16 (1.04-1.28)] and peri-endoscopy (8 h) group [P = 0.01, OR = 0.15 (0.03-0.68)] were independent predictors of survival at 28 d. The CDI incidence (5.7%) was comparable to that in the general medical population (5%).
  
  
  CONCLUSIONS
  Antibiotics administered up to 8 h following endoscopy were associated with improved survival at 28 d. CDI incidence was comparable to that in other patient groups.
authors.affiliation: National Institute for Health Research Nottingham Digestive Diseases Centre Biomedical Research Unit, Nottingham University Hospitals NHS Trust, E Level West Block, Queens Medical Centre Campus, Derby Road, Nottingham, NG7 2UH, United Kingdom.
authors.forename: Matthew R L
authors.initials: MR
authors.lastname: Brown
authors.forename: Graeme
authors.initials: G
authors.lastname: Jones
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Nash
authors.forename: Mark
authors.initials: M
authors.lastname: Wright
authors.forename: Indra Neil
authors.initials: IN
authors.lastname: Guha
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D019072:Antibiotic Prophylaxis; D016360:Clostridioides difficile / Q000187:drug effects*; D003015:Clostridium Infections / Q000209:etiology / Q000517:prevention & control; D004724:Endoscopy / Q000009:adverse effects; D004932:Esophageal and Gastric Varices / Q000382:microbiology / Q000401:mortality / Q000601:surgery; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000382:microbiology / Q000401:mortality / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000900:Anti-Bacterial Agents