Brief Article
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World J Gastroenterol. Nov 14, 2010; 16(42): 5317-5323
Published online Nov 14, 2010. doi: 10.3748/wjg.v16.i42.5317
Antibiotic prophylaxis in variceal hemorrhage: Timing, effectiveness and Clostridium difficile rates
Matthew RL Brown, Graeme Jones, Kathryn L Nash, Mark Wright, Indra Neil Guha
Matthew RL Brown, Indra Neil Guha, 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
Graeme Jones, Department of Microbiology, Southampton University Hospital Trust, Level B, Southampton General Hospital, Southampton, S016 6YD, United Kingdom
Kathryn L Nash, Mark Wright, Liver Unit, Southampton University Hospital Trust, Level F, Southampton General Hospital, Southampton, SO16 6YD, United Kingdom
Author contributions: Brown MRL and Guha IN conceived the study, and undertook the data collection and statistical analysis; Jones G, Nash KL and Wright M all contributed equally to the data interpretation and discussion; Brown MRL and Guha IN wrote the manuscript.
Correspondence to: Indra Neil Guha, MRCP, PhD, Associate Professor of Hepatology, 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. neil.guha@nottingham.ac.uk
Telephone: +44-115-8231162 Fax: +44-115-9709955
Received: June 14, 2010
Revised: July 9, 2010
Accepted: July 16, 2010
Published online: November 14, 2010
Abstract

AIM: 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%).

CONCLUSION: 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.

Keywords: Variceal hemorrhage; Mortality; Antibiotics; Prophylaxis; Clostridium difficile