Antibiotic prophylaxis to prevent infection in patients with Child-Pugh A cirrhosis with upper gastrointestinal bleed: an open label randomised controlled trial.

BACKGROUND AND AIMS

Although beneficial in reducing the risk of bacterial infections in patients with advanced decompensated cirrhosis after upper gastrointestinal (GI) bleed, the utility of prophylactic antibiotics in those with Child-Pugh A cirrhosis is not known. We studied if prophylactic antibiotics can be withheld in this cohort.

METHODS

This was a single-centre, open-label randomised-controlled-trial with non-inferiority design. Patients of Child-Pugh A cirrhosis with upper-GI bleed and hemodynamic stability were randomised to receive either no prophylactic antibiotics (test-group) or ceftriaxone [standard of care (SOC)] for 72 h alongside standard medical management. The primary outcome was infection at day-5 in both arms. Secondary outcomes included failure to control bleed, mortality at day-5, and at 6 weeks.

RESULTS

Eligible patients (n = 180; mean age 45.1 ± 13.1 years, 76.9% males; median MELDNa 9 [interquartile-range: 7-12]) of predominant non-viral etiology (alcohol: 43.4%; non-alcoholic steatohepatitis: 21.7%) were randomised, of whom outcomes could be reliably assessed for 172 and 140 patients at 5-day and 6-week follow-up, respectively. Rate of day-5 infections in test-group [7.0% (95% CI 2.8-15.1%)] was non-inferior to SOC arm [11.6% (95% CI 6.02-20.8%); absolute risk difference: -4.7% (95% CI -13.3% to 4.0%; non-inferior at 10% margin)]. Spontaneous bacterial peritonitis following post-bleed ascites was the most common site of infection in both groups (10/16; 66.7%). Rates of failure to control bleed [0% vs 4.9; absolute-risk-difference: -4.6% (95% CI -9.1% to 0.2%)], day-5 mortality [0% vs 2.5%; absolute-risk-difference: -2.3% (-5.5% to 0.9%)], and 6-week mortality [1.4% vs 2.5%; absolute-risk-difference: -1.6% (-6.5% to 3.2%)] were comparable in both arms.

CONCLUSION

Among patients with Child-Pugh A cirrhosis with hemodynamic stability, withholding prophylactic antibiotics after upper GI bleed was not associated with increased risk of post-bleed infections.