Prophylactic Antibiotics Investigated for Severe ALD

A randomized clinical trial conducted among patients hospitalized with severe alcohol-related hepatitis revealed that the combination of amoxicillin-clavulanate with prednisolone did not reduce mortality when compared with placebo with prednisolone.

The randomized, double-blind clinical trial followed patients with biopsy-proven severe alcohol-related hepatitis —defined as a Maddrey function score ≥32 and Model for End-stage Liver Disease [MELD] score ≥21—from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium for 180 days. Of the 284 patients, 145 were randomized to receive prednisolone combined with amoxicillin-clavulanate while 147 were treated with prednisolone plus placebo. A final follow-up visit was made on November 19, 2019, the authors reported.

The primary outcome was all-cause mortality at 60 days. Among the secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection; and incidence of hepatorenal syndrome. Proportions of patients with MELD score of under 17 at 60 days and those with a Lille score of less than 0.45 at 7 days were also assessed.

The authors reported, “mortality at 60 days was 17.3% in the amoxicillin-clavulanate group compared with 21.3% in the placebo group, a nonsignificant difference (hazard ratio, 0.77; 95% CI, 0.45-1.31).”

The investigators further found, “Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, −11.8% [95% CI, −23.0% to −0.7%]; subhazard ratio, 0.62; [95% CI, 0.41-0.91]; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes.”

Liver failure, infections, and gastrointestinal disorders were the most frequently occurring adverse events in both the antibiotic-treated group (25, 23, and 15, respectively) and the placebo group (20, 46, and 15, respectively.)

“These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis,” the investigators concluded.

Reference:

Louvet A, Labreuche J, Thong Dao T et al. Effect of prophylactic antibiotics on mortality in severe alcohol-related hepatitis: a randomized clinical trial. JAMA. 2023;329(18):1558-1566. doi:10.1001/jama.2023.4902