Prophylactic use of norfloxacin reduced the incidence of bacterial infections and improved transplant-free survival among patients with acute-on-chronic liver failure (ACLF), according to study results published in the American Journal of Gastroenterology.
Researchers conducted a randomized controlled trial at the Asian Institute of Gastroenterology’s Department of Hepatology in Hyderabad, India, from October 14, 2019, to May 12, 2021. Investigators randomly assigned 143 patients with ACLF into 2 groups: a treatment group (n=72), receiving 400 mg of norfloxacin once daily for 30 days, and a control group (n=71), receiving an oral placebo with standard medical therapy.
The researchers analyzed blood work consisting of a hemogram, kidney and liver function tests, C-reactive protein levels, procalcitonin levels, arterial blood gas levels, and the international normalized ratio (INR) at baseline, day 30, and day 90. They also performed ascitic fluid analysis as well as blood and urine analyses to detect bacterial and fungal infections.
After 30 and 90 days, the investigators compared incidence of bacterial infections, change in endotoxin levels, transplant-free survival, and drug tolerance between the 2 groups.
By days 30 and 90, 26% and 54% of the entire cohort developed bacterial infections, respectively. Comparing the 2 groups on day 30, 18.1% (13/72; 95% CI, 10-28.9) of the norfloxacin group and 33.8% (24/71; 95% CI, 23-46) of the placebo group developed bacterial infections. At day 90, 46% (33/72; 95% CI, 34-58) of the norfloxacin group and 62% (44/71; 95% CI, 49.67-73.23) of the placebo group developed bacterial infections. Most infections occurred in the urinary tract and the peritoneal cavity.
By day 30, the norfloxacin group demonstrated the largest mean change in endotoxin levels compared with the placebo group (-13.9±3.4 EU/mL vs. -8.66±2.91 EU/mL; P =.01), reflecting norfloxacin’s effective suppression of endotoxemia.
Compared to 64.8% of the placebo group, 77.8% of the norfloxacin group had a transplant-free survival by day 30 (56/72; 95% CI, 66.43-86.73 vs. 46/71; 95% CI, 52.54-75.75; P =.084). At day 90, the transplant-free survival in the norfloxacin group was 58.3% compared with 43.7% in the placebo group (42/72; 95% CI, 46.11-69.84 vs. 31/71; 95% CI, 31.91-55.95; P =.058)
Only 2 patients in each group stopped treatment due to adverse events. Four patients in the norfloxacin group and 3 in the placebo group developed drug-related side effects.
At the end of the study, 35% of patients in the norfloxacin group and 51% of patients in the placebo group died (P =.053). Primary cause of death was sepsis followed by progressive liver failure, acute variceal bleeding, cardiovascular events, and COVID-19 infection.
“…[N]orfloxacin was able to suppress endotoxemia and prevent [hepatic encephalopathy] and bacterial infections in patients with ACLF,” the study authors concluded. “Hence norfloxacin administered once a day is safe and effective in improving [transplant-free survival] and favorably modifies the course of ACLF but at the risk of candiduria.”
Limited generalizability and difficulty recruiting patients with grade 3 ACLF prior to liver transplantation or death (only 10% of patients in this sample had grade 3 ACLF) affected study results.
Kulkarni AV, Tirumalle S, Premkumar M, et al. Primary Norfloxacin prophylaxis for APASL-defined acute-on-chronic liver failure: A placebo-controlled double-blind randomized trial. Am J Gastroenterol. 2022;117(4):607-616. doi:10.14309/ajg.0000000000001611
This article originally appeared on Gastroenterology Advisor