Norfloxacin prevents bacterial infections in patients with liver failure

Primary norfloxacin prophylaxis is both safe and effective in preventing bacterial infections in patients with acute-on-chronic liver failure (ACLF), a study has shown.

Norfloxacin also reduces the incidence of bacterial infections in those with alcohol-associated hepatitis (AAH) on steroid therapy but increases the risk of candiduria.

ACLF patients included in this randomized, double-blind, placebo-controlled trial were identified using the Asian Pacific Association for the Study of the Liver (APASL) criteria. Eligible participants (n=143) were randomly assigned to receive either oral norfloxacin 400 mg (n=72) or matched placebo (n=71) once daily for 30 days.

The primary outcome was the incidence of bacterial infections at days 30 and 90, while the secondary outcome was transplant-free survival (TFS) at days 30 and 90.

The two groups showed similar baseline demographics, biochemical variables, and severity scores. [Am J Gastroenterol 2022;117:607-616]

Kaplan-Meier analysis revealed a significantly lower incidence of bacterial infections in the norfloxacin group compared to the placebo group both at day 30 (norfloxacin: 18.1 percent, 95 percent confidence interval [CI], 10‒28.9; placebo: 33.8 percent, 95 percent CI, 23‒46; p=0.03) and day 90 (norfloxacin: 46 percent, 95 percent CI, 34‒58; placebo: 62 percent, 95 percent CI, 49.67‒73.23; p=0.02).

Likewise, TFS was greater with norfloxacin than with placebo at day 30 (norfloxacin: 77.8 percent, 95 percent CI, 66.43‒86.73; placebo: 64.8 percent, 95 percent CI, 52.54‒75.75; p=0.084) and at day 90 (norfloxacin: 58.3 percent, 95 percent CI, 46.11‒69.84; placebo: 43.7 percent, 95 percent CI, 31.91‒55.95; p=0.058), albeit nonsignificantly.

About a third (30 percent) of infections were caused by multidrug-resistant organisms. Of note, concomitant candiduria developed in more patients on norfloxacin than on placebo (25 percent vs 2.63 percent).

Alcohol-associated hepatitis

“Severe AAH (which most often presents as ACLF in our setting) is associated with a higher risk of infection at diagnosis,” the researchers said. “In addition, steroids increase the risk of infections, especially in nonresponders.” [Gastroenterology 2009;137:541-548]

Norfloxacin prophylaxis effectively reduced the incidence of bacterial infections in AAH patients receiving concomitant steroid therapy.

“Owing to its excellent bioavailability, favourable pharmacodynamics and pharmacokinetics, and ability to reduce endotoxemia, norfloxacin may be preferred over amoxicillin-clavulanate for patients with AAH,” the researcher said.

“However, norfloxacin is not available ubiquitously, and trimethoprim-sulfamethoxazole or ciprofloxacin may be an effective alternative in such scenarios,” they added. [J Dig Dis 2014;15:260-267; J Hepatol 2008;48:774-779]

The present study was limited by only including patients with ACLF according to the APASL criteria and those with ascites. Patients with hepatic encephalopathy (HE) were excluded to avoid the confounding effect of rifaximin. Moreover, only 10 percent of participants were in grade III ACLF at inclusion.

“[T]o date, no studies have evaluated the role of norfloxacin alone in the prevention of HE in patients with ACLF,” the researchers said. “In this unique trial, norfloxacin was able to suppress endotoxemia and prevent HE and bacterial infections in patients with ACLF.”

Thus, norfloxacin once daily is safe and effective in improving TFS and positively modifying the course of ACLF, but at the risk of developing candiduria, according to the researchers.