Other Infections

EASL 2017: Norfloxacin Reduces Risk of Death for People with Decompensated Cirrhosis

Long-term prophylaxis with the antibiotic norfloxacin significantly reduced the incidence of death in people with decompensated cirrhosis over a 6-month follow-up period, according to a French randomized trial reported at the EASL International Liver Congress this week in Amsterdam.

[Produced in collaboration with infohep.org]

Norfloxacin is a fluoroquinolone antibiotic. Its use has been proposed as a means of preventing bacterial infections in people with very advanced, or decompensated cirrhosis. When liver function is severely reduced in late-stage cirrhosis, bacteria from the gut can leak into the liver, causing infections and promoting inflammation, so leading to worsening cirrhosis.

Some liver specialists are concerned that prolonged use of fluoroquinolone antibiotics can lead to the development of antibiotic resistance, encouraging the development of hard-to-treat gram-negative bacterial infections in people already at high risk of bacterial infection.

The French study was designed to test the effect of a 6-month course of daily norfloxacin (400 mg) on mortality and the incidence of severe liver complications or liver transplantation in people with decompensated cirrhosis.

People were eligible to join the study if they had Child-Pugh C cirrhosis, but the study excluded people with HIV coinfection and people with hepatocellular carcinoma.

The study recruited 291 patients at 18 hospitals in France. Participants were randomized in a double-blinded manner to receive either norfloxacin (n = 144) or placebo (n = 147) and attended the clinic once a month for follow-up visits.

The study population was largely composed of people with alcoholic cirrhosis (80% in the norfloxacin arm and 74% in the placebo arm). Two-thirds of participants in the norfloxacin arm and 74% inf the placebo arm were male, and the average age was 55.

Participants had a median MELD score of 21, and a Child-Pugh score of 11. 86% of the norfloxacin group had ascites (abdominal fluid accumulation), and 44% of the norfloxacin group and 47% of the placebo group were receiving beta-blocker treatment to manage portal hypertension and ascites, as a consequence of cirrhosis.

After 6 months of study treatment, a high proportion of participants (46%) had discontinued treatment, 12% by their own wish, 15% due to death, 9% due to liver transplant, and 9% due to spontaneous bacterial peritonitis.

By intent-to-treat analysis, the incidence of death was 43% lower in the norfloxacin group (adjusted hazard ratio 0. 57), a significant reduction in risk. People in the norfloxacin group were significantly less likely to develop an infection during the first 6 months too (23.9% vs 32.3%), especially gram-negative bacterial infections.

There was no significant difference in the other secondary outcomes of liver transplantation, hepatic encephalopathy, variceal hemorrhage, or kidney dysfunction.

"This study shows that long-term oral antibiotic therapy may improve the prognosis of patients with life-threatening liver disease. However, overuse of broad spectrum antibiotics is a subject that has been thoroughly debated over the years," lead author Richard Moreau of Beaujon Hospital in Clichy, France, said in an EASL press statement. "The results from this study provide evidence that 6 months of norfloxacin therapy reduces the risk of infections and death in the short-term, but not in the long-term."

4/22/17

Sources

R Moreau, L Elkrief, C Bureauet al. A randomized trial of 6-month norfloxacin therapy in patients with Child-Pugh class C cirrhosis.International Liver Congress, Amsterdam. EASL International Liver Congress. Amsterdam, April 19-23, 2017. Abstract GS-001.

EASL. ILC 2017: Long-term antibiotic prophylaxis can decrease short- term mortality in patients with life-threatening advanced liver disease. Press release. April 20, 2017.