Norfloxacin yields survival gains in certain patients with advanced cirrhosis
The fluoroquinolone norfloxacin does not appear to reduce 6-month mortality in patients with advanced cirrhosis, according to a study. However, the drug confers survival benefits among those with low ascites fluid protein concentrations.
A total of 291 adult patients with Child-Pugh class C cirrhosis who had not received recent fluoroquinolone therapy were randomized to treatment with norfloxacin 400 mg (n=144) or placebo (n=147) once-daily for 6 months.
Patients were evaluated monthly for the first 6 months and at 9 and 12 months thereafter. The primary endpoint was 6-month mortality, estimated by the Kaplan-Meier method, which censored spontaneous bacterial peritonitis, liver transplantation or loss during follow up.
The 6-month mortality estimate did not differ significantly between the two treatment groups, 14.8 percent with norfloxacin vs 19.7 percent with placebo (p=0.21).
However, competing risk analysis taking liver transplantation into account showed that the cumulative incidence of death at 6 months was less common in the norfloxacin group than in the placebo group (subdistribution hazard ratio [SHR], 0.59; 95 percent CI, 0.35–0.99).
The protective effect of the drug on the risk of death at 6 months was pronounced among patients with lower ascites fluid protein concentrations (<15 g/L; SHR, 0.35; 0.13–0.93) and absent among those with higher ascites fluid protein concentrations (≥15 g/L; SHR, 1.39; 0.42–4.57).
Norfloxacin substantially reduced the incidence of any and Gram-negative bacterial infections without increasing infections caused by Clostridium difficile or multiresistant bacteria. This suggests that the drug may prevent some infections, but not the development of spontaneous bacterial peritonitis and other noninfectious, liver-related complications, as researchers pointed out.