DDW 2011: Rifaximin Reduces SBP Risk, Improves Transplant-Free Survival

Intestinal decontamination with rifaximin prevents spontaneous bacterial peritonitis and improves transplant-free survival in cirrhotic patients with ascites.

Intestinal decontamination with rifaximin effectively prevents spontaneous bacterial peritonitis (SBP) and improves transplant-free survival in cirrhotic patients with ascites, according to a presentation at Digestive Disease Week 2011.

SBP, said Ibrahim A. Hanouneh, MD, gastroenterology fellow at Cleveland Clinic, Cleveland OH, occurs in 8-25% of cirrhotic patients with ascites. The in-hospital mortality rate among these patients ranges from 10-30%, and SBP recurs within a year in 70% of those who survive an episode.

AASLD (American Association for the Study of Liver Disease) practice guidelines recommend the use of antibiotics such as norfloxacin or trimethoprim/sulfamethoxazole for primary prophylaxis of SBP in high-risk cirrhotic with ascites.

There is, however, no current consensus on whether prophylactic antibiotics provide a long-term survival benefit. In addition, there is a concern that prophylactic antibiotics can lead to the emergence of resistant gut flora which can subsequently cause spontaneous infection.

Rifaximin is a poorly absorbed, well-tolerated antibiotic with low bacterial resistance risk. It is broad spectrum and covers Gram-positive and Gram-negative organisms, aerobes as well as anaerobes, Hanouneh said.

To determine whether rifaximin prevents SBP in cirrhotic patients with ascites, and to determine whether rifaximin provides survival benefit for cirrhotic patients with ascites, Hanouneh reviewed all patients seen at the Cleveland Clinic liver transplant unit between 2003 and 2007 (N=664). Among these, 434 with ascites clinically significant enough to justify paracentesis were included in the evaluation. They were stratified by use of rifaximin (rifaximin=49; no rifaximin=355), which had been given primarily for hepatic encephalopathy at a dose of 400 mg TID. Those who had received primary SBP prophylaxis with norfloxacin or trimethoprim/sulfamethoxazole (N=8), with histories of SBP (N=14), SBP in the setting of a GI bleed (N-=2) or prior transplantation (N=6) were excluded. Patients were followed until organ transplant or death.

Mean patient age was ~54 years (~60% male, ~83% Caucasian). Encephalopathy was more common in the rifaximin group (100% versus 32%, P<0.001), as was elevated Child’s Pugh (a cirrhosis severity scale) (11.5% versus 10.4%, P<0.001).

After about 60 months of follow-up, 118 (29%) of patients had developed SBP, 5 in the rifaximin group and 113 in the no rifaximin group (p=0.001). Based on that, the NNT (number needed to treat) to prevent 1 SBP with rifaximin treatment is 5, Hanouneh said.

A multivariable analysis of factors associated with SBP revealed rifaximin (hazard ratio [HR]=0.28, P=0.007) and MELD score (Mayo End-Stage Liver Disease score)(HR=1.06, P<0.001), another marker of disease severity and mortality in persons with chronic alcoholic liver disease, as significant factors,

After adjusting for MELD score, Child’s Pugh score, serium sodium and ascetic fluid total protein, there was a 72 percent reduction in the rate of SBP in the rifaximin group. Analysis showed also greater transplant-free survival in the rifaximin group (72% versus 57%, p=0.04). Multivariable analysis of transplant-free survival factors showed significance for rifaximin (HR=0.54; P=0.039) and for MELD score (HR= 1.09; P<0.001).

Hanouneh concluded, “Intestinal decontamination with rifaximin is an effective measure to prevent SBP and improve transplant-free survival in cirrhotic patients with ascites.” Hanouneh commented at the DDW press conference, “I would not make recommendations based on this study now because it was retrospective. If the findings are confirmed prospectively, I would.”