Friday, May 13, 2011

DDW: Rifaximin Cuts Peritonitis in Cirrhosis

By John Gever, Senior Editor, MedPage Today
Published: May 12, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

CHICAGO -- The nonabsorbable antibiotic rifaximin appeared to reduce the incidence of bacterial peritonitis in patients with advanced liver cirrhosis, according to a study presented here.

In a retrospective analysis of 404 patients at risk for spontaneous bacterial peritonitis, only 10% of patients treated with rifaximin developed the condition compared with 31% of those receiving no antibiotic prophylaxis (P=0.001), reported Ibrahim Hanouneh, MD, of the Cleveland Clinic.
Assuming that the drug therapy was responsible, these outcomes meant that treating five patients with rifaximin prevented one case of bacterial peritonitis, Hanouneh told attendees at Digestive Disease Week.
Rifaximin is not approved for or routinely used off-label for peritonitis prevention, but is given regularly for hepatic encephalopathy, Hanouneh explained at a press briefing on the study.
However, published guidelines have recommended other antibiotic regimens for prophylaxis against spontaneous bacterial peritonitis in cirrhosis patients with ascites, which occurs in an estimated 8% to 25% of such patients.
The condition is very serious -- inhospital mortality ranges from 10% to 30% -- Hanouneh said, and most of those who survive have another episode within a year.
He said rifaximin would appear to be a nearly ideal prophylactic drug for the condition. Its systemic absorption is very poor, it covers a broad range of bacterial species (including Gram-negative and Gram-positive organisms), and it does not appear to promote emergence of resistance.
Because some patients with advanced cirrhosis had received rifaximin for other reasons at the Cleveland Clinic, Hanouneh and colleagues thought it would be worthwhile to see whether they developed bacterial peritonitis.
They pulled records of all patients with cirrhosis marked by ascites seen in the liver transplant clinic from 2003 to 2007. After excluding those with previous episodes of spontaneous bacterial peritonitis, prophylaxis with other antibiotics, transplant recipients, and those with GI bleeding, they were left with 404 records for analysis.
Of those, 49 had received rifaximin, mainly for hepatic encephalopathy, 355 had not.
The groups were similar in terms of age, gender and racial balance, ascitic protein levels, serum albumin, bilirubin, creatinine, MELD score, and international normalized ratio.
The major difference was that all of the patients receiving rifaximin had hepatic encephalopathy compared with only 32% of the control group.
The analysis period began when paracentesis was conducted. Median follow-up was 4.2 months, although 49 patients (seven rifaximin, 42 control) had follow-up through 30 months.
A Kaplan-Meier curve indicated that the benefit of rifaximin was apparent immediately. About 10% of the control group developed bacterial peritonitis within the first few weeks, compared with only one patient receiving rifaximin.
In multivariate analysis, only one factor other than rifaximin treatment was significantly associated with the risk of peritonitis – MELD score – and it was relatively weak, with a hazard ratio of 1.06 (95% CI 1.03 to 1.10).
In contrast, the presence of rifaximin therapy was a powerful predictor, with a hazard ratio of 0.28 (95% CI 0.11 to 0.71).
Rifaximin was also associated with significantly improved transplant-free survival. Some 72% of patients taking the drug survived with their native livers, compared with 57% of the control group (P=0.04).
In multivariate analysis, the hazard ratio for transplant or death with rifaximin was 0.54 (95% CI 0.30 to 0.97), Hanouneh reported.
Ascitic fluid cultures were negative in the five rifaximin-treated patients who developed bacterial peritonitis. In the control group, cultures were positive in 36%, evenly divided between Gram-negative and Gram-positive species.
"Intestinal decontamination with rifaximin is an effective measure to prevent [spontaneous bacterial peritonitis] and improve transplant-free survival in cirrhotic patients with ascites," Hanouneh told attendees.
At the press briefing, he acknowledged that it was possible that the indications for rifaximin therapy in these patients, or some other factor associated with the treatment, were actually responsible for the study findings.
Consequently, he said, a randomized trial should be conducted before the drug could be recommended for peritonitis prophylaxis in this population.
"I realize this is retrospective data, but it does look promising in improving transplant-free survival," commented Nicholas Talley, MD, of the University of Newcastle in Australia, who moderated the press briefing.
"We need a randomized study," he added. "We really shouldn't believe it till then, but it is intriguing information."

The study had no commercial funding.
Hanouneh declared he had no relevant financial interests. One co-author reported relationships with Vertex, Roche, Centocor, and Schering-Plough.
Talley reported relationships with ARYx Therapeutics, AstraZeneca, Boehringer Ingelheim, Falk Pharma, Focus Medical Communications, Forest, Ironwood Pharmaceuticals, Janssen-Cilag, MD Evidence, Meritage Pharmaceuticals, Procter & Gamble, and Zeria.

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