COMMENTARY

Oral Norfloxacin vs Intravenous Ceftriaxone for the Prophylaxis of Bacterial Infection in Cirrhotic Patients With Gastrointestinal Bleeding

David A. Johnson, MD, FACG, FACP

Disclosures

December 14, 2006

Norfloxacin vs Ceftriaxone in the Prophylaxis of Infections in Patients With Advanced Cirrhosis and Hemorrhage

Fernandez J, Ruiz del Arbol L, Gomez C, et al
Gastroenterology. 2006;131:1049-1056

It has been well recognized that the development of bacterial infection is a major potential problem in cirrhotic patients presenting with gastrointestinal hemorrhage. Studies have demonstrated a prevalence of bacterial infections in these patients ranging from 25% to 65%.[1,2] In patients with ascites, the development of spontaneous bacterial peritonitis (SBP) is a well-recognized complication among those with cirrhosis who present with gastrointestinal bleeding.

The administration of nonabsorbable antibiotics has been shown to reduce the incidence of bacterial infections in cirrhotic patients presenting with gastrointestinal bleeding. As such, administration of antibiotics is standard of care in this population. Prior studies demonstrating that oral administration of norfloxacin, a poorly absorbed quinolone, is effective against gram-negative bacteria (but not against anaerobes or gram-positive organisms)[3] have led to this drug being the most commonly used prophylaxis in these patients.[4] However, more recent studies have suggested that this strategy may not be the best approach. The prevalence of quinolone-resistant bacteria in the fecal flora, coupled with the increased incidence of SBP associated with these organisms, substantiates the concern regarding the use of norfloxacin. Furthermore, there are a significant number of infections in these patients that are in fact due to gram-positive bacteria, which are not covered by norfloxacin.

This current randomized controlled trial aimed to compare the efficacy of norfloxacin (oral) vs ceftriaxone (intravenous [IV]) for the prevention of bacterial infections in cirrhotic patients with gastrointestinal hemorrhage. This multicenter prospective study from Spain involved patients with cirrhosis admitted for gastrointestinal bleeding. The diagnosis of cirrhosis was established by clinical, laboratory, and radiologic criteria. A total of 1369 patients with gastrointestinal bleeding were screened, 124 of whom met the criteria for randomization; 111 patients were then randomized to treatment (57 received oral norfloxacin 400 mg twice daily x 7 days; 54 received IV ceftriaxone 1 g/day x 7 days). All patients were followed closely with particular emphasis on the detection of bacterial infections. Blood, ascitic fluid, and urine cultures were taken whenever patients developed signs of infection. The endpoint of the trial was the prevention of bacterial infection within 10 days of beginning the study medication.

Only 6 of the 57 (11%) patients treated with IV ceftriaxone developed a bacterial infection during the study period compared with 26% of patients who received norfloxacin (P = .03). The rate of SPB was also lower among patients who received the IV ceftriaxone vs oral norfloxacin (12% vs 2%; P = .03). Independent variables predictive of the development of bacterial infections were: the type of antibiotic used (ceftriaxone vs norfloxacin), failure to control bleeding, and the related transfusion requirement at inclusion.

These study findings should change the standard practice pattern that clinicians have followed for managing cirrhotic patients with gastrointestinal bleeding. Clearly, the standard of care has been to prescribe norfloxacin, but this study demonstrates that the value of this agent as prophylaxis in this patient population is poor. The low efficacy is likely reflective of the changes in the epidemiology of bacterial infections seen in patients with cirrhosis. In the past, these infections have traditionally been due to gram-negative bacteria, although the incidence of infections due to gram-positive bacteria has been increasing significantly. Also notable is the fact that the incidence of infections due to gram-negative bacteria that are quinolone resistant is relatively high.[5] Intravenous ceftriaxone appears to have set the new standard as a prophylaxis strategy for the prevention of bacterial infections in patients with advanced cirrhosis and gastrointestinal bleeding.

Abstract URL: $$www$$/medline/abstract/17030175

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