Effect of long-term trimethoprim-sulfamethoxazole prophylaxis on ascites formation, bacterial translocation, spontaneous bacterial peritonitis, and survival in cirrhotic rats

Selective intestinal decontamination with norfloxacin is useful in preventing spontaneous bacterial peritonitis in cirrhotic patients and also in cirrhotic rats. The emergence of norfloxacin-resistant infections in these patients warrants a search for alternative therapies. The aim of this study was to evaluate the effect of long-term trimethoprim-sulfamethoxazole administration on carbon tetrachloride (CCl4)-induced cirrhosis in rats with specific attention to intestinal flora, bacterial translocation, spontaneous bacterial peritonitis (SBP), and survival. Male Sprague-Dawley rats received CCl4 administered weekly by gavage. After eight weeks of CCl4 administration rats were randomly allocated into two groups. Group I received daily overnight trimethoprim-sulfamethoxazole diluted in phenobarbital water during follow-up and group II did not. The rats were killed when gravely ill, and a laparotomy was performed to culture samples of cecal stool, mesenteric lymph nodes, and portal and inferior vena caval blood. There was a trend toward a reduction in the incidence of bacterial translocation (8/17 vs 11/14, respectively) and SEP (5/17 vs 7/14, respectively) in treated rats that were killed just before death compared to untreated rats. A decrease in the incidence of bacterial translocation caused by gramnegative bacilli was observed in group I (17.6% vs 78.6%, P < 0.01). The development of ascites was delayed in group I (P < 0.05) and survival was prolonged in group I (P < 0.05), despite a higher CCl4 dose in this group (P < 0.05), In conclusion, long-term prophylactic trimethoprim-sulfamethoxazole administration in CCl4-induced cirrhosis in rats delayed the development of ascites, prolonged survival, and reduced the incidence of gramnegative bacterial translocation but not of SEP, without increasing gram-positive episodes. These data suggest that trimethoprim-sulfamethoxazole might be a good alternative to norfloxacin for preventing gram-negative bacterial translocation.