title: Effect of long-term trimethoprim-sulfamethoxazole prophylaxis on ascites formation, bacterial translocation, spontaneous bacterial peritonitis, and survival in cirrhotic rats.
abstract: 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 SBP (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 gram-negative 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 gram-negative bacterial translocation but not of SBP, without increasing gram-positive episodes. These data suggest that trimethoprim-sulfamethoxazole might be a good alternative to norfloxacin for preventing gram-negative bacterial translocation.
authors.affiliation: Department of Medicine, University of Louisville, Kentucky, USA.
authors.forename: C
authors.initials: C
authors.lastname: Guarner
authors.forename: B A
authors.initials: BA
authors.lastname: Runyon
authors.forename: M
authors.initials: M
authors.lastname: Heck
authors.forename: S
authors.initials: S
authors.lastname: Young
authors.forename: M Y
authors.initials: MY
authors.lastname: Sheikh
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D001201:Ascites / Q000517:prevention & control; D018988:Bacterial Translocation / Q000187:drug effects*; D002252:Carbon Tetrachloride Poisoning; D016905:Gram-Negative Bacterial Infections / Q000517:prevention & control*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000382:microbiology* / Q000401:mortality; D008297:Male; D010538:Peritonitis / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination