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

Dig Dis Sci. 1999 Oct;44(10):1957-62. doi: 10.1023/a:1026649730012.


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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Infective Agents / therapeutic use*
  • Antibiotic Prophylaxis*
  • Ascites / prevention & control
  • Bacterial Translocation / drug effects*
  • Carbon Tetrachloride Poisoning
  • Gram-Negative Bacterial Infections / prevention & control*
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / microbiology*
  • Liver Cirrhosis, Experimental / mortality
  • Male
  • Peritonitis / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • Trimethoprim, Sulfamethoxazole Drug Combination / therapeutic use*


  • Anti-Infective Agents
  • Trimethoprim, Sulfamethoxazole Drug Combination