Gentamycin reduces bacteremia and mortality rates associated with the treatment of experimental peritonitis with recombinant tissue plasminogen activator.

Abstract

Recombinant tissue plasminogen activator (rtPA), administered intraperitoneally, reduces intra-abdominal abscess formation in rats with fecal peritonitis at the costs of increased mortality and early Escherichia coli bacteremia. It was determined whether or not mortality and bacteremia could be prevented by gentamycin in these rats. Fecal peritonitis was induced by intraperitoneal injection of sterile feces contaminated with 10(8) (experiment 1) or 10(4) (experiment 2) colony forming units (cfu) E. coli and 10(4) cfu Bacteroides fragilis. Male Wistar rats were randomly assigned to receive either methyl hydroxy propyl cellulose (MHPC) gel alone (M) or 0.5 mg/mL rtPA dissolved in MHPC gel (M-tPA). Three hours after inoculation, one-half of the rats in each of these groups received 6 mg/kg gentamycin sulfate (G) intramuscularly (group M-G and M-tPA-G). At one, three, six, 12, and 24 hours after inoculation, blood cultures were taken. At five days after inoculation, intra-abdominal abscess formation was assessed and abscesses were cultured (experiment 2). All rats in groups M and M-tPA in experiment 1 developed bacteremia and died within 24 hours. Bacteremia occurred significantly earlier in group M-tPA compared with group M (p < 0.05). Gentamycin significantly reduced the number of rats with bacteremia, the bacteria concentration in the blood, and mortality rates. Although in experiment 2 none of the rats developed bacteremia, gentamycin prevented mortality associated with the use of rtPA. The number of abscesses in groups M-tPA and M-tPA-G was significantly lower than in those in groups M and M-G (p < 0.01). Gentamycin did not influence the number of abscesses. Gentamycin reduces bacteremia and mortality rates in rats with fecal peritonitis treated with rtPA intraperitoneally to prevent intra-abdominal abscess formation.