Plasminogen activator, but not systemic antibiotic therapy, prevents abscess formation in an experimental model of secondary peritonitis.

Abstract

Intra-abdominal abscesses are sources of recurrent or ongoing abdominal sepsis. They are an important target for prevention and treatment during or after surgical treatment of peritonitis. Experimental data suggest that fibrinolytic therapy may be effective when antibiotics are not. Peritonitis was induced via intra-abdominal injection of a faeces and bacteria mixture in male Wistar rats. Surgical debridement was performed after 1 h. Next to untreated controls, animals were treated with antibiotics (ceftriaxone plus metronidazole), recombinant tissue plasminogen activator (rtPA) or both. Abdominal fluid samples were taken at 24, 72 and 120 h for interleukin 6, interleukin 10 and tumour necrosis factor alpha measurements and cell counts. After 5 days the abdomen was inspected for the presence of abscesses. Antibiotics did not significantly affect abscess formation. However, giving rtPA significantly reduced the number of rats with abscesses and the abscess load per rat, both in the absence and presence of concomitant antibiotic therapy. No adverse side-effects were observed and no meaningful differences in the local inflammatory response were found. In this rat model, rtPA consistently reduced abscess formation after surgical treatment of secondary peritonitis. It therefore represents a promising adjuvant to conventional therapy.