The purpose of this study was to determine the effect of an immunostimulative
polymer,
Copovithane (Cpv), plus
antibiotics (
netilmicin and
clindamycin) in a murine model of fecal
peritonitis. Cpv augments humoral immunity with little effect on T cells and is nontoxic. Cpv 100 mg/kg iv administered at the onset of
sepsis increased median survival time (MST) by 40-55% over untreated controls. Four experiments were performed. Cpv in combination with
antibiotics when given at the time of onset of
sepsis was significantly more effective than
antibiotics alone (MST 235 vs 105 hr, P less than 0.05 at 144, 168, 192, 216 hr). In the second and third experiments Cpv alone and with
antibiotics was administered 15 hr after the onset of
sepsis. Cpv significantly augmented survival over controls in the second experiment (MST 87 vs 60 hr, P less than 0.025 at 96 hr). Cpv plus
antibiotics was significantly better than
antibiotics alone in the third experiment (MST 111 vs 64 hr, P less than 0.05 at 72 hr, P less than 0.005 at 120 hr). In the final experiment, Cpv did not inhibit growth of 20 bacterial species in
agar and liquid media. Cpv significantly enhances survival in murine fecal
peritonitis even when administered after the onset of
sepsis; furthermore Cpv plus
antibiotics in established
peritonitis produces longer survival than
antibiotics alone. Synthetic
immunomodulators such as Cpv could eventually play a significant role in the management of peritoneal
infection in humans.