Enhanced survival in antibiotic-treated murine fecal peritonitis by administration of copovithane, a selective immunostimulative polymer.
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.
D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000254:growth & development; D002219:Carbamates / Q000627:therapeutic use*; D002981:Clindamycin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005839:Gentamicins / Q000627:therapeutic use*; D007114:Immunization; D007167:Immunotherapy; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009428:Netilmicin / Q000627:therapeutic use*; D010538:Peritonitis / Q000188:drug therapy* / Q000401:mortality; D011108:Polymers; D011205:Povidone / Q000627:therapeutic use*
D002219:Carbamates; D005839:Gentamicins; D011108:Polymers; C038184:copovithane; D002981:Clindamycin; D009428:Netilmicin; D011205:Povidone