Effects of muramyl dipeptide and clindamycin in a murine abdominal abscess model.
Peritonitis and subsequent local and remote complications are an important source of morbidity and mortality, which persist despite the best available treatment. Reasonable therapeutic efforts, therefore, have included stimulation of host defenses with immune adjuvants, recently typified by muramyl dipeptide (MDP). Murine abdominal abscesses were created by intraperitoneal injection of Bacteroides fragilis and autoclaved fecal suspensions, and the effects of MDP and clindamycin on these abscesses were evaluated. At 10(4) colony-forming units (CFU) per milliliter of Bacteroides fragilis, intraperitoneal clindamycin was effective in reducing both the incidence of abscess formation as well as the number of abscesses per mouse as compared with controls at doses of 5 mg/kg and 2 mg/kg (P less than 0.01). The effect was more significant when the drug was given 30 min prior than when given after injection of organisms (P less than 0.02). At 10(7) and 10(8) CFU/ml, pretreatment with MDP increased abscess formation (P less than 0.05, P less than 0.01), an effect that was obscured by clindamycin administration, which decreased number of abscesses from controls irrespective of pretreatment with MDP. Abscesses were present on the third day after injection, and MDP, paradoxically, had increased the number of abscesses by the fifth day. Clindamycin reduced abscess formation at all concentrations of bacteria and had a dose and time-dependent response. MDP increased abscess formation only at high concentrations of Bacteroides fragilis, but clindamycin abolished this effect and reduced the number of abscesses to similar levels in both the clindamycin alone and clindamycin + MDP groups.(ABSTRACT TRUNCATED AT 250 WORDS)
D000005:Abdomen; D000038:Abscess / Q000188:drug therapy*; D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000627:therapeutic use*; D000818:Animals; D002981:Clindamycin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D051379:Mice; D010538:Peritonitis / Q000188:drug therapy; D051381:Rats
D002981:Clindamycin; D000119:Acetylmuramyl-Alanyl-Isoglutamine