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Effects of muramyl dipeptide and clindamycin in a murine abdominal abscess model
Abstract:
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)
Insights
Muramyl dipeptide (MDP) unexpectedly increased abdominal abscesses in mice, but clindamycin effectively reduced abscess formation, even when combined with MDP. This highlights clindamycin
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Peritonitis and its complications remain significant causes of morbidity and mortality.
- Immune adjuvants like muramyl dipeptide (MDP) have been explored to enhance host defenses.
- Bacterial infections, particularly those involving Bacteroides fragilis, can lead to abdominal abscesses.
Purpose of the Study:
- To evaluate the effects of muramyl dipeptide (MDP) and clindamycin on murine abdominal abscesses.
- To determine the efficacy of clindamycin in reducing abscess formation caused by Bacteroides fragilis.
- To investigate the combined effects of MDP and clindamycin on abscess development.
Main Methods:
- Murine abdominal abscesses were induced by intraperitoneal injection of Bacteroides fragilis and fecal suspensions.
- The impact of varying doses of clindamycin and pretreatment with MDP on abscess incidence and number was assessed.
- Dose and time-dependent responses of clindamycin were analyzed.
Main Results:
- Clindamycin significantly reduced abscess incidence and number at lower bacterial concentrations (10(4) CFU/ml), with earlier administration being more effective.
- At higher bacterial concentrations (10(7) and 10(8) CFU/ml), MDP pretreatment paradoxically increased abscess formation.
- Clindamycin administration abolished the abscess-promoting effect of MDP and reduced abscess numbers in all tested groups.
Conclusions:
- Clindamycin demonstrates significant efficacy in reducing abdominal abscesses caused by Bacteroides fragilis in a dose- and time-dependent manner.
- While MDP may increase abscess formation at high bacterial loads, its effect is counteracted by clindamycin treatment.
- Clindamycin is a crucial therapeutic agent for managing abdominal abscesses, irrespective of immune adjuvant co-administration.