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Comparative study of clindamycin, imipenem, oxacillin and vancomycin in the infected granuloma pouch model
E Brauner1, S Gorbach, P Davey
1Department of Community Health, Tufts University School of Medicine, Boston, MA 02111.
Abstract:
In a rat granuloma pouch model, Staphylococcus aureus infection was treated with clindamycin, oxacillin or vancomycin and Bacteroides fragilis infection with clindamycin or imipenem. The model simulates a subcutaneous abscess and has the advantage of permitting frequent sampling of exudate for bacterial counts and antibiotic levels in the same animal. In staphylococcal infection all drugs reduced the bacterial counts in the infected pouch by 1-1.7 log, with a significant effect lasting for 3 h after the last injection. A 1.06-1.4 log reduction lasted for 24 h with clindamycin and oxacillin, but there was only an 0.3 log reduction at 24 h with vancomycin. The ratio of the drug concentration in the infected pouch to the MIC was highest with clindamycin (2.3) compared to oxacillin (1.6) and vancomycin (0.8). With Bact. fragilis infection the bacterial counts dropped 1.5 log at 3 h after the last injection with clindamycin and imipenem. At 24 h the counts were reduced 1.0 log with clindamycin and 0.5 log with imipenem. The ratios of pouch fluid concentration to MIC was 7.6 and 4.08 for imipenem and clindamycin, respectively, at 3 h, and 1.0 and 2.3 for imipenem and clindamycin at 24 h.
Insights
Clindamycin and oxacillin showed sustained antibacterial effects against Staphylococcus aureus in a rat abscess model. Clindamycin demonstrated superior efficacy against Bacteroides fragilis compared to imipenem over 24 hours.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Subcutaneous abscesses are challenging to treat due to localized infection.
- Evaluating antibiotic efficacy in simulated abscess environments is crucial for treatment selection.
Purpose of the Study:
- To compare the efficacy of clindamycin, oxacillin, and vancomycin against Staphylococcus aureus.
- To assess the effectiveness of clindamycin and imipenem against Bacteroides fragilis in a rat granuloma pouch model.
Main Methods:
- A rat granuloma pouch model was utilized to simulate subcutaneous abscesses.
- Bacterial counts and antibiotic levels in exudate were frequently sampled.
- Antibiotic efficacy was evaluated based on bacterial log reduction and drug concentration to minimum inhibitory concentration (MIC) ratios.
Main Results:
- Clindamycin and oxacillin provided a 1.06-1.4 log reduction in Staphylococcus aureus counts for 24 hours, unlike vancomycin.
- Clindamycin exhibited a higher drug concentration to MIC ratio (2.3) against Staphylococcus aureus compared to oxacillin (1.6) and vancomycin (0.8).
- Clindamycin showed a more sustained reduction in Bacteroides fragilis counts (1.0 log at 24h) compared to imipenem (0.5 log at 24h), with higher concentration to MIC ratios at 24h.
Conclusions:
- Clindamycin and oxacillin demonstrate prolonged efficacy in treating Staphylococcus aureus abscesses.
- Clindamycin appears more effective than imipenem for Bacteroides fragilis infections in this model, particularly at later time points.