Antibiotic effects on bacterial viability, toxin production, and host response

The efficacy of an antibiotic in human or experimental infection is presumed to be proportional to its in vitro antimicrobial activity, yet antibiotics having comparable in vitro activity may have markedly different efficacies in vivo. For example, we have reported that clindamycin is more efficacious than penicillin in experimental gas gangrene caused by Clostridium perfringens in animals. To explain these differences, we compared the dynamics of bacterial killing and suppression of toxin synthesis. In addition, we investigated the ability of clindamycin and penicillin to modulate lipopolysaccharide-induced cytokine production in human peripheral blood mononuclear cells. Our results suggest that clindamycin affects protein synthesis in both prokaryotic and eukaryotic cells. These data may, in part, explain why the efficacy of clindamycin is greater than that of penicillin and demonstrate that clindamycin may be important immune modulator.