Bacteriological evaluation of midecamycin acetate and its metabolites

In vitro midecamycin acetate was shown to have broad spectrum of antibacterial activities similar to those of other macrolides (midecamycin, josamycin, 9-propionyl josamycin and 2'-ethylsuccinyl erythromycin), which include Gram-positive organisms, a part of Gram-negative organisms and anaerobes. Metabolites of midecamycin acetate also showed certain degree of antibacterial activities although they gave higher MIC values than midecamycin acetate. The antibacterial activities of midecamycin acetate were potentiated in the medium with pH 7 or pH 8 and little affected by inoculum size or addition of human serum into the medium. Both midecamycin acetate and its metabolites were found to have relatively high protein binding rates. In vivo therapeutic experiments in experimental infections in mice, midecamycin acetate was shown to be much superior to other drugs tested in the therapeutic efficacy against intraperitoneal infections caused by Staph. aureus, Strept. pyogenes, Strept. pneumoniae and Cl. perfringens. In infections transnasally induced by Strept. pneumoniae, midecamycin acetate showed therapeutic efficacy 2 or 5 times greater than that of josamycin or midecamycin, despite that MICs of midecamycin acetate were equal to josamycin or midecamycin. Moreover, midecamycin acetate showed high therapeutic efficacy for subcutaneous infections due to Staph. aureus, suggesting that it exerts pronounced antibacterial activities against not only systemic infections but also local infections.