In vitro activity of midecamycin diacetate, a 16-membered macrolide, against Streptococcus pyogenes isolated in France, 1995-1999.
OBJECTIVE: To compare the in vitro activity of midecamycin diacetate to that of five other macrolides (erythromycin, clarithromycin, roxithromycin, azithromycin, and josamycin) and of clindamycin against 146 clinical isolates of Streptococcus pyogenes, with regard to three different phenotypes of erythromycin resistance. METHODS: Susceptibility pattern and resistance phenotype were determined by disk diffusion method and double disk test. Minimal inhibitory concentrations of antibiotics were obtained by the agar dilution method and evaluated according to the recommendations of the 'Comité de l'Antibiogramme de la Société Française de Microbiologie' (CA-SFM). The major determinants of erythromycin resistance in S. pyogenes (ermB, ermTR and mefA genes) were investigated by specific amplification protocols. RESULTS: Most of the isolates of S. pyogenes collected during 1995-99 were susceptible to midecamycin (93.8%), erythromycin (90.4%), clarithromycin (93.2%), roxithromycin (91.8%), azithromycin (88.4%), josamycin (94.5%), and clindamycin (94.5%). According to the CA-SFM criteria, 132 of the 146 isolates studied were susceptible to erythromycin (MICs < or = 1 mg/L), four were intermediate (MICs 2-4 mg/L), and 10 were resistant (MICs > 4 mg/L). Only nine isolates were midecamycin resistant (MICs > 4 mg/L), and the others were susceptible. The increased activity of midecamycin (MIC90 < or = 0.06 mg/L), as compared to erythromycin (MIC90 = 0.5 mg/L) and to other 14- or 15-membered macrolides, was related to the absence of the ermB determinant in seven isolates which displayed an efflux phenotype (five isolates) or an inducible resistance phenotype due to an ermTR determinant (two isolates). CONCLUSION: Midecamycin diacetate is active against most S. pyogenes strains isolated in France and may represent an attractive alternative to the treatment of streptococcal infections due to resistant isolates with efflux of erythromycin.