High frequency of erythromycin A resistance and distribution of mefE and ermB genes in clinical isolates of Streptococcus pneumoniae in Japan

The ermB and mefE genes are important in terms of their responsibility for macrolide resistance in Streptococcus pneumoniae. We investigated the distribution of the ermB and mefE genes in erythromycin A-resistant S. pneumoniae isolated in our hospital during the period 1995-1998. All amoxicillin-low-susceptible isolates were considered to be resistant to erythromycin A. All isolates with resistance to erythromycin A (minimum inhibitory concentrations [MICs], > or =0.5 microg/ml) possessed ermB or mefE genes. The MICs of erythromycin A for most mefE-positive isolates ranged from 0.5 to 2 microg/ml. On the other hand, approximately 85% of ermB-positive isolates demonstrated high-level resistance to erythromycin A (MICs, > or =4 microg/ml) while the others showed low-level resistance (MICs, 0.5 to 2 microg/ml). In ermB-positive isolates with low-level resistance, high-level resistant mutants were selected with a frequency of 3.1 x 10(-6)-1.8 x 10(-3) on agar containing 4-32 MIC of erythromycin A, whereas in mefE-positive isolates, no high-level resistant mutants were detected. Mutants from ermB-positive isolates with low-level resistance showed reversibility and heterogeneity. Our data indicated a wide distribution of erythromycin A-resistant isolates with mefE or ermB genes among amoxicillin-low-susceptible S. pneumoniae in Japan. In addition, it is likely that ermB-positive isolates with low-level resistance show heterogeneous high-level resistance.