Erythromycin-resistant Streptococcus pneumoniae isolates from young carriers were tested for their antimicrobial susceptibility; additionally, inducibility of macrolide and clindamycin resistance was investigated in pneumococci carrying erm(A), erm(B), or mef(A). Of 125 strains tested, 101 (81%) were multidrug resistant. Different levels of induction were observed with erythromycin, miocamycin, and clindamycin in erm(B) strains; however, in erm(A) strains only erythromycin was an inducer. Induction did not affect macrolide MICs in mef(A) strains.The predominant mechanisms of resistance to erythromycin and the other macrolides in Streptococcus pneumoniae are through target site modification by methylation that prevents the binding of the antibiotic to its ribosomal target, encoded by the erm(B) gene (16), or through efflux of the antibiotic, mediated by the mef(A) gene (13). Methylation of the ribosomal target of the antibiotics leads to cross-resistance to macrolides (M), lincosamides (L), and streptogramin B (S B ), the so-called MLS B phenotype. Erm methylase synthesis can be inducible or constitutive (10, 11). Alterations in ribosomal proteins L4 and L22 or 23S rRNA have been reported to cause resistance in S. pneumoniae (1). Antibiotic efflux confers resistance only to the 14-and 15-member macrolides (1, 4, 5, 7).Recently, S. pneumoniae isolates resistant to erythromycin due to carriage of the erm(A) gene have been reported (15). The macrolide resistance determinant erm(A) gene was previously described as erm(TR) in S. pyogenes (12) and now is reclassified as erm(A) (9).The present study was undertaken to compare differences in antimicrobial susceptibility between S. pneumoniae isolates harboring erm(A) and those carrying either the erm(B) or mef(A) gene and to investigate the effect of induction on the expression of macrolide resistance in erm(A)-, erm(B)-, or mef(A)-positive pneumococci. The presence of genes coding for macrolide resistance was studied by PCR as described previously (8,12,13).(This work was presented in part at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, Calif., 27 to 30 September 2002 [abstract no. C2-1977).One hundred twenty-five erythromycin-resistant S. pneumoniae isolates carrying the erm(A), erm(B), or mef(A) gene, recovered from 2,448 carriers younger than 2 years between February 1997 and February 1999 (14, 15), were evaluated for their susceptibility to 10 antibiotics representing different classes of antimicrobial agents. These agents were 14-member (erythromycin and clarithromycin), 15-member (azithromycin), and 16-member ring macrolides (miocamycin), lincosamides (clindamycin), streptogramins (quinupristin/dalfopristin), ketolides (telithromycin), penicillin G, tetracycline, and chloramphenicol. Antimicrobial susceptibility tests were performed by the agar dilution method as previously described (3). Plates were incubated in ambient air at 37°C. Antibiotics were obtained from their respective manufacturers. Miocamycin was from Meiji Sei...