In vitro selection of Streptococcus pneumoniae strains with decreased susceptibility to beta-lactams and macrolides

Epidemiologic studies have focused on prior antibiotic use as a risk factor in the development of strains of Streptococcus pneumoniae with decreased susceptibility to penicillin, Oral beta-lactam and macrolide drugs are also commonly used to treat clinical infections, The aim of our study was to develop drug-resistant pneumococcal strains by serial daily passages in antibiotics at concentrations below the minimum inhibitory concentration (MIC), Gradient plates of penicillin, amoxicillin, amoxicillin plus clavulanic acid, cefaclor, cefuroxime, cefixime, dirithromycin, and roxithromycin were inoculated using a spiral inoculator, Three pneumococcal strains were tested, two of which were susceptible to penicillin (serotypes 03 [MIC, 0.030 mu g/mL] and 23F [MIC, 0.015 mu g/mL]) and one intermediate to penicillin (serotype 6B [MIC, 0.250 mu g/mL]), Results were expressed as the number of serial passages necessary to increase the MIC (range, 30 to 60 mu g/mL). With cefuroxime, cefixime, and roxithromycin, MICs increased more rapidly than with cefaclor and dirithromycin. Pneumococcal variants selected with cephalosporins and macrolides showed cross-resistance in the same antibiotic class, Erythromycin resistance was detected by using disk diffusion for resistance to macrolide variants, Variants selected with aminopenicillin or penicillin had increased MICs to all beta-lactam antibiotics, These results suggest the importance of identifying antibiotics with slow-acting selective properties.