IN-VITRO SELECTIVE ANTIBIOTIC CONCENTRATIONS OF BETA-LACTAMS FOR PENICILLIN-RESISTANT STREPTOCOCCUS-PNEUMONIAE POPULATIONS

Therapeutic regimens containing beta-lactam antibiotics are selecting penicillin-resistant Streptococcus pneumoniae populations all over the world. The selective pressure after 4 h of exposure to different conc entrations of amoxicillin, cefixime, cefuroxime, and cefotaxime for lo w-level or high-level penicillin-resistant S. pneumoniae was evaluated in an in vitro model with mixed populations with penicillin susceptib ilities of 0.015, 0.5, 1, and 2 mug/ml. The antibiotic concentration s electing for low-level resistance strongly reduced the susceptible pop ulation. Increasing antibiotic concentrations tended to decrease the t otal proportion of penicillin-resistant bacteria because of reduced nu mbers of the low-level-resistant population. The antibiotic concentrat ion selecting for high-level resistance produced fewer resistant popul ations, but most of the organisms selected represented high-level resi stance. In general, amoxicillin was a good selector for the low-level- resistant population and a poor selector for high-level resistance; ce furoxime and cefotaxime were poor selectors for low-level resistance a nd better selectors than amoxicillin for high-level penicillin resista nce. Cefixime was the best selector of low-level penicillin resistance . When only resistant populations were mixed, the strains with high-le vel resistance were selected even at low antibiotic concentrations. De termination of the effects of selective antibiotic concentrations on m ixed cultures of bacteria expressing different antibiotic resistance l evels may help researchers to understand the ecology and epidemiology of penicillin-resistant S. pneumoniae populations.