InVitro Selective Antibiotic Concentrations ofP-Lactams for Penicillin-Resis tant Streptococcus pneumoniae Populations

S.pneumoniae wasevaluated inaninvitro modelwithmixedpopulations withpenicillin susceptibilities of0.015, 0.5, 1, and2,ug/ml. Theantibiotic concentration selecting forlow-level resistance strongly reduced thesusceptible population. Increasing antibiotic concentrations tended todecrease thetotal proportion ofpenicillin-resis tant bacteria because ofreduced numbers ofthelow-level-resistant population. Theantibiotic concentration selecting forhigh-level resistance produced fewer resistant populations, butmostoftheorganisms selected represented high-level resistance. Ingeneral, amoxicillin wasa goodselector forthelow-level-resistant population andapoorselector forhigh-level resistance; cefuroxime andcefotaxime werepoorselectors for low-level resistance andbetter selectors thanamoxicillin forhigh-level penicillin resistance. Cefixime wasthe bestselector oflow-level penicillin resistance. Whenonly resistant populations weremixed, thestrains with high-level resistance wereselected evenatlowantibiotic concentrations. Determination oftheeffects ofselective antibiotic concentrations onmixed cultures ofbacteria expressing different antibiotic resistance levels mayhelp researchers tounderstand theecology andepidemiology ofpenicillin-resis tant S.pneumoniae populations. Theevolution ofpenicillin resistance inStreptococcus pneumoniae hastaken thewestern worldbysurprise. Ten years ago,theproportion ofEuropean orAmerican strains that haddeveloped resistance to 3-lactam drugs remained verylow(1,6).Spain wasthefirst western country toshow animpressive increase intherateofisolates requiring MICs of>0.1,ug/ml, whichincreased fromless than7%ofstrains in1979toamaximumof44%in1989(4). Inrecent years, the rateofpenicillin-resis tant