Effect of low-level resistance on subsequent enrichment of fluoroquinolone-resistant Streptococcus pneumoniae in rabbits.

BACKGROUND: We measured the effect of low-level fluoroquinolone resistance in Streptococcus pneumoniae on the development of high-level resistance within the context of the mutant selection window. METHODS: Rabbits infected with S. pneumoniae were treated with ciprofloxacin or moxifloxacin concentrations that simulated pharmacokinetics in treated humans; bacteria obtained from lungs were examined for fluoroquinolone susceptibility. RESULTS: Ciprofloxacin enriched resistant mutants from a wild-type strain; moxifloxacin did not. However, moxifloxacin enriched resistant mutants from a parC mutant; the drug concentration at the top of the selection window was determined. CONCLUSIONS: A parC resistance mutation facilitates the enrichment of high-level resistance, as was predicted by in vitro measurements.