Fluoroquinolone resistance among isolates of Streptococcus pneumoniae arises de novo in a stepwise manner through both target (DNA gyrase and DNA topoisomerase IV) and non-target mutations. Variants with intermediate susceptibility can increase the frequency at which highly resistant mutants are subsequently recovered; consequently, enrichment of moderately susceptible mutants is expected to accelerate the development of fluoroquinolone resistance. Consideration of the rate at which clinical susceptibility is being lost leads to a prediction of widespread fluoroquinolone resistance even though the absolute prevalence of resistance is currently low in many countries (about 1% for levofloxacin in the USA). In vitro experiments suggest that resistance might be restricted by dosing strategies that maintain fluoroquinolone concentrations high enough to prevent growth of mutant subpopulations. However, the animal and clinical tests required for implementation of those strategies have yet to be carried out. As the potential usefulness of the strategies for fluoroquinolone therapy with S. pneumoniae is likely to be eroded by existing treatment regimens, the time available for in vivo testing appears to be limited.
All Science Journal Classification (ASJC) codes
- Microbiology (medical)
- DNA gyrase
- DNA topoisomerase IV
- Mutant prevention concentration
- Mutant selection window
- Streptococcus pneumoniae