In Vivo Fluconazole Pharmacodynamics and Resistance Development in a Previously Susceptible Candida albicans Population Examined by Microbiologic and Transcriptional Profiling

摘要: Antimicrobial drug resistance can limit the ability to effectively treat patients. Numerous factors have been proposed impact development of antimicrobial resistance, including those specific and dosing regimen. The field investigation that examines relationship between regimen outcome is termed pharmacokinetics pharmacodynamics. Our prior in vivo investigations examined fluconazole pharmacodynamics modulation isogenic resistant susceptible Candida albicans populations a mixed-inoculum design (1). goal current studies was examine on emergence from parent population over time using murine systemic-candidiasis model. Both microbiologic transcriptional endpoints were during evolution cell populations. As our previous investigation, more frequently administered prevented phenotype. Conversely, regimens produced prolonged sub-MIC concentrations associated with development. also demonstrated striking pharmacodynamic exposures mRNA abundance resistance-associated efflux pumps. Global profiling progressive phenotype provides insight into mechanisms underlying this complex physiologic process.