title: Assessment of echinocandin regimens by pharmacokinetic/pharmacodynamic analysis against Candida spp. in paediatric patients.
abstract: This study aimed to investigate the cumulative fraction of response of various echinocandin (caspofungin, micafungin and anidulafungin) dosing regimens against Candida spp. in paediatric patients with invasive fungal infections (IFIs). Monte Carlo simulations were performed using previously published pharmacokinetic parameters and pharmacodynamic data to evaluate the ability of each echinocandin regimen in terms of fAUC/MIC (free drug area under the concentration-time curve/minimum inhibition concentration ratio) targets of caspofungin, micafungin and anidulafungin. Pharmacodynamic targets were attained in paediatric patients by both caspofungin regimens as well as by a high micafungin dosing regimens against Candida albicans and Candida glabrata. However, the results for anidulafungin suggested that the dosing regimens recommended were not optimal for paediatric patients. In addition, the predicted efficacy of all of the echinocandins against Candida parapsilosis was low. This is the first study to assess caspofungin, micafungin and anidulafungin therapy using Monte Carlo simulation. These results rationalise and optimise the dosage regimens of caspofungin, micafungin and anidulafungin against C. albicans, C. glabrata and C. parapsilosis for paediatric patients with IFIs.
authors.affiliation: Basic Medical College, Tianjin Medical University, 22# Qixiangtai Road, Heping District, Tianjin 300070, China.
authors.forename: Gaoqi
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Tianjin First Central Hospital, 24# Fukang Road, Nankai District, Tianjin 300192, China. Electronic address: zlq0713@aliyun.com.
authors.forename: Liqin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Basic Medical College, Tianjin Medical University, 22# Qixiangtai Road, Heping District, Tianjin 300070, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Liao
authors.affiliation: Basic Medical College, Tianjin Medical University, 22# Qixiangtai Road, Heping District, Tianjin 300070, China.
authors.forename: Tingyue
authors.initials: T
authors.lastname: Ge
authors.affiliation: Basic Medical College, Tianjin Medical University, 22# Qixiangtai Road, Heping District, Tianjin 300070, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000077612:Anidulafungin; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002175:Candida / Q000187:drug effects*; D058365:Candidiasis, Invasive / Q000188:drug therapy*; D000077336:Caspofungin; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D054714:Echinocandins / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D055666:Lipopeptides / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077551:Micafungin; D008826:Microbial Sensitivity Tests; D009010:Monte Carlo Method
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077612:Anidulafungin; D000077336:Caspofungin; D000077551:Micafungin
keywords: Echinocandins; Invasive fungal infection; Paediatric; Pharmacokinetic/pharmacodynamic