Assessment of echinocandin regimens by pharmacokinetic/pharmacodynamic analysis against Candida spp. in paediatric patients

- The efficacy of caspofungin, micafungin and anidulafungin regimens in paediatric patients was evaluated.
- Monte Carlo simulation based on PK/PD theory was used to calculate probabilities of target attainment and cumulative fraction of response.
- Both caspofungin regimens and high micafungin dosing regimens were effective against Candida albicans and Candida glabrata.
- The recommended dosing regimens of anidulafungin were not optimal for paediatric patients.
- For Candida parapsilosis, all three echinocandins may be not sufficient to achieve optimal activity.

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.