Pharmacokinetic/pharmacodynamic adequacy of echinocandins against Candida spp. in intensive care unit patients and general patient populations

• First study of PK/PD target attainment of echinocandins in critically ill patients.
• Considerable PTA variability was observed for anidulafungin and micafungin in different patient populations.
• For Candida albicans and C. glabrata, caspofungin is a reasonable choice for general and ICU patients.
• For C. parapsilosis, an increased dose up to 100 mg once daily of caspofungin is needed.
• For anidulafungin and micafungin, administering higher doses is needed in clinical applications.

This study evaluated whether contemporary echinocandin regimens achieved pharmacokinetic/pharmacodynamic targets in ICU patients and general patient populations (GPPs) and assessed caspofungin (CAS) regimens in hepatic impairment (HI) patients. A Monte Carlo simulation was performed using previously published data. Recommended dosing regimens of echinocandins in ICU patients, GPPs and healthy volunteers were evaluated: 70 mg loading dose then 50 mg maintenance dose (70/50 mg) for CAS; 100 mg q24h for micafungin (MCF); and 200/100 mg for anidulafungin (ANF). Moreover, CAS 70 mg and 100 mg q24h in GPPs, and CAS 70/50 mg and 70/35 mg in mild and moderate HI patients, respectively, were evaluated. Cumulative fraction of response (CFR) was calculated for each dosing regimen. For Candida albicans, CFRs for the recommended doses of CAS, MCF and ANF were 95.8%, 13.5% and 50.5% in ICU patients and 96.3%, 42.4% and 61.6% in GPPs, respectively; for Candida glabrata, CFRs were 99.4%, 90.6% and 44.6% in ICU patients and 99.5%, 97.1% and 59.8% in GPPs. For Candida parapsilosis, CFRs of echinocandins for standard regimens were <70%; only CAS 100 mg q24h achieved the target CFR. CAS 70/50 mg and 70/35 mg in mild and moderate HI patients were appropriate. Considerable interindividual variability was observed. For C. albicans and C. glabrata, CAS is good choice both for ICU and other patient populations, but for C. parapsilosis an increased dose should be considered. For MCF and ANF, administering higher doses with longer dosing intervals achieves better target attainment and should be investigated in clinical trials.