In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 64, No. 12 ( 2020-11-17)
Abstract:
This study evaluated the impact of a high loading dose of caspofungin (CAS) on the pharmacokinetics of CAS and the pharmacokinetic-pharmacodynamic (PK-PD) target attainment in patients in intensive care units (ICU). ICU patients requiring CAS treatment were prospectively included to receive a 140-mg loading dose of CAS. Plasma CAS concentrations (0, 2, 3, 5, 7, and 24 h postinfusion) were determined to develop a two-compartmental population PK model. A Monte Carlo simulation was performed and the probabilities of target attainment (PTAs) were computed using previously published MICs. PK-PD targets were ratios of area under the concentration-time curve from 0 to 24 h (AUC 0–24h ) divided by the MIC (AUC 0–24h /MIC) of 250, 450, and 865 and maximal concentration ( C max ) divided by the MIC ( C max /MIC) of 5, 10, 15, and 20. Among 13 included patients, CAS clearance was 0.98 ± 0.13 liters/h and distribution volumes were V 1 = 9.0 ± 1.2 liters and V 2 = 11.9 ± 2.9 liters. Observed and simulated CAS AUC 0–24h were 79.1 (IQR 55.2; 108.4) and 81.3 (IQR 63.8; 102.3) mg · h/liter during the first 24 h of therapy, which is comparable to values usually observed in ICU patients at day 3 or later. PTAs were 〉 90% for MICs of 0.19 and 0.5 mg/liter, considering AUC/MIC = 250 and C max /MIC = 10 as PK-PD targets, respectively. Thus, a high loading dose of CAS (140 mg) increased CAS exposure in the first 24 h of therapy, allowing early achievement of PK-PD targets for most Candida strains. Such a strategy seems to improve treatment efficacy, though further studies are needed to assess the impact on clinical outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT02413892.)
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.01545-20
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2020
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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