Table 1.

Patient characteristics, treatment data and isavuconazole exposure metrics in two patients concomitantly treated with isavuconazole and extracorporeal membrane oxygenation.

	Patient 1	Patient 2
Demographics
Age, years	61	52
Sex	Male	Female
Biogeographical ancestry a	Near Eastern	Near Eastern
Body weight, kg	81.3	67.0
BMI, kg/m2	24.3	27.5
Clinical characteristics
Length of ICU stay b, days	30	48
Host factors c	COVID-19 infection needing intensive care	COVID-19 infection needing intensive care
APACHE II score on admission	18	28
SOFA score d	10	15
Serum albumin d, g/L	25.7	44.8
ALT d, U/L	15	167
AST d, U/L	14	152
eGFR (CKD-EPI) d, mL/min/1.73 m2	46	NA e
CRRT during isavuconazole therapy	No	Yes
Total duration of CRRT, days	NA	36
Duration of CRRT until extensive PK sampling, days	NA	24
Deceased during ICU admission	Yes	Yes
ECMO support
Indication of ECMO support	COVID-19-associated ARDS	COVID-19-associated ARDS
ECMO modality	Veno-venous	Veno-venous
ECMO oxygenator	Medos Hilite 7000LT	Medos Hilite 7000LT/Eurosets A.L.ONE
ECMO blood pump	Medos Deltastream DP3	Medos Deltastream DP3
Priming solution	Plasma-Lyte A	Plasma-Lyte A
Priming volume, mL	670	670
Total duration of ECMO support, days	22	43
Duration of ECMO support at initiation of isavuconazole, days	NA	28
Duration of ECMO support until extensive PK sampling, days	1	31
ECMO circuit exchanges f	No exchanges	Days 12, 17 *, 27
Isavuconazole therapy
Indication	Probable CAPA g	Probable CAPA g
Therapy duration, days	10	16
Duration of isavuconazole therapy until extensive PK sampling, days	7	4
Maintenance dose on the extensive PK sampling day	300 mg q24h h	200 mg q24h
Trough concentrations i, mg/L	Day 4: 1.4 ** Day 7: 1.5 Day 9: 2.2 **	Day 4: 1.0 Day 7: 0.8 ** Day 14: 1.0 **

ALT: alanine aminotransferase; APACHE II: Acute Physiology and Chronic Health Evaluation II score; ARDS: acute respiratory distress syndrome; AST: aspartate aminotransferase; BMI: body mass index; CAPA: COVID-19-associated pulmonary aspergillosis; CKD-EPI: Chronic Kidney Disease Epidemiology Collaboration; COVID-19: coronavirus disease 2019; CRRT: continuous renal replacement therapy; ECMO: extracorporeal membrane oxygenation; eGFR: estimated glomerular filtration rate; ICU: intensive care unit; NA: not applicable; SOFA: Sequential Organ Failure Assessment. ^a Biogeographical ancestry was defined by the standardized biogeographic grouping system of PharmGKB [29]. The Near Eastern genetic ancestry group includes populations from Northern Africa, the Middle East and the Caucasus. For the covariate effect of race on clearance in the population pharmacokinetic model by Desai et al., both patients were classified as “predominantly Caucasian” [28]. ^b From admission to the intensive care unit until death. ^c Host factors for COVID-19-associated pulmonary aspergillosis according to the 2020 European Confederation of Medical Mycology (ECMM) and the International Society of Human and Animal Mycology (ISHAM) consensus criteria [4]. ^d Measured on the day of extensive pharmacokinetic sampling. ^e Patient 2 received continuous veno-venous hemofiltration on the day of extensive pharmacokinetic sampling. ^f The days of ECMO circuit exchanges were calculated in relation to the initiation of ECMO support. The asterisk (*) indicates an exchange of solely the ECMO oxygenator. ^g The classification was performed according to the 2020 ECMM and ISHAM consensus criteria for COVID-19-associated pulmonary aspergillosis [4]. ^h The standard maintenance dose of 200 mg q24h was increased to 300 mg q24h one day before extensive pharmacokinetic sampling. ⁱ The days of trough concentration determination were calculated in relation to the initiation of isavuconazole therapy. The double asterisk (**) indicates trough concentrations that were determined via routine therapeutic drug monitoring.