Between January 2021 and October 2024, 40 patients with 76 samples were screened. The main reason for exclusion was incorrect sampling time (n = 5 patients and 10 samples). A total of 35 patients with 66 available pCASconc were included. The cohort comprised 20 female patients (57.1%) and 15 male patients (42.9%), with a median age of 44 (41–69) years. The primary ICU admission diagnoses were acute respiratory distress syndrome (ARDS) (10/35, 28.6%) and septic shock (10/35, 28.6%). The median Simplified Acute Physiology Score II (SAPSII) at ICU admission was 54 (33–70) (Table 1).

Caspofungin was prescribed for proven candidemia (14/35, 40%), empirical treatment (7/35, 20%), combination therapy for aspergillosis (5/35, 14.3%), and invasive candidiasis (n = 9/35, 25.7%). The main species identified were Candida albicans and C. parapsilosis. At caspofungin initiation, 22 patients (62.9%) had septic shock, and ICU mortality was 34.3%.

A total of 19 samples in 9 patients were collected during PAN-CRRT and 47 samples in 31 patients without PAN-CRRT (22 without RRT and 9 on IHD). Samples were distributed as follows: 17 pCASconc at 12 h, 18 at 18 h, and 31 at 24 h. Ten non-PAN-CRRT samples were collected during an IHD period with a median of 12 (7–18) h after the end of the last IHD session.

Among PAN-CRRT samples (n = 19), 12 (63.2%) were collected during continuous veno-venous hemofiltration (CVVH) and 7 (36.8%) during continuous veno-venous hemodiafiltration (CVVHDF), with a median dialysis dose of 25 (25–28) mL/kg/h. The median exposure to CRRT between caspofungin infusion and sampling time was 18 (17–22) h. The median duration of filter use prior to sampling, available for 10/19 (52.6%) PAN-CRRT samples, was 31.5 (21.5–63.5) h (35.5 (23.8–47.3) h at H12, n = 2; 48.5 (36.5–55.5) h at H18 n = 4; and 36.8 (21.8–31.3) h at H24, n = 4). Patients without PAN-CRRT and without IHD had a median plasma creatinine of 43 (36–74) µmol/L and a glomerular filtration rate of 125 (93–144) mL/min.

Table 2 summarizes pCASconc and patients characteristics by group. Caspofungin treatment duration and doses did not significantly differ between groups. In the 24-h measurement group, more PAN-CRRT patients were treated with extra-corporeal membrane oxygenation (ECMO) and aspartate aminotransferase was significantly higher. In the 18-h measurement groups, transaminases and bilirubin levels were higher in PAN-CRRT patients, though not significantly. Albuminemia was similar between groups.

Figure 1 shows pCASconc across sampling times groups. In the 12-h measurement group, median pCASconc did not significantly differ between patients with and without PAN-CRRT [6.0 (5.7–7.7) mg/L vs. 5.7 (3.4–7.8) mg/L, p = 0.45]. However, median pCASconc was higher in PAN-CRRT patients in the 18-h group [5.3 (4.1–6.9) mg/L vs. 3.3 (1.9–3.7) mg/L, p = 0.04] and in the 24-h group [5.3 (3.9–5.8) mg/L vs. 3.1 (2.5–4.5) mg/L, p = 0.01].

pCASconc at H12, H18, and H24 according to CRRT status. CRRT continuous renal replacement therapy, pCASconcplasma caspofungin concentration, H12, H18, and H24 number of hours between last infusion and measurement. *p < 0.05; ns = p > 0.05

To explore the potential impact of treatment duration on plasma caspofungin concentrations, we assessed the correlation between the number of days of caspofungin treatment and pCASconc at H12, H18, and H24 in patients with and without PAN-CRRT (Fig. 2). No significant correlation was observed in any subgroup. Spearman correlation coefficients were low and not statistically significant in any panel, suggesting that treatment duration did not influence pCASconc at these time points.

Correlation between days of caspofungin treatment and plasma caspofungin concentrations (pCASconc) at H12, H18, and H24 in patients with and without PAN-CRRT. Scatter plots show the relationship between the duration of caspofungin treatment (in days) and plasma caspofungin concentrations (pCASconc, in mg/L) at different sampling time points. a, c, and e correspond to patients without PAN-CRRT at H12, H18, and H24, respectively; b, d, and f correspond to patients with PAN-CRRT at the same time points. Each figure part includes a linear trend line and reports the Spearman correlation coefficient (r) along with the two-tailed p value

Among the 14 patients with candidemia, 11 were in the group without PAN-CRRT and 3 in the group with PAN-CRRT. Persistent candidemia occurred in 3 patients: 2/11 (18.2%) in the group without PAN-CRRT and 1/3 (33%) in the group with PAN-CRRT. The latter had an intravascular device infection (ECMO cannula) that could not be removed.