Table 2 Overview of clinical PK/PD studies reporting abdominal (ascitic and peritoneal fluid) concentrations of antifungals
Author | Type of study | Population | ATF | Samples | Results | Notes |
|---|---|---|---|---|---|---|
Lin [99] | Prospective monocentric PK study | Adults with suspected or confirmed invasive candidiasis N = 19 (4 Surgical) | Voriconazole Prophylaxis (n = 9) Treatment (n = 10) | Day 1 and then TDM data Day 1: h1, h2, h4, h6, h8, and h12 Peritoneal samples obtained from drain | Low and lower fluctuations of voriconazole concentrations in the PF than in the plasma Penetration ratio: 0.54 (single dose) and 0.67 (multiple doses) 81% of steady state concentration reached the PK/PD target | No IAC Heterogeneity of the population and voriconazole indication Intensive sampling only at Day 1 Peritoneal samples obtained from drain |
Tortora [87] | Observational retrospective study | Children with liver transplantation N = 6 (5 months–242 months) | Liposomal amphotericin B 3 mg/kg | Plasma: TDM Day 1 to 4 PF Day 1 to 4 Peritoneal samples obtained from drain | Peritoneal concentrations were lower than plasma with a correlation coefficient of 0.72 None of the patient reached the PK/PD target attainment in the PF | No IAC TDM data Peritoneal samples obtained from drain |
Garbez [57] | Prospective monocentric PK study Blood (n = 159) and peritoneal (n = 29) samples | Adults with secondary peritonitis N = 11 SAPS II 38 [24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77] SOFA 7 [0–12] | Caspofungin 70 mg then 50 or 70 mg (< > 80 kg) | Day 1, between 3 and 4 PF day 1 h1, h1.5, h2, h4, h6, h12 and h24 Peritoneal samples obtained from drain | High PK variability Penetration ratio: 0.33 Adequate PTA for most susceptible species in patients with Free Fat Mass < 50 kg | IAC = 10% (n = 1/10) No unbound concentration Peritoneal samples obtained from drain at day 1 No ATF concentrations during surgery |
Welte [74] | Prospective monocentric PK study Blood, ascitic fluid and peritoneal fluid samples | Adults with proven or suspected invasive fungal infections N = 29 ANF = 11 CSF = 6 MCF = 13 | Caspofungin 70 mg then 50 mg Anidulafungin 200 mg then 100 mg Micafungin 100 mg q24h | Day 1: h4, h8, h12, h18, and h24 Paracentesis on-demand Ascitic fluid from drain | Echinocandin concentrations in ascites fluid were lower than the simultaneous plasma levels | Nine patients with peritonitis with only 2 IAC Highly heterogenous population No unbound concentration Ascitic fluid from drain No ATF concentrations during surgery |
Garbez [72] | Prospective monocentric PK study Blood (n = 171) and peritoneal (n = 42) samples | Adults with secondary peritonitis N = 12 SAPS II 40 [29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67] | Micafungin 100 mg q24h | Day 1, between 3 and 5 h1, h1.5, h2, h4, h6, h12 and h24 Peritoneal samples obtained from drain | High PK variability Penetration ratio: 0.25 (Day 1) and 0.4 (Day 3–5) Adequate PTA for most susceptible species in patients with Free Fat Mass < 65 kg | IAC = 50% (n = 5/10) No unbound concentration Peritoneal samples obtained from drain No ATF concentrations during surgery |
Gioia [73] | Prospective monocentric PK study Blood and peritoneal samples | Adults with PPO N = 23 ANF = 11 CSF = 8 MCF = 4 | Caspofungin 70 mg then 50 mg Anidulafungin 200 mg then 100 mg Micafungin 100 mg q24h | Day 4 h1, h6, h12, h24h | Most PF ATF concentrations < 1 μg/mL Penetration ratio: 0.3 | IAC = 74% (n = 17/23) No unbound concentration Peritoneal samples obtained from drain No ATF concentrations during surgery |
Pérez Civantos [75] | Prospective multicentric PK study Blood and peritoneal samples | Adults with secondary and tertiary peritonitis N = 31 Apache II 22.7 ± 5.9 SOFA 10.3 ± 3.5 | Anidulafungin 200 mg then 100 mg q24 | Day 2, after LD and 1 MD h1, h3, h6, h12, h18 and h24 Peritoneal samples obtained from drain | ANF exposure PF < plasma Penetration ratio: 0.3 | IAC = 12% (n = 4/31) No unbound concentration Peritoneal samples obtained from drain No ATF concentrations during surgery |
Dupont [71] | Prospective multicentric PK study Blood samples | Adults with complicated IAIs N = 14 SAPS II 54 [45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67] | Anidulafungin 200 mg then 100 mg q24 | Day 1: T0, Tmax, T24; day 3: T0, Tmax, T24; day 5: T0, Tmax, T3, T4, T6, T12 and T24 | Higher volume of distribution and lower half-life compared to other types of ICU patients | IAC = 85% (n = 12/14) No unbound concentration, nor peritoneal samples No ATF concentrations during surgery |
Garcia-de-Lorenzo [76] | Prospective monocentric PK study Blood and peritoneal samples | Adults with severe burn injuries or complicated IAIs N = 10 (IAI) SOFA 5 [1.5–7.5] | Micafungin 1.5 mg/kg (BW) | Day 1, between 3 and 4 h1, h3, h5, h8, h18 and h24 Peritoneal samples obtained from drain | Penetration ratio: 0.29 | IAC = 4 No unbound concentration No ATF concentrations during surgery |
Grau [70] | Prospective monocentric PK study Blood and peritoneal samples | Adults with PPO N = 10 Apache II 15 [12,13,14,15,16,17,18,19,20,21,22,23,24] SOFA 5 [1.5–7.5] | Micafungin 100 mg | 3 days after MCF initiation Before, h1, h3, h5, h8, h18 and h24 Peritoneal samples issues from a Jackson-Pratt drain | MCF exposure PF < plasma Penetration ratio: 0.3 Cmax achieved in 5-8h in the PF 100% PTA: C. albicans (MIC 0.016 mg/l) C. parapsilosis (MIC 0.25 mg/L) | IAC = 40% (n = 4/10) No unbound concentration Peritoneal samples obtained at Day 3 d, from drain No ATF concentrations during surgery |
Pea [48] | Case-series Blood, bile, and ascites samples | Transplanted adult patients non-critically ill patients N = 3 (1 cholangitis, 2 peritonitis) | Fluconazole LD 400 mg then 100–200 mg q24h depending on renal function | At steady state, from plasma, bile drains or paracentesis for ascitic fluid | Penetration ratio bile: 0.5 Penetration ratio ascites: 0.8 | Documented candidiasis 100% Non-critically ill patients No unbound concentration No ATF concentrations during surgery |