Anidulafungin dosing in critically ill patients with continuous venovenous haemodiafiltration

Anidulafungin is indicated as a first-line treatment for invasive candidiasis in critically ill patients. In the intensive care unit, sepsis is the main cause of acute renal failure, and treatment with continuous renal replacement therapy (CRRT) has increased in recent years. Antimicrobial pharmacokinetics is affected by CRRT, but few studies have addressed the optimal dosage for anidulafungin during CRRT. We included 12 critically ill patients who received continuous venovenous haemodiafiltration to treat acute renal failure. Anidulafungin was infused on 3 consecutive days, starting with a loading dose (200 mg) on Day 1, and doses of 100 mg on Days 2 and 3. Blood and ultradiafiltrate samples were collected on Day 3 (during steady-state) before, and at regular intervals after, the infusion had started. Anidulafungin concentrations were determined with HPLC. On Day 3, peak plasma concentrations with the 100 mg dose were 6.2aEuroS +/- aEuroS1.7 mg/L and 7.1aEuroS +/- aEuroS1.9 mg/L in the arterial and venous samples, respectively. The mean, pre-filter trough concentration was 3.0aEuroS +/- aEuroS0.6 mg/L. The mean AUC(0-24) values for plasma anidulafungin were 93.9aEuroS +/- aEuroS19.4 and 104.1aEuroS +/- aEuroS20.3mg center dot h/L in the arterial and venous samples, respectively. There was no adsorption to synthetic surfaces, and the anidulafungin concentration in the ultradiafiltrate was below the limit of detection. The influence of CRRT on anidulafungin elimination appeared to be negligible. Therefore, we recommend no adjustments to the anidulafungin dose for patients receiving CRRT.