Pharmacokinetic properties of micafungin in critically ill patients diagnosed with invasive candidiasis [PublishAheadOfPrint]

Background: The estimated attributable mortality rate for invasive candidiasis (IC) in the Intensive Care Unit (ICU) setting varies from 30-40%. Physiological changes in critically ill patients may affect the distribution and elimination of micafungin and therefore dosing adjustments might be mandatory. Objective: To determine the pharmacokinetic parameters of micafungin in critically ill patients and assess the probability of target attainment (PTA). Methods: Micafungin plasma concentrations were measured to estimate the pharmacokinetic properties of micafungin. MIC values were determined for Candida isolates to assess the PTA for the patients. Results: Data from 19 patients with suspected or proven invasive candidiasis were available for analysis. The median (IQR) AUC_0-24h was 89.6 mg*h/L (75.4-113.6); this was significantly lower than the median (IQR) micafungin AUC_0-24h 152.0 mg*h/L (136.0-162.0) and 134.0 mg*h/L (118.0-148.6) in healthy volunteers (P = <0.0001 and P = <0.001, respectively). All Candida isolates were susceptible to micafungin with a median (IQR) MIC of 0.016 mg/L (0.012-0.023). The median (IQR) AUC_0-24h/MIC ratio was 5684 (4325-7578) and three of the 17 evaluable patients (17.6%) diagnosed with proven invasive candidiasis did not meet the AUC/MIC target of 5000. Conclusions: The micafungin exposure was lower in critically ill patients than in healthy volunteers. The variability in micafungin exposure in this ICU population could be explained by the patient's bodyweight. Our findings suggest that healthier patients (SOFA score <10) weighing more than 100 kg and receiving 100 mg micafungin daily are at risk for inappropriate micafungin exposure and potentially inadequate antifungal treatment.

http://ift.tt/2xaL6jL