Pharmacokinetic/pharmacodynamics variability of echinocandins in critically ill patients: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE:Anidulafungin, caspofungin and micafungin are three widely used echinocandin drugs licensed for the treatment of invasive fungal infections, and their clinical use is widespread. To evaluate pharmacokinetic/pharmacodynamics variability of echinocandins in critically ill patients by comparing the differences in pharmacokinetic parameters between critically ill patients and healthy volunteers or general patients. METHODS:MEDLINE, EMBASE, The Cochrane Library and Pubmed were searched from inception until 6 September 2018. Studies investigating the pharmacokinetic parameters of echinocandins in critically ill patients, healthy volunteers or general patients were included. Our primary outcomes included AUC0-24 h , Cmax and Cmin (24 hours). Two reviewers independently reviewed all titles, abstracts and text, and extracted data. We applied R software (R 2017) to conduct meta-analysis. RESULTS AND DISCUSSION:Of 3235 articles screened, 17 studies were included in the data synthesis. Descriptive data from single-arm studies show that critically ill patients who received caspofungin had more stable AUC0-24 h than those who received anidulafungin and micafungin. The Cmax of critically ill patients who received caspofungin and micafungin was similar to healthy volunteers. However, the Cmax in critically ill patients who received anidulafungin was lower than in healthy volunteers. The Cmin and T1/2 of critically ill patients who received caspofungin were larger than in healthy volunteers. The Vd and CL of critically ill patients receiving anidulafungin and micafungin were larger than in healthy volunteers. WHAT IS NEW AND CONCLUSION:This systematic review provides an analysis of the pharmacokinetic/pharmacodynamics variability of echinocandins in critically ill patients. Based on the limited data available, caspofungin has less pharmacokinetic/pharmacodynamics variability than anidulafungin and micafungin.