Variability of PKPD of Micafungin (MF) in Critically Ill Patients (CIP)

M. Jiménez, S. Torrado, S. Domingo, M. De la Torre, F. Martinez, M. A. Gonzalez, P. Merino, R. Cantón, M. Sanchez Garcia;

Author address: 

Hosp. Clin. San Carlos, Madrid, SPAIN, Facultad de Farmacia, Madrid, SPAIN, Hosp. Ramón y Cajal, Madrid, SPAIN.

Abstract: 

Background: Variability of antimicrobial PKPD may be associated with low target tissue concentrations and treatment failure. We sought to determine MF PKPD parameters in plasma and body fluids of CIP.Methods: Demographic, biometric, microbiological, blood chemistry and outcome data were collected. Plasma and body fluids (pleural, mediastinal, peritoneal or pancreatic) were drawn over a 24 h period after 3 days of iv therapy with 100 or 150 mg/24 h. A reversed-phase validated High-Performance Liquid Chromatography assay with fluorometric detection of MF was developed. Results: We studied 9 CIP (5 women), 6 had peritonitis, 1 acute pancreatitis and 2 mediastinitis after heart surgery caused byCandida albicans in 3 and C. glabrata in 3 patients, and 3 had negative cultures. MIC90 for MF ranged between 0.004 and 0.015 mg/L. Mean plasma albumin was 1.98±0.57 mg/dL, median plasma creatinine was 0.55 mg/dL. The weight-adjusted MF dose ranged from 1.18 to 2.73 mg/kg of MF. Plasma Cmax ranged from 1.4 to 13.6 mg/L, Cmax/MIC90 ratio from 93 to 906, AUC24 from 16 to 158 and AUC24/MIC ratio from 713 to 13876. In peritoneal, mediastinal and pleural fluids Cmax ranged from 0.08 to 5.71 mg/L and Cmax/MIC90 ratio from 5 to 380, whereas in pancreatic collection exudates Cmax was between 0.02 and 0.03, Cmax /MIC90 ratio 1.3-2 and AUC24 was 0. For plasma Cmax > 3 mg/L, pleural, mediastinal and peritoneal Cmax ranged from 0.28 to 5.7, whereas for Cmax
2013

abstract No: 

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Full conference title: 

53rd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC, 53rd (2013)