Tiziana Gasperetti1, René Welte1, Herbert Oberacher2, Jana Marx1, Ingo Lorenz3, Peter Schellongowski4, Thomas Staudinger4, Karin Burgmann4, Philipp Eller5, Tobias Santner6, Andrea Griesmacher6, Hartwig Pfisterer6, Stephan Eschertzhuber7,8, Maria Aigner9,10, Michael Joannidis11, Romuald Bellmann12. 1. Clinical Pharmacokinetics Unit, Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. 2. Institute of Legal Medicine and Core Facility Metabolomics, Medical University of Innsbruck, Innsbruck, Austria. 3. General and Surgical ICU, University Hospital for Anaesthesia and Intensive Care, Medical University of Innsbruck, Innsbruck, Austria. 4. Intensive Care Unit, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria. 5. Intensive Care Unit, Department of Internal Medicine, University Hospital of Graz, Graz, Austria. 6. Central Institute for Medical and Chemical Laboratory Diagnostics, Innsbruck General Hospital, Innsbruck, Austria. 7. Transplant ICU, University Hospital for Anaesthesia and Intensive Care, Innsbruck General Hospital and Innsbruck Medical University Innsbruck, Innsbruck, Austria. 8. Department of Anaesthesia and Critical Care, District Hospital of Hall in Tyrol, Hall in Tyrol, Austria. 9. Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria. 10. INNPATH GmbH, Tirol Kliniken, Innsbruck, Austria. 11. Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria. 12. Clinical Pharmacokinetics Unit, Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria. romuald.bellmann@i-med.ac.at.
Abstract
PURPOSE: Wound infections caused by Candida are life-threatening and difficult to treat. Echinocandins are highly effective against Candida species and recommended for treatment of invasive candidiasis. As penetration of echinocandins into wounds is largely unknown, we measured the concentrations of the echinocandins anidulafungin (AFG), micafungin (MFG), and caspofungin (CAS) in wound secretion (WS) and in plasma of critically ill patients. METHODS: We included critically ill adults with an indwelling wound drainage or undergoing vacuum-assisted closure therapy, who were treated with an echinocandin for suspected or proven invasive fungal infection. Concentrations were measured by liquid chromatography with UV (AFG and MFG) or tandem mass spectrometry detection (CAS). RESULTS: Twenty-one patients were enrolled. From eight patients, serial WS samples and simultaneous plasma samples were obtained within a dosage interval. AFG concentrations in WS amounted to < 0.025-2.25 mg/L, MFG concentrations were 0.025-2.53 mg/L, and CAS achieved concentrations of 0.18-4.04 mg/L. Concentrations in WS were significantly lower than the simultaneous plasma concentrations and below the MIC values of some relevant pathogens. CONCLUSION: Echinocandin penetration into WS displays a high inter-individual variability. In WS of some of the patients, concentrations may be sub-therapeutic. However, the relevance of sub-therapeutic concentrations is unknown as no correlation has been established between concentration data and clinical outcome. Nevertheless, in the absence of clinical outcome studies, our data do not support the use of echinocandins at standard doses for the treatment of fungal wound infections, but underline the pivotal role of surgical debridement.
PURPOSE: Wound infections caused by Candida are life-threatening and difficult to treat. Echinocandins are highly effective against Candida species and recommended for treatment of invasive candidiasis. As penetration of echinocandins into wounds is largely unknown, we measured the concentrations of the echinocandins anidulafungin (AFG), micafungin (MFG), and caspofungin (CAS) in wound secretion (WS) and in plasma of critically illpatients. METHODS: We included critically ill adults with an indwelling wound drainage or undergoing vacuum-assisted closure therapy, who were treated with an echinocandin for suspected or proven invasive fungal infection. Concentrations were measured by liquid chromatography with UV (AFG and MFG) or tandem mass spectrometry detection (CAS). RESULTS: Twenty-one patients were enrolled. From eight patients, serial WS samples and simultaneous plasma samples were obtained within a dosage interval. AFG concentrations in WS amounted to < 0.025-2.25 mg/L, MFG concentrations were 0.025-2.53 mg/L, and CAS achieved concentrations of 0.18-4.04 mg/L. Concentrations in WS were significantly lower than the simultaneous plasma concentrations and below the MIC values of some relevant pathogens. CONCLUSION:Echinocandin penetration into WS displays a high inter-individual variability. In WS of some of the patients, concentrations may be sub-therapeutic. However, the relevance of sub-therapeutic concentrations is unknown as no correlation has been established between concentration data and clinical outcome. Nevertheless, in the absence of clinical outcome studies, our data do not support the use of echinocandins at standard doses for the treatment of fungal wound infections, but underline the pivotal role of surgical debridement.
Authors: M J Asensio; M Sánchez; B Galván; E Herrero; L Cachafeiro; A Agrifoglio; E Perales; S Luque; A García-de-Lorenzo Journal: Intensive Care Med Date: 2014-12-03 Impact factor: 17.440
Authors: Carlos J Rodriguez; David R Tribble; Debra L Malone; Clinton K Murray; Elliot M Jessie; Mansoor Khan; Mark E Fleming; Benjamin K Potter; Wade T Gordon; Stacy A Shackelford Journal: Mil Med Date: 2018-09-01 Impact factor: 1.437
Authors: Constance McGraw; Matthew Carrick; Francie Ekengren; Gina Berg; Mark Lieser; Alessandro Orlando; Robert Madayag; Allen Tanner Ii; Michael Kelly; Kaysie Banton; David Bar-Or Journal: Injury Date: 2019-10-14 Impact factor: 2.586
Authors: Asma Lat; George R Thompson; Michael G Rinaldi; Sheryl A Dorsey; Gennethel Pennick; James S Lewis Journal: Antimicrob Agents Chemother Date: 2009-11-23 Impact factor: 5.191
Authors: A García-de-Lorenzo; S Luque; S Grau; A Agrifoglio; L Cachafeiro; E Herrero; M J Asensio; S M Sánchez; J A Roberts Journal: Antimicrob Agents Chemother Date: 2016-09-23 Impact factor: 5.191
Authors: Peter G Pappas; Carol A Kauffman; David R Andes; Cornelius J Clancy; Kieren A Marr; Luis Ostrosky-Zeichner; Annette C Reboli; Mindy G Schuster; Jose A Vazquez; Thomas J Walsh; Theoklis E Zaoutis; Jack D Sobel Journal: Clin Infect Dis Date: 2015-12-16 Impact factor: 9.079
Authors: René Welte; Herbert Oberacher; Bernhard Schwärzler; Michael Joannidis; Romuald Bellmann Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2019-12-12 Impact factor: 3.205