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Clinical Therapeutics

Low but Sufficient Anidulafungin Exposure in Critically Ill Patients

Marjolijn J. P. van Wanrooy, Michael G. G. Rodgers, Donald R. A. Uges, Jan P. Arends, Jan G. Zijlstra, Tjip S. van der Werf, Jos G. W. Kosterink, Jan-Willem C. Alffenaar
Marjolijn J. P. van Wanrooy
aUniversity of Groningen, University Medical Center Groningen, Department of Hospital and Clinical Pharmacy, Groningen, the Netherlands
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Michael G. G. Rodgers
bUniversity of Groningen, University Medical Center Groningen, Department of Critical Care, Groningen, the Netherlands
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Donald R. A. Uges
aUniversity of Groningen, University Medical Center Groningen, Department of Hospital and Clinical Pharmacy, Groningen, the Netherlands
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Jan P. Arends
cUniversity of Groningen, University Medical Center Groningen, Department of Medical Microbiology, Groningen, the Netherlands
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Jan G. Zijlstra
bUniversity of Groningen, University Medical Center Groningen, Department of Critical Care, Groningen, the Netherlands
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Tjip S. van der Werf
dUniversity of Groningen, University Medical Center Groningen, Departments of Internal Medicine and Pulmonary Diseases and Tuberculosis, Groningen, the Netherlands
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Jos G. W. Kosterink
aUniversity of Groningen, University Medical Center Groningen, Department of Hospital and Clinical Pharmacy, Groningen, the Netherlands
eUniversity of Groningen, Department of Pharmacy, Pharmacotherapy and Pharmaceutical Care Division, Groningen, the Netherlands
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Jan-Willem C. Alffenaar
aUniversity of Groningen, University Medical Center Groningen, Department of Hospital and Clinical Pharmacy, Groningen, the Netherlands
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DOI: 10.1128/AAC.01607-13
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ABSTRACT

The efficacy of anidulafungin is driven by the area under the concentration-time curve (AUC)/MIC ratio. Patients in intensive care may be at risk for underexposure. In critically ill patients with an invasive Candida infection, the anidulafungin exposure and a possible correlation with disease severity or plasma protein levels were explored. Concentration-time curves were therefore obtained at steady state. Anidulafungin concentrations were measured with a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The MIC values of the Candida species were determined with the Etest. The target AUC/MIC ratio was based on European Committee on Antimicrobial Susceptibility Testing (EUCAST) data. Twenty patients were included. The patients received a maintenance dose of 100 mg once daily after a loading dose of 200 mg on the first day. The mean (±standard deviation) AUC, maximum concentration of drug in plasma (Cmax), and minimum concentration of drug in plasma (Cmin) were 69.8 ± 24.1 mg · h/liter, 4.7 ± 1.4 mg/liter, and 2.2 ± 0.8 mg/liter, respectively. The MIC values of all cultured Candida species were below the EUCAST MIC breakpoints. The exposure to anidulafungin in relation to the MIC that was determined appeared sufficient in all patients. The anidulafungin exposure was low in our critically ill patients. However, combined with the low MICs of the isolated Candida strains, the lower exposure observed in comparison to the exposure in the general patient population resulted in favorable AUC/MIC ratios, based on EUCAST data. No correlation was observed between anidulafungin exposure and disease severity or plasma protein concentrations. In patients with less-susceptible Candida albicans or glabrata strains, we recommend considering determining the anidulafungin exposure to ensure adequate exposure. (This trial has been registered at ClinicalTrials.gov under registration no. NCT01047267.)

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Low but Sufficient Anidulafungin Exposure in Critically Ill Patients
Marjolijn J. P. van Wanrooy, Michael G. G. Rodgers, Donald R. A. Uges, Jan P. Arends, Jan G. Zijlstra, Tjip S. van der Werf, Jos G. W. Kosterink, Jan-Willem C. Alffenaar
Antimicrobial Agents and Chemotherapy Dec 2013, 58 (1) 304-308; DOI: 10.1128/AAC.01607-13

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Low but Sufficient Anidulafungin Exposure in Critically Ill Patients
Marjolijn J. P. van Wanrooy, Michael G. G. Rodgers, Donald R. A. Uges, Jan P. Arends, Jan G. Zijlstra, Tjip S. van der Werf, Jos G. W. Kosterink, Jan-Willem C. Alffenaar
Antimicrobial Agents and Chemotherapy Dec 2013, 58 (1) 304-308; DOI: 10.1128/AAC.01607-13
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