Fungicidal activity and PK/PD of caspofungin as tools to guide antifungal therapy in a fluconazole-resistant C. parapsilosis candidemia

Abstract

Candida parapsilosis may be responsible for bloodstream infections (BSI) and it is characterised by an increased incidence of fluconazole resistance. A 75-year old woman with severe comorbidities received the insertion of a peripherally inserted central venous catheter. Fluconazole did not prevent a C. parapsilosis BSI hence caspofungin was started after a nephrotoxic first-line treatment with amphotericin B. The ratio of peak plasma concentration over the minimum inhibitory concentration (C_max/MIC) was adopted to maximise efficacy of caspofungin. MIC and plasma C_max values were obtained by broth microdilution and LC-MS, respectively. Interestingly, daily doses of 1 mg/kg (total daily dose, 50 mg) allowed the achievement of C_max/MIC values > 10. The optimised regimen was safe and effective, leading to negative blood culture at day 8. The patient was discharged home at day 21. Therefore, individualised dosing regimens of caspofungin may be effective and safe even in the case of C. parapsilosis BSI.

Keywords:

• Candida parapsilosis
• fluconazole resistance
• caspofungin
• PK/PD
• dose personalisation
• therapeutic drug monitoring