title: 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 (Cmax/MIC) was adopted to maximise efficacy of caspofungin. MIC and plasma Cmaxvalues 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 Cmax/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.
authors.affiliation: a First Infectious Diseases Unit , Ospedale Cotugno, Azienda Ospedaliera dei Colli , Napoli , Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Tascini
authors.affiliation: b Emergency Medicine Unit , Azienda Ospedaliera Universitaria Pisana , Pisa , Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Sozio
authors.affiliation: c Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy.
authors.forename: Antonello
authors.identifier: http://orcid.org/0000-0002-2661-6183
authors.initials: A
authors.lastname: Di Paolo
authors.affiliation: b Emergency Medicine Unit , Azienda Ospedaliera Universitaria Pisana , Pisa , Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Tintori
authors.affiliation: d Infectious Diseases Unit , Azienda Ospedaliera Universitaria Pisana , Pisa , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Leonildi
authors.affiliation: e Department of Pharmaceutical Sciences-Medicine Management , Azienda Ospedaliera Universitaria Pisana , Pisa , Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Bertolino
authors.affiliation: b Emergency Medicine Unit , Azienda Ospedaliera Universitaria Pisana , Pisa , Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Carmassi
authors.affiliation: d Infectious Diseases Unit , Azienda Ospedaliera Universitaria Pisana , Pisa , Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Tagliaferri
authors.affiliation: d Infectious Diseases Unit , Azienda Ospedaliera Universitaria Pisana , Pisa , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Menichetti
authors.affiliation: f Infectious Diseases Clinic , Università Politecnica delle Marche , Torrette , Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Barchiesi
mesh_terms: D000368:Aged; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000074429:Candida parapsilosis; D058387:Candidemia / Q000188:drug therapy*; D000077336:Caspofungin; D055499:Catheter-Related Infections / Q000188:drug therapy*; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D015725:Fluconazole; D006801:Humans; D055666:Lipopeptides / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D015725:Fluconazole; D000077336:Caspofungin
keywords: Candida parapsilosis; PK/PD; caspofungin; dose personalisation; fluconazole resistance; therapeutic drug monitoring