Dosage-dependent antifungal efficacy of V-echinocandin (LY303366) against experimental fluconazole-resistant oropharyngeal and esophageal candidiasis

V. Petraitis, R. Petraitiene, A. H. Groll, T. Sein, R. L. Schaufele, C. A. Lyman, A. Francesconi, J. Bacher, S. C. Piscitelli, T. J. Walsh

Research output: Contribution to journalArticle

Abstract

V-echinocandin (VER-002; LY303366) is a semisynthetic derivative of echinocandin B and a potent inhibitor of fungal (1, 3)-β-D-glucan synthase. We studied the antifungal efficacy, the concentrations in saliva and tissue, and the safety of VER-002 at escalating dosages against experimental oropharyngeal and esophageal candidiasis caused by fluconazole-resistant Candida albicans in immunocompromised rabbits. Study groups consisted of untreated controls, animals treated with VER-002 at 1, 2.5, and 5 mg/kg of body weight/day intravenously (i.v.), animals treated with fluconazole at 2 mg/kg/day i.v., or animals treated with amphotericin B at 0.3 mg/kg/day. VER-002-treated animals showed a significant dosage-dependent clearance of C. albicans from the tongue, oropharynx, esophagus, stomach, and duodenum in comparison to that for untreated controls. VER-002 also was superior to amphotericin B and fluconazole in clearing the organism from all sites studied. These in vivo findings are consistent with the results of in vitro time-kill assays, which demonstrated that VER-002 has concentration-dependent fungicidal activity. Esophageal tissue VER-002 concentrations were dosage proportional and exceeded the MIC at all dosages. Echinocandin concentrations in saliva were greater than or equal to the MICs at all dosages. There was no elevation of serum hepatic transaminase, alkaline phosphatase, bilirubin, potassium, or creatinine levels in VER-002-treated rabbits. In summary, the echinocandin VER-002 was well tolerated, penetrated the esophagus and salivary glands, and demonstrated dosage-dependent antifungal activity against fluconazole-resistant esophageal candidiasis in immunocompromised rabbits.

Original languageEnglish (US)
Pages (from-to)471-479
Number of pages9
JournalAntimicrobial Agents and Chemotherapy
Volume45
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

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anidulafungin
Echinocandins
Fluconazole
Candidiasis
Amphotericin B
Rabbits
Candida albicans
Saliva
Esophagus
Oropharynx
Transaminases
Salivary Glands
Duodenum
Bilirubin
Tongue
Alkaline Phosphatase
Creatinine
Stomach
Potassium
Body Weight

ASJC Scopus subject areas

  • Pharmacology (medical)

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Dosage-dependent antifungal efficacy of V-echinocandin (LY303366) against experimental fluconazole-resistant oropharyngeal and esophageal candidiasis. / Petraitis, V.; Petraitiene, R.; Groll, A. H.; Sein, T.; Schaufele, R. L.; Lyman, C. A.; Francesconi, A.; Bacher, J.; Piscitelli, S. C.; Walsh, T. J.

In: Antimicrobial Agents and Chemotherapy, Vol. 45, No. 2, 2001, p. 471-479.

Research output: Contribution to journalArticle

Petraitis, V, Petraitiene, R, Groll, AH, Sein, T, Schaufele, RL, Lyman, CA, Francesconi, A, Bacher, J, Piscitelli, SC & Walsh, TJ 2001, 'Dosage-dependent antifungal efficacy of V-echinocandin (LY303366) against experimental fluconazole-resistant oropharyngeal and esophageal candidiasis', Antimicrobial Agents and Chemotherapy, vol. 45, no. 2, pp. 471-479. https://doi.org/10.1128/AAC.45.2.471-479.2001
Petraitis, V. ; Petraitiene, R. ; Groll, A. H. ; Sein, T. ; Schaufele, R. L. ; Lyman, C. A. ; Francesconi, A. ; Bacher, J. ; Piscitelli, S. C. ; Walsh, T. J. / Dosage-dependent antifungal efficacy of V-echinocandin (LY303366) against experimental fluconazole-resistant oropharyngeal and esophageal candidiasis. In: Antimicrobial Agents and Chemotherapy. 2001 ; Vol. 45, No. 2. pp. 471-479.
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AU - Petraitiene, R.

AU - Groll, A. H.

AU - Sein, T.

AU - Schaufele, R. L.

AU - Lyman, C. A.

AU - Francesconi, A.

AU - Bacher, J.

AU - Piscitelli, S. C.

AU - Walsh, T. J.

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