1187. Acquired multidrug antifungal resistance in Candida lusitaniae during therapy
Session: Poster Abstract Session: Resistance Mechanisms
Friday, October 9, 2015
Room: Poster Hall
Posters
  • ID_week_2015_SAA.pdf (744.5 kB)
  • Background: Candida lusitaniae (C. lusitaniae) is intrinsically susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins and few missense mutations in the C. lusitaniae FKS1 hot spots 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during therapy with amphotericin B (AMB), caspofungin (CAS) and azoles for persistent candidemia in an immunocompromised child with severe enterocolitis and visceral adenoviral disease. 

    Methods: Molecular analysis of resistance mechanism was undertaken.

    Results:

    As documented from restriction fragment length polymorphisms, the C. lusitaniae isolates were related with each other. From antifungal susceptibilities and molecular analysis, 5 different profiles (P) were obtained. Since no clinical breakpoints exist for C. lusitaniae, those established in C. albicans were used to define resistance. These profiles included P1 (CAS-, fluconazole (FLC)-susceptible) while being on AMB Tx for 3 months), P2 (FLC-susceptible but CAS-resistant while on CAS Tx for 2 weeks), P3 (CAS-susceptible but FLC-resistant while on azoles and CAS combined Tx initially followed by azoles alone for a week), P4 (CAS- and FLC-resistant while on both drugs Tx for three weeks) and P5 (FLC-susceptible but CAS-resistant). CAS resistance was associated with cross-resistance not only to micafungin and anidulafungin but also to AMB. Analysis of CAS resistance revealed 3 novel FKS1 mutations in CAS-resistant isolates (S638Y on P2; S631Y on P4; S638P on P5). FLC resistance could be linked with overexpression of a major facilitator gene (MFS7) in C. lusitaniae P2 and P4 and was associated with cross-resistance to 5-flurocytosine. 

    Conclusion:

    This clinical report describes resistance of C. lusitaniae to all common antifungals. While candins or azole resistance followed monotherapy, multidrug antifungal resistance emerged during combined therapy.

    Sandra Asner, MD, MSc1, Stefano Giulieri, MD1, Manuel Diezi, MD1, Oscar Marchetti, MD1 and Dominique Sanglard, MD, PhD2, (1)University Hospital Lausanne, Lausanne, Switzerland, (2)University of Lausanne and University Hospital Center, Lausanne, Switzerland

    Disclosures:

    S. Asner, None

    S. Giulieri, None

    M. Diezi, None

    O. Marchetti, None

    D. Sanglard, None

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