Acquired Flucytosine Resistance during Combination Therapy with Caspofungin and Flucytosine for Candida glabrata Cystitis

Caroline Charlier; Carine El Sissy; Sophie Bachelier-Bassi; Anne Scemla; Gilles Quesne; Emilie Sitterlé; Christophe Legendre; Olivier Lortholary; Marie-Elisabeth Bougnoux

doi:10.1128/AAC.02265-15

Acquired Flucytosine Resistance during Combination Therapy with Caspofungin and Flucytosine for Candida glabrata Cystitis

Antimicrob Agents Chemother. 2015 Nov 2;60(1):662-5. doi: 10.1128/AAC.02265-15. Print 2016 Jan.

Authors

Caroline Charlier¹, Carine El Sissy², Sophie Bachelier-Bassi³, Anne Scemla⁴, Gilles Quesne², Emilie Sitterlé², Christophe Legendre⁴, Olivier Lortholary⁵, Marie-Elisabeth Bougnoux⁶

Affiliations

¹ Université Paris Descartes Sorbonne Paris Cité, Service de Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker-Pasteur, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Institut Imagine, Paris, France caroline.charlier@aphp.fr.
² Université Paris Descartes Sorbonne Paris Cité, Service de Microbiologie Clinique, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
³ Unité Biologie et Pathogénicité Fongiques, INRA, USC2019, Institut Pasteur, Paris, France.
⁴ Université Paris Descartes Sorbonne Paris Cité, Service de Transplantation Rénale, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France.
⁵ Université Paris Descartes Sorbonne Paris Cité, Service de Maladies Infectieuses et Tropicales, Centre d'Infectiologie Necker-Pasteur, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Institut Imagine, Paris, France.
⁶ Université Paris Descartes Sorbonne Paris Cité, Service de Microbiologie Clinique, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France Unité Biologie et Pathogénicité Fongiques, INRA, USC2019, Institut Pasteur, Paris, France.

Abstract

Treatment of Candida glabrata cystitis remains a therapeutic challenge, and an antifungal combination using flucytosine is one option. We describe two patients with refractory C. glabrata cystitis who failed flucytosine combined with caspofungin with early-acquired high-level resistance to flucytosine due to nonsense mutations in the FUR1 gene. Rapidly acquired flucytosine resistance with microbiological failure should discourage combination of caspofungin and flucytosine during urinary candidiasis.

Publication types

Case Reports

MeSH terms

Aged
Antifungal Agents / administration & dosage*
Base Sequence
Candida glabrata / drug effects*
Candida glabrata / genetics
Candida glabrata / isolation & purification
Candida glabrata / metabolism
Candidiasis / drug therapy*
Candidiasis / microbiology
Candidiasis / pathology
Caspofungin
Codon, Nonsense
Cystitis / drug therapy*
Cystitis / microbiology
Cystitis / pathology
Drug Resistance, Fungal / drug effects*
Drug Resistance, Fungal / genetics
Drug Therapy, Combination
Echinocandins / administration & dosage*
Female
Flucytosine / administration & dosage*
Fungal Proteins / genetics
Fungal Proteins / metabolism
Gene Expression
Humans
Lipopeptides / administration & dosage*
Male
Molecular Sequence Data
Nucleobase Transport Proteins / genetics
Nucleobase Transport Proteins / metabolism
Treatment Failure
Urinary Bladder / microbiology
Urinary Bladder / pathology

Substances

Antifungal Agents
Codon, Nonsense
Echinocandins
Fungal Proteins
Lipopeptides
Nucleobase Transport Proteins
Flucytosine
Caspofungin

Grants and funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.