Intermittent posaconazole regimen to treat superficial Scytalidium dimidiatum infection

ARTICLE

Auteur(s) : Jean Dunand¹, Claude Viguie², André Paugam²

¹Service de Microbiologie-Hygiène, Hôpital Ambroise-Paré, 92100 Boulogne, France
²Service de Parasitologie-Mycologie, Hôpital Cochin, 27 rue du Faubourg St Jacques, 75014 Paris, France

In tropical and subtropical areas (South Asia, Africa, the West Indies and South America), the filamentous fungi Scytalidium dimidiatum (the anamorphic form of Natrassia mangiferae, formally known as Hendersonula toruloidea) is frequently responsible for skin and nail lesions similar to those of dermatophytosis [1]. These superficial lesions are difficult to treat due to the non-response to the available antifungal drugs [2]. Posaconazole is a new triazole antifungal drug that is structurally derived from itraconazole but with a broader activity and which has been successfully used to treat refractory eumycetoma and chromoblastomycosis [3]. As we recently demonstrated that posaconazole is effective in vitro against S. dimidiatum [4], we decided to study its efficacy in humans in vivo.

A 42-year-old black woman, native of Cameroon living in France since 2002, presented with a 30-year history of scaly plantar skin and onychomycosis. She had no history of immune deficiency and there was no past history of any other significant illness. The lesions involved the nails of the first, third and fifth fingers of the right hand, and all toes on both feet. During the previous 3 years she had tried various topical (ciclopirox, amorolfine, bifonazole) and oral antifungal treatments (itraconazole, terbinafine) without any improvement of the lesions (figures 1A,C). Direct microscopic examination of samples from the lesions revealed hyphae. Cultures yielded numerous colonies of S. dimidiatum. Minimum inhibitory concentrations of the isolate against itraconazole and posaconazole were 2 and 0.125 μg/mL (Etest method), respectively.

We choose to treat the patient with pulses of posaconazole, as previously used with itraconazole for the treatment of onychomycosis [5] or chromoblastomycosis [6]. The patient was treated with pulse doses of posaconazole: 400 mg twice daily oral suspension taken with a meal on the first five days of each month repeated for 3 months (12 weeks).

At the end of the treatment (third pulse) the patient reported a clear relief of the sensation of discomfort in the fingers and toes and a marked improvement was observed in the plantar lesions as well as in the nails (figures 1B, D). There were no side effects to the drug and the patient was very compliant. But 3 months later, at a consultation control, we observed resurgence of clinical signs of skin and nail infections and the skin and nail samples (direct, cultures) confirmed the recurrence of the infection. This failure was not due to a selection of resistant Scytalidium dimidiatum by the treatment, as we demonstrated with the antifungal susceptibility of the strain, which did not show any increase in the MIC against posaconazole. This data shows a partial response to posaconazole in the treatment of superficial scytalidiosis. The optimal dose and duration of treatment need to be defined by further studies to allow a better outcome.

Acknowledgements

References

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