Onychomycosis Insensitive to Systemic Terbinafine and Azole Treatments Reveals Non-Dermatophyte Moulds as Infectious Agents

Baudraz‐Rosselet, F.; Ruffieux, Catherine; Lurati, Massimo; Bontems, Olympia; Monod, Michel

doi:10.1159/000277762

Cited by 69 publications

(60 citation statements)

References 33 publications

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“…The TRFLP assay does not allow the identification of dermatophytes to the species level, but in practice, identifying the genus to which an infecting fungus belongs is what is most relevant for the dermatologist with respect to onychomycosis. The two anthropophilic species T. rubrum and T. interdigitale are the causes of 99% of tinea unguium (22,31,35,37), and both species respond well to standard treatment with azoles and terbinafine, whereas special treatments may need to be prescribed for NDF onychomycosis (4). In other tinea infections, in particular tinea capitis, the treatment sometimes varies, depending on the species involved, and therefore, only in these cases would species determination be of any use.…”

Section: Discussionmentioning

confidence: 99%

“…Routinely, one portion of each clinical sample was examined in a dissolving solution using a fluorochrome (4,5,30). The solution was prepared by dissolving 1 g of sodium sulfide (Na 2 S) (Sigma, St. Louis, MO) in 7.5 ml distilled water and subsequently adding 2.5 ml ethanol.…”

Section: Methodsmentioning

confidence: 99%

“…Correct identification of the infectious agent in nail infections is essential, as Fusarium spp. and nondermatophyte molds have been shown to be resistant to systemic terbinafine and azole treatments (4).…”

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confidence: 99%

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Identification of Infectious Agents in Onychomycoses by PCR-Terminal Restriction Fragment Length Polymorphism

Verrier

Pronina²,

Peter³

et al. 2012

J Clin Microbiol

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A fast and reliable assay for the identification of dermatophyte fungi and nondermatophyte fungi (NDF) in onychomycosis is essential, since NDF are especially difficult to cure using standard treatment. Diagnosis is usually based on both direct microscopic examination of nail scrapings and macroscopic and microscopic identification of the infectious fungus in culture assays. In the last decade, PCR assays have been developed for the direct detection of fungi in nail samples. In this study, we describe a PCR-terminal restriction fragment length polymorphism (TRFLP) assay to directly and routinely identify the infecting fungi in nails. Fungal DNA was easily extracted using a commercial kit after dissolving nail fragments in an Na 2 S solution. Trichophyton spp., as well as 12 NDF, could be unambiguously identified by the specific restriction fragment size of 5=-end-labeled amplified 28S DNA. This assay enables the distinction of different fungal infectious agents and their identification in mixed infections. Infectious agents could be identified in 74% (162/219) of cases in which the culture results were negative. The PCR-TRFLP assay described here is simple and reliable. Furthermore, it has the possibility to be automated and thus routinely applied to the rapid diagnosis of a large number of clinical specimens in dermatology laboratories.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Identification of Infectious Agents in Onychomycoses by PCR-Terminal Restriction Fragment Length Polymorphism

Verrier

Pronina²,

Peter³

et al. 2012

J Clin Microbiol

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“…It has been reported that the classical systemic treatments for onychomycosis caused by dermatophytes (e.g. itraconazole, fluconazole and griseofulvin) may fail when the nail infection is caused by NDMs 15 . There is also a recommendation for topical amphotericin B to be considered as a first-line treatment of NDM onychomycosis 6 .…”

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confidence: 99%

Non-dermatophytic moulds and yeasts as agents of onychomycosis in a Malaysian medical centre

Ding

Rahman

Khaithir

et al. 2017

Bangladesh J Med Sci

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Abstract:Objective: Onychomycosis can be caused by numerous fungi, with geographical and temporal factors influencing the prevalence of the various aetiological agents. We set out to identify and classify the various fungi cultured from the nail clippings of patients diagnosed with onychomycosis in UKM Medical Centre, Malaysia. Methods: This retrospective study involved cases of onychomycosis diagnosed from January 2013 to July 2014. For each fungus, mycological diagnosis was achieved by direct microscopic examination of the nail clipping(s) followed by morphological identification of the fungus following culture on various artificial media. Results: A total of 180 fungal isolates were cultured from the nail clippings of 146 different patients. Non-dermatophytic moulds accounted for most of the fungal isolates (59.8%), followed by yeasts (35.7%) and dermatophytes (4.5%). Overall, Candida was the most frequently isolated fungal genus and Aspergillus was the most frequently cultured mould genus. Out of the three dermatophyte genera, two (Microsporum and Trichophyton) were isolated. Conclusion: In our centre, non-dermatophytic moulds and yeasts are a lot more prevalent as causative agents of onychomycosis than dermatophytes.

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“…Efinaconazole possesses broader-spectrum antifungal activity than existing antifungals against dermatophyte and nondermatophyte molds and yeasts (14). It has potent in vitro antifungal activity against nondermatophytes, such as Scopulariopsis brevicaulis and Fusarium species, which cause nail infections that respond poorly to oral drugs (15). Thus, efinaconazole may be effective in treating nondermatophyte onychomycosis.…”

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confidence: 99%

The Low Keratin Affinity of Efinaconazole Contributes to Its Nail Penetration and Fungicidal Activity in Topical Onychomycosis Treatment

Sugiura

Sugimoto

Hosaka

et al. 2014

Antimicrob Agents Chemother

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Onychomycosis is a common fungal nail disease that is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. Keratin affinity of topical drugs is an important physicochemical property impacting therapeutic efficacy. To be effective, topical drugs must penetrate the nail bed and retain their antifungal activity within the nail matrix, both of which are adversely affected by keratin binding. We investigated these properties for efinaconazole, a new topical antifungal for onychomycosis, compared with those of the existing topical drugs ciclopirox and amorolfine. The efinaconazole free-drug concentration in keratin suspensions was 14.3%, significantly higher than the concentrations of ciclopirox and amorolfine, which were 0.7% and 1.9%, respectively (P < 0.001). Efinaconazole was released from keratin at a higher proportion than in the reference drugs, with about half of the remaining keratin-bound efinaconazole removed after washing. In single-dose in vitro studies, efinaconazole penetrated full-thickness human nails into the receptor phase and also inhibited the growth of Trichophyton rubrum under the nail. In the presence of keratin, efinaconazole exhibited fungicidal activity against Trichophyton mentagrophytes comparable to that of amorolfine and superior to that of ciclopirox. In a guinea pig onychomycosis model with T. mentagrophytes infection, an efinaconazole solution significantly decreased nail fungal burden compared to that of ciclopirox and amorolfine lacquers (P < 0.01). These results suggest that the high nail permeability of efinaconazole and its potent fungicidal activity in the presence of keratin are related to its low keratin affinity, which may contribute to its efficacy in onychomycosis.

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Onychomycosis Insensitive to Systemic Terbinafine and Azole Treatments Reveals Non-Dermatophyte Moulds as Infectious Agents

Cited by 69 publications

References 33 publications

Identification of Infectious Agents in Onychomycoses by PCR-Terminal Restriction Fragment Length Polymorphism

Identification of Infectious Agents in Onychomycoses by PCR-Terminal Restriction Fragment Length Polymorphism

Non-dermatophytic moulds and yeasts as agents of onychomycosis in a Malaysian medical centre

The Low Keratin Affinity of Efinaconazole Contributes to Its Nail Penetration and Fungicidal Activity in Topical Onychomycosis Treatment

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