Antifungal susceptibility patterns of yeasts and filamentous fungi isolated from nail infection

Ataídes, Fábio Silvestre; Chaul, M.H.; Essal, F.E. El; Costa, Carolina Rodrigues; Souza, Lúcia Kioko Hasimoto e; Fernandes, Orionalda F. L.; Silva, M.R.R.

doi:10.1111/j.1468-3083.2011.04315.x

Cited by 17 publications

(29 citation statements)

References 40 publications

(52 reference statements)

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“…One limitation of this study is that we did not measure the in vitro activity of other azoles against these isolates. However, the luliconazole MIC range, MIC 50 and MIC 90 values, and GM MICs that were measured in the current study compared favorably those reported in the literature for other azoles against dermatophytes, including itraconazole, voriconazole, posaconazole, ketoconazole, and the investigational agents efinaconazole and ravuconazole (Table 3) (15)(16)(17)(18)(19)(20). Although direct in vitro comparisons with newer azoles are warranted, none of these other azoles, except for itraconazole, currently have an FDA-approved indication for the treatment of onychomycosis.…”

supporting

confidence: 68%

Luliconazole Demonstrates Potent In Vitro Activity against Dermatophytes Recovered from Patients with Onychomycosis

Wiederhold

Fothergill

McCarthy

et al. 2014

Antimicrob Agents Chemother

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The in vitro activities of luliconazole, amorolfine, ciclopirox, and terbinafine were determined against 320 dermatophyte isolates from large toenails of onychomycosis patients enrolled into an ongoing phase 2b/3 clinical study. The geometric mean MIC for luliconazole was 0.00022 g/ml against all isolates, compared to 0.0194 to 0.3107 g/ml for the three other agents. The in vitro potency of luliconazole was maintained regardless of the dermatophyte species.O nychomycosis (tinea unguium) is a fungal infection of the nail bed and or plate and is associated with significant morbidity (1). Besides causing cosmetic concerns, this mycosis can result in pain or discomfort, acute bacterial cellulitis associated with spread of infection to the skin, and social stigma (2, 3). The prevalence of onychomycosis is estimated to be between 2 and 14%, with a rate of 13.8% reported in North America (1, 4). Risk factors for infection include increasing age, male gender, dystrophic nails, tinea pedis, and poor peripheral circulation (1, 3, 4). These infections are caused primarily by dermatophytes, including Trichophyton rubrum and T. mentagrophytes, and to a lesser extent by other dermatophytes (e.g., Epidermophyton floccosum), Candida species, and nondermatophytic molds (e.g., Acremonium, Fusarium, and Scopulariopsis species) (5, 6). Luliconazole is a novel imidazole currently under development. Pharmacokinetic and safety results from phase 1 studies in patients with onychomycosis have demonstrated high concentrations of luliconazole within the nail plates of the great toe and have shown that this agent is well tolerated when administered as a 10% solution (7). In vitro studies with a limited number of isolates have also reported potent activity of this agent against dermatophytes and other causative agents of dermatophytosis, including onychomycosis (8-10). Results from animal models and small clinical studies have also suggested in vivo efficacy against dermatophytosis (11-13). Our objective was to measure the in vitro activity of luliconazole against dermatophytes isolated at screening from toenails in an ongoing phase 2b/3 study of patients with mild to moderate toenail onychomycosis (www.clinicaltrials.gov, identifier NCT01431820). In addition, the in vitro activities of amorolfine, ciclopirox, and terbinafine, three products approved and most often used for treatment of onychomycosis in the United States and the European Union, were also determined.Three hundred twenty dermatophytes obtained from patients with confirmed toenail onychomycosis (positive KOH and culture and clinical diagnosis) during screening were used in this study. This included 308 Trichophyton rubrum and 10 T. mentagrophytes isolates and one each of Trichophyton tonsurans and Epidermophyton floccosum. All isolates were clinical strains that had been freshly subcultured and not previously frozen. Stock solutions of amorolfine, ciclopirox, terbinafine, and luliconazole were prepared in dimethyl sulfoxide (DMSO) and further diluted in RPMI 1640 buffered to a...

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supporting

confidence: 68%

Luliconazole Demonstrates Potent In Vitro Activity against Dermatophytes Recovered from Patients with Onychomycosis

Wiederhold

Fothergill

McCarthy

et al. 2014

Antimicrob Agents Chemother

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“…Overall, the geometric mean MIC of itraconazole for half of the isolates was Ͻ0.1 mg/liter, and the highest GM was 0.59 mg/liter (16), followed by 0.42 mg/liter (8). Our results showed good in vitro activity of itraconazole against T. rubrum (GM, 0.26 mg/liter); however, itraconazole was less active than the three new triazoles tested.…”

mentioning

confidence: 54%

“…For many years, griseofulvin was the only approved systemic antidermatophytic agent (4). However, nowadays, many potent antifungal agents are available for the treatment of dermatophytosis, such as allylamines and triazoles, which have more potent activity and fewer side effects (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The expansion of information on in vitro susceptibility testing of dermatophytes to new antifungal agents will help in the selection and development of antifungal drug regimens.…”

mentioning

confidence: 99%

Comparison of the In Vitro Activities of Newer Triazoles and Established Antifungal Agents against Trichophyton rubrum

Deng

Zhang

Seyedmousavi

et al. 2015

Antimicrob Agents Chemother

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D ermatophytosis caused byTrichophyton rubrum is the most common cutaneous fungal infection worldwide (1), which represents the cause of between 80% and 90% of all chronic and recurrent infections (2). These infections establish an important public health problem because of the prolonged treatment required for the disease, because of the frequent recurrence of infection, and because they are generally considered difficult to manage (3). Reliable in vitro susceptibility testing would therefore be useful for selecting the most suitable antifungal treatment. For many years, griseofulvin was the only approved systemic antidermatophytic agent (4). However, nowadays, many potent antifungal agents are available for the treatment of dermatophytosis, such as allylamines and triazoles, which have more potent activity and fewer side effects (5-19). The expansion of information on in vitro susceptibility testing of dermatophytes to new antifungal agents will help in the selection and development of antifungal drug regimens.The aim of the current study was to compare in vitro the activities of three newer triazoles, voriconazole, posaconazole, and isavuconazole, and four established antifungal agents against T. rubrum infection. One hundred eleven clinical isolates of T. rubrum were collected from seven dermatology clinics in Shanghai, China. Morphological identifications were confirmed by sequence-based analysis of the internal transcribed spacer of the rRNA gene region. The in vitro activities of seven antifungal agents were determined according to the CLSI reference guideline M38-A2 (20), with minor modifications. Two reference strains, Trichophyton mentagrophytes (strain ATCC MYA-4439) and Candida parapsilosis (strain ATCC 22019), were included as quality controls. Student's t test with the statistical SPSS package (version 9.0) was used, and P values of Ͻ0.05 were considered statistically significant. Table 1 lists the MIC ranges, geometric mean (GM) MICs, MIC 50 s, and MIC 90 s of seven antifungal agents against 111 T. rubrum strains. Terbinafine, voriconazole, posaconazole, isavuconazole, itraconazole, and griseofulvin had low MICs against all tested strains, whereas fluconazole did not show inhibitory effects. Similar results have been achieved in other studies (Table 2); however, limited data are available for the newer triazoles isavuconazole and posaconazole.Terbinafine was one of the most effective antifungal agents against T. rubrum among the 7 fungal agents tested, and our findings confirm those of previous studies (5-19) ( Table 2). We compared the in vitro activities of the 3 newer triazoles isavuconazole, posaconazole, and voriconazole with that of itraconazole. Three newer triazoles offered good in vitro activity against T. rubrum (Table 1). All isolates were far more susceptible to the 3 newer triazoles than to itraconazole (Table 1) and comparable to those reported by other studies (7,9,10,14,17,18).Isavuconazole is a novel broad-spectrum triazole agent and has the same mechanism of action as the other tr...

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“…Moreover, this species represents frequent cause of onychomycosis in several countries, including Brazil (4) , Chile (16) , México (17) , and Iran (18) . Although all 87 isolates of C. parapsilosis studied in our work have been identifi ed by phenotypic methods, we were not able to differentiate among the C. parapsilosis complex species, which are phenotypically identical.…”

Section: In Vitro Susceptibility Testingmentioning

confidence: 99%

“…Candida parapsilosis is a common yeast species found in cases of onychomycosis and candidemia associated with infected intravascular devices (3) (4) (5) (6) . In State of Goiás, Brazil, C. parapsilosis was found in 52.5% of nail samples and was the second most commonly isolated species (24.2%) from blood cultures (4) (7) . Previous work has shown that C. parapsilosis isolates may exhibit genotypic differences, allowing the classification of new species by restriction polymorphism analysis of the secondary alcohol dehydrogenase (SADH) gene.…”

mentioning

confidence: 99%

Molecular identification and antifungal susceptibility profiles of Candida parapsilosis complex species isolated from culture collection of clinical samples

Ataídes

Costa

Souza

et al. 2015

Rev. Soc. Bras. Med. Trop.

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Introduction:Candida parapsilosis is a common yeast species found in cases of onychomycosis and candidemia associated with infected intravascular devices. In this study, we differentiated Candida parapsilosis sensu stricto, Candida orthopsilosis, and Candida metapsilosis from a culture collection containing blood and subungual scraping samples. Furthermore, we assessed the in vitro antifungal susceptibility of these species to fl uconazole, itraconazole, voriconazole, posaconazole, amphotericin B, and caspofungin. Methods: Differentiation of C. parapsilosis complex species was performed by amplifi cation of the secondary alcohol dehydrogenase (SADH) gene and digestion by the restriction enzyme BanI. All isolates were evaluated for the determination of minimal inhibitory concentrations using Etest, a method for antifungal susceptibility testing. Results: Among the 87 isolates, 78 (89.7%) were identifi ed as C. parapsilosis sensu stricto, fi ve (5.7%) were identifi ed as C. orthopsilosis, and four (4.6%) were identifi ed as C. metapsilosis. Analysis of antifungal susceptibility showed that C. parapsilosis sensu stricto isolates were less susceptible to amphotericin B and itraconazole. One C. parapsilosis sensu stricto isolate was resistant to amphotericin B and itraconazole. Moreover, 10.2% of C. parapsilosis sensu stricto isolates were resistant to caspofungin. Two C. parapsilosis sensu stricto isolates and one C. metapsilosis isolate were susceptible to fl uconazole in a dose-dependent manner. Conclusions: We reported the fi rst molecular identifi cation of C. parapsilosis complex species in State of Goiás, Brazil. Additionally, we showed that although the three species exhibited differences in antifungal susceptibility profi les, the primary susceptibility of this species was to caspofungin.

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Antifungal susceptibility patterns of yeasts and filamentous fungi isolated from nail infection

Abstract: C. parapsilosis was the most common fungal species isolated from patients with onychomycosis. The different response obtained by in vitro susceptibility testing to drugs shows the importance of these methods to assist clinicians in choosing the best therapeutic option.

Cited by 17 publications

References 40 publications

Luliconazole Demonstrates Potent In Vitro Activity against Dermatophytes Recovered from Patients with Onychomycosis

Luliconazole Demonstrates Potent In Vitro Activity against Dermatophytes Recovered from Patients with Onychomycosis

Comparison of the In Vitro Activities of Newer Triazoles and Established Antifungal Agents against Trichophyton rubrum

Molecular identification and antifungal susceptibility profiles of Candida parapsilosis complex species isolated from culture collection of clinical samples

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