Generic selectors
Exact matches only
Search in title
Search in content
Filter by Categories
15th National Conference of the IAOMFP, Chennai, 2006
Abstract
Abstracts from current literature
Acne in India: Guidelines for management - IAA Consensus Document
Addendum
Announcement
Art & Psychiatry
Article
Articles
Association Activities
Association Notes
Award Article
Book Review
Brief Report
Case Analysis
Case Letter
Case Letters
Case Notes
Case Report
Case Reports
Clinical and Laboratory Investigations
Clinical Article
Clinical Studies
Clinical Study
Commentary
Conference Oration
Conference Summary
Continuing Medical Education
Correspondence
Corrigendum
Cosmetic Dermatology
Cosmetology
Current Best Evidence
Current Issue
Current View
Derma Quest
Dermato Surgery
Dermatopathology
Dermatosurgery Specials
Dispensing Pearl
Do you know?
Drug Dialogues
e-IJDVL
Editor Speaks
Editorial
Editorial Remarks
Editorial Report
Editorial Report - 2007
Editorial report for 2004-2005
Errata
Erratum
Focus
Fourth All India Conference Programme
From Our Book Shelf
From the Desk of Chief Editor
General
Get Set for Net
Get set for the net
Guest Article
Guest Editorial
History
How I Manage?
IADVL Announcement
IADVL Announcements
IJDVL Awards
IJDVL AWARDS 2015
IJDVL Awards 2018
IJDVL Awards 2019
IJDVL Awards 2020
IJDVL International Awards 2018
Images in Clinical Practice
In Memorium
Inaugural Address
Index
Knowledge From World Contemporaries
Leprosy Section
Letter in Response to Previous Publication
Letter to Editor
Letter to the Editor
Letter to the Editor - Case Letter
Letter to the Editor - Letter in Response to Published Article
LETTER TO THE EDITOR - LETTERS IN RESPONSE TO PUBLISHED ARTICLES
Letter to the Editor - Observation Letter
Letter to the Editor - Study Letter
Letter to the Editor - Therapy Letter
Letter to the Editor: Articles in Response to Previously Published Articles
Letters in Response to Previous Publication
Letters to the Editor
Letters to the Editor - Letter in Response to Previously Published Articles
Letters to the Editor: Case Letters
Letters to the Editor: Letters in Response to Previously Published Articles
Medicolegal Window
Messages
Miscellaneous Letter
Musings
Net Case
Net case report
Net Image
Net Letter
Net Quiz
Net Study
New Preparations
News
News & Views
Obituary
Observation Letter
Observation Letters
Oration
Original Article
ORIGINAL CONTRIBUTION
Original Contributions
Pattern of Skin Diseases
Pearls
Pediatric Dermatology
Pediatric Rounds
Perspective
Presedential Address
Presidential Address
Presidents Remarks
Quiz
Recommendations
Regret
Report
Report of chief editor
Report of Hon : Treasurer IADVL
Report of Hon. General Secretary IADVL
Research Methdology
Research Methodology
Resident page
Resident's Page
Resident’s Page
Residents' Corner
Residents' Corner
Residents' Page
Retraction
Review
Review Article
Review Articles
Revision Corner
Self Assessment Programme
SEMINAR
Seminar: Chronic Arsenicosis in India
Seminar: HIV Infection
Short Communication
Short Communications
Short Report
Special Article
Specialty Interface
Studies
Study Letter
Supplement-Photoprotection
Supplement-Psoriasis
Symposium - Contact Dermatitis
Symposium - Lasers
Symposium - Pediatric Dermatoses
Symposium - Psoriasis
Symposium - Vesicobullous Disorders
SYMPOSIUM - VITILIGO
Symposium Aesthetic Surgery
Symposium Dermatopathology
Symposium-Hair Disorders
Symposium-Nails Part I
Symposium-Nails-Part II
Systematic Reviews and Meta-analyses
Systematic Reviews and Meta-analysis
Tables
Technology
Therapeutic Guidelines
Therapeutic Guidelines - IADVL
Therapeutics
Therapy
Therapy Letter
View Point
Viewpoint
What’s new in Dermatology
View/Download PDF

Translate this page into:

Original Article
ARTICLE IN PRESS
doi:
10.25259/IJDVL_359_2021

Effectiveness and safety of topical amphotericin B in 30% dimethyl sulfoxide cream versus 30% dimethyl sulfoxide cream for nondermatophyte onychomycosis treatment: A pilot study

Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Department of Pharmacy General Pharmaceutical Production Division, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
Corresponding author: Dr. Sumanas Bunyaratavej, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkoknoi, Bangkok, Thailand. consultskin@yahoo.com
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Leeyaphan C, Suiwongsa B, Komesmuneeborirak P, Kiratiwongwan R, Wongdama S, Prasong W, et al. Effectiveness and safety of topical amphotericin B in 30% dimethyl sulfoxide cream versus 30% dimethyl sulfoxide cream for nondermatophyte onychomycosis treatment: A pilot study. Indian J Dermatol Venereol Leprol, doi: 10.25259/IJDVL_359_2021.

Abstract

Background:

Although topical amphotericin B cream is effective for the treatment of nondermatophyte mold onychomycosis in vitro, studies of its effectiveness and safety in vivo are limited.

Objectives:

We studied the effectiveness and safety of topical 0.3% amphotericin B in 30% dimethyl sulfoxide cream (amphotericin B cream) in nondermatophyte mold onychomycosis using the vehicle cream 30% dimethyl sulfoxide cream as control.

Methods:

This randomized controlled study was conducted between January 2019 and November 2020. Patients diagnosed with nondermatophyte mold onychomycosis were randomly divided into two groups of ten patients each: one treated with amphotericin B cream and the other with the vehicle cream. Clinical and mycological cure as well as safety were evaluated.

Results:

Ten patients each treated with amphotericin B cream and the vehicle cream were included in the study, but only nine patients in the vehicle cream group were available for follow up. All the 19 evaluable patients had distal lateral subungual onychomycosis and the great toenails were affected in 18 (94.7%) of these. Mycological cure was achieved in 8 (80%) patients treated with amphotericin B cream and in 4 (44.4%) patients using the control (vehicle) cream. Clinical cure was achieved in 7 (70%) patients treated with amphotericin B cream, but only in 2 (22.2%) patients on the control cream. No adverse events were observed.

Limitations:

The small sample size and the fact that PCR fungal identification that provides accurate identification of fungal species was not performed are limitations of our study.

Conclusion:

Topical amphotericin B cream was both very effective and safe in the treatment nondermatophyte mold onychomycosis. The control (vehicle) cream containing 30% dimethyl sulfoxide also demonstrated some antifungal activity.

Keywords

amphotericin B
dimethyl sulfoxide
fungi
onychomycosis
topical

Plain Language Summary

Onychomycosis is a fungal infection of the nail caused by dermatophytes, nondermatophyte molds (NDMs), and yeasts. Currently, the incidence of nondermatophyte mold onychomycosis is increasing affecting 24 to 50% of the population. However, the most effective treatment for it is limited. Topical amphotericin B is an antifungal drug that has been found to be effective for the treatment of nondermatophyte mold onychomycosis in laboratories. Nonetheless, studies on its effectiveness and safety in patients are limited. The researchers, from the Thailand, aimed to investigate the effectiveness and safety of topical 0.3% amphotericin B in 30% dimethyl sulfoxide (DMSO) cream and 30% DMSO cream in treating onychomycosis caused by nondermatophyte molds. Patients diagnosed with nondermatophyte mold onychomycosis were divided into two groups including 0.3% amphotericin B in 30% DMSO cream and 30% DMSO cream (10 patients/group). Treatment responses which include ‘clinical cure’ (>95% visible clearing of the nail), ‘mycological cure’ (the fungus has been killed), and safety were evaluated. Their findings showed that the clinical cure rate for 0.3% amphotericin B in 30% DMSO cream was higher than that for 30% DMSO cream (70% vs 22%), while mycological cure was achieved in 80% and 44% of the patients treated with 0.3% amphotericin B in 30% DMSO cream and 30% DMSO cream, respectively. No side effects were reported during the study period. The authors concluded that topical 0.3% amphotericin B in 30% DMSO cream showed excellent effectiveness and safety for the treatment of nondermatophyte mold onychomycosis.

Introduction

Onychomycosis is a common problem caused by dermatophytes, nondermatophyte molds and yeasts.1 The prevalence of nondermatophyte mold onychomycosis is increasing, especially in tropical countries with reported prevalence rates of 24.1% to 51.6%.2-5 The most common nondermatophyte molds isolated are Scopulariopsis brevicaulis, Fusarium species, Aspergillus species, Neoscytalidium dimidiatum and Acremonium species,6 with Neoscytalidium dimidiatum being the most prevalent organism in Thailand.4,7

Treatment modalities for nondermatophyte mold onychomycosis include the use of oral and topical antifungal drugs, and either chemical or surgical nail avulsion.1,6,8-11 Amphotericin B is an antifungal from the polyene class of antimicrobial compounds with broad fungicidal properties and a low rate of resistance.12 It binds to ergosterol in the fungal cell membrane forming permeable channels resulting in the leakage of ions and metabolites, thus causing cell death.16-18 Topical amphotericin B been found to be efficacious in vitro against nondermatophyte molds with minimum inhibitory concentrations ranging from 0.06 to 1 μg/ml.5,13-15 As it is highly lipophilic, a drug delivery vehicle such as dimethyl sulfoxide is often used to enhance its therapeutic effect.19

Dimethyl sulfoxide is a stable, highly polar, water-soluble compound with antifungal properties, frequently used as a solvent to the enhance penetration of antifungal drugs. 20,21 An extemporaneous ointment preparation of amphotericin B in 30% dimethyl sulfoxide was shown to achieve concentrations well above the minimum inhibitory concentrations for nondermatophyte molds in vitro in a nail model.22 However, published in vivo studies of topical amphotericin B for this condition have been few. In this study we report the effectiveness and safety of topical amphotericin B in 30% dimethyl sulfoxide in nondermatophyte mold onychomycosis treatment.

Materials and Methods

Study design

This randomized, double-blind clinical trial was conducted at the Nail Clinic, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand, between January 2019 and November 2020. The trial was registered with ClinicalTrials. gov (NCT03814343) and the study protocol was approved by Siriraj Institutional Review Board (no. Si 799/2018). All patients provided signed informed consent. Patients were assigned to two groups using mixed-blocked randomization. The first group received topical amphotericin B cream while the second received the vehicle cream.

Subjects

Twenty patients with nondermatophyte mold onychomycosis were enrolled and randomized into two groups of ten each. All patients were over 18 years of age and none had been treated with oral, topical or intravenous antifungal therapies during the preceding 36 weeks. Patients with dermatophyte onychomycosis, mixed onychomycosis or other concomitant nail diseases (such as psoriatic nail or paronychia) and immunocompromised patients were excluded.

Nondermatophyte mold onychomycosis was diagnosed as per the criteria of Gupta et al. which included positive microscopic examination of nail clippings in 20% potassium hydroxide solution, isolation of nondermatophyte molds on at least two occasions on fungal culture from repeated samplings, exclusion of dermatophytes and histological examination.6

Preparation of medication

Amphotericin B (Amphotret, Bharat Serums and Vaccines Ltd., New Delhi, India) was mixed with 30% dimethyl sulfoxide cream (Emplura, Merck, Kenilworth, N.J., USA) to achieve the desired amphotericin B concentration of 3 mg/ml. The 30% dimethyl sulfoxide cream served as control. Both the preparations were stored in identical aluminum tubes at temperatures ranging from 2°C to 8°C.

Patients were instructed to apply a pea-sized amount of cream once daily before bedtime to the affected nails and to wrap them in tape overnight to enhance penetration of the medication. No other systemic antifungal agent was given during the study period.

Treatment, follow-up and measurement

Patients were directed to apply the medication continuously for 36 weeks. The clinical status, mycological test results, adherence to the drug regimen and adverse events were assessed at 0, 12, 24 and 36 weeks. Subsequent evaluations after the treatment period (clinical status, mycological test results and adverse events) were performed at 48, 60 and 72 weeks. The severity of onychomycosis was assessed based on the Onychomycosis Severity Index (OSI).23 Clinical evaluation was performed by two treatment-blinded investigators (CL and SB); “clinical cure” was defined as >95% clinically normal. The assessment of efficacy was based on mycological tests results with “mycological cure” being defined as negative potassium hydroxide test and fungal culture results.24

Statistical analysis

The data were analyzed using descriptive statistics. Fisher’s exact test was employed to compare the differences among the categorical variables. The continuous variables with and without normal distribution were analyzed using independent t-tests and Mann–Whitney U-tests, respectively. P ≤ 0.05 was deemed statistically significant. Data were analyzed using PASW Statistics for Windows (version 18; SPSS Inc., Chicago, Ill., USA).

Results

A total of 20 patients with nondermatophyte mold onychomycosis were selected for the study. One of the ten patients in the control group was excluded from the analysis as she did not attend the follow-up sessions. The demographic data and clinical characteristics of these 19 patients are listed in Table 1. The mean (SD) age was 68.9 (8.6) years and 10 (52.6%) patients were male. There were no significant differences in the underlying diseases, disease duration, onychomycosis severity and predisposing factors in the two groups. All 19 patients had distal lateral subungual onychomycosis and the great toenails were affected in 18 (94.7%) of the patients. A concomitant fungal foot infection was noted in 12 (63.2%) patients. Neoscytalidium spp. were isolated on fungal cultures in 15 (78.9%) and Fusarium spp. in 4 (21.1%) cases. Most of the patients (18/19; 94.7%) reported good adherence to the treatment.

Table 1:: Demographic data and clinical characteristics of patients diagnosed with nondermatophyte onychomycosis
Parameters Total (n, 19) Topical amphotericin B cream (n, 10) Vehicle cream (n, 9) P-value
Sex
Male 10 (52.6) 5 (50.0) 5 (55.6) 1.000
Female 9 (47.4) 5 (50.0) 4 (44.4)
Age (years), mean±SD 68.9 ± 8.6 70.7±6.8 66.9±10.3 0.351
Disease duration (months), median (min, max) 41.0 (9.0,124.0) 42.5 (10.0,87.0) 41.0 (9.0,124.0) 0.191
OSI score, median (min, max) 3.0 (1.0,13.0) 1.5 (1.0,12.0) 3.0 (1.0,13.0) 0.511
Predisposing factors for onychomycosis
Hyperhidrosis of the feet 5 (26.3) 4 (40.0) 1 (11.1) 0.303
Impaired circulation 2 (10.5) 2 (20.0) 0 0.474
History of foot trauma 7 (36.8) 4 (40.0) 3 (33.3) 1.000
History of contact with pets 7 (36.8) 3 (30.0) 4 (44.4) 0.650
Physical examination
Most severely affected toenails
Big toenails 18 (94.7) 9 (90.0) 9 (100.0) 1.000
Third toenails 1 (5.3) 1 (10.0) 0
Depth of nail involvement
<1/3 16 (84.2) 8 (80.0) 8 (88.9) 1.000
1/3–2/3 3 (15.8) 2 (20.0) 1 (11.1)
Fungal culture results
Neoscytalidium spp. 15 (78.9) 7 (70.0) 8 (88.9) 0.582
Fusarium spp. 4 (21.1) 3 (30.0) 1 (11.1)
Concomitant fungal foot infection 12 (63.2) 6 (60.0) 6 (66.7) 1.000
Concurrent foot deformity 8 (42.1) 4 (40.0) 4 (44.4) 1.000
Clinical cure rate 9 (47.4) 7 (70.0) 2 (22.2) 0.070
Time to clinical cure (months), mean±SD (n=9) 10.6±4.6 10.4±5.3 11.0±0 0.786
Mycological cure rate 12 (63.2) 8 (80.0) 4 (44.4) 0.170
Time to mycological cure (months), mean±SD (n=12) 8.8±5.2 9.5±6.0 7.5±3.4 0.482
P<0.05 indicates statistical significance. OSI: Onychomycosis severity index, SD: Standard deviation

Clinical cure was seen in 7 of the 10 (70%) patients who received amphotericin B cream but in only 2 of 9 (22.2%) patients treated with the vehicle cream. The mycological cure rates for amphotericin B were also higher than for the vehicle cream (80% vs. 44.4%). The two mycological failures in the amphotericin B cream group had Neoscytalidium spp. onychomycosis. No adverse events were reported during the 72 weeks of the study in either group. Figure 1 shows representative photographs of clinical improvement in onychomycosis treated with amphotericin B cream and vehicle cream.

Figure 1a:: Amphotericin B at baseline. Representative photographs of clinical improvement in onychomycosis treated with amphotericin B cream and vehicle cream
Figure 1b:: Amphotericin B at 3 months. Representative photographs of clinical improvement in onychomycosis treated with amphotericin B cream and vehicle cream
Figure 1c:: Amphotericin B at 6 months. Representative photographs of clinical improvement in onychomycosis treated with amphotericin B cream and vehicle cream
Figure 1d:: Amphotericin B at 12 months. Representative photographs of clinical improvement in onychomycosis treated with amphotericin B cream and vehicle cream
Figure 1e:: 30% Dimethyl sulfoxide cream at baseline. Representative photographs of clinical improvement in onychomycosis treated with amphotericin B cream and vehicle cream
Figure 1f:: 30% Dimethyl sulfoxide cream at 3 months. Representative photographs of clinical improvement in onychomycosis treated with amphotericin B cream and vehicle cream
Figure 1g:: 30% Dimethyl sulfoxide cream at 6 months. Representative photographs of clinical improvement in onychomycosis treated with amphotericin B cream and vehicle cream
Figure 1h:: 30% Dimethyl sulfoxide cream at 12 months. Representative photographs of clinical improvement in onychomycosis treated with amphotericin B cream and vehicle cream

Discussion

There is no currently recommended standard treatment for nondermatophyte mold onychomycosis.25 In this study we demonstrate not only the high effectiveness of amphotericin B in 30% dimethyl sulfoxide cream in nondermatophyte mold onychomycosis, but also modest effectiveness of the vehicle cream containing only 30% dimethyl sulfoxide.

Studies on the topical treatment of nondermatophyte mold onychomycosis are few. Earlier reports have noted a 44% mycological response rate with 8% ciclopirox nail lacquer in 18 patients with Neoscytalidium spp. onychomycosis at 12 months and 89.3% mycological cure with 5% amorolfine nail lacquer in N. dimidiatum onychomycosis.25, 26 In the latter study, a mycological cure of 32% was noted in those patients receiving only 40% urea cream with occlusion.26 Combined treatment of nondermatophyte mold onychomycosis with 5% amorolfine nail lacquer and neodymium-doped yttrium aluminum garnet (Nd: YAG) 1064-nm laser resulted in only a marginally higher mycological cure rate of 65% as compared to 60% in those using 5% amorolfine nail lacquer alone.27

Amphotericin B has excellent in vitro activity against nondermatophyte molds.5,13-15 In a study from Switzerland mycological cure was achieved with 0.2 % topical amphotericin B in 50% dimethyl sulfoxide in 7 (87.5%) of 8 treatment-resistant nondermatophyte mold onychomycosis patients at 12 months.17 This compares well with the mycological cure rate of 80% in our study, although we used 0.3% amphotericin B in 30% dimethyl sulfoxide cream.27

The mycological and clinical cure rates of 44% and 22%, respectively, with the 30% dimethyl sulfoxide vehicle cream was an unexpected finding in our study. Dimethyl sulfoxide has both keratolytic 28,29 and antifungal properties and has been shown to inhibit the growth of dermatophytes and yeasts in vitro.21,30, 31

Limitations

Limitations of the study include the small sample size and the non-availability of PCR fungal identification which provides accurate identification of fungal species was not used in this study. As all cases were the distal lateral subungual type, treatment response according to clinical type of onychomycosis could not be identified. Although all four cases of fusarium spp onychomycosis responded to amphotericin B in our study, it is difficult to draw any firm conclusions owing to the small numbers.

Validation through a larger sample size is needed to conclusively demonstrate the effects of not only amphotericin B, but also the 30% dimethyl sulfoxide vehicle cream for nondermatophyte mold onychomycosis treatment.

Conclusion

Amphotericin B in 30% dimethyl sulfoxide was effective and safe in the treatment of nondermatophyte mold onychomycosis. However, the vehicle cream containing 30% dimethyl sulfoxide also showed some effectiveness in nondermatophyte mold onychomycosis.

Acknowledgments

The authors thank Dr. Chulalak Komoltri for her statistical advice and Miss Lalita Matthapan for her help in data collection.

Declaration of patient consent

Institutional Review Board (IRB)/Institutional Ethics Committee (IEC) permission obtained for the study.

Financial support and sponsorship

This study was supported by grants from La Roche-Posay.

Conflicts of interest

There are no conflicts of interest.

References

  1. , , . Therapies for the treatment of onychomycosis. Clin Dermatol. 2013;31:544-54.
    [CrossRef] [PubMed] [Google Scholar]
  2. , , , . Eclipsed phenomenon: The relationship between nail and foot infections in patients presenting with nondermatophyte infections after dermatophyte infections in onychomycosis. Br J Dermatol. 2020;183:158-9.
    [CrossRef] [PubMed] [Google Scholar]
  3. , , , , , . Distinct characteristics of Scytalidium dimidiatum and non-dermatophyte onychomycosis as compared with dermatophyte onychomycosis. J Dermatol. 2015;42:258-62.
    [CrossRef] [PubMed] [Google Scholar]
  4. , , . Prevalence of foot diseases in outpatients attending the institute of Dermatology, Bangkok, Thailand. Clin Exp Dermatol. 2004;29:87-90.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , , , , , et al. In vitro antifungal susceptibility of Neoscytalidium dimidiatum clinical isolates from Malaysia. Mycopathologia. 2017;182:305-13.
    [CrossRef] [PubMed] [Google Scholar]
  6. , , , , , . Systematic review of nondermatophyte mold onychomycosis: Diagnosis, clinical types, epidemiology, and treatment. J Am Acad Dermatol. 2012;66:494-502.
    [CrossRef] [PubMed] [Google Scholar]
  7. , , , , . Survey and comparison of clinical and laboratory findings among subjects with fingernail and toenail onychomycosis. Southeast Asian J Trop Med Public Health. 2020;51:528-34.
    [Google Scholar]
  8. , , . Scytalidium hyalinum onychomycosis successfully treated with 5% amorolfine nail lacquer. Br J Dermatol. 1999;140:555.
    [CrossRef] [PubMed] [Google Scholar]
  9. , , . Onychomycosis caused by nondermatophytic molds: Clinical features and response to treatment of 59 cases. J Am Acad Dermatol. 2000;42:217-24.
    [CrossRef] [Google Scholar]
  10. , , , , . Scytalidium and scytalidiosis: What's new in 2012? J Mycol Med. 2013;23:40-6.
    [CrossRef] [PubMed] [Google Scholar]
  11. , , . Onychomycosis. Clin Dermatol. 2010;28:151-9.
    [CrossRef] [PubMed] [Google Scholar]
  12. . Amphotericin B: Spectrum and resistance. J Antimicrob Chemother. 2002;49:7-10.
    [CrossRef] [PubMed] [Google Scholar]
  13. , , , , , . Genotyping and in vitro antifungal susceptibility of Neoscytalidium dimidiatum isolates from different origins. Int J Antimicrob Agents. 2009;34:351-4.
    [CrossRef] [PubMed] [Google Scholar]
  14. , . In vitro activity of amphotericin B, itraconazole, voriconazole, posaconazole, caspofungin and terbinafine against Scytalidium dimidiatum and Scytalidium hyalinum clinical isolates. J Antimicrob Chemother. 2008;61:835-7.
    [CrossRef] [PubMed] [Google Scholar]
  15. , , , , . In Vitro Antifungal Susceptibility of Nondermatophytic Keratinophilic Fungi Bilbao, Spain: Revista Iberoamericana de Micologia; . p. 142-7.
    [Google Scholar]
  16. , , . Exploring the role of nanoparticles in amphotericin B delivery. Curr Pharm Des. 2017;23:509-21.
    [CrossRef] [PubMed] [Google Scholar]
  17. , , , , , , et al. Efficacious treatment of non-dermatophyte mould onychomycosis with topical amphotericin B. Dermatology. 2011;223:289-92.
    [CrossRef] [PubMed] [Google Scholar]
  18. , , . Amphotericin B topical microemulsion: Formulation, characterization and evaluation. Colloids Surf B Biointerfaces. 2014;116:351-8.
    [CrossRef] [PubMed] [Google Scholar]
  19. , , , , , , et al. Nanoemulsion gel-based topical delivery of an antifungal drug: In vitro activity and in vivo evaluation. Drug Deliv. 2016;23:642-7.
    [CrossRef] [PubMed] [Google Scholar]
  20. , , , , . Antifungal activity of dimethyl sulfoxide against Botrytis cinerea and phytotoxicity on tomato and lettuce plants. Plant Biosyst. 2020;154:455-62.
    [CrossRef] [Google Scholar]
  21. . Dimethyl sulfoxide (DMSO) inhibits the germination of Candida albicans and the arthrospores of Trichophyton mentagrophytes. Nihon Ishinkin Gakkai Zasshi. 2008;49:125-8.
    [CrossRef] [PubMed] [Google Scholar]
  22. , , . Amphotericin B topical extemporaneous preparations for the treatment of nondermatophytic onychomycosis. Asian J Pharm Clin Res. 2020;13:135-9.
    [CrossRef] [Google Scholar]
  23. , , , , , , et al. A new classification system for grading the severity of onychomycosis: Onychomycosis severity index. Arch Dermatol. 2011;147:1277-82.
    [CrossRef] [PubMed] [Google Scholar]
  24. , , , , , , et al. Onychomycosis: A review. J Eur Acad Dermatol Venereol. 2020;34:1972-90.
    [CrossRef] [PubMed] [Google Scholar]
  25. , , , , . Onychomycosis due to Neoscytalidium treated with oral terbinafine, ciclopirox nail lacquer and nail abrasion: A pilot study of 25 patients. Mycopathologia. 2013;175:75-82.
    [CrossRef] [PubMed] [Google Scholar]
  26. , , , , , . Efficacy of 5% amorolfine nail lacquer in Neoscytalidium dimidiatum onychomycosis. J Dermatolog Treat. 2016;27:359-63.
    [CrossRef] [PubMed] [Google Scholar]
  27. , , , , , , et al. Randomized controlled trial comparing long-pulsed 1064-Nm neodymium: Yttrium-aluminum-garnet laser alone, topical amorolfine nail lacquer alone, and a combination for nondermatophyte onychomycosis treatment. J Cosmet Dermatol. 2020;19:2333-8.
    [CrossRef] [PubMed] [Google Scholar]
  28. , , . The use of urea for the treatment of onychomycosis: A systematic review. J Foot Ankle Res. 2019;12:22.
    [CrossRef] [PubMed] [Google Scholar]
  29. , . Dimethyl sulfoxide: History, chemistry, and clinical utility in dermatology. J Clin Aesthet Dermatol. 2012;5:24-6.
    [Google Scholar]
  30. . The effect of dimethyl sulfoxide (DMSO) on the growth of dermatophytes. Nihon Ishinkin Gakkai Zasshi. 2006;47:313-8.
    [CrossRef] [PubMed] [Google Scholar]
  31. , , , . Dimethyl sulfoxide induces oxidative stress in the yeast Saccharomyces cerevisiae. FEMS Yeast Res. 2013;13:820-30.
    [CrossRef] [PubMed] [Google Scholar]
Show Sections