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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 256-261

Evaluating the role of nondermatophyte fungi as a causative agent of tinea pedis and its relation to diabetes


1 Lecturer of Dermatology and Venereology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
2 Professor of Dermatology and Venereology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
3 Professor of Microbiology, Faculty of Veterinary Medicine, Zagazig University, Egypt
4 Doctor in Students Hospital, M.B.B.Ch Faculty of Medicine for Girls, Al-Azhar University 2013, Al-Azhar University, Cairo, Egypt

Date of Submission19-Feb-2020
Date of Decision20-Feb-2020
Date of Acceptance02-Mar-2020
Date of Web Publication29-Jun-2020

Correspondence Address:
MD Mervat Hamdino
Lecturer of Dermatology and Venereology, Faculty of Medicine (for Girls), Al-Azhar University, Abbassia, Cairo, 11517
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjamf.sjamf_30_20

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  Abstract 


Background Nondermatophyte fungi are highly suspected as a pathogen in tinea pedis cases with culture negative results for dermatophytes. The study of antifungal susceptibility restricts the resistance and provides the efficacy of an antifungal drug, especially in diabetic patients.
Aim To evaluate the presence of nondermatophyte fungi (yeast and mold) as a causative agent in tinea pedis, in diabetic versus nondiabetic patients, with reference to antifungal sensitivity test through the available antifungal drugs.
Patients and methods A total of 60 adult patients were enrolled in this study (30 diabetics and 30 nondiabetics) having tinea pedis. Skin scrapings from all patients were collected, and complete mycological diagnosis was done. Yeast and mold isolates were subjected to disc diffusion antifungal susceptibility testing using Mueller–Hinton agar.
Results Yeasts were the most common isolates in 26 (43.3%) cases, followed by dermatophytes nine (15%), nondermatophyte mold eight (13.3%), and mixed infection two (3.3%). There was no statically significant relation between diabetes and causative organisms, with P value more than 0.05. Yeast and mold isolates showed high sensitivity against itraconazole followed by fluconazole.
Conclusion Nondermatophyte fungi are becoming increasingly prevalent in tinea pedis. There is a nonsignificant relation between causative agent and diabetes, and the best choice of antifungal treatment of nondermatophyte fungi in our work is itraconazole.

Keywords: antifungal, diabetes, nondermatophyte fungi, susceptibility, tinea pedis


How to cite this article:
Hamdino M, Elsayed S, Taha M, Elkady E. Evaluating the role of nondermatophyte fungi as a causative agent of tinea pedis and its relation to diabetes. Sci J Al-Azhar Med Fac Girls 2020;4:256-61

How to cite this URL:
Hamdino M, Elsayed S, Taha M, Elkady E. Evaluating the role of nondermatophyte fungi as a causative agent of tinea pedis and its relation to diabetes. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 Jul 12];4:256-61. Available from: http://www.sjamf.eg.net/text.asp?2020/4/2/256/288274




  Introduction Top


Tinea pedis is still considered as a major public health problem affecting quality of life, because of the prolonged period of treatment and the recurrence of infection [1]. Tinea pedis in diabetic patients represents a portal of entry for various types of infections and contributes to the severity of diabetic foot [2]. Thus, it is necessary for diabetic patients to receive an accurate diagnosis and appropriate management of tinea pedis [2]. The efficacy of antifungal treatment may be reduced or delayed in diabetic patients probably because of impaired lower extremity circulation, immune dysregulation, concomitant medications, secondary infections [3], increased prevalence of unusual fungus strains [4], or different antifungal drug susceptibility of certain fungal micro-organisms [5]. Although the therapeutic efficacy of terbinafine, itraconazole, and fluconazole is well known for dermatophytosis in general population, limited data exist on nondermatophyte fungi, regarding diabetic population [6].

So, the aim of this study was to investigate the presence of nondermatophyte fungi (yeast and mold) as a causative agent in tinea pedis, in diabetic versus nondiabetic patients, with reference to antifungal sensitivity test through the available antifungal drugs to determine the proper antifungal for nondermatophyte fungi.


  Patients and methods Top


This cross-sectional comparative study included 60 adult patients (30 diabetics and 30 nondiabetics) having tinea pedis. They were randomly selected from the Dermatology Outpatient Clinic of Al-Zahraa University Hospital during the period October 2018–March 2019. The study was approved by the Research Ethics Committee of the Faculty of Medicine for Girls, Al-Azhar University. Patients who received any topical antifungals within 2 weeks or/and systemic antifungals 1 month before the study were excluded. Informed written consent was obtained from all patients before participation in this study.

Patients were classified into two groups:
  1. Group A: 30 diabetic patients.
  2. Group B: 30 nondiabetic patients. Patients with no history suggestive of diabetes confirmed by laboratory tests (fasting blood sugar, postprandial blood sugar, and glycated hemoglobin).


Patients in both groups were subjected to the following:
  1. Collection of specimens: Skin scrapings from the interdigital space and/or plantar site were collected in sterile petri dish for direct examination and culture under aseptic precautions.
  2. Direct microscopic examination: it was done after treatment with 20% potassium hydroxide for the presence of fungal elements.
  3. Culture: all specimens were inoculated on two tubes of Sabouraud dextrose agar plates without cycloheximide and two tubes of dermatophyte test medium. Cultures were routinely incubated at 30°C.
  4. Identification: the identification of filamentous fungi was based on macroscopic and microscopic examination in the lactophenol cotton blue and subculture on the differential bromocresol purple for dermatophytes and potato dextrose agar for mold.
    • The identification of yeast was carried out using Gram-stained smear and subculture on Candida chromogenic agar.
  5. Antifungal sensitivity test: disc diffusion antifungal susceptibility testing using Mueller–Hinton agar was performed according to Clinical and Laboratory Standards Institute (CLSI) recommendations CLSI 44-A (2009) for yeast [7] and CLSI 51-A (2010) [8] for mold. Antifungal sensitivity for yeast and mold was performed against itraconazole, fluconazole, ketoconazole, voriconazole, and caspofungin, and nystatin for yeast only.


Statistical analysis

Data were collected, revised, coded, and entered to the Statistical Package for Social Science (IBM SPSS; IBM Corp, Armonk, NY, USA, Version 23 for Microsoft Windows; IBM). Qualitative variables were presented as number and percentages. The comparison between groups with qualitative data were done by using χ2 test and Fisher exact test instead of the χ2 only when the expected count in any cell found less than 5. The comparisons between two independent groups with quantitative data and parametric distribution were done by using independent t test. The confidence interval was set to 95%, and the margin of error accepted was set to 5%. So, the P value was considered significant at the level of less than 0.05.


  Results Top


This study included 60 adult patients with tinea pedis (30 diabetics and 30 nondiabetics). A total of 54 (90%) specimens were positive for the presence of fungal filaments by potassium hydroxide examination, and 45 (75%) specimens were positive for mycological culture. The culture-positive results were significantly higher among specimens that were microscopically positive (81.5%) (P<0.001) ([Table 1]).
Table 1 Relation between potassium hydroxide and culture results

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Identification of 45 fungal isolates obtained demonstrated yeasts in 26 (43.3%) cases, dermatophytes in nine (15%) cases, nondermatophyte mold (NDM) in eight (13.3%) cases, and mixed culture in two (3.3%) cases. So, the total isolated nondermatophyte fungi (yeast and mold) were 36 (59.9%). The most frequently isolated yeast was Candid albicans in 10 (16.6%) cases. The predominant dermatophyte was Trichophyton mentagrophytes in five (8.3%) cases followed by Trichophyton rubrum four (6.6%) cases. Concerning the NDM, there was a predominance of Fusarium solani in three (5%) cases ([Table 2]).
Table 2 Identification of 45 fungal isolates obtained from 60 specimens of tinea pedis

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There was no statically significant relation between diabetes and causative organisms, with P value more than 0.05 ([Table 3]).
Table 3 Relation between diabetes and causative organism

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Antifungal susceptibility tests for yeast isolates showed that 90.9% were sensitive to itraconazole, 72.7% sensitive to fluconazole, 54.5% sensitive to voriconazole, 54.5% sensitive to caspofungin, and 27.2% sensitive to both ketoconazole and nystatin ([Figure 1]).
Figure 1 Bar chart of antifungal susceptibility of yeasts.

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Concerning the antifungal susceptibility testing for isolated mold, it revealed that 50% were sensitive to itraconazole and 25% sensitive to fluconazole ([Figure 2]).
Figure 2 Bar chart of antifungal susceptibility of NDM. NDM, nondermatophyte mold.

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[Figure 3] and [Figure 4] show examples of isolated species and antifungal susceptibility tests.
Figure 3 (a) Trichophyton rubrum white to yellow fluffy floccose surface with reddish reverse on DTM. (b) Fusarium solani woolly white colonies on SDA. (c) Candid albicans: white, pasty and smooth colonies on both SDA media and DTM. (d) Candida parapsilosis: white rough surface colony on SDA. DTM, dermatophyte test medium; SDA, Sabouraud dextrose agar.

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Figure 4 (a) Candida parapsilosis antifungal susceptibility. Itraconazole: sensitive, ketoconazole: resistant, caspofungin: sensitive, nystatin: intermediate sensitivity, fluconazole: resistant, voriconazole: resistant. (b) Rhodotorula rubra antifungal susceptibility test. Itraconazole: sensitive, ketoconazole: sensitive, fluconazole: resistant, voriconazole: resistant, caspofungin: resistant, nystatin: sensitive. (c) Fusarium solani antifungal susceptibility test. All tested antifungal: resistant.

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  Discussion Top


In our study, direct microscopic examination of clinical samples was positive in 90% (54/60) of patients and mycological culture showed positive results in 45/60 (75%) patients, The culture-positive results were significantly higher among specimens that were microscopically positive (81.5%) (P<0.001). These results are comparable with many other works as in the study by Patel et al. [9], which revealed that 62.12% of superficial fungal infections were positive by direct microscopy, whereas 29.29% were positive by culture. Moreover, Abdo et al. [10] found that direct microscopy was positive in 85.7%, whereas mycological culture showed positive results in 60%.

The negative culture growth from microscopically positive samples can be explained by a false positive microscopy result owing to artifacts and a true negative culture. Alternatively, direct microscopy may be truly positive and the negative culture is a false negative, that is, a small specimen was taken, or the patient may have been receiving some form of antifungal treatment.

The culture results in the current study showed that yeast isolates were the most common isolates (43.3%), followed by dermatophyte isolates (15%), then NDMs isolate (13.3%), and finally, mixed infection (3.3%), So, the total isolated nondermatophyte fungi (yeast and mold) were 36 (59.9%), with no statistically significant relation between diabetes and causative organisms (P>0.05).

In the present study, the most commonly isolated yeast was C. albicans (16.6%) followed by Candida parapsilosis (13.3%). The predominant dermatophyte was Trichophyton mentagrophytes (8.3%) followed by Trichophyton rubrum (6.6%), and F. solani was the most common species detected among the isolated mold, in three (5%) cases, with nonsignificant difference between diabetics and nondiabetics.

The predominance of nondermatophyte fungi in our study is in agreement with the results of a study from Algeria done by Djeridane et al. [11], in which they found that yeast isolates were the most common etiological agents of tinea pedis (54%) followed by dermatophytes (40.8%) and then NDM (5.2%).

Moreover, Diongue et al. [12] found that yeast took the upper hand (55%), followed by NDM (30%), and then dermatophytes (15%). In contrast to our study, Veraldi et al. [13] found that dermatophytes had the highest infestation index followed by yeast. The study by El Fekih et al. [14] had isolated dermatophytes and yeasts only without NDM, whereas Pérez-Gonzàlez et al. [15] in Spain isolated only dermatophytes.

The increased incidence of nondermatophyte fungi in our study in both groups could be owing to an improvement of techniques of diagnosis and geographic variation in mold distribution.

In the current study, nonsignificant difference in the isolated fungi between diabetic and nondiabetic groups was found. Similar to our finding, Romano et al. [16] and Dogra et al. [17] found no correlations between dermatophytosis and duration or type of diabetes, its complications, or glucose and glycosylated hemoglobin levels.

In contrast to our finding, the Alteras and Saryt [18] study findings showed diabetics to be statistically significantly more commonly affected with foot infections caused by dermatophytes (57.0%) and Candida species (31.0%) than nondiabetics (40.0%; 5.0%). Moreover, there was no statistically significant association between the incidence of toe web space colonization with yeasts and dermatophytosis and the duration of diabetes in either patients with insulin-dependent diabetes mellitus or noninsulin dependent diabetes mellitus in a study from Croatia, but the difference according to the type of diabetes was statistically significant [19].

The nonsignificant difference between diabetics and nondiabetics could be explained by the proper education of these patients (mainly urban population and accessibility of physicians of any specialty), and also the fact that our patients had well-controlled diabetes.

All tested yeast isolates in our study were 90.9% sensitive to itraconazole, 72.7% sensitive to fluconazole, 54.5% sensitive to voriconazole, 54.5% sensitive to caspofungin, and 27.2% sensitive to both ketoconazole and nystatin.

Antifungal susceptibility tests of NDMs (mainly Fusarium species) showed that all tested species were 50% sensitive to itraconazole and 25% sensitive to fluconazole.

In agreement with our study, Oz et al. [20] found that the minimal inhibitory concentration values of itraconazole increased against NDMs and yeasts. Similar results were reported by other studies, in which the minimal inhibitory concentration value of itraconazole and fluconazole was high against isolates of Fusarium spp. [21],[22], but they disagreed with our study as they found F. solani isolates resistant to all antifungal. This could be owing to the characteristics of Fusarium spp. to be refractory, as explained by Al-Hatmi et al. [22]. In contrast to our study, Toukabri et al. [23] found that Fusarium spp., Scopulariopsis brevicaulis, and Aspergillus terreus were resistant to fluconazole and itraconazole.


  Conclusion Top


This study demonstrated that nondermatophyte fungi are becoming increasingly prevalent in tinea pedis with nonsignificant relation between causative agent and diabetes, and the best choice of antifungal treatment of nondermatophyte fungi in tinea pedis infection is itraconazole followed by fluconazole in our work.

Recommendations

We recommend the following:
  1. Doing antifungal sensitivity tests especially for management of cases clinically unresponsive to treatment.
  2. Future studies correlating in vitro and in vivo results are needed.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Elewski BE. The effect of toenail onychomycosis on patient quality of life. Int J Dermatol 1997; 36:754–756.  Back to cited text no. 1
    
2.
Rich P. Onychomycosis and tinea pedis in patients with diabetes. J Am Acad Dermatol 2000; 43:130–134.  Back to cited text no. 2
    
3.
Robbins JM. Treatment of onychomycosis in the diabetic patient population. J Diabetes Complications 2003; 17:98–104.  Back to cited text no. 3
    
4.
Chincholikar DA, Pal RB. Study of fungal and bacterial infections of the diabetic foot. Indian J Pathol Microbiol 2002; 45:15–22.  Back to cited text no. 4
    
5.
Manfredi M, McCullough MJ, Polonelli L, Conti S, Al-Karaawi ZM, Vescovi P, Porter SR. In vitro antifungal susceptibility to six antifungal agents of 229 Candida isolates from patients with diabetes mellitus. Oral Microbiol Immunol 2006; 21:177–182.  Back to cited text no. 5
    
6.
Farkas B, Paul C, Dobozy A, Hunyadi J, Horváth A, Fekete G. Terbinafine (Lamisil) treatment of toenail onychomycosis in patients with insulin-dependent and non-insulin-dependent diabetes mellitus: a multicentre trial. Br J Dermatol 2002; 146:254–260.  Back to cited text no. 6
    
7.
Nweze EI, Mukherjee PK, Ghannoum MA. Agar-based disk diffusion assay for susceptibility testing of dermatophytes. J Clin Microbiol 2010; 48:3750–3752.  Back to cited text no. 7
    
8.
Espinel-Ingroff A. Novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases. Rev Iberoam Micol 2009; 26:15–22.  Back to cited text no. 8
    
9.
Patel P, Mulla S, Patel D, Shrimali G. A study of superficial mycosis in south Gujarat region. Natl J Comm Med 2010; 1:85–88.  Back to cited text no. 9
    
10.
Abdo HM, Abdel-Hamed MR, Al-Hosiny IM. KOH mount versus culture in the diagnosis of tinea capitis. Gulf J Dermatol Venereol 2011; 18:34–39.  Back to cited text no. 10
    
11.
Djeridane A, Djeridane Y, Ammar-Khodja A. Epidemiological and aetiological study on tinea pedis and onychomycosis in Algeria. Mycos 2006; 49:190–196.  Back to cited text no. 11
    
12.
Diongue K, Ndiaye M, Diallo MA, Seck MC, Badiane AS, Diop A et al. Fungal interdigital tinea pedis in Dakar (Senegal). J Mycol Med 2016; 26:312–316.  Back to cited text no. 12
    
13.
Veraldi S, Esposito L, Gorani A. Tinea pedis acquired in mosques. Mycos J 2018; 61:794–795.  Back to cited text no. 13
    
14.
El Fekih N, Belghith I, Trabelsi S et al. Epidemiological and etiological study of foot mycosis in Tunisia. Actas Dermosifiliogr 2012; 103:520–524.  Back to cited text no. 14
    
15.
Pérez-Gonzàlez M, Torres-Rodriguez JM, Martinez-Roig A et al. Prevalence of tinea pedis, tinea unguium of toenails and tinea capitis in school children from Barcelona. Rev Iberoam Micol J 2009; 26:228–232.  Back to cited text no. 15
    
16.
Romano C, Massai L, Asta F et al. Prevalence of dermatophytic skin and nail infections in diabetic patients. Mycoses 2001; 44:83–86.  Back to cited text no. 16
    
17.
Dogra S, Kumar B, Bhansali A, Chakrabarty A. Epidemiology of onychomycosis in patients with diabetes mellitus in India. Int J Dermatol 2002; 41:647–651.  Back to cited text no. 17
    
18.
Alteras I, Saryt E. Prevalence of pathogenic fungi in the toe webs and toe-nail of diabetic patients. Mycopathologia 1979; 67:157–159.  Back to cited text no. 18
    
19.
Mlinaric-Missoni E, Kalenic S, Vaic-Babic V. Species distribution and frequency of isolation of yeasts and dermatophytes from toe webs of diabetic patients. Acta Dermatovenerol Croat 2005; 13:85–92.  Back to cited text no. 19
    
20.
Oz Y, Qoraan I, Oz A et al. Prevalence and epidemiology of tinea pedis and toenail onychomycosis and antifungal susceptibility of the causative agents in patients with type 2 diabetes in Turkey. Int J Dermatol 2017; 56:68–74.  Back to cited text no. 20
    
21.
Tortorano AM, Richardson M, Roilides E et al. ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp.and others. Clin Microbiol Infect J 2014; 20:27–46.  Back to cited text no. 21
    
22.
Al-Hatmi AM, van Diepeningen AD, Curfs-Breuker I et al. Specific antifungal susceptibility profiles of opportunists in the Fusarium fujikuroi complex. J Antimicrob Chemother 2015; 70:1068–1071.  Back to cited text no. 22
    
23.
Toukabri N, Dhieb C, El Euch D et al. Prevalence, etiology, and risk factors of tinea pedis and tinea unguium in Tunisia. Can J Infect Dis Med Microbiol 2017; 2017:6835725.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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