Frequency of Cutaneous Fungal Infections and Azole Resistance of the Isolates in Patients with Diabetes Mellitus

Raiesi, Omid; Siavash, Mansour; Mohammadi, Faezeh; Chabavizadeh, Javaher; Mahaki, Behzad; Maherolnaghsh, Mehrnoush; Dehghan, Parvin

Frequency of Cutaneous Fungal Infections and Azole Resistance of the Isolates in Patients with Diabetes Mellitus

Document Type : Original Article

Authors

¹ Department of Mycology and Parasitology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

² Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

³ Department of Mycology and Parasitology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

⁴ Department of Biostatistics, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Diabetic patients are more susceptible to cutaneous fungal infections. The higher blood sugar levels cause increasing the cutaneous fungal infections in these patients. The main objective of this study was to find the frequency of fungal infections among cutaneous lesions of diabetic patients and to investigate azole antifungal agent susceptibility of the isolates. Materials and Methods: In this study, type 1diabetes (n = 78) and type 2 diabetes (n = 44) comprised 47 cases (38.5%) with diabetic foot ulcers and 75 cases (61.5%) with skin and nail lesions were studied. Fungal infection was confirmed by direct examination and culture methods. Antifungal susceptibility testing by broth microdilution method was performed according to the CLSI M27-A and M38-A references. Results: Out of 122 diabetic patients, thirty (24.5%) were affected with fungal infections. Frequency of fungal infection was 19.1% in patients with diabetic foot ulcer and 28% of patients with skin and nail lesions. Candida albicans and Aspergillus flavus were the most common species isolated from thirty patients with fungal infection, respectively. Susceptibility testing carried out on 18 representative isolates (13 C. albicans, five C. glabrata) revealed that 12 isolates (10 C. albicans and two C. glabrata isolates) (66.6%) were resistant (minimum inhibitory concentration [MIC] ≥64 mg/ml) to fluconazole (FCZ). Likewise, eight isolates (80%) of Aspergillus spp. were resistant (MIC ≥4 mg/ml), to itraconazole. Conclusion: Our finding expands current knowledge about the frequency of fungal infections in diabetic patients. We noted the high prevalence of FCZ-resistant Candida spp., particularly in diabetic foot ulcers. More attention is important in diabetic centers about this neglected issue.

Keywords

References

1.	Murphy-Chutorian B, Han G, Cohen SR. Dermatologic manifestations of diabetes mellitus: A review. Endocrinol Metab Clin North Am 2013;42:869-98.
2.	Larijani B, Zahedi F. Epidemiology of diabetes mellitus in Iran. J Diabetes Metab Disord 2002;1:7.
3.	Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA 2005;293:217-28.
4.	Rangel-Guerra R, Martínez HR, Sáenz C. Mucormycosis. Report of 11 cases. Arch Neurol 1985;42:578-81.
5.	Lehrer RI, Howard DH, Sypherd PS, Edwards JE, Segal GP, Winston DJ. Mucormycosis.Ann Intern Med. 93.5 th ed.; 1980:93-108.
6.	Romano G, Moretti, Di Benedetto A, Giofrè C, Di Cesare E, Russo G, et al. Skin lesions in diabetes mellitus: Prevalence and clinical correlations. Diabetes Res Clin Pract 1998;39:101-6.
7.	Bakker K, Riley P. The year of the diabetic foot. Diabetes Voice 2005;50:11-4.
8.	Aye M, Masson EA. Dermatological care of the diabetic foot. Am J Clin Dermatol 2002;3:463-74.
9.	Chellan G, Shivaprakash S, Karimassery Ramaiyar S, Varma AK, Varma N, Thekkeparambil Sukumaran M, et al. Spectrum and prevalence of fungi infecting deep tissues of lower-limb wounds in patients with type 2 diabetes. J Clin Microbiol 2010;48:2097-102.
10.	Rex J, Alexander B, Andes D, Arthington-Skaggs B, Brown S, Chaturveli V. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard – Third edition (M27-A3). Vol. 28. Wayne, PA: Clinical and Laboratory Standards Institute (CLSI); 2008.
11.	Espinel-Ingroff A, Dawson K, Pfaller M, Anaissie E, Breslin B, Dixon D, et al. Comparative and collaborative evaluation of standardization of antifungal susceptibility testing for filamentous fungi. Antimicrob Agents Chemother 1995;39:314-9.
12.	Espinel-Ingroff A, Fothergill A, Ghannoum M, Manavathu E, Ostrosky-Zeichner L, Pfaller M, et al. Quality control and reference guidelines for CLSI broth microdilution susceptibility method (M 38-A document) for amphotericin B, itraconazole, posaconazole, and voriconazole. J Clin Microbiol 2005;43:5243-6.
13.	Pfaller MA. Antifungal drug resistance: Mechanisms, epidemiology, and consequences for treatment. Am J Med 2012;125 1 Suppl: S3-13.
14.	Borzotta AP, Beardsley K. Candida infections in critically ill trauma patients: A retrospective case-control study. Arch Surg 1999;134:657-64.
15.	Church D, Elsayed S, Reid O, Winston B, Lindsay R. Burn wound infections. Clin Microbiol Rev 2006;19:403-34.
16.	Delamaire M, Maugendre D, Moreno M, Le Goff MC, Allannic H, Genetet B. Impaired leucocyte functions in diabetic patients. Diabet Med 1997;14:29-34.
17.	Pecoraro RE, Reiber GE, Burgess EM. Pathways to diabetic limb amputation. Basis for prevention. Diabetes Care 1990;13:513-21.
18.	Vandeputte P, Larcher G, Bergès T, Renier G, Chabasse D, Bouchara JP. Mechanisms of azole resistance in a clinical isolate of Candida tropicalis. Antimicrob Agents Chemother 2005;49:4608-15.
19.	Brun S, Bergès T, Poupard P, Vauzelle-Moreau C, Renier G, Chabasse D, et al. Mechanisms of azole resistance in petite mutants of Candida glabrata. Antimicrob Agents Chemother 2004;48:1788-96.
20.	Krcmery V, Barnes AJ. Non-albicans Candida spp. causing fungaemia: Pathogenicity and antifungal resistance. J Hosp Infect 2002;50:243-60.
21.	Mahajan S, Koranne RV, Sharma SK. Cutaneous manifestation of diabetes mellitus. Indian J Dermatol Venereol Leprol 2003;69:105-8. [PUBMED] [Full text]
22.	Bansal E, Garg A, Bhatia S, Attri AK, Chander J. Spectrum of microbial flora in diabetic foot ulcers. Indian J Pathol Microbiol 2008;51:204-8. [PUBMED] [Full text]
23.	Saba F, Hadi SM, Rabe'eh F, Javad NM, Monavvar A, Mohsen G, et al. Mycotic infections in diabetic foot ulcers in Emam Reza Hospital, Mashhad, 2006-2008. Jundishapur J Microbiol 2011;4:11-16.
24.	Mlinariæ-Missoni E, Kaleniæ S, Vukeliæ M, De Syo D, Belicza M, Vaziæ-Babiæ V. Candida infections in diabetic foot ulcers. Diabetol Croat 2005;34:29-35.
25.	Lugo-Somolinos A, Sánchez JL. Prevalence of dermatophytosis in patients with diabetes. J Am Acad Dermatol 1992;26:408-10.
26.	Gupta AK, Konnikov N, MacDonald P, Rich P, Rodger NW, Edmonds MW, et al. Prevalence and epidemiology of toenail onychomycosis in diabetic subjects: A multicentre survey. Br J Dermatol 1998;139:665-71.
27.	Dorko E, Baranová Z, Jenca A, Kizek P, Pilipcinec E, Tkáciková L. Diabetes mellitus and candidiases. Folia Microbiol (Praha) 2005;50:255-61.
28.	Manfredi M, McCullough MJ, Polonelli L, Conti S, Al-Karaawi ZM, Vescovi P, et al. In vitro antifungal susceptibility to six antifungal agents of 229 Candida isolates from patients with diabetes mellitus. Oral Microbiol Immunol 2006;21:177-82.
29.	Mayser P, Freund V, Budihardja D. Toenail onychomycosis in diabetic patients: Issues and management. Am J Clin Dermatol 2009;10:211-20.

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