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Inicio Enfermedades Infecciosas y Microbiología Clínica Cutaneous infection due to Mucor irregularis (Rhizomucor variabilis) in a immuno...
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Vol. 35. Núm. 1.
Páginas 56-57 (Enero 2017)
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Vol. 35. Núm. 1.
Páginas 56-57 (Enero 2017)
Scientific letter
DOI: 10.1016/j.eimc.2016.06.008
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Cutaneous infection due to Mucor irregularis (Rhizomucor variabilis) in a immunocompetent traveller
Infeccion cutanea por Mucor irregularis en una viajera inmunocompetente
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Cristina Martinez-Mugicaa, Susana Rojo Albab, Jose A. Bogab, Azucena Rodriguez-Guardadoc,
Autor para correspondencia
azucenarodriguez@telecable.es

Corresponding author.
a Pharmacy Unit, Hospital Universitario Central de Asturias, Oviedo, Spain
b Microbiology Unit, Hospital Universitario Central de Asturias, Oviedo, Spain
c Tropical Diseases Unit, Hospital Universitario Central de Asturias, Oviedo, Spain
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Cutaneous mucormycosis is an uncommon disease characterized by acute onset, an angioinvasive character and rapid progression caused by saprophytic fungi of the order Mucorales. It is usually associated with immunosuppression and/or predisposing factors such as neutropenia, diabetes, organ transplantation, malignancies or traumatic injuries.1,2 Zygomycosis caused by Mucor irregularis (formerly Rhizomucor variabilis var. variabilis) mainly affects immunocompetent patients1–3 and it is a rare disease, characterized by inflammation, ulceration and destruction of surrounding tissue, leading to a deformation of the affected limb, and it is potentially fatal if left untreated.3

Few cases have been reported worldwide mainly in Asia,3–5 and more recently outside.6 We describe below the first reported case to our knowledge of M. irregularis isolated in an immunocompetent Spanish patient.

The patient was a Spanish 28-year-old female, resident in Spain, with no relevant clinical history. She was attended in Tropical Diseases Unit of Hospital Universitario Central de Asturias in April 2014. She reported that two months earlier, during a one-month stay in Guatemala, she observed bites on both lower limbs, whose size increased progressively, with cyclical occurrence of scab and itching skin sensation, and sometimes releasing purulent material. On physical examination, crusted skin lesions with well-defined edges and inflammatory halo were observed on both legs.

M. irregularis was isolated in microbiological culture, and identified by macroscopic and microscopic study of its morphology. It was a gray and fast-growing filamentous fungi in Sabouraud agar. In sample preparation for microscopic characterization, non-septate hyphae with rhizoids were observed. Sporangiophores were subspherical, over 100μm in maximum diameter. There was a subspheric columella and spores 10μm long. Fungi did not grow at 45°C, allowing differentiation of M. irregularis from the other species.7 The confirmation by molecular methods was not possible. Susceptibility testing was performed using E-test strips (bioMerieux) and showed only susceptibility to Amphotericin. Patient began receiving an initial dose of 300mg of intravenous liposomal amphotericin B, followed by 200mg/day during 4 days and 240mg/day the following 15 days (a total dose of 4.7g of liposomal amphotericin B), associated with 50mg/day of caspofungin during 19 days. Due to her worsening renal function (rise of creatinine level from 0.71mg/dl to 1.34mg/dl) and the poor response to initial treatment, treatment with topical amphotericin B was added. The pharmacy department developed an oil-in-water gel for the topical delivery of amphotericin B (1.25%), resulting in a significant improvement of skin lesions. For hospital discharge (length of stay: 20 days), systemic therapy was stopped, and the patient continued with local antifungal treatment. All microbiological tests showed no evidence of fungi. During the follow-up, there was a complete improvement of lesions.

Since M. irregularis was first isolated in 1991, skin infection caused by this fungus has been described as an endemic emerging mucormycosis in China.1,3,4 Moreover, in recent years it has been spreading around the world: first to other Asian countries,2 and later to the United States,6 and Europe.8 Nevertheless, the presence of M. irregularis had never been reported neither from Spain, nor from Central America, where the patient was infected. The diagnosis was made based on the characteristics of the fungus following Hoog et al algorithms.7 Although it would have been advisable to be confirmed by molecular biology techniques, they were not available in the center.

First-line treatment of cutaneous mucormycosis consists of liposomal amphotericin B therapy and surgical resection.9 In this case, a superficial debridement combined with medical therapy was carried out. Despite microbiological test results showing susceptibility only to amphotericin B, caspofungine was added to the therapeutic regimen since some in vitro studies have shown synergy between these two antifungal agents.10 Furthermore, these findings were confirmed in clinical practice in some of the cases reported, in which a combination of caspofungin and liposomal amphotericin B or posaconazole was effective in treating M. irregularis infection.11

Regarding the additional administration of topical amphotericin, this strategy is similar to that used in the case reported by de Hemashettar et al. in 2011,11 in which local fluconazole was added to systemic therapy in order to treat the infection. In this case, the gel formulation of amphotericin B enabled better contact with the infective agent, providing an increased pharmacological effect of the antifungal agent and limiting nephrotoxicity, making it possible to continue with treatment despite the renal function deterioration observed during the course of hospital treatment.

In conclusion M. irregularis is an endemic emerging mucormycosis, which has not been previously described in Spain, or in Central America, where the patient contracted the infection. The synergistic combination of amphotericin B with intravenous caspofungin and topical amphotericin B may be useful in the treatment of this mucormycosis.

References
[1]
Y. Zhao, Q. Zhang, L. Li, J. Zhu, K. Kang, L. Chen.
Primary cutaneous mucormycosis caused by Rhizomucor variabilis in an immunocompetent patient.
Mycopathologia, 168 (2009), pp. 243-247
[2]
H. Tomita, E. Muroi, M. Takenaka, K. Nishimoto, H. Kakeya, H. Ohno, et al.
Rhizomucor variabilis infection in human cutaneous mucormycosis.
Clin Exp Dermatol, 36 (2011), pp. 312-314
[3]
X. Lu, Z. Liu, Y. Shen, X. She, G. Lu, P. Zhan, et al.
Primary cutaneous zygomycosis caused by Rhizomucor variabilis: a new endemic zygomycosis? A case report and review of 6 cases reported from China.
Clin Infect Dis Off Publ Infect Dis Soc Am, 49 (2009), pp. e39-e43
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Mucor irregularis infection and lethal midline granuloma: a case report and review of published literature.
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Primary cutaneous mucormycosis caused by Mucor irregularis in an immunocompetent patient.
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Med Mycol, 49 (2011), pp. 714-723
[7]
G.S. Hoog, J. Guarro, J. Gene, M.J. Figuerras.
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[8]
B. Rammaert, C. Angebault, A. Scemla, S. Fraitag, N. Lerolle, M. Lecuit, et al.
Mucor irregularis-associated cutaneous mucormycosis: case report and review.
Med Mycol Case Rep, 6 (2014), pp. 62-65
[9]
W. Tehmeena, W. Hussain, H.R. Zargar, A.R. Sheikh, S. Iqbal.
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[10]
S. Zhang, R. Li, J. Yu.
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Antimicrob Agents Chemother, 57 (2013), pp. 3395-3397
[11]
B.M. Hemashettar, R.N. Patil, K. O’Donnell, V. Chaturvedi, P. Ren, A.A. Padhye.
Chronic rhinofacial mucormycosis caused by Mucor irregularis (Rhizomucor variabilis) in India.
J Clin Microbiol., 49 (2011), pp. 2372-2375
Copyright © 2016. Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica
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