Fungemia and Cutaneous Zygomycosis Due to Mucor

Jpn. J. Infect. Dis., 62, 146-148, 2009

Short Communication Fungemia and Cutaneous Zygomycosis Due to Mucor circinelloides in an Intensive Care Unit Patient: Case Report and Review of Literature Murat Dizbay, Esra Adisen1, Semra Kustimur2, Nuran Sari, Bulent Cengiz3, Burce Yalcin2, Ayse Kalkanci2*, Ipek Isik Gonul4, and Takashi Sugita5 Department of Infectious Diseases, 1Department of Dermatology, 2Department of Microbiology, 3Department of Neurology, and 4Department of Pathology, Gazi University School of Medicine, Ankara, Turkey, and 5Department of Microbiology, Meiji Pharmaceutical University, Tokyo 204-8588, Japan (Received February 6, 2008. Accepted December 26, 2008) SUMMARY: Mucor spp. are rarely pathogenic in healthy adults, but can cause fatal infections in patients with immuosuppression and diabetes mellitus. Documented mucor fungemia is a very rare condition in the literature. We described a fungemia and cutaneous mucormycosis case due to Mucor circinelloides in an 83-year-old woman with diabetes mellitus who developed acute left frontoparietal infarctus while hospitalized in a neuro- logical intensive care unit. The diagnosis was made based on the growth of fungi in the blood, skin biopsy cultures, and a histopathologic examination of the skin biopsy. The isolates were identified as M. circinelloides by molecular methods. This case is important in that it shows a case of cutaneous mucormycosis which developed after fungemia and provides a contribution to the literature regarding Mucor fungemia.

Mucormycosis manifests as a rhinoorbitocerebral, pulmo- not associated with an invasive fungal disease. In addition, nary, gastrointestinal, cutaneous, or disseminated disease. The paranasal sinus and pulmonary computed tomography (CT) most frequently isolated pathogens are Rhizopus, Mucor, results were not indicative of any invasive fungal disease. Cuninghamella, and Absidia. Although mucormycosis tends On the 24th day of treatment a slightly erythematous and to invade blood vessels and generates a disseminated disease, oedamatous area began to develop on the patient’s right hand. documented mucor fungemia is very rare, and blood cultures During dermatological examination, a centrally located necrotic are mostly negative (1). Herein, we describe a case of fungemia thick crust layer was observed. This slightly erythematous and cutaneous mucormycosis due to Mucor circinelloides in a and oedamatous lesion covered the whole dorsal aspect of neurological intensive care unit patient with diabetes mellitus the hand extending to the forearm. The lesion resembled that and discuss it in the light of the current literature. of cellulitis, but on palpation a purulant exudation and An 83-year-old diabetic woman was admitted to our emer- hemorragic drainage were observed (Figure 1). Samples for gency service with complaints of conciousness disturbance bacterial and fungal culture were taken from the exudate. and sudden onset right hemiplegia. She had been receiving Histopathological examination of a deep excisional biopsy oral antidiabetic treatment, and the level of HbA1c was 7.5%. material revealed pathognomonic changes of broad, irregular, She had never received insulin treatment. The patient was nonseptate, branching fungal hyphae and spores relevant to intubated because of increased difficulty in breathing and mucormycosis by hematoxylin and eosin (H&E) stain. Necro- transferred to the Neurology Intensive Care Unit. She was sis and a neutrophilic infiltrate were additional characteristic mechanically ventilated in this unit. During physical examina- features (Figure 2). These findings were consistent with deep tion on the 8th day of admission, her temperature was 38.3°C. fungal infection of the skin. In additon a skin biopsy culture Her lung examination revealed crackles on bilateral lower yielded a mold similar to that in the blood culture. Microscopic lung fields. The leukocyte count was 13,500 cells/mm3 with examination showed the absence of stolons, apophyses, and 78% neutrophils. A chest radiograph revealed a paracardiac rhizoids. Both isolates were morphologically identified as a pulmonary infiltration in the right lung. The patient was started on intravenous ampicillin-sulbactam 1.5 g per 6 h. Sputum and blood cultures were negative at this time. On the 10th day, her body temperature was normal, and she was stable over the following week. On the 17th day, her body tempera- ture rose to 38.5°C, and her clinical condition worsened. Deep tracheal aspirate culture grew Pseudomonas aeruginosa, and the patient’s antibiotic therapy was switched to intravenous piperacillin-tazobactam 4.5 g per 8 h. Four days later, the microbiology laboratory reported a growth of mold on a blood culture. In fact, this growth pattern was not taken into account at the beginning, since it was considered to be contamina- tion. This was because the patients’clinical findings were

*Corresponding author: Mailing address: Department of Micro- Fig. 1. Slightly erythematous and oedamatous area on the hand with a biology, Gazi University School of Medicine, 06500, Besevler, centrally located necrotic thick crust layer. On palpation a purulant Ankara, Turkey. E-mail: [email protected] exudation and hemorragic drainage were observed.

146 risk for disseminated mucormycosis, because they are often immunosuppressed as a result of malnutrition and medica- tions (including corticosteroids) and may be hyperglicemic as a result of parenteral hyperalimentation or diabetes mellitus. In our case, when oral antidiabetic treatment was initiated, the patient’s blood glucose level was 120 mg/dl. The skin lesion on the right hand appeared 6 days after the fungemia. Therefore, we concluded that cutaneous lesions occurred secondary to bloodstream infection. The primary source of infection was not detected in this case. The CT scan of the lungs, paranasal sinuses and brain revealed no foci for mucormycosis. Cutaneous involvement is seen in 19% of mucormycosis cases. Clinical features of cutaneous mucor- Fig. 2. Histopathological examination of a deep excisional biopsy mycosis range from skin swelling or pustulas to necrotic ul- material revealed pathognomonic changes of broad, irregular, nonseptate, cerations and echtyma gangrenosum-like lesions. Cutaneous branching fungal hyphae and spores relevant with mucormycosis by hematoxylin and eosin (H&E) stain. Necrosis and a neutrophilic mucormycosis can occur through hematogenous dissemina- infiltrate were additional characteristic features (×100). tion from other organs (3%), but cutaneous infection can also spread to other noncontiguous organs (20%) (1). Diagnosis of mucormycosis remains difficult. Culture positivity is seen in only half of patients. Mucor fungemia is a very rare clinical condition, even if the disseminated form is not uncommon. There are very limited data in the literature about positive blood cultures in mucormycosis cases. Nakamura et al. re- ported a case of peritoneal mucormycosis with positive blood culture, but the diagnosis was made post-mortem (4). In a study by Chan-Tack et al., a case of fungemia due to M. circinelloides associated with a central venous catheter was reported (5). They stated that early diagnosis of mucormycosis led to a succesful outcome in this case. In another study by Aboltins et al., a case of Mucor indicus fungemia secondary to gastrointestinal mucormycosis was presented (6). In both Fig. 3. Microscopic examination of Mucor colony showed the absence of these cases, mucormycosis was treated with amphotericin of stolons, apophyses, and rhizoids (×100). B in the early stage of the disease and the patients recovered well. Unfortunately, the antifungal therapy was initiated late in our case despite the growth on the blood culture. The anti- Mucor sp. (Figure 3). A treatment of classical amphotericin fungal therapy was only started after the growth of fungi from B 1 mg/kg/day therapy was started. The isolate was identified the skin biopsy specimen. It can be postulated that detecting on the species level by DNA sequencing at the Molecular the fungi on blood cultures is important for the early diagnosis Mycology Laboratory at Meiji Pharmaceutical University in of disseminated mucormycosis and may be related to survival. Tokyo. Ribosomal DNA including the complete ITS1-5.8S- Molecular techniques using genomic targets within the ITS2 region was amplified with the fungal universal prim- rRNA complex have been shown to be reliable for Mucor ers. PCR products were purified and sequenced (Applied spp. There is a close relationship between M. circinelloides Biosystems, Foster City, Calif., USA). The sequence of our and M. racemosus using the 18S and 28S rRNA gene targets. case isolates was identical to that of DQ118991 (2,3). The Thus, we confirmed the sequence data obtained from a case molecular product was identified as M. circinelloides. Two strain with the data for reference strains. Also, M. circinelloides reference strains were obtained from the Japanese Society grew well at 37°C, at which M. racemosus is not known to for Culture Collection. DNA sequence data were also obtained grow. Mucor spp. have been associated with invasive for NBRC 4554 and NBCR 5774 M. circinelloides reference zygomycosis, but fungemia and cutaneous involvement have strains. Reference strains and case strains showed 99.9% rarely been reported (5,6). M. circinelloides was the causa- sequence homology when they were compared with the data tive agent in four cases with cutaneous mucormycosis deposited in GenBank for M. circinelloides. The genotypic (3,4,7,8). identification was confirmed by thermotolerance, as M. In conclusion, our case once again emphasizes that many circinelloides grow well at 37°C, but M. racemosus is not cases of mucormycosis are undiagnosed; therefore, publish- known to grow at elevated temperatures. Reference strains ing more case reports and sharing our experience in this and case strains grew well at 37°C. Ventilator-associated fun- difficult-to- diagnose disease may provide a better understand- gal pneumonia was ruled out by the pulmonary CT results. ing of the different aspects of this rare clinical entity. The cranial CT was re-evaluated regarding the mucormyco- sis, and the hypodens appearance at the left cerebral hemi- REFERENCES sphere, temporoparietal area was considered to be consistent 1. Roden, M.M., Zaoutis, T.E., Buchanan, W.L., et al. (2005): Epidemiology with acute infarction rather than an infection. The tissue cul- and outcome of zygomycosis: a review of 929 reported cases. Clin. ture obtained from the paranasal sinus was negative. Despite Infect. 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