© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Transplant Infectious Disease, ISSN 1398-2273
Case report
Treatment for a eumycetoma infection caused by Aspergillus in an immunocompromised host: a case report S. Hopps, A. Roach, C. Yuen, E. Borders. Treatment for a eumycetoma infection caused by Aspergillus in an immunocompromised host: a case report. Transpl Infect Dis 2015: 17: 94–97. All rights reserved Abstract: Eumycetoma is a chronic infection of the skin and subcutaneous tissue caused by filamentous fungi, which usually occurs in tropical or subtropical countries. We report a case of an immunocompromised patient presenting with presumed eumycetoma in the United States and his subsequent treatment with voriconazole. The use of voriconazole and liposomal amphotericin B halted the progression and allowed gradual resolution of the infection. The patient will require close monitoring and long-term therapy with voriconazole to obtain a clinical cure. Voriconazole and liposomal amphotericin B are potential initial treatment options, with long-term voriconazole maintenance therapy, for an Aspergillusinduced eumycetoma.
S. Hopps1, A. Roach1, C. Yuen2, E. Borders1 1
College of Pharmacy, Department of Clinical and Administrative Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA, 2 Stephenson Oklahoma Cancer Center, Section of Hematology and Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA Key words: eumycetoma; Aspergillus; voriconazole; liposomal amphotericin B; hematopoietic stem cell transplant Correspondence to: Sarah Hopps, University of Oklahoma – Pharmacy, 1110 N. Stonewall Ave, Oklahoma City, OK 73117, USA Tel: 405-271-6878, x47209 Fax: 405-217-6430 E-mail: [email protected]
Received 28 July 2014, revised 16 September 2014, accepted for publication 25 September 2014 DOI: 10.1111/tid.12321 Transpl Infect Dis 2015: 17: 94–97
A mycetoma is a chronic infection of the skin and subcutaneous tissue, which usually occurs in tropical or subtropical countries (1). The World Health Organization has recently listed mycetoma as a “neglected tropical disease,” owing to the low cure rate and need for additional treatment options (2). A mycetoma infection begins as a small, localized lesion, and slowly spreads and evolves over months or years into the mature infection that produces granules and seropurulent discharge in tracts (3). Exposure to the pathogen is typically from the soil (2). The infection can be caused by a bacteria or a fungus. When it is caused by filamentous fungi, it is called a eumycetoma. The most common fungus that typically causes eumycetoma is Madurella mycetomatis in tropical countries (2). In these countries, eumycetoma is treated with an
94
antifungal, either itraconazole or ketoconazole, along with surgical intervention including wide local excision, debridement, or amputation (2, 4). One study reported a cure rate of 25.8%, highlighting the difficulty of cure in these patients with the available treatment options (4). This study also found that a longer treatment duration was a predictor of cure (odds ratio 1.9; 95% confidence interval 1.2–3.1). Several cases have been reported utilizing the newer azole antifungals for eumycetoma in tropical areas; however, only one case report assessed voriconazole treatment in a patient with an Aspergillus-induced mycetoma, to our knowledge (5, 6). We report a case of an immunocompromised patient presenting with presumed eumycetoma in the United States and his subsequent treatment with voriconazole.
Hopps et al: Treatment for Aspergillus eumycetoma
Case report A 66-year-old man initially presented to clinic with erythema, warmth, and induration of the right thigh. The patient had previously been treated for myelofibrosis with allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigenmatched sibling donor, 1 year before this presentation. HSCT was complicated with steroid refractory graftversus-host disease (GVHD) of the gastrointestinal tract and liver, requiring therapy with infliximab, which was completed 5 months before the current presentation. The patient was originally prescribed sulfamethoxazole/trimethoprim for presumed cellulitis, which was confirmed by magnetic resonance imaging (MRI). However, he developed progression of the infection despite oral antibiotic treatment. The wound culture showed moderate growth of Corynebacterium species, and light growth of coagulase-negative staphylococci, which grew only in broth. The patient was therefore started on intravenous (IV) vancomycin. One week later, the patient noted increased pain in the right thigh, where the wound was located. The infection site showed more confined erythema, but with increased drainage and warmth. No surgical debridement could be performed, and the patient was placed on broader antibiotic coverage with the addition of IV ceftriaxone to the vancomycin. Two weeks later, the patient reported a spreading infection and new fever. A skin biopsy sample was obtained and a fungal etiology was considered, because this condition was refractory to broad-spectrum antibiotic therapy in an immunocompromised individual and considering his history of exposure to farm animals. The patient was started on IV meropenem and voriconazole, which resulted in clinical improvement over several days. The skin biopsy revealed pigmented mycelial (fungal) elements, which could be consistent with a eumycetoma. A computed tomography scan of the lower extremity showed diffuse subcutaneous soft tissue edema about the right lower extremity with skin thickening. At the level of the thigh, the affected area appeared the greatest posteriorly and laterally, with marked induration/skin thickening that appeared more prominent compared to the previous MRI. This subcutaneous soft tissue swelling extends distally, where it was greatest at the lateral aspect of the knee, as well as the anterior and lateral aspects of the tibia/fibula. On exam, the site showed a non-resolving weeping pustular and nodular rash with surrounding erythema and edema extending from the thigh down to the foot.
Based on skin biopsy results, meropenem was discontinued and oral voriconazole was continued at 200 mg q12h. After 2 weeks on voriconazole, his wound had modestly improved although still had purulent drainage. Total bilirubin was noted to have elevated to 5.3 mg/dL with mildly elevated aspartate aminotransferase (AST) and a supratherapeutic voriconazole level of 12 mcg/ mL (goal 1.5–6 mcg/mL). Voriconazole dose was reduced to 200 mg daily. A repeat skin biopsy revealed necrotizing granulomas, which are usually associated with acid-fast bacilli. This prompted a deeper tissue biopsy by general surgery and culture for further evaluation. The second tissue culture grew Aspergillus and Penicillium species of fungus, and IV micafungin was added for double coverage. An MRI revealed worsening cutaneous and subcutaneous disease, without bone involvement, 8 weeks after the initiation of voriconazole and 5 days after the combination of voriconazole and micafungin. The Infectious Disease team recommended the initiation of liposomal amphotericin B (LAmB) instead of voriconazole and micafungin. After 2 weeks of treatment with LAmB, the wound showed significant clinical improvement. The minimum inhibitory concentration of Aspergillus for amphotericin B was 8 mcg/mL, for micafungin was
Case report
Treatment for a eumycetoma infection caused by Aspergillus in an immunocompromised host: a case report S. Hopps, A. Roach, C. Yuen, E. Borders. Treatment for a eumycetoma infection caused by Aspergillus in an immunocompromised host: a case report. Transpl Infect Dis 2015: 17: 94–97. All rights reserved Abstract: Eumycetoma is a chronic infection of the skin and subcutaneous tissue caused by filamentous fungi, which usually occurs in tropical or subtropical countries. We report a case of an immunocompromised patient presenting with presumed eumycetoma in the United States and his subsequent treatment with voriconazole. The use of voriconazole and liposomal amphotericin B halted the progression and allowed gradual resolution of the infection. The patient will require close monitoring and long-term therapy with voriconazole to obtain a clinical cure. Voriconazole and liposomal amphotericin B are potential initial treatment options, with long-term voriconazole maintenance therapy, for an Aspergillusinduced eumycetoma.
S. Hopps1, A. Roach1, C. Yuen2, E. Borders1 1
College of Pharmacy, Department of Clinical and Administrative Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA, 2 Stephenson Oklahoma Cancer Center, Section of Hematology and Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA Key words: eumycetoma; Aspergillus; voriconazole; liposomal amphotericin B; hematopoietic stem cell transplant Correspondence to: Sarah Hopps, University of Oklahoma – Pharmacy, 1110 N. Stonewall Ave, Oklahoma City, OK 73117, USA Tel: 405-271-6878, x47209 Fax: 405-217-6430 E-mail: [email protected]
Received 28 July 2014, revised 16 September 2014, accepted for publication 25 September 2014 DOI: 10.1111/tid.12321 Transpl Infect Dis 2015: 17: 94–97
A mycetoma is a chronic infection of the skin and subcutaneous tissue, which usually occurs in tropical or subtropical countries (1). The World Health Organization has recently listed mycetoma as a “neglected tropical disease,” owing to the low cure rate and need for additional treatment options (2). A mycetoma infection begins as a small, localized lesion, and slowly spreads and evolves over months or years into the mature infection that produces granules and seropurulent discharge in tracts (3). Exposure to the pathogen is typically from the soil (2). The infection can be caused by a bacteria or a fungus. When it is caused by filamentous fungi, it is called a eumycetoma. The most common fungus that typically causes eumycetoma is Madurella mycetomatis in tropical countries (2). In these countries, eumycetoma is treated with an
94
antifungal, either itraconazole or ketoconazole, along with surgical intervention including wide local excision, debridement, or amputation (2, 4). One study reported a cure rate of 25.8%, highlighting the difficulty of cure in these patients with the available treatment options (4). This study also found that a longer treatment duration was a predictor of cure (odds ratio 1.9; 95% confidence interval 1.2–3.1). Several cases have been reported utilizing the newer azole antifungals for eumycetoma in tropical areas; however, only one case report assessed voriconazole treatment in a patient with an Aspergillus-induced mycetoma, to our knowledge (5, 6). We report a case of an immunocompromised patient presenting with presumed eumycetoma in the United States and his subsequent treatment with voriconazole.
Hopps et al: Treatment for Aspergillus eumycetoma
Case report A 66-year-old man initially presented to clinic with erythema, warmth, and induration of the right thigh. The patient had previously been treated for myelofibrosis with allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigenmatched sibling donor, 1 year before this presentation. HSCT was complicated with steroid refractory graftversus-host disease (GVHD) of the gastrointestinal tract and liver, requiring therapy with infliximab, which was completed 5 months before the current presentation. The patient was originally prescribed sulfamethoxazole/trimethoprim for presumed cellulitis, which was confirmed by magnetic resonance imaging (MRI). However, he developed progression of the infection despite oral antibiotic treatment. The wound culture showed moderate growth of Corynebacterium species, and light growth of coagulase-negative staphylococci, which grew only in broth. The patient was therefore started on intravenous (IV) vancomycin. One week later, the patient noted increased pain in the right thigh, where the wound was located. The infection site showed more confined erythema, but with increased drainage and warmth. No surgical debridement could be performed, and the patient was placed on broader antibiotic coverage with the addition of IV ceftriaxone to the vancomycin. Two weeks later, the patient reported a spreading infection and new fever. A skin biopsy sample was obtained and a fungal etiology was considered, because this condition was refractory to broad-spectrum antibiotic therapy in an immunocompromised individual and considering his history of exposure to farm animals. The patient was started on IV meropenem and voriconazole, which resulted in clinical improvement over several days. The skin biopsy revealed pigmented mycelial (fungal) elements, which could be consistent with a eumycetoma. A computed tomography scan of the lower extremity showed diffuse subcutaneous soft tissue edema about the right lower extremity with skin thickening. At the level of the thigh, the affected area appeared the greatest posteriorly and laterally, with marked induration/skin thickening that appeared more prominent compared to the previous MRI. This subcutaneous soft tissue swelling extends distally, where it was greatest at the lateral aspect of the knee, as well as the anterior and lateral aspects of the tibia/fibula. On exam, the site showed a non-resolving weeping pustular and nodular rash with surrounding erythema and edema extending from the thigh down to the foot.
Based on skin biopsy results, meropenem was discontinued and oral voriconazole was continued at 200 mg q12h. After 2 weeks on voriconazole, his wound had modestly improved although still had purulent drainage. Total bilirubin was noted to have elevated to 5.3 mg/dL with mildly elevated aspartate aminotransferase (AST) and a supratherapeutic voriconazole level of 12 mcg/ mL (goal 1.5–6 mcg/mL). Voriconazole dose was reduced to 200 mg daily. A repeat skin biopsy revealed necrotizing granulomas, which are usually associated with acid-fast bacilli. This prompted a deeper tissue biopsy by general surgery and culture for further evaluation. The second tissue culture grew Aspergillus and Penicillium species of fungus, and IV micafungin was added for double coverage. An MRI revealed worsening cutaneous and subcutaneous disease, without bone involvement, 8 weeks after the initiation of voriconazole and 5 days after the combination of voriconazole and micafungin. The Infectious Disease team recommended the initiation of liposomal amphotericin B (LAmB) instead of voriconazole and micafungin. After 2 weeks of treatment with LAmB, the wound showed significant clinical improvement. The minimum inhibitory concentration of Aspergillus for amphotericin B was 8 mcg/mL, for micafungin was
