# Pulmonary Phaeohyphomycosis Caused byPhaeoacremonium in a Kidney Transplant Recipient: Successful Treatment with Posaconazole

Authors: Saivaralaxmi Monaganti; Carlos A. Q. Santos; Andrea Markwardt; Morgan A. Pence; Daniel C. Brennan
Journal: Case Reports in Medicine
 (2014)

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## Abstract

We report a rare case of pulmonary phaeohyphomycosis in a 49-year-old woman 6 years after kidney transplantation. She presented with dyspnea, cough, and fatigue. Her chest CT scan revealed nodular opacities in the right upper lung. A fine needle aspirate biopsy culture yieldedPhaeoacremonium and surgical pathology of the biopsy showed chronic inflammation. We successfully treated her with posaconazole and managed drug interactions between posaconazole and tacrolimus. This is the second reported case of biopsy-proven pulmonary infection by Phaeoacremonium in a kidney transplant recipient and successfully treated with posaconazole.


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## Body

## 1. Background

Phaeoacremonium species are well known plant pathogens causing stunted growth and dieback of various woody hosts especially grapevines and have been isolated from necrotic woody tissue of Prunus species [1, 2].Phaeoacremonium species are dematiaceous fungi characterized by the presence of melanin or melanin-like pigments and are widely distributed in the environment particularly in soil, wood, and decomposing plant debris. Phaeohyphomycosis is a collective term for cutaneous, subcutaneous, and systemic disease caused by dematiaceous fungi. Pulmonary phaeohyphomycosis is a rare opportunistic infection of immunocompromised hosts. A review of 34 cases of dematiaceous fungal infections in organ transplant recipients revealed an overall mortality of 57% among patients with systemic disease and 7% among those with skin, soft-tissue, or joint infections [3].This is only the second case of biopsy-proven pulmonary infection byPhaeoacremonium in a kidney transplant recipient and the first report of successful treatment with posaconazole. Moreover, management of drug interactions between posaconazole and tacrolimus was successfully done, thereby preventing supratherapeutic levels of tacrolimus and avoiding kidney injury.


## 2. Case Report

A 49-year-old Caucasian female who underwent a living related kidney transplant 6 years before presented with progressive dyspnea, cough, and fatigue over 6 months that failed to improve after the administration of several antibiotic courses. She had been on tacrolimus and prednisone for maintenance immunosuppression. She lived in a rural area, had exposure to chicken sheds and barns, and was a gardener. A chest CT scan revealed nodular opacities in the right upper lobe (Figure1(a)), and she underwent bronchoscopy with bronchoalveolar lavage and transbronchial fine needle aspiration biopsy of the right upper lobe nodules.(a) Chest CT scan before starting posaconazole showing reticulonodular opacities in the right upper lobe. (b) CT scan one month after starting posaconazole showing resolution of most of the opacities.
(a)
(b)Phaeoacremoniumspecies grew from the biopsy culture within four days of incubation. Identification was assigned based on macroscopic and microscopic morphology. Initially, the surface of the mold was olive in color, becoming greyish-black upon subculture. The texture was velvety, and the reverse was black. Microscopically, pigmented hyphae with tapering, funnel-shaped phialides were observed, and conidia were hyaline and oblong, forming clusters at the tip of the phialides. Macroscopic and microscopic morphology was consistent withPhaeoacremonium species. Surgical pathology of the biopsy showed chronic inflammation but no fungal hyphae. Culture for acid fast bacilli from the biopsy specimen was negative for mycobacteria. Culture of bronchial fluid yieldedDactylaria constricta and fewMycobacterium avium-intracellulare complex.Given that her biopsy culture yieldedPhaeoacremonium and showed chronic inflammation, we started oral posaconazole 200 mg QID and reduced her tacrolimus dose from 2 mg BID to 1 mg Q day. A repeat chest CT scan one month after the institution of antifungal therapy showed improvement (Figure 1(b)), and she reported reduced cough and shortness of breath. Two months after commencing treatment, we changed her posaconazole dose to 400 mg BID for greater ease of administration. She received posaconazole for 4 months and her symptoms resolved (Figure 2).Figure 2
Graph showing serum creatinine and blood tacrolimus levels before, during, and after posaconazole treatment with tacrolimus dose adjustments.


## 3. Discussion

To et al. reported the first case of biopsy-provenPhaeoacremonium parasiticum lung infection in a kidney transplant recipient. In contrast to our case, the patient was severely immunocompromised due to chemotherapy for posttransplant lymphoproliferative disease. He showed initial improvement with voriconazole and caspofungin but succumbed after a prolonged period of neutropenic fever. Shah et al. described a case of probablePhaeoacremonium lung infection in a lung transplant recipient. The patient developed cavitary lung nodules in the native lung a few months after single lung transplantation. Biopsy of one of the nodules showed chronic inflammation with possible granulomatous lesions.Phaeoacremonium parasiticum grew only from the bronchoalveolar lavage culture but not from the biopsy culture. The patient improved after the administration of voriconazole and caspofungin [21, 26].Phaeoacremonium species are typically isolated from thorns, wood, and soil. Human infection can be caused by traumatic implantation or occurs in the setting of immunocompromising conditions. Twenty-seven cases of human infections withPhaeoacremonium species have been reported in the literature. In immunocompetent hosts,Phaeoacremonium has been reported to cause subcutaneous phaeohyphomycosis, osteomyelitis, endophthalmitis, and onychomycosis. Successful outcomes have been achieved with debridement and antifungals (Table 1). In immunocompromised patients,Phaeoacremonium causes more severe disease and has been reported to cause endocarditis, brain abscesses, cavitary lung nodules, and disseminated infections. Disseminated infections in severely immunocompromised hosts are associated with poor outcomes and death (Table 2).Table 1
Skin and subcutaneous infection, osteomyelitis, endophthalmitis, and onychomycosis due toPhaeoacremoniumspecies.
Number
Reference
Species
Age/sex
Underlying condition
Clinical disease
Treatment
Outcome
1
Padhye et al., 1998 [4]
P. inflatipes
83/F
None
Subcutaneous infection of the foot
Excision
Complete healing
2
Matsui et al., 1999 [5]
P. rubrigenum
61/F
Rheumatoid arthritis
Subcutaneous mass of the foot
ExcisionItraconazoleFluconazole
Recurred
3
Kitamura et al., 2000 [6]
P. parasiticum
59/F
None
Subcutaneous nodule below the knee
Excision
Complete healing
4
Guarro et al., 2003 [7]
P. aleophilum
19/M
None
Fistulized nodule on the ankle
Excision (six times)Itraconazole
Cured
5
Guarro et al., 2003 [7]
P. rubrigenum
55/M
Renal transplant
Multiple nodules of ankle and foot
ExcisionItraconazoleTerbinafineFluconazole
Not resolved
6
Llinas et al., 2005 [8]
Phaeoacremoniumspecies
54/F
Myelodysplastic syndrome, IgA deficiency
Olecranon bursitis
ExcisionItraconazole
Resolved
7
Baddley et al., 2006.[9]
P. parasiticum
40/M
Cardiac transplant
Multiple skin lesions
Amphotericin B, ItraconazoleDebridement
Died
8
Hemashettar et al., 2006 [10]
P. krajdenii
41/M
None
Mycetoma
ItraconazoleDebridement
Recurred
9
Marques et al., 2006 [11]
P. parasiticum
49/M
Renal transplant
Draining cystic tumors on the foot
ItraconazoleAmphotericin B
Improved
10
Huynh et al., 2007 [12]
P. parasiticum
19/M
Penetrating globe injury
Endophthalmitis
Amphotericin BVoriconazole
Improved
11
Farina et al., 2007 [13]
P. parasiticum
41/M
Kidney transplant
Subcutaneous nodule on the forefinger
Excision
Resolved
12
Baradkar et al., 2009 [14]
P. parasiticum
26/F
None
Subcutaneous abscess on the forearm
Debridement Amphotericin B Itraconazole
Resolved
13
Sun et al., 2011 [15]
P. parasiticum
55/M
None
Onychomycosis
Diseased nail was trimmed offTopical sulconazole
Cured
14
Aguilar et al., 2011.[16]
P. parasiticum
52/F
Type 2 diabetes hypothyroidism.
Eumycetoma
Surgery (multiple times), Itraconazole
Improved
15
Baradkar et al., 2011 [17]
P. infalitipes
30/M
None
Subcutaneous mass of the foot
Debridement, Amphotericin B, Itraconazole
Cured
16
Choi et al., 2011 [18]
Phaeoacremoniumspecies
54/M
Renal transplant
Subcutaneous mass on the third finger
Excision
Resolved
17
Mazzurco et al., 2012 [19]
Phaeoacremoniumspecies
74/M
Rheumatoid arthritis, on infliximab
Nodule on the leg
ExcisionItraconazole
Resolved
18
Furudate et al., 2012 [20]
P. rubrigenum
76/F
Still's disease, on prednisolone
Subcutaneous nodules on the  leg
Debridement, Itraconazole
Resolved
19
To et al., 2012 [21]
P. parasiticum
69/M
Diabetes mellitus
Right knee Pain and swelling
Arthrotomy and drainage, Itraconazole, total knee replacement
Improved
20
Guarro et al., 2006 [22]
P. venezuelense
28/M
Chronic myeloid leukemia
Subcutaneous mycoses
Surgical excision
Not knownTable 2
Invasive and disseminated infections due toPhaeoacremoniumspecies.
Number
Reference
Species
Age/sex
Underlying condition
Clinical disease
Treatment
Outcome
21
Heath et al., 1997 [23]
P. parasiticum
45/M
Liver transplant
Infective endocarditis, fungemia,  and skin lesion
Amphotericin B, fluconazole
Died
22
Wang et al., 2005 [24]
P. inflatipes
18- month boy
Aplastic anemia
Fungemia
Amphotericin B
Died
23
Baddley et al., 2006 [9]
P. parasiticum
31/F
Aplastic anemia
Fungemia, skin lesions
Amphotericin B
Died
24
McNeil et al., 2011 [25]
P. parasiticum
24/M
Chronic granulomatous disease, end-stage kidney disease
Brain abscess
Amphotericin B, voriconazole, caspofungin
Died
25
To et al., 2012 [21]
P. parasiticum
26/M
Renal transplant
Cavitary lesion of lung
Voriconazole  Caspofungin
Responded, but died
26
Shah et al., 2013 [26]
P. parasiticum
74/M
Lung transplant
Lung nodules of native lung
Caspofungin Voriconazole
Improved
27
Larbcharoensub et al., 2013 [27]
Scedosporium apiospermumandP. parasiticum
49 y/o
Renal transplant
Multiple brain abscesses
Voriconazole
Improved
28
Present case
Phaeoacremoniumspecies
49/F
Renal transplant
Lung nodules
Posaconazole
ImprovedThe other dematiaceous fungus isolated from this patient wasDactylaria constricta. It grew only from culture of bronchial fluid and not from the biopsy.Mycobacterium avium-intracellulare complex (MAC) also grew only from the culture of bronchial fluid. Given our patient’s exposure history (gardening, exposure to sheds and barns) and no growth of these organisms from the biopsy specimen, it is likely that these organisms were merely colonizers of her respiratory tract and not pathogens. Moreover, resolution of her illness without treatment for MAC suggests that it was not a pathogen.There is no standard antifungal regimen described forPhaeoacremonium in the literature. Posaconazole is the most recently approved triazole with an extended spectrum of activity against a wide variety of fungi. Posaconazole was chosen over other azoles because it is well tolerated and has a favorable side effect profile and a low potential of drug interactions compared to other azoles. Posaconazole inhibits the metabolism of calcineurin inhibitors. Failure to adjust tacrolimus dosing can result in supratherapeutic levels of tacrolimus and harm the kidney [28]. Our patient responded well to the treatment with no relapse of infection during 4 years of follow-up. Her kidney allograft continues to function well, with creatinine levels ranging between 1 and 1.3 mg/dL.



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