Antifungal therapy and surgical drainage for the treatment of a cerebral abscess caused by in a Scedosporium apiospermum renal transplant patient-a case report

the asexual form of , Scedosporium apiospermum, Pseudallescheria boydii is a filamentous, opportunistic fungus which can be found in environmental sources all over the world. It is a human pathogen mostly associated with lung, bone and joint infections and less frequently with infections of the central nervous system (CNS). The latter is generally related to the patient’s immune state, and occurs most frequently in immunocompromised patients. We present the case of a 64-year-old male patient with a background of chronic kidney failure secondary to nephroangiosclerosis and a renal transplantation who presented with left-sided hemiplegia and dysarthria. A brain MRI revealed a hyperintense lesion with ring enhancement at the right paramedian posterior frontal subcortical area with an associated vasogenic edema. A stereotactic biopsy of the lesion revealed the presence of . The patient received a S. apiospermum combined therapy of voriconazole and terbinafine with surgical drainage, which led to temporarily clinical and radiological improvement.


Introduction
Scedosporium apiospermum is a filamentous fungus causing a rare but serious opportunistic infection.It is the asexual form of Pseudallescheria boydii and is found in many environmental sources including soil and fresh water, but most commonly in stagnant or contaminated water 1 .The infection may be acquired by inhaling the microorganism or after traumatic inoculation through the skin 2 .The sites of infection include the lungs, sinuses, bones, skin, joints and notoriously, the central nervous system (CNS) 3 .S. apiospermum can infect the CNS of both healthy 4 and immunocompromised hosts.Cerebral abscess is the most common clinical manifestation of S. apiospermum brain infections, although cases of meningitis and, less frequently, ventriculitis have also been reported 5 .Brain abscesses may be found as one or multiple lesions 6 .The overall mortality rate of patients infected with this pathogen is higher than 70% 7 .Solid organ transplant and its associated immunosuppression are important risk factors for infections with Scedosporium species 8 .Here we present a case of CNS infection caused by S. apiospermum in a patient who had received a kidney transplant and was treated with dual antifungal therapy and surgical drainage.The patient initially responded well to the therapy.

Clinical case
A 64 year-old male patient underwent deceased-donor kidney transplantation following a chronic kidney failure secondary to nephroangiosclerosis.The past medical history was significant for hypertension, hyperlipidemia, peripheral vascular disease, chronic anemia and deep venous thrombosis of right lower extremity.Family history was significant for cardiomyopathy in one brother and diabetes in another.The immunosuppressive medication consisted of tacrolimus 3 mg every 12 hours, prednisone 20 mg daily and mycophenolate mofetil 500 mg every 12 hours.Seventeen days after transplantation, he presented left-sided hemiplegia and dysarthria.A brain MRI was performed, which revealed a hyperintense lesion with ring enhancement at the right paramedian posterior frontal subcortical area with an associated vasogenic edema (Figure 1).
A stereotactic biopsy was performed and tissue examination revealed the presence of a filamentous fungus that was identified as S. apiospermum (Figure 2).The sample was also cultured in Sabouraud's dextrose agar medium at 25°C for a period of 14 days (Figure 3), the culture turned a dark brown color.
The patient started a treatment with voriconazole (6 mg/Kg po q12h for two days, then 4 mg/Kg q12h VO) and terbinafine (250 mg po daily) and subsequently was subjected to surgical drainage by craniotomy in order to remove the infected tissue.
The patient was on terbinafine for 4 months and continued to be on voriconazole for almost a year.At a follow up visit he showed significant recovery from the left-sided palsy and also an absence of dysarthria.The brain MRI follow-up images showed an improvement in the brain lesion.
Unfortunately, 8 months later the patient clinical course was complicated and he eventually died of problems unrelated to fungal CNS disease.

Discussion
Solid organ transplant recipients are highly susceptible to invasive fungal infections 9 .
During the last few decades there has been a marked increase in the number of immunocompromised patients who have suffered Scedosporium infections, the most frequent cases being infections of the CNS 10 .
Solid organ transplant patients are susceptible to invasive fungal infections as their immunity might be compromised due to the use of immunosuppressant drugs 11 .Therefore S. apiospermum should be considered in the differential diagnosis of immunocompromised patients presenting with a brain abscess 12 .Within the nervous system, abscesses may be located in brain hemispheres, the cerebellum, the brain stem or the spinal cord, where they may cause alterations of consciousness levels, signs of meningeal irritation or focal neurological deficits 13 .
If not adequately treated, fungal brain abscesses in immunocompromised patients often result in poor prognosis.The diagnosis of an invasive fungal infection such as S. apiospermum is based on the combination of histopathological, microbiological and clinical findings 14 .As the clinical and histopathological presentations of S. apiospermum infections are similar to those of other fungi such as Aspergillus and Fusarium spp., a culture is necessary for accurate diagnosis.Furthermore, while most species of Aspergillus (except for Aspergillus terreus) are sensitive to amphotericin, S. apiospermum is usually resistant 15 .In addition, PCR techniques are important to diagnose as well as to distinguish between different species 16 .
There are many treatment options described in the literature, but there is an ongoing controversy over which treatment is most suitable for S. apiospermum infections.Voriconazole has emerged as a possible treatment option, since it shows high activity against several species of fungi, including S. apiospermum 17 .Several reports have shown the successful use of voriconazole synergistically combined with terbinafine against S. apiospermum 18 and S. prolificans.Furthermore, many authors recommend the surgical drainage of brain abscesses caused by S. apiospermum 19 .Therefore, a combined antifungal therapy along with an aggressive surgical approach is recommended for therapeutic success 20 .

Conclusion
S. apiospermum infection of the CNS is a rare but it is an extremely serious medical condition.Immediate diagnosis in the event of brain abscess in an immunocompromised patient is crucial and the choice of a suitable medical treatment is a priority.Despite the aggressive surgical treatment and the appropriate anti-fungal therapy used, mortality rates continue to be high.

Open Peer Review
Current Referee Status: No competing interests were disclosed.Competing Interests:

Figure 3 .
Figure 3. S. apiospermum culture in Sabouraud's dextrose agar medium.The culture grew in Sabouraud's dextrose agar medium at 25°C and turned a dark brown color on the 14 th day.

Figure 1 .
Figure 1.Brain MRI T2-weighted image.A hyperintense lesion with ring enhancement at the right paramedian posterior frontal subcortical area with an associated vasogenic edema is shown.
of Pediatrics, Aristotle University of Thessaloniki, Thessaloniki, Greece This is an interesting rare case of brain abscess due to Scedosporium apiospermum in a kidney transplant immunocompromised patient, indeed relatively early (17 days) post-transplantation.The report reads nicely and the Discussion is thoughtful.However, there are a few points that the authors should take into consideration:Have the authors performed an antifungal susceptibility testing?In addition, any molecular identification?It is apiospermum complex now.Please, add ESCMID Guidelines for rare fungi as a reference.This is a document that should be definitely cited and used in clinical practice.Tortorano AM Clin Microbiol Infect.2014 Apr;20 et al.Suppl 3:27-46.Page 2. VO should be po I have read this submission.I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.