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F1000Research 2014, 3:70 Last updated: 25 DEC 2016 CASE REPORT Antifungal therapy and surgical drainage for the treatment of a cerebral abscess caused by Scedosporium apiospermum in a renal transplant patient - a case report [version 1; referees: 1 approved, 1 approved with reservations] Maria Isabel Garzón, Claudio Abiega, Abel H. Zarate, Pablo E. Sanchez, Marcela F. Medeot, Carlos Chiurchiu, Jorge de La Fuente, Juan Pablo Caeiro Department of Medicine, Hospidal Privado de Córdoba S.A., Córdoba, X5002IRA, Argentina v1 First published: 13 Mar 2014, 3:70 (doi: 10.12688/f1000research.3535.1) Latest published: 13 Mar 2014, 3:70 (doi: 10.12688/f1000research.3535.1) Abstract Scedosporium apiospermum, the asexual form of 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 S. apiospermum. The patient received a combined therapy of voriconazole and terbinafine with surgical drainage, which led to temporarily clinical and radiological improvement. Open Peer Review Referee Status: Invited Referees 1 2 report report version 1 published 13 Mar 2014 1 Corrado Girmenia, Sapienza University of Rome Italy 2 Emmanuel Roilides, Aristotle University of Thessaloniki Greece Discuss this article Comments (0) Corresponding author: Juan Pablo Caeiro ([email protected]) How to cite this article: Garzón MI, Abiega C, Zarate AH et al. Antifungal therapy and surgical drainage for the treatment of a cerebral abscess caused by Scedosporium apiospermum in a renal transplant patient - a case report [version 1; referees: 1 approved, 1 approved with reservations] F1000Research 2014, 3:70 (doi: 10.12688/f1000research.3535.1) Copyright: © 2014 Garzón MI et al. This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Data associated with the article are available under the terms of the Creative Commons Zero "No rights reserved" data waiver (CC0 1.0 Public domain dedication). Grant information: The author(s) declared that no grants were involved in supporting this work. Competing interests: No competing interests were disclosed. First published: 13 Mar 2014, 3:70 (doi: 10.12688/f1000research.3535.1) F1000Research Page 1 of 6 F1000Research 2014, 3:70 Last updated: 25 DEC 2016 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 water1. The infection may be acquired by inhaling the microorganism or after traumatic inoculation through the skin2. 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 healthy4 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 reported5. Brain abscesses may be found as one or multiple lesions6. 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 species8. 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 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. 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. Figure 2. Microscopic examination of S. apiospermum (from culture). Methylene blue staining showing the morphology of S. apiospermum: unicellular microconidia attached to filaments by conidiophores (original magnification 400×). 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. 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 14th day. Page 2 of 6 F1000Research 2014, 3:70 Last updated: 25 DEC 2016 Discussion Solid organ transplant recipients are highly susceptible to invasive fungal infections9. 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 CNS10. Solid organ transplant patients are susceptible to invasive fungal infections as their immunity might be compromised due to the use of immunosuppressant drugs11. Therefore S. apiospermum should be considered in the differential diagnosis of immunocompromised patients presenting with a brain abscess12. 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 deficits13. 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 findings14. 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 resistant15. In addition, PCR techniques are important to diagnose as well as to distinguish between different species16. 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. apiospermum17. Several reports have shown the successful use of voriconazole synergistically combined with terbinafine against S. apiospermum18 and S. prolificans. Furthermore, many authors recommend the surgical drainage of brain abscesses caused by S. apiospermum19. Therefore, a combined antifungal therapy along with an aggressive surgical approach is recommended for therapeutic success20. 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. Consent Written informed consent for publication of clinical details and clinical images was obtained from the patient’s family. Author contributions MIG, PES and JPC contributed to the design of the study. All the authors contributed to writing the manuscript and agreed to the final contents. Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. References 1. Harun A, Gilgado F, Chen SC, et al.: Abundance of Pseudallescheria/ Scedosporium species in the Australian urban environment suggests a possible source for scedosporiosis including the colonization of airways in cystic fibrosis. Med Mycol. 2010; 48(Suppl 1): S70–S76. PubMed Abstract | Publisher Full Text 512–516. PubMed Abstract | Publisher Full Text 7. Kantarcioglu AS, Guarro J, De Hoog GS: Central nervous system infections by members of the Pseudallescheria boydii species complex in healthy and immunocompromised hosts: epidemiology, clinical characteristics and outcome. Mycoses. 2008; 51(4): 275–290. PubMed Abstract | Publisher Full Text 2. de Hoog GS, Marvin-Sikkema FD, Lahpoor GA, et al.: Ecology and physiology of the emerging opportunistic fungi Pseudallescheria boydii and Scedosporium prolificans. Mycoses. 1994; 37(3–4): 71–78. PubMed Abstract | Publisher Full Text 8. 3. Troke P, Aguirrebengoa K, Arteaga C, et al.: Treatment of scedosporiosis with voriconazole: clinical experience with 107 patients. Antimicrob Agents Chemother. 2008; 52(5): 1743–1750. PubMed Abstract | Publisher Full Text | Free Full Text Shoham S: Emerging fungal infections in solid organ transplant recipients. Infect Dis Clin North Am. 2013; 27(2): 305–16. PubMed Abstract | Publisher Full Text | Free Full Text 9. Wilson HL, Kennedy KJ: Scedosporium apiospermum brain abscesses in an immunocompetent man with silicosis. Med Mycol Case Rep. 2013; 2: 75–8. PubMed Abstract | Publisher Full Text | Free Full Text Pappas PG, Alexander BD, Andes DR, et al.: Invasive fungal infections among organ transplant recipients: results of the Transplant-Associated Infection Surveillance Network (TRANSNET). Clin Infect Dis. 2010; 50(8): 1101–1111. PubMed Abstract | Publisher Full Text 10. Cortez KJ, Roilides E, Quiroz-Telles F, et al.: Infections caused by Scedosporium spp. Clin Microbiol Rev. 2008; 21(1): 157–97. PubMed Abstract | Publisher Full Text | Free Full Text Kubak BM, Huprikar SS; the ASTIDCoP: Emerging & rare fungal infections in solid organ transplant recipients. Am J Transplant. 2009; 9(Suppl 4): S208–S226. PubMed Abstract | Publisher Full Text 11. Castiglioni B, Sutton DA, Rinaldi MG, et al.: Pseudallescheria boydii (Anamorph Scedosporium apiospermum). Infection in solid organ transplant recipients in a tertiary medical center and review of the literature. Medicine (Baltimore). 2002; 81(5): 333–348. PubMed Abstract 4. 5. 6. Leechawengwongs M, Milindankura S, Liengudom A, et al.: Multiple Scedosporium apiospermum brain abscesses after near-drowning successfully treated with surgery and long-term voriconazole: a case report. Mycoses. 2007; 50(6): Page 3 of 6 F1000Research 2014, 3:70 Last updated: 25 DEC 2016 12. 13. 14. Husain S, Muñoz P, Forrest G, et al.: Infections due to Scedosporium apiospermum and Scedosporium prolificans in transplant recipients: clinical characteristics and impact of antifungal agent therapy on outcome. Clin Infect Dis. 2005; 40(1): 89–99. PubMed Abstract | Publisher Full Text Berenguer J, Diaz-Mediavilla J, Urra D, et al.: Central nervous system infection caused by Pseudallescheria boydii: case report and review. Rev Infect Dis. 1989; 11(6): 890–896. 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Schaenman JM, DiGiulio DB, Mirels LF, et al.: Scedosporium apiospermum soft tissue infection successfully treated with voriconazole: potential pitfalls in the transition from intravenous to oral therapy. J Clin Microbiol. 2005; 43(2): 973–977. PubMed Abstract | Publisher Full Text | Free Full Text 18. Morio F, Horeau-Langlard D, Gay-Andrieu F, et al.: Disseminated Scedosporium/ Pseudallescheria infection after double-lung transplantation in patients with cystic fibrosis. J Clin Microbiol. 2010; 48(5): 1978–1982. PubMed Abstract | Publisher Full Text | Free Full Text 19. Nesky MA, McDougal EC, Peacock JE Jr: Pseudallescheria boydii brain abscess successfully treated with voriconazole and surgical drainage: case report and literature review of central nervous system pseudallescheriasis. Clin Infect Dis. 2000; 31(3): 673–677. PubMed Abstract | Publisher Full Text 20. Gosbell IB, Toumasatos V, Yong J, et al.: Cure of orthopaedic infection with Scedosporium prolificans, using voriconazole plus terbinafine, without the need for radical surgery. Mycoses. 2003; 46(5–6): 233–236. PubMed Abstract | Publisher Full Text Page 4 of 6 F1000Research 2014, 3:70 Last updated: 25 DEC 2016 Open Peer Review Current Referee Status: Version 1 Referee Report 02 July 2015 doi:10.5256/f1000research.3786.r4590 Emmanuel Roilides Department 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: 1. Have the authors performed an antifungal susceptibility testing? In addition, any molecular identification? It is apiospermum complex now. 2. 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 et al. Clin Microbiol Infect. 2014 Apr;20 Suppl 3:27-46. 3. 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. Competing Interests: No competing interests were disclosed. Referee Report 03 June 2014 doi:10.5256/f1000research.3786.r4093 Corrado Girmenia Department of Hematology, Sapienza University of Rome, Rome, Italy This is an interesting case report of an unusual fungal infection in an immunocompromised patient. The metodology in the diagnostic approach and the description of the case are both adequate. 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. Competing Interests: No competing interests were disclosed. F1000Research Page 5 of 6 F1000Research 2014, 3:70 Last updated: 25 DEC 2016 F1000Research Page 6 of 6