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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 23  |  Issue : 1  |  Page : 38-42

Fungal brain abscess: Clinical experience and review of literature


Department of Microbiology, Government Medical College, Kerala Health University, Thiruvananthapuram, Kerala, India

Date of Submission27-May-2021
Date of Decision18-Jun-2021
Date of Acceptance04-Jul-2021
Date of Web Publication16-Sep-2021

Correspondence Address:
Dr. R Jyothi
Department of Microbiology, Government Medical College, Thiruvananthapuram, Kerala
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jacm.jacm_51_21

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  Abstract 


Fungal brain abscess is an unusual but serious complication associated with immunosuppression. Two case reports of fungal brain abscess are presented here. The first case is of a young female who developed multiple Scedosporium apiospermum brain abscesses after near-drowning with the aspiration of contaminated mud and water. The second case is of a young male with a history of intravenous drug abuse who developed Cladophialophora bantiana brain abscess. C. bantiana, a dematiaceous fungus, is a rare aetiological agent of intracerebral abscesses and such infections carry high mortality due to the delay in the diagnosis and absence of standardized therapy. Both patients recovered after the removal of abscesses along with long-term antifungal treatment with amphotericin B and voriconazole.

Keywords: Brain abscess, Cladophialophora bantiana, Scedosporium apiospermum


How to cite this article:
Sidharth S, Jyothi R, Saritha N, Sahira H, Sarada Devi K L. Fungal brain abscess: Clinical experience and review of literature. J Acad Clin Microbiol 2021;23:38-42

How to cite this URL:
Sidharth S, Jyothi R, Saritha N, Sahira H, Sarada Devi K L. Fungal brain abscess: Clinical experience and review of literature. J Acad Clin Microbiol [serial online] 2021 [cited 2021 Dec 8];23:38-42. Available from: https://www.jacmjournal.org/text.asp?2021/23/1/38/326049




  Introduction Top


Fungal infections of the central nervous system (CNS) are increasingly being recognised worldwide due to the widespread use of corticosteroids, cytotoxic drugs and antibiotics. The infection is generally seen in immunocompromised patients, yet some are known to affect the immunocompetent host too. Although the involvement of the CNS in most cases occurs as a part of disseminated infection, few fungi are predominantly neurotropic.[1] Scedosporium apiospermum and Cladophialophora bantiana are rare aetiology of brain abscesses. These infections carry high mortality despite combined surgical and antifungal therapy.


  Case Reports Top


Case report 1

A 26-year-old female who is a known case of “bipolar affective disorder” was admitted following an attempted suicide by jumping into an unused well. She was resuscitated and admitted to the intensive care unit as she developed aspiration pneumonia. Endotracheal tracheal aspirate culture yielded Klebsiella pneumoniae and she was treated with piperacillin + tazobactam, metronidazole, amikacin and the symptoms subsided. On day 4, she developed fever spikes followed by right upper limb weakness for which magnetic resonance imaging (MRI) was taken which showed multiple brain abscess [Figure 1]. The antibiotics were changed to meropenem and vancomycin. The pus drained by burr hole craniotomy was sent to the microbiology laboratory for culture along with endotracheal aspirate. Direct microscopy of pus with 10% Potassium hydroxide (KOH) showed fungal elements and was presumptively informed to the clinician. The patient was started on injection Amphotericin B. The specimen was inoculated onto blood agar, chocolate agar and Sabouraud's dextrose agar (SDA) and all showed fungal growth within 48 h [Figure 2]. S. apiospermum was isolated from both brain abscess and endotracheal aspirate specimens. The treatment was changed to injection Voriconazole and fluconazole. The identification of fungus was confirmed by MALDI TOF-MS and gene sequencing was also done. Follow-up period was uneventful. Treatment was continued with oral voriconazole and oral terbinafine.
Figure 1: Magnetic resonance imaging brain with multiple abscess - Scedosporium

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Figure 2: Growth of scedosporium on blood agar

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Case report 2

Twenty-four-year-old male patient, with a history of intravenous drug abuse, admitted with distal weakness in the left side of the upper and lower limb with loosening of sandals while walking. The patient had a 20-day history of fever, associated with headache, and was started with parenteral ceftriaxone but the headache and neurological deficits continued. MRI was taken and showed lesions suggestive of Tuberculoma (right frontoparietal intracranial space-occupying lesion) [Figure 3]. Magnetic resonance (MR) spectroscopy showed a trehalose peak suggestive of the fungal lesion. Brain biopsy samples (both abscess aspirate and tissue) were received in the microbiology laboratory. Grams stain of the sample showed hyphae [Figure 4] and 10% KOH mount revealed numerous darkly pigmented septate fungal hyphae and was immediately informed to the clinician, thereby the patient was started on parenteral amphotericin B and voriconazole. Samples were inoculated onto SDA tubes at 22°C and 37°C. Growth appeared on SDA tubes by the 6th day [Figure 5] and Lactophenol cotton blue mount showed dematiaceous septate hyphae with single-celled, smooth-walled, ellipsoid conidia in long chains in acropetal arrangement arising from undifferentiated conidiophores [Figure 6] and was identified as C. bantiana. It was identified by the slide culture. The patient was started on amphotericin B and a cumulative dose of 4000 mg was achieved. Fever and headache started subsiding, and treatment was continued with oral voriconazole 200 mg twice daily and oral terbinafine 250 mg twice daily which resulted in remarkable improvement of neurological deficits.
Figure 3: Magnetic resonance imaging brain with multiple abscess - Cladophialophora bantiana

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Figure 4: Grams stain of the pus showing hyphae of Cladophialophora bantiana

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Figure 5: Sabouraud's dextrose agar tube showing growth of Cladophialophora bantiana

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Figure 6: Showing Lactophenol cotton blue mount of Cladophialophora bantiana

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  Discussion Top


Neurotropic fungi, S. apiospermum and C. bantiana are rare aetiology of brain abscess. S. apiospermum is a ubiquitous saprophytic filamentous fungus found in sewage, soil, manure, polluted water, indoor plant pots and greenhouses and causes isolated cutaneous infections, osteomyelitis, sclerokeratitis, endophthalmitis and sepsis. Scedosporium spp. is the most common mould infection in pneumonia resulting from near-drowning and uncommon in immunocompromised patients, but scedosporiosis is the most common mould infection in nearly-drowned pneumonia in non-immunocompromised hosts.[2],[3],[4] Early initiation of appropriate medication (voriconazole) is critical and early therapy discontinuation must be avoided. Surgical debridement combined with voriconazole is the appropriate treatment.[5] The overall mortality of scedosporiosis after near-drowning is approximately 74% while the prognostic factors remain largely unknown. The mortality rates are high regardless of the patient's immune status (immunocompetent or immunocompromised) or the infection type and/or location.[6] The main reason for the poor prognosis is the resistance to conventional antifungal agents, including amphotericin B and difficulty in early diagnosis. In vitro susceptibility studies have shown that S. apiospermum isolates are susceptible to miconazole, voriconazole and posaconazole, resistant to fluconazole and flucytosine, and appear to have variable susceptibility to ketoconazole, itraconazole and amphotericin B. Most successfully treated cases were reported relatively recently, and the beneficial effect of voriconazole was underlined. According to a review of cases, it is suggested that voriconazole may be used very early in cases of suspected scedosporiosis after near-drowning or even prophylactically in all near-drowned patients.[7] In some reported cases, a combination of voriconazole and terbinafine demonstrated good results, especially when an aggressive surgical debridement was required and long-term antifungal therapy was necessary.[8],[9] In this case, long-term voriconazole with terbinafine treatment gave a good result.

Brain abscess is one of the best-described syndromes produced by dark-walled fungi.[10] The disease manifests with the headache of indolent onset, low grade or no fever and development of focal neurologic signs. There is rarely a history of exposure to dust or mould, with no obvious pulmonary portal and no evidence of dissemination outside CNS. The abscess may be single or multiple, well-localised within the cerebral cortex. The multiple brain abscesses which are seen frequently also suggest its dissemination through the bloodstream. The rarely occurring cutaneous or subcutaneous infections result from its traumatic inoculation. The diagnosis of these infections requires observation of the fungi in invading tissue, recovery of the fungi in culture from an otherwise sterile site. Its growth rate is moderate and takes around 7–8 days of incubation to see visible growth. This fungus grows at both room temperature and 370°C. The colonies mature within 15 days and they show a velvety texture and olivaceous-grey to brown discolouration with a black reverse. C. bantiana has few important microscopic features which help in its identification. The fungus shows hyaline-to-brown, septate hyphae. Smooth walled, single-celled, pale olivaceous, ellipsoidal to spindle-shaped conidia of approximately (2.5–5 × 6–11) μm in size are seen. They are arranged in long, strongly coherent (non-fragile) chains and rarely show branching. Subsequently, de Hoog et al.[6] transferred it to genus Cladophialophora spp in 1995. The chains of the conidia arise directly from the hyphae. Chlamydoconidia are seen occasionally.[5] Melanin causes the hyphae and conidia to be darkly pigmented and is a virulence factor for all the pigmented moulds It is thought to confer a protective advantage by scavenging free radicals and hypochlorite that are produced by phagocytic cells in their oxidative burst and that would normally kill most organisms.[11]

This fungus can cause CNS infections in immunocompetent young individuals with no underlying risk factors for the fungal invasion.[12],[13] The infection with C. bantiana is commonly reported in transplant recipients, intravenous drug abusers or patients on steroids. The condition may be mistaken for tubercular abscess.[14] Although extracranial infection is extremely rare, the fungus has also been reported to cause cutaneous and subcutaneous phaeohyphomycosis.[12],[14]

Cerebral phaeohyphomycosis is one of the most difficult conditions to treat. The overall mortality was 65.2%, which was significantly high in immunosuppressed patients (77.1%) compared to immunocompetent hosts (56.3%). The survival was more (54.0%) in patients where complete excision was possible.[15] When left untreated, the CNS infections which are caused by C. bantiana can be fatal within 1–6 months.[16] There is no standard therapy for C. bantiana brain abscess. Recently, ESCMID and ECMM joint guidelines recommended complete excision of encapsulated abscess combined with antifungal mono or combination therapy.[17] Monotherapy is not preferred as it often results in treatment failure.[13] Although amphotericin B has antifungal activity against C. bantiana, the fungus may have innate or acquired resistance to it.[18],[19],[20] In an Indian case series, mixed results were noted with the drug. Flucytosine has antifungal activity against C. bantiana and also has excellent penetration into the cerebrospinal fluid.[13] Because of the increasing risk of resistance, it has to be used in combination with other antifungal agents. Ketoconazole, miconazole and fluconazole are not recommended.[16] In spite of having negligible activity, fluconazole has been used in some of the cases because of its low cost. Voriconazole has a fungicidal effect on C. bantiana.[5] It has good penetration into the CNS, but its minimal inhibitory concentration for C. bantiana is high. Caspofungin has poor antifungal activity against this fungus. Posaconazole and itraconazole have the best in vitro activity against C. bantiana, followed by isavuconazole. Posaconazole appears to be the promising drug against C. bantiana as it also has good penetration into the CNS.[20] However, it must be noted that the action of posaconazole against C. bantiana is static and not cidal.[21] It should be emphasised in the clinical fraternity that advanced imaging techniques including MR spectroscopy are far from being perfect in the establishment of the aetiological diagnosis. The culture and identification of the causative fungal agent are indispensable for its management. The identification of the fungus up to the species level is crucial in selecting the antifungal agent, as the choice of the antifungal agent varies with the species. The isolation of fungus from the clinical samples should always accompany correlational histopathology.


  Conclusions Top


Scedosporiosis should always be suspected in individuals who have suffered near-drowning events. Awareness as well as a high index of suspicion among the clinicians is the key to diagnose these potentially fatal neurotropic fungal infections. Although the therapy is difficult, newer azoles such as posaconazole have shown some promising results. The duration of treatment is usually determined by radiological follow-up and improvement of clinical condition. A multidisciplinary approach among neurosurgeons, infectious disease specialists and microbiologists can scale down the mortality rates due to fungal brain abscesses.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Kim SH, Ha YE, Youn JC, Park JS, Sung H, Kim MN, et al. Fatal scedosporiosis in multiple solid organ allografts transmitted from a nearly-drowned donor. Am J Transplant 2015;15:833-40.  Back to cited text no. 2
    
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Cortez KJ, Roilides E, Quiroz-Telles F, Meletiadis J, Antachopoulos C, Knudsen T, et al. Infections caused by Scedosporium spp. Clin Microbiol Rev 2008;21:157-97.  Back to cited text no. 3
    
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Katragkou A, Dotis J, Kotsiou M, Tamiolaki M, Roilides E. Scedosporium apiospermum infection after near-drowning. Mycoses 2007;50:412-21.  Back to cited text no. 7
    
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Signore SC, Dohm CP, Schütze G, Bähr M, Kermer P. Scedosporium apiospermum brain abscesses in a patient after near-drowning - a case report with 10-year follow-up and a review of the literature. Med Mycol Case Rep. 2017 Jun 10;17:17-19. doi: 10.1016/j.mmcr.2017.06.001. PMID: 28649485; PMCID: PMC5470598.  Back to cited text no. 8
    
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Troke P, Aguirrebengoa K, Arteaga C, Ellis D, Heath CH, Lutsar I, et al. Treatment of scedosporiosis with voriconazole: Clinical experience with 107 patients. Antimicrob Agents Chemother 2008;52:1743-50.  Back to cited text no. 9
    
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John Bennett, Raphael Dolin, Martin J. Blaser. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. In: Brain abscess. 8th ed. Ch. 90. Philadelphia: Elsevier, Saunders; 2015. p. 1248.  Back to cited text no. 10
    
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Jacobson ES. Pathogenic roles for fungal melanins. Clin Microbiol Rev 2000;13:708-17.  Back to cited text no. 11
    
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Revankar SG, Sutton DA, Rinaldi MG. Primary central nervous system phaeohyphomycosis: A review of 101 cases. Clin Infect Dis 2004;38:206-16.  Back to cited text no. 12
    
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Horré R, de Hoog GS. Primary cerebral infections which were caused by melanised fungi: A review. Studies in Mycology May 1999; 176-93.  Back to cited text no. 14
    
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Chakrabarti A, Kaur H, Rudramurthy SM, Appannanavar SB, Patel A, Mukherjee KK et al. Brain abscess due to Cladophialophora bantiana: A review of 124 cases. Med Mycol 2016;54:111-9.  Back to cited text no. 15
    
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Badali H, de Hoog GS, Curfs-Breuker I, Klaassen CH, Meis JF. Use of amplified fragment length polymorphism to identify 42 cladophialophora strains related to cerebral phaeohyphomycosis with in vitro antifungal susceptibility. J Clin Microbiol 2010;48:2350-6.  Back to cited text no. 20
    
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Ajantha GS, Raghavendra D. Kulkarni.Cladophialophora bantiana, the Neurotropic Fungus – A Mini Review [Internet]. 2011 November;5:1301-1306. Available from:http://www.jcdr.net//back_issues.asp?issn=0973-709x&year=2011&month=November&volume=5&issue=6&page=1301&id=1593.  Back to cited text no. 21
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]



 

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