|Year : 2017 | Volume
| Issue : 4 | Page : 620-622
Cladophialophora bantiana brain abscess: A report of two cases treated with voriconazole
Ram Gopalakrishnan1, Nandini Sethuraman2, R Madhumitha1, Kalpesh Sukhwani1, Nitin Bansal1, Indira Poojary3, Arunaloke Chakrabarti4
1 Department of Infectious Diseases, Apollo Hospitals, Chennai, Tamil Nadu, India
2 Department of Microbiology, Apollo Hospitals, Chennai, Tamil Nadu, India
3 Department of Microbiology, Apollo Speciality Hospitals, Chennai, Tamil Nadu, India
4 Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
|Date of Web Publication||1-Feb-2018|
Dr. Nandini Sethuraman
Department of Microbiology, Apollo Hospitals, No. 21, Greams Lane, Off Greams Road, Chennai - 600 006, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Cerebral phaeohyphomycosis is an infection caused by a number of dematiaceous fungi, characterised by the presence of melanised hyphae in the invaded tissue. Cladophialophora bantiana is the most common species affecting the humans, which has a predilection for causing the central nervous system infections resulting in high mortality. We hereby report a success story of two cases of brain abscess caused by C. bantiana who were treated with surgical source reduction and voriconazole therapy.
Keywords: Brain abscess, cerebral phaeohyphomycosis, Cladophialophora bantiana
|How to cite this article:|
Gopalakrishnan R, Sethuraman N, Madhumitha R, Sukhwani K, Bansal N, Poojary I, Chakrabarti A. Cladophialophora bantiana brain abscess: A report of two cases treated with voriconazole. Indian J Med Microbiol 2017;35:620-2
|How to cite this URL:|
Gopalakrishnan R, Sethuraman N, Madhumitha R, Sukhwani K, Bansal N, Poojary I, Chakrabarti A. Cladophialophora bantiana brain abscess: A report of two cases treated with voriconazole. Indian J Med Microbiol [serial online] 2017 [cited 2018 Oct 22];35:620-2. Available from: http://www.ijmm.org/text.asp?2017/35/4/620/224441
| ~ Introduction|| |
Brain abscess can be caused by bacteria, mycobacteria, fungi, or parasites and the reported incidence ranges from 0.4 to 0.9 cases per 100,000 population. Among fungal brain abscesses, cerebral phaeohyphomycosis is an infection caused by a number of dematiaceous fungi, characterised by the presence of melanised hyphae in the invaded tissue. Around 25 phaeoids are known to cause phaeohyphomycosis, of which Cladophialophora bantiana is the most common species affecting the central nervous system (CNS) of humans. The reason for its predilection for CNS infection by this fungus is not known.
Many recent cases have been reported from India including a series of 21 culture-proven cases, but management is not well defined and mortality rates are very high., We herein report two cases of brain abscess caused by C. bantiana who were successfully treated with surgical resection and systemic voriconazole therapy.
| ~ Case Reports|| |
Case report 1
A 69-year-old hypertensive male presented with right lower limb weakness with progressive difficulty in walking for the last 2 months. He also complained of difficulty in doing overhead activity with his right hand. He gave no history of seizures, headache or fever. Examination revealed slightly unsteady gait and reduced power in the right upper limb with pronator drift. Magnetic resonance imaging (MRI) of the brain showed a large peripherally enhancing cystic space-occupying lesion in the left posterior parietal region with peri-lesional oedema causing mass effect [Figure 1]a. Left posterior para-sagittal parietal craniotomy with drainage of abscess with partial excision of the abscess wall was done. Microscopic examination of potassium hydroxide (KOH) preparation of the pus showed septate-pigmented fungal hyphae [Figure 1]b. Histopathology showed necrotising inflammation with pigmented fungal infection. The pus aspirate was inoculated onto Sabouraud's dextrose agar (SDA) and potato dextrose agar (PDA), which were incubated both at 37°C and at 30°C. After 5 days of incubation, culture plates showed growth of olivaceous grey-to-blackish, velvety colonies with black pigmentation [Figure 1]c. A lactophenol cotton blue (LPCB) mount of the isolate showed dematiaceous septate hyphae with single-celled, smooth-walled, ellipsoid conidia in long chains in acropetal arrangement arising from undifferentiated conidiophores, suggestive of C. bantiana [Figure 1]d. Subsequently, amplification of the DNA and sequencing of internal transcribed spacer region of ribosomal DNA confirmed the identification as C. bantiana. The patient was treated with intravenous voriconazole 600 mg daily in two divided doses for 2 weeks, followed by oral voriconazole 400 mg for 3 months with therapeutic drug monitoring (TDM) maintaining trough levels >2 μg/ml. His right limb power gradually improved, and at 6-month review, he was doing well.
|Figure 1: (a) Magnetic resonance imaging of the brain of Case 1 showing a large peripherally enhancing cystic space-occupying lesion in the left posterior parietal region. (b) Potassium hydroxide mount from pus showing dematiaceous septate hyphae. (c) Sabouraud's dextrose agar plate showing colonies of Cladophialophora bantiana. (d) Lactophenol cotton blue mount showing single-celled, smooth-walled, ellipsoid conidia in long chains in acropetal arrangement arising from undifferentiated conidiophores, suggestive of Cladophialophora bantiana. (e) Computed tomography of the brain from case 2 showing a space occupying lesion in the right fronto-parietal region with peri-lesional oedema. (f) Magnetic resonance imaging of the brain from Case 2 showing a cerebral abscess in right frontal peri-ventricular white matter with peri-lesional oedema, mass effect and midline shift|
Click here to view
Case report 2
A 65-year-old male with chronic renal failure on maintenance haemodialysis for the preceding 15 months presented with progressive decline in sensorium for 7 days and one episode of generalised tonic–clonic seizures. On examination, Glasgow Coma Score (GCS) was 5 and there was left hemiparesis. Computed tomography (CT) of the brain showed a space-occupying lesion in the right fronto-parietal region with peri-lesional oedema and no midline shift [Figure 1]e. MRI of the brain was suggestive of cerebral abscess in the right frontal peri-ventricular white matter with peri-lesional oedema, mass effect and midline shift [Figure 1]f. Stereotactic aspiration of the cerebral abscess with removal of all pus and necrotic tissue was done. Pus drained showed septate and pigmented branching hyphae on KOH mount. The pus aspirate was inoculated onto SDA and PDA, which after 5 days of incubation showed growth of olivaceous grey-to-blackish, velvety colonies with LPCB morphology, suggestive of C. bantiana. He was treated with intravenous voriconazole 600 mg in two divided doses daily for 10 days. His GCS improved, but he had gait apraxia and urinary incontinence. He was then switched to oral voriconazole 400 mg daily and was discharged, with TDM to maintain trough levels >2 μg/ml. He was improving at 6-month follow-up.
| ~ Discussion|| |
C. bantiana is a dematiaceous fungus with distinct neurotropism. Cladophialophora brain abscess, though a rare disease, is not uncommon in India as the majority of cases are reported from this country. The pathogenesis of primary CNS phaeohyphomycosis is not clearly known at present. The haematogenous route is the most likely source of CNS infection, presumably from an initial sub-clinical pulmonary or cutaneous/subcutaneous focus. Inhalation or traumatic sub-cutaneous inoculation is the probable means of exposure for these environmental fungi. The common feature amongst agents of phaeohyphomycosis is the presence of melanin in their cell walls, which plays an important role in virulence. 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.,
Early diagnosis is a challenge due to the rarity and lack of specific symptoms and signs of the disease. In a recent review, it was found that the mean duration of symptoms before the diagnosis was 115 days, indicating lack of awareness and difficulty in diagnosis. Brain imaging is not characteristic for C. bantiana and the findings on CT or MRI may be similar to that of any bacterial or tuberculous abscess. Therefore, sample collection by an invasive procedure, direct microscopy and culture is considered essential for diagnosis.
There is no well-defined standard therapy for C. bantiana-causing brain abscess. In a large review reported by Revankar et al., the combination of amphotericin B, 5-FC and itraconazole was associated with improved survival; 5-FC was considered an important component of this combination regimen because of its good CNS penetration. However, lipid-based formulations of amphotericin B have not been well studied and C. bantiana has also been reported to be resistant to amphotericin B with treatment failure.,
Recently azoles have been used for the treatment of brain abscess caused by C. bantiana. Experimental studies in murine models have shown good response with newer triazoles such as posaconazole. Fluconazole crosses the blood–brain barrier well but has little activity against C. bantiana. In the largest case series, Chakrabarti et al. found that fluconazole MIC was high (range 8 to ≥64 μg/ml) and newer azoles such as voriconazole and posaconazole had good in vitro susceptibilities against C. bantiana in 13 isolates studied. Voriconazole has been successfully used in C. bantiana brain abscess.
Several factors led to good recovery of neurological status in both our patients. Surgical drainage of pus helps in the removal of necrotic tissue and better penetration of the antifungal agent. Both patients received intravenous voriconazole immediately post-operative, followed by oral administration once oral intake and absorption were ensured. TDM to maintain voriconazole trough levels above 2 μg/ml was crucial in ensuring adequate drug penetration to the abscess. The issue of sub-therapeutic blood levels, due to individual variation in the metabolism of voriconazole and drug interactions, is important while managing any patient on this drug. Prolonged therapy is possibly essential to prevent disease recurrence.
| ~ Conclusion|| |
We conclude that in the absence of comparative trials, good surgical drainage of pus and prolonged voriconazole therapy with TDM is the current treatment of choice for patients with brain abscess caused by C. bantiana.
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
Conflicts of interest
There are no conflicts of interest.
| ~ References|| |
Nicolosi A, Hauser WA, Musicco M, Kurland LT. Incidence and prognosis of brain abscess in a defined population: Olmsted County, Minnesota, 1935-1981. Neuroepidemiology 1991;10:122-31.
Revankar SG, Sutton DA, Rinaldi MG. Primary central nervous system phaeohyphomycosis: A review of 101 cases. Clin Infect Dis 2004;38:206-16.
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.
Garg N, Devi I, Vajramani G, Nagarathna S, Sampath S, Chandramouli B, et al
. Central nervous system cladosporiosis: An account of ten culture-proven cases. Neurol India 2007;55:282-8.
] [Full text]
Jacobson ES. Pathogenic roles for fungal melanins. Clin Microbiol Rev 2000;13:708-17.
Butler MJ, Day AW. Fungal melanins: A review. Can J Microbiol 1998;44:1115-36.
McGinnis MR, Pasarell L.In vitro
testing of susceptibilities of filamentous ascomycetes to voriconazole, itraconazole, and amphotericin B, with consideration of phylogenetic implications. J Clin Microbiol 1998;36:2353-5.
Al-Abdely HM, Najvar LK, Bocanegra R, Graybill JR. Antifungal therapy of experimental cerebral phaeohyphomycosis due to Cladophialophora bantiana
. Antimicrob Agents Chemother 2005;49:1701-7.
Lyons MK, Blair JE, Leslie KO. Successful treatment with voriconazole of fungal cerebral abscess due to Cladophialophora bantiana
. Clin Neurol Neurosurg 2005;107:532-4.