Brain abscess in renal transplant recipients: Report of three cases

Amongst the infections in kidney transplant recipients, brain abscess represents an uncommon life-threatening complication. Mortality continues to be high despite improvements in diagnostics and therapeutics.

We conducted an observational study, describing the incidence, presentation, implicating pathogen, management and outcome of brain abscess following kidney transplantation at our centre.

Amongst the 1492 patients who underwent kidney transplantation at our centre between June 1991 and January 2023 (cumulative follow-up: 4936 patient-years), five females and four males, developed brain abscesses. The incidence proportion (risk) is 0.6% with an incidence rate of 6.03 cases per 1000 patient years. The median duration from transplant to development of brain abscess was 5 weeks (range: 4 weeks to 9 years). The commonest presentation was a headache. A definitive microbiological diagnosis was established in eight out of nine patients. The commonest implicated organism was a dematiaceous fungus, Cladophialophora bantiana (3 patients, 33.3%). Despite the reduction in immunosuppression, surgical evacuation and optimal medical therapy, five (55.55%) patients succumbed to their illness.

Brain abscesses following kidney transplantation is an uncommon, life-threatening condition. It usually occurs in the early post-transplant period and the presentation is often subtle. Unlike immunocompetent individuals, a fungus is the most common causative organism in those with solid organ transplants. The management includes a reduction in immunosuppression, early antimicrobial therapy, and surgical decompression.

Although rare, both Cladophialophora bantiana (C. bantiana) and Toxoplasma gondii have been known to be associated with brain abscess in renal transplant recipients (RTRs), however co-infection has never been reported till date. In the present case, 40 years old renal transplant recipient on curtailed immunosuppressive therapy presented with progressive headache and altered sensorium. The computed tomography of head showed multiple ring-enhancing discrete lesions in the left frontal lobe, with moderate perilesional oedema. Left frontal craniotomy and aspiration revealed thick yellowish brown pus, which on culture showed the growth of dematiaceous fungal hyphae “C. bantiana” and co-infection with “Toxoplasma” was confirmed by PCR as well as serology (both IgM and IgG – Toxoplasma) positivity. Stereotactic aspiration/open craniotomy and drainage is imperative to arrive at microbiological diagnosis and provide timely therapy to the patient.

The epidemiology of invasive fungal infections in immunocompromised patients is rapidly changing. Several of the fungi have worldwide distribution. However, some have specific geographical distribution. Sinocranial aspergillosis, mostly described from countries with temperate climates, occurs mostly in otherwise immunocompetent individuals Most of the systemic fungal pathogens have been associated with central nervous system (CNS) involvement. The major advances in CNS fungal infections are in the pathobiology, new diagnostic tools, and new therapies. In spite of these developments, there is still considerable delay in the diagnosis of CNS fungal infection. CNS fungal infections are associated with considerable morbidity and mortality. To achieve good outcomes early diagnosis and early institution of appropriate therapies are the key issues.

Cerebral phaeohyphomycosis is a fungal infection of the brain typically caused by Cladophialophora bantiana, Exophiala dermatitidis, and Rhinocladiella mackenziei, all of which belong to the order Chaetothyriales. The disease results in black, necrotic brain tissue, black pus, and black cerebrospinal fluid. Pathogens usually reach the brain through the bloodstream or lymphatic fluid and occasionally through direct spreading or accidental inoculation. Patients can present with hemiparesis, tonic spasm, headache, fever, sensory variation, cerebral irritation, and even psychotic behavioural changes. Radiological images are characterised by ring-enhanced signs and hyperdense and hypodense lesions. Pathological features frequently include black-to-brown necrotic tissue or dark-coloured pus, granulomatous inflammation, giant cell vasculitis, and pigmented fungal elements, which are easily seen on a direct potassium hydroxide smear, a rapid method for diagnosis. Black fungi can be cultured from a biopsy specimen. Combined antifungal chemotherapy, surgical debridement, and careful immunological interventions are strongly recommended to eradicate these intractable infections.

Nocardia species est une bactérie aérobie tellurique, à l’origine d’infections opportunistes, principalement pulmonaires chez l’homme. Elle rend compte de 1 à 2 % des abcès cérébraux. L’abcès cérébral à Nocardia se distingue par son mauvais pronostic.

Nous en rapportons cinq observations cliniques et, à la lumière des données de la littérature, cherchons à établir les éventuelles caractéristiques radiocliniques des abcès cérébraux à Nocardia et en déterminer la prise en charge optimale.

Le mode de révélation clinique est souvent insidieux, sur un terrain d’immunodépression sous-jacent patente ou latente, l’hyperthermie n’est pas systématique. L’aspect radiologique est celui d’une lésion à centre nécrotique, en cocarde, à coque épaisse polylobée, unique ou multiple. La réalisation première de prélèvements par biopsie ou énucléation chirurgicale, puis l’instauration d’une antibiothérapie adaptée parentérale conditionnent le pronostic.

Nocardia species is an aerobic soil-saprophyte bacterium, responsible for rare opportunistic infections, mainly reported in immunocompromised patients. Nocardia brain abscess accounts for 1 to 2% of cerebral abscesses. Prognosis is poor.

We describe clinical, radiological and bacteriological findings along with therapeutic aspects for five patients and review the literature on Nocardia cerebral abscess.

The clinical features of Nocardia brain abscess are insidious and nonspecific, occurring frequently with a medical background of obvious or latent immunodeficiency; fever, if any, is observed subordinate to extracerebral nocardiosis. Computerized tomography scan and conventional magnetic resonance (MR) scan show lesions with a necrotic core and multilobed thick walls enhancing after injection of gadolinium or iodine. Abscesses are mainly located in the brain stem, basal ganglia and cerebral cortex of the frontal, parietal and occipital lobes; cerebellar and spinal locations are uncommon. MR diffusion-weighted imaging with calculation of apparent diffusion coefficient and proton MR spectroscopy can provide additional data for accurate differential diagnosis between abscess and other necrotic lesions, such as tumor and cyst formations. Bacteriological identification has progressed with advances in molecular microbiology: 16S rRNA sequencing, allowing a more rapid routine identification of Nocardia strains from clinical samples. Clinical management of patients with a Nocardia brain abscess relies upon early use of intravenous antibiotics adapted to the strains identified and their susceptibility. Most Nocardia strains display susceptibility to cotrimoxazol, amikacin and linezolid, but develop β-lactamase activity.

Early pus samples, obtained by biopsy or surgical resection, are needed to establish a certain bacteriological diagnosis and initiate appropriate intravenous antibiotics.