Nocardia farcinica masquerading as intracerebral metastases in advanced metastatic prostatic cancer

Abstract

A 67-year-old man with metastatic prostate cancer and underlying asymptomatic pancytopenia presented with a 1-week history of general malaise, left leg weakness and facial numbness. Initial brain imaging demonstrated two rim-enhancing lesions felt to represent intracerebral metastasis. Following neurosurgical referral, a multidisciplinary meeting decision was made for best supportive care and dexamethasone was given. He developed multiple cutaneous lesions, which on incision and drainage revealed Nocardia farcinica. Repeat brain imaging showed enlargement of the existing cavitating lesions and appearance of new lesions, now typical of cerebral abscesses. A diagnosis of disseminated nocardiosis with cutaneous and intracerebral infection was reached. He started taking empirical treatment with intravenous meropenem, co-trimoxazole and subsequent addition of amikacin, with little improvement. On further review of sensitivities, moxifloxacin was added. Following over 1 month of antimicrobial treatment, his neurological symptoms, cutaneous lesions and repeat MRI of the brain had improved.

Background

Nocardia are aerobic, Gram-positive bacilli which can be found extensively throughout the world in soil, decomposing vegetation and water. Nocardia can present as an opportunistic infection, either localised or disseminated nocardiosis, affecting two or more organs.^{1 2} Although up to one-third of nocardiosis infection occurs in immunocompetent individuals, it most commonly affects those with compromised cell-mediated immunity receiving immunosuppressive therapy including corticosteroids, organ transplant recipients, lymphoma patients and HIV carriers.³

Previous reviews have suggested that pulmonary nocardiosis is the most common presentation of Nocardia infection, with extrapulmonary infection usually presenting with abscess formation following haematological spread, often in the central nervous system (CNS).^{2 4 5} Primary cutaneous or subcutaneous nocardiosis can occur secondary to contamination with soil following skin breakdown or injury and can also affect immunocompetent individuals.²

This case discusses disseminated nocardiosis with cutaneous and CNS involvement in a patient with advanced metastatic prostate cancer not on systemic anticancer therapy or immunosuppression at the time of presentation. It also highlights the difficulties faced in reaching an accurate diagnosis, as well as the challenges regarding antibiotic choice in the presence of pre-existing pancytopenia.

Case presentation

A 67-year-old man with a background of metastatic prostate cancer presented with a history of general malaise, left leg weakness and facial numbness developing over a 1-week period. He was initially diagnosed in 2006 with a T2N0M1 adenocarcinoma of the prostate, Gleason 9 (4+5) in 6/6 cores. Investigations showed disease progression with extensive spinal and bony metastases despite receiving multiple lines of treatment in the subsequent 10 years after his initial diagnosis, including luteinising hormone-releasing hormone analogues, bicalutamide, abiraterone, radiotherapy to vertebral levels C2–T1 and T8–T11 and bilateral orchidectomy. His most recent chemotherapy treatment was eight cycles of docetaxel completed in 2016 2 years prior to this presentation, and he most recently received radium 223 for 5 months in 2017 a year prior to this presentation, with a treatment response on MRI. Prior to this admission, the patient had been receiving recurrent blood transfusions for asymptomatic pancytopenia. At his last oncology review, it was discussed that there were no further treatment options available and that the focus would be on palliative care and symptom management in the community. In the months prior to this admission, the patient’s haemoglobin levels were below 75 g/L, platelet counts were under 70×10⁹/L and neutrophil counts were under 0.5×10⁹/L, which highlighted the extent of his pancytopenia. This was thought likely to represent bone marrow infiltration and disease progression from his prostate cancer, in combination with possible latent effects of previous marrow toxicity from his chemotherapy and radiotherapy.

Investigations

Initial admission investigations with CT of the head demonstrated two rim-enhancing lesions. Further imaging with an MRI of the brain revealed two lesions, one complex multilobulated in the vermis and one in the right parietal lobe, showing restricted diffusion (figure 1). The presentation and imaging were initially discussed with the neurosurgical team for consideration of surgical resection or radiotherapy. The decision following review by the neuro-oncology multidisciplinary meeting was that the lesions represented intracerebral metastasis secondary to prostate cancer and based on the advanced stage of his cancer it was felt that best supportive care would be the most appropriate management. He started taking dexamethasone 8 mg two times per day but showed little symptomatic improvement.

Figure 1.

Admission MRI of the brain with contrast performed pre treatment, T2 Flair, axial view. (A) Right parietal lobe lesion showing restricted diffusion. (B) Complex multilobulated lesion in the vermis, with some locules demonstrating restricted diffusion.

Differential diagnosis

During admission, several cutaneous lesions developed, including to his right forearm, right leg, left forearm and axilla, which subsequently progressed to blood filled blisters and he developed fevers of up to 38.5°C (figure 2). Following incision and drainage of the right forearm lesion and further culture of the left arm lesion, Nocardia farcinica was isolated. Further review of the presentation and repeat MRI of the brain showed considerable deterioration since admission imaging, with enlargement of the cavitated lesions and appearances now typical of cerebral abscesses, with new lesions seen in the right frontoparietal operculum, left temporal lobe and medulla (figure 3A). On further neuro-oncology review of the significant progression of the cerebral lesions, in the context of confirmed cutaneous nocardiosis, these were now felt to also represent Nocardia infection rather than metastasis.

Figure 2.

Cutaneous lesions. (A) Right leg cutaneous lesion. (B) Right forearm cutaneous lesion, Nocardia farcinica isolated following incision and drainage.

Figure 3.

Comparison of MRI of the brain with contrast T2 Flair, axial view: 1 month post admission, pre antimicrobial treatment, post dexamethasone versus 1 month post antimicrobial treatment. (A) Radiological appearance deteriorated considerably since admission imaging. The cavitated lesions shown previously have enlarged and the appearance is now typical of cerebral abscesses. (A1) Right parietal lobe lesion. (A2) Vermis lesion. (B) Improvement of the degree of restriction diffusion, enhancement and signal changes of several lesions within the white matter of both cerebral hemispheres and cerebellum since the previous MRI and reduction of the local mass effect. (B1) Right parietal lesion. (B2) Vermis lesion.

Treatment

He started taking treatment for disseminated nocardiosis (cutaneous and cerebral lesions) with intravenous meropenem 2 g three times per day and intravenous co-trimoxazole 1440 mg four times per day, with addition of intravenous amikacin after 5 days treatment.⁶ For clarification of intracranial pathology following some clinical deterioration, repeat imaging was performed 11 days after commencing treatment. As expected, no response in the cerebral lesions and no development of new cutaneous abscesses were noted. External review of culture sensitivities showed that the N. farcinica was sensitive to co-trimoxazole, moxifloxacin, amikacin and meropenem. Moxifloxacin was, therefore, added. Amikacin was subsequently stopped after 24 days treatment and his co-trimoxazole dose titrated due to difficulties with pancytopenia.

Outcome and follow-up

Following completion of over 1 month of combination antibiotic treatment, his cutaneous and intracerebral lesions improved with settling of his fevers, inflammatory markers and symptoms. Repeat MRI of the brain imaging also demonstrated improvement of the degree of restriction diffusion, enhancement and signal changes of several lesions within the white matter of both cerebral hemispheres and cerebellum, with reduction of the local mass effect (figure 3B). The patient continued on antimicrobials with treatment duration of at least 6 months and up to 12 months recommended.³ He has now been discharged for a period of rehabilitation and to continue moxifloxacin and co-trimoxazole, with further repeat MRI of the brain and infectious diseases team follow-up planned.

Discussion

To the best of our knowledge, this is the first reported case of disseminated N. farcinica presenting as cerebral abscesses in a patient with prostate cancer.

Nocardia is a rare opportunistic infection most commonly affecting immunocompromised individuals and presenting as pulmonary disease transmitted via inhalation.^{1 7} Previous studies report that the species N. asteroides sensu stricto type VI, N. cyriacigeorgica, N. farcinica, N. nova and N. brasiliensis are most commonly associated with clinical disease.^{2 8 9} The CNS is the organ most commonly involved in disseminated disease, representing over 30% of cases and is particularly prevalent in cases of N. farcinica infection.^{7 10} Use of corticosteroid is significantly associated with CNS Nocardia infection.⁴ CNS involvement can present as headache, fever or focal neurological deficit and usually results in abscess formation.^{11 12} In this case, the patient’s moderate pancytopenia is likely to have been a predisposing factor for opportunistic infections.

N. farcinica and N. brasiliensis have been reported as the most abundant species associated with cutaneous involvement and can occur through direct skin inoculation, also seen in immunocompetent individuals.¹ In our case, the patient’s underlying pancytopenia may have contributed to his susceptibility to nocardiosis. Other known predisposing factors for nocardiosis include diabetes mellitus, malnutrition, solid organ transplantation and HIV; however, this patient did not have any of these factors. Disseminated nocardiosis and CNS involvement have been shown to confer a worse outcome, with N. farcinica suggested as the most pathogenic Nocardia sp due to its invasiveness and least susceptibility to antimicrobials.¹

The characteristic presentation of Nocardia brain abscesses seen on imaging typically are hyperdense multiloculated ring lesions, with possible surrounding oedematous changes. However, further clarity can be gained by the use of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps to distinguish abscesses from other possible differential diagnoses, such as intracerebral metastases. Brain abscesses may present as homogenously hyperintense on DWI and hypointense on ADC imaging.¹³ This is important as a delay in nocardiosis diagnosis and initiation of treatment can have an adverse prognostic outcome.¹⁴ Nocardia sp vary in their sensitivity and show multiple antimicrobial resistance particularly to third-generation cephalosporins, with in vitro susceptibility studies recommended in difficult to treat cases.^{1 15}

Our case highlights the challenges involved in diagnosing nocardiosis, with lesions often being mistaken for alternative pathology, including cerebral metastases as in this case. This raises the importance of clinicians having an awareness of opportunistic CNS infection pathogens, such as Nocardia, and considering alternative causes of intracerebral lesions, particularly in immunocompromised individuals who present atypically or fail to respond to the third-generation cephalosporins. Following neurosurgical review, this patient was for best supportive care and started taking dexamethasone, which may have inadvertently worsened the Nocardia infection. Therefore, early recognition and promptly starting the appropriate treatment is paramount in successful outcomes.

Learning points.

• This is a rare case of disseminated Nocardia farcinica with cutaneous and central nervous system (CNS) involvement, a rare opportunistic infection, presenting as cerebral abscesses in a patient with advanced prostate cancer.

• An awareness of opportunistic CNS infection pathogens, such as Nocardia, and alternative causes of intracerebral lesions are particularly important to consider in immunocompromised individuals who present atypically or fail to respond to the third-generation cephalosporins.

• This case also highlights that early recognition of CNS infections and promptly commencing the appropriate treatment can result in successful outcomes.