Key-words:
Brain abscess - Nocardia araoensis - nocardiosis
Introduction
Nocardial brain abscess is a rare central nervous system (CNS) infection with high
morbidity and mortality. Most of the human infections, i.e., about 90%, are due to
Nocardia asteroides group comprising N. asteroides complex, Nocardia farcinica, and
Nocardia nova. Other species rarely cause human infections. Here, we report a case
of left parieto-occipital abscess caused by a rare species, Nocardia araoensis, the
methods of diagnosis, treatment, and review of literature.
Case Report
A 73-year-old male, known case of diabetes mellitus, was diagnosed as autoimmune hemolytic
anemia a year ago and was started on oral steroids at another center. He continued
to take these medications for a year, without further consultation or blood tests.
He presented to us with a 1-month history of memory deficit and gait imbalance. On
examination, he had a right inferior quadrantanopia and a Grade 4 power in his right
upper and lower limbs.
Magnetic resonance imaging (MRI) brain with contrast showed multiple, large, predominately
cystic lesions in the left parieto-occipital region with significant edema and local
mass effect. The contents of the cyst demonstrated restricted diffusion. Following
contrast, most of these lesions enhanced in a smooth ring fashion. Some of the ring-enhancing
lesions were peripherally placed with dural thickening and enhancement. Susceptibility
imaging is showed small areas of low signal within the affected region in keeping
with hemorrhagic areas. A diagnosis of multiloculated brain abscess was made. A differential
of high-grade glioma was also considered [[Figure 1]].
Figure 1: Contrast-enhanced magnetic resonance imaging brain showing multiloculated ring-enhancing
lesion in the left parieto-occipital region
Since the lesion was close the motor cortex, he underwent navigation-assisted left
parietal burr hole and biopsy of the lesion under general anesthesia. Intraoperatively,
the dura was thickened with subdural pus and granulation tissue. Tissue was taken
for bacterial and fungal cultures and tuberculosis diagnostic panel.
Postoperative computed tomography scan showed the biopsy tract up to the lesion [[Figure 2]].
Figure 2: Postoperative computed tomography scan showing the biopsy tract up to the lesion
On bacteriological assessment, direct Gram stain of brain abscess showed occasional
inflammatory cells, and no organisms were seen. The sample was inoculated on nutrient
agar, blood agar, MacConkey agar, and brain–heart infusion broth and incubated at
37°C.
Colonies grew on media after 48 h of incubation. On blood agar, chalky white irregular
growth of colonies was seen [[Figure 3]]. Gram stain from colony showed Gram-positive filamentous branching bacilli with
beaded appearance [[Figure 4]]. Acid-fast bacillus stain using 1% sulfuric acid showed pink-colored bacilli of
about 4–7 μm × 0.5 μm [[Figure 5]]. Culture was sent for matrix-assisted laser desorption-ionization–time-of-flight
mass spectrometry (MALDI-TOFMS) for identification of the pathogen, which was reported
as N. araoensis. Mycobacteria were not detected in culture and gene expert. No fungus
was isolated from the sample.
Figure 3: Chalky white irregular growth of colonies seen on blood agar medium
Figure 4: Gram stain showing Gram-positive filamentous branching bacilli with beaded appearance
Figure 5: Pink-colored bacilli on acid-fast bacillus stain using 1% sulfuric acid
The corticosteroids were slowly tapered and stopped. He was started on injection meropenem
and combination of oral trimethoprim/sulfamethoxazole for 6 weeks with monitoring
of the serum creatinine and complete blood picture. An MRI was repeated at 1 month
which showed a minimal reduction in size of the left parieto-occipital abscess. The
lobulated lesion had compartmentalized into few discrete ring-enhancing lesions. No
new lesions were noted [[Figure 6]]. He developed altered renal parameters at the 2nd month of oral trimethoprim/sulfamethoxazole
combination and was hence switched to amoxicillin and clavulanate. A repeat MRI at
6 months showed the lesion further shrinking in size with reduction of the edema [[Figure 7]]. The treatment was continued for a period of 12 months. The patient improved clinically
to a Grade 5 power in his right upper and lower limbs, and visual assessment also
showed complete resolution of the visual field defect.
Figure 6: Follow-up contrast-enhanced magnetic resonance imaging showing compartmentalized
lobulated lesion with few discrete ring-enhancing lesions and no new lesions
Figure 7: Follow-up contrast-enhanced magnetic resonance imaging at 6 months showing the lesion
further shrinking in size with reduction of the edema
His MRI at 12 months showed complete radiological resolution of the lesion and the
surrounding edema [[Figure 8]].
Figure 8: Follow-up contract-enhanced magnetic resonance imaging at 12 months showing complete
radiological resolution of the lesion and the surrounding edema
Discussion
Nocardiosis of the CNS is a rare infection, comprising 1%–2% of all cerebral abscesses.
It is responsible for a higher mortality rate in comparison to other causes of cerebral
abscesses (30% vs. 10%).[[1]]
Most of the human infections, i.e., about 90%, are due to N. asteroides group comprising
of N. asteroides complex, N. farcinica, and N. nova. Other species rarely cause human
infections. It may present as acute, subacute, or chronic infections. It usually affects
immunocompromised patients as the index case who was on prolonged oral corticosteroids.[[2]],[[3]],[[4]],[[5]],[[6]]
N. araoensis (referring to Arao city, where the bacterium was isolated) is an aerobic,
Gram-positive, partially acid-fast, nonmotile actinomycete that forms a branched substrate
mycelium. It is a ubiquitous organism found in soil, water, decomposing vegetation,
and organic matter.
N. araoensis grows at 45°C which is also shown by some other species such as N. farcinica,
Nicotiana africana, Nocardia flavorosea, and Nocardia higoensis, but based on sugar
fermentation, citrate utilization, urea decomposition, and 16s rRNA sequencing/MALDI-TOFMS
techniques, N. araoensis species identification can be confirmed.[[7]],[[8]],[[9]],[[10]]
There are only a few case reports with N. araoensis causing meningitis [[11]] and pulmonary [[7]] and skin diseases.[[12]] The presentation may vary on the location of involvement. N. araoensis caused a
large multiloculated cerebral abscess in this immunocompromised patient. The management
involves craniotomy and excision in noneloquent locations. However, in this case,
since the lesion was multiloculated and involved eloquent cortex, the option of navigation-guided
biopsy was chosen to isolate the incriminating organism.
Mamelak et al. in their article after reviewing 131 cases reported focal deficits
in 42%, nonfocal findings in 27%, and seizures in 30% of cases. They found extraneural
nocardia in 66% of the cases; pulmonary (38%) and cutaneous/subcutaneous (20%) locations
were the most frequent. Multiple abscesses were found in 38% and 34% were immunocompromised.
They encountered a mortality rate of 24% after initial craniotomy and excision, 50%
after aspiration/drainage, and 30% after nonoperative therapy. The mortality rate
was 33% in patients with single abscesses and 66% in those with multiple abscesses.[[13]]
Even though the MRI can favor the diagnosis of cerebral abscess, only a biopsy can
give a definitive diagnosis. High grade gliomas and tuberculous/cryptococcal abscesses
may appear alike on MR imaging and need to kept as the differential. The tendency
to initiate empirical therapy for suspected tuberculous abscess is very high, especially
in multiloculated lesions involving the eloquent cortex. This misdiagnosis will result
in progression of the disease and treatment failure and lead to the development of
drug resistance. Hence, early tissue diagnosis is essential before the initiation
of any treatment.
Conventionally, bacterial infections were isolated on the basis of biochemical, metabolic
profiling and confirmed with 16S rRNA and 18S rRNA gene sequencing. However, recently,
the MALDI-TOFMS technique has evolved as a novel and potential tool for microbial
identification and diagnosis. This process is rapid, sensitive for confirmation of
the organism.[[9]] This technique was used in this case to clinch the diagnosis.
Treatment with sulfonamides in combination with trimethoprim is most effective and
should be continued for at least 1 year. However, in cases of allergy or nonresponsiveness
to sulfa agents, second-line agents such as minocycline, imipenem, or aminoglycoside
in combination with a third-generation cephalosporin may be used with reasonably good
success as in our case. We managed this case with a 6-week regimen of injectable meropenem
and oral sulfamethoxazole-trimethoprim combination and oral amoxicillin-clavulanate
for 12 months, which resulted in complete clinical and radiological resolution of
the disease process.
Lee et al. suggested that craniotomy and excision is necessary in most cases of nocardial
brain abscesses.[[14]] Patients with comorbid illness or surgically difficult lesions can be successfully
managed by a burr-hole aspiration, biopsy, and prolonged course of antibiotics as
done in the index case. Whether this is due to the low virulence of the new species,
N. araoensis, needs to be studied further.
Conclusion
N. araoensis is a rare cause of brain abscess and needs to be suspected in immunocompromised
individuals. MALDI-TOFMS techniques are helpful in species characterization. Early
diagnosis and prolonged treatment can result in complete clinical and radiological
resolution.
Declaration of patient consent
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understand that their names and initials will not be published and due efforts will
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