Brain Abscess Caused by Nocardia asteroides in a Diabetic Patient: A Rare Case Report

Abstract

Nocardial brain abscess is usually associated with immunodeficiency, but can sometimes emerge in healthy individuals. This infection can be acquired through inhalation or direct inoculation of the bacteria, followed by dissemination to various organs, including the brain, through blood circulation. Mortality rate due to nocardial cerebral abscess is three times higher than that associated with cerebral abscess caused by other types of bacteria. Moreover, patients with Nocardia asteroides-associated brain abscess show poorer prognosis compared to patients with brain abscess caused by other Nocardia species, which is probably due to the high tendency of N. asteroides to become resistant to numerous antibiotics. It is, therefore, of paramount importance to diagnose and treat N. asteroides cerebral abscess in patients as soon as possible. The current paper is a rare report of a brain abscess caused by N. asteroides in a diabetic patient who failed to respond to multiple antibiotics (trimethoprim/sulfamethoxazole and amikacin), but improved by receiving imipenem and linezolid, and was finally successfully treated by surgical operation and long-term antibiotic therapy (imipenem and linezolid).

Introduction

Nocardia species are Gram-positive, filamentous, branching, strict aerobe, and relatively slow-growing bacteria which belong to the order Actinomycetales [1,2]. These organisms have maintained a saprophytic existence in soil (the main reservoir of the bacteria), sludge, contaminated water, plants, and spoiled material throughout the world. Aerosols can transmit Nocardia species directly into the lung, leading to the development of lung lesions called pulmonary nocardiosis. The other type of infection caused by these bacteria is cutaneous lesions which are acquired through the traumatic percutaneous inoculation of the bacteria. These lesions are often presented as localized nodular processes, with the central nervous system involvement, which are often developed through the hematogenous dissemination of the bacteria [3].

Cerebral abscess is a rare but serious type of nocardial infection, the mortality rate of which is three times higher than that associated with abscesses caused by other types of bacteria [4]. Moreover, the cerebral abscess due to N. asteroides has a higher mortality rate compared to that caused by other Nocardia species which is probably due to the high tendency of N. asteroides to become resistant to numerous antibiotics [5]. This is a rare report of a brain abscess caused by N. asteroides in a diabetic patient in Iran.

Case Presentation

A 71-year-old man with type 2 diabetes mellitus was presented to the Ali-Ibn-Abi Taleb Hospital in the city of Zabol, Sistan and Baluchestan province, Iran, with slow speech, persistent headache, dyspnea, and fever for 4 weeks before referral, and recent neurological symptoms such as dizziness without vomiting, seizure, or paralysis. The patient was a farmer living in a small village in Zabol who had fallen off a tree, which had led to shoulder injury and scratching. His examination revealed that the patient was suffering from a 2-month history of subcutaneous abscess of the right shoulder by an unknown agent. Because of the mixed bacterial flora in the lesion, the microbiological analysis of the abscess was not conclusive.

The body temperature, heart rate, and blood pressure of the patient were 39°C, 98/min, and 140/100 mmHg, respectively at the time of primary hospital admission. Laboratory evaluations demonstrated that the blood cell count and glucose levels were normal and the blood hemoglobin level was 15g/dL with an elevated erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) levels up to 9 mm/hr and mg/L. Other laboratory findings such as alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine levels were 221 U/liter, 49 U/liter, 86 U/liter, and 121 μmol/L, respectively. In addition, analysis of the peripheral blood lymphocyte subsets showed CD3+CD4+ of 420 cells/μL (47%), CD3+CD8+ of 241 cells/μL (27%), and a CD4+/CD8+ ratio of 1.70. Blood, cerebrospinal fluid (CSF), and urine samples were negative for bacterial growth. The PPD skin and anti-HIV 1, 2 tests were also negative. Chest and paranasal sinus X-ray and urine analysis were normal. CSF analysis revealed 19 WBC (39% lymphocytes, 5% monocytes, 56% PMNs)/mm³, protein and glucose levels of 89 mg/dL and 78 mg/dL, respectively.

A contrast-enhanced computed tomography scan (CT scan) of the brain revealed an enhanced lesion with marked peripheral edema in the frontal lobe. Magnetic resonance (MR) images with gadolinium revealed a heterogeneous lesion with a significant amount of perilesional edema (Figure 1). Finally, surgical operation was undertaken and the abscess was drained.

Figure 1.

Coronal MR views of case showing a right temporal-parietal brain abscess.

Gram staining revealed branching Gram-positive filamentous rods. These rods appeared acid fast in a modified Ziehl-Neelsen staining procedure. Cultures on chocolate agar and blood agar plates revealed a pure growth of small white colonies appearing after 2 days incubation at 37°C. The grown colonies are shown in Figure 2. Results of the phenotypic (resistance to lysozyme, growth at 37°C, catalase, lack of decomposition of casein, tyrosine, and xanthine) and molecular tests led to the identification of N. asteroides [6-8]. Polymerase chain reaction (PCR) products of 16S rRNA gene were sequenced and analyzed (Accession number: KX951411) by NCBI GenBank and Ribosomal Database for data analysis. The results showed 100% similarity to the reference strain of N. asteroides (ATCC 19247).

Figure 2.

Small white colonies of N. asteroides.

Antimicrobial susceptibility testing was carried out by E-test for amikacin, tobramycin, cefotaxime, amoxicillin-clavulanic, imipenem, ciprofloxacin, and trimethoprim-sulfamethoxazole antibiotics and the bacterium was resistant to all the tested antibiotics except imipenem and ciprofloxacin. Empirical treatment using multiple antibiotics (trimethoprim/sulfamethoxazole 20 mg/kg/day IV and amikacin 15 mg/kg/day) had been unsuccessful. However, the patient was improved by replacing the antibiotics with imipenem (500 mg IV every 6 hours) and linezolid (600 mg orally, every 12 hours) and finally treated by surgical operation and long-term antibiotic therapy using imipenem and linezolid.

Discussion

Nocardia asteroides complex consists of different species with heterogeneous antimicrobial susceptibility patterns including N. abscessus, N. asteroides, N. brevicatena, N. cyriacigeorgica, N. farcinica, N. nova complex, and N. transvalensis complex. N. asteroides is the main species responsible for nocardial pneumonia among immunocompromised and immunocompetent individuals. Immunosuppression due to malignancy, long-term corticosteroid therapy, diabetes mellitus, lymphopenia, and autoimmune diseases are associated with increased incidence of Nocardia infections. The patient in this report had type 2 diabetes as a chronic immunosuppressive disease.

Nocardiosis in humans often occurs through either pulmonary inhalation or direct skin contact with the bacteria, followed by dissemination through the vascular tissue (13.5%). Nocardial brain abscesses, which mostly occur as early lesions with no evidence of extra-cranial lesions, are responsible for about 1% to 2% of all brain abscesses. The most common clinical manifestations observed in patients with nocardial brain abscess are seizures and focal neurological deficits [9,10]. Essien and colleagues [11] reported a rare case of brain abscess in a woman with systemic lupus erythematosus (SLE). One month after the initiation of immune suppression treatment, complications such as homonymous hemianopia, nausea and headache started, and an abscess in the occipital region was detected by MRI. In the CSF culture, N. asteroides was identified and therapy was started with intravenous (IV) meropenem and oral linezolid for 3 months, following which the patient was cured completely. Similar to our study, antibiotic therapy by a carbapenem and linezolid was effective against microorganism.

Moreover, Effendi et al. [12] reported a brain abscess caused by N. thailandica in a lymphocytic leukemia patient. Abscess culture and DNA sequencing were used for the detection of the infectious agent. Similar to the current case, trimethoprim/sulfamethoxazole treatment was unsuccessful. The patient was treated with IV ceftriaxone (2 grams daily for 5 months) while, in our study the isolate was completely resistant to a third-generation cephalosporin antibiotic, cefotaxime. In another study conducted by Stuebe et al., a metastasis mimicking brain abscess was described in an immunocompromised patient [13]. Nocardia was detected by culture from the biopsy sample and combination therapy using trimethoprim/sulfamethoxazole and ceftriaxone, followed by amoxicillin/clavulanic acid and minocycline was performed for 12 months. In our study, no susceptibility was observed to amoxicillin-clavulanic and trimethoprim-sulfamethoxazole and administration of the latter was also not efficient.

In another report by Browne et al. [14], a case of nocardial brain abscess was described in a patient with diabetes mellitus and similar to the present case, the patient was suffering from lung abscesses. N. cyriacigeorgica was defined as the underlying infectious agent and empirical therapy was started for the patient using IV ceftriaxone and oral trimethoprim-sulfamethoxazole. In contrast to our study, this regimen was successful and the patient’s neurological complications improved rapidly. Another case of brain abscess by N. cyriacigeorgica was reported by Gabay et al. [15]. This case was an immunocompromised patient (due to steroid therapy) who was completely cured with a trimethoprim\sulfamethoxazole and meropenem regimen.

Unlike the mentioned studies, treatment of nocardial brain abscess is not always successful – leading to patient’s death. Several records of death have been reported in the literature; for instance, despite antibiotic treatment with cefoperazone sodium and sulbactam sodium, a patient died because of a brain abscess in the frontal lobe by N. farcinica [16]. In addition, in a case series reported by Campioli et al. [17], 14 patients out of 24, were completely cured and 8 patients died following antibiotic therapy alone or combined with surgery. Most of the cured patients in this study were treated by combination therapy using trimethoprim-sulfamethoxazole and linezolid/ceftriaxone/moxifloxacin. In the above studies, trimethoprim-sulfamethoxazole was an effective part of combination therapies, but we found that its prescription in combined regimen was unsuccessful.

As discussed in the above brief literature review, brain abscess can be caused by different Nocardia species. Although in most studies, trimethoprim-sulfamethoxazole, linezolid, ceftriaxone, and moxifloxacin have been used for empirical therapy, these antibiotic regimens are not always successful and, therefore, precise identification of Nocardia species and determination of antibiotic susceptibility pattern are needed for proper treatment.

Diagnosis of Nocardia species via common culture-based methods could be difficult due to the overgrowth of the faster growing competitors. Moreover, some species are biochemically inactive and show inert activity in different biochemical tests. Molecular methods, such as PCR-sequencing of the 16S rRNA gene, are reliable and fast methods for identification of Nocardia species [18].

It occasionally happens that nocardial brain abscesses mimic necrotic metastasis of brain tumors in imaging methods such as CT scan; therefore, immediate diagnosis and treatment or early surgical intervention are required [19]. Surgical management is often followed by antibiotic therapy. In this report, the patient received the first line anti-nocardial therapy after the surgery, which failed to treat the patient. The therapy was then switched to long-term use of imipenem and linezolid, after which the patient completely recovered from the infection. Immunosuppressed patients and those with CNS diseases should receive at least 12 months of antimicrobial therapy because of the high relapse rate of this infection [20].

Conclusion

This is a rare report of a brain abscess caused by N. asteroides in a type 2 diabetic patient in Iran. The majority of patients with nocardial infections are immunocompromised, and diabetes mellitus, as a chronic immunosuppressive disease, was the major risk factor for the nocardial brain abscess reported in the patient in this study. The etiological agent in this case report was confirmed by culture of the brain biopsy and molecular detection of the cultured microorganism. Although the investigated isolate was resistant to different classes of antibiotics including trimethoprim-sulfamethoxazole, cefotaxime, amoxicillin-clavulanic, amikacin, and tobramycin, successful treatment was achieved through early diagnosis and surgical removal of the mass lesion, followed by long-term antibiotic therapy (imipenem and linezolid).

Glossary

ESR

erythrocyte sedimentation rate

CRP

C reactive protein

ALP

alkaline phosphatase

AST

aspartate aminotransferase

ALT

alanine aminotransferase

CSF

cerebrospinal fluid

CT

computed tomography

MR

magnetic resonance

PCR

polymerase chain reaction

SLE

systemic lupus erythematosus

IV

intravenous

Author Contributions

HAR, HH, MK: Contributed to the design and investigation of study; TS, PA: Writing the manuscript; HK: Supervision.

Funding

The study received no funding.