Introduction:
Nocardiosis is a bacterial infection usually seen in individuals with a compromised immune system. The condition primarily causes infectious pulmonary disease, which shows up as abscesses in the lungs that may extend through the chest wall. The infection can spread through the bloodstream throughout the body. The effect of the disease may also be seen in the brain and skin. In healthy individuals, the infection may be localized but widespread in ones with a weaker immune system. Due to its severity under weaker immunity, this is known as an opportunistic infection occurring secondary to cell-mediated immune defects like AIDS (acquired immune deficiency syndrome), transplant patients, or patients under chemotherapy or steroids.
Who Is Susceptible to Nocardiosis?
The prevalence of nocardiosis is estimated at approximately 500 to 1000 annual cases in the United States. There is no observed racial predilection, but men are at a higher risk than women by a factor of three. With no observed age predilection, the average age of diagnosed cases was in the 40s.
What Causes Nocardiosis?
The prime causative organism for Nocardiosis belongs to the genus Nocardia which are aerobic, unicellular, filamentous, gram-positive bacterias, ubiquitous saprophytes present in the soil, decaying organic matter, and fresh and salt water. More than 100 species from the genus have been identified over the last decade, with just a handful being the most important members from a pathologic point of view. These are the members of a former complex called Nocardia asteroides that was later separated into Nocardia abscessus, Nocardia brevicatena-paucivorans complex, Nocardia nova complex, Nocardia transvalensis complex, Nocardia farcinica, Nocardia asteroides sensu stricto, and Nocardia cyriacigeorgica.
Primary cutaneous nocardiosis is seen in individuals, often in the rural agricultural scenario, who get infected due to direct inoculation of the organism into the skin secondary to a traumatic event. This may also occur post-surgically due to the use of improper sterilization protocols. Pulmonary nocardiosis occurs due to the inhalation of infected aerosols. The infections may then spread throughout the body from these initial points of inoculation.
Some people are at a greater risk of acquiring nocardiosis than others. These individuals carry underlying risk factors like
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Alcoholism.
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Chronic lung disease.
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Pulmonary alveolar proteinosis.
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Organ transplant.
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Corticosteroid usage.
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Blood cancers.
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Kidney failure.
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Lupus.
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HIV (human immunodeficiency virus).
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Hypogammaglobulinemia.
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Anti-tumor necrosis factor antibody treatment.
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Cushing syndrome.
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Systemic vasculitis.
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Immunomodulating treatment.
What Are the Clinical Features of Nocardiosis?
The symptoms of nocardiosis can be segregated based on their presence across various organs and organ systems.
1. Primary Cutaneous Nocardiosis: Red, painful, warm swelling around the site of primary cutaneous inoculation similar to a simple cellulitis lesion. In severe cases, suppurative localized necrosis may occur.
2. Lymphocutaneous Nocardiosis: Ascending regional lymphadenopathy is seen along with symptoms of primary cutaneous nocardiosis. The lymph nodes may show ulcerations with weeping necrotic or purulent pus drainage in severe cases.
3. Pulmonary Nocardiosis: The lungs may present as acute, subacute, or chronic versions of the infections. There might be the presence of inflammatory bronchial mass, pneumonia, fever, productive cough, night sweats, weight loss, blood in cough, dyspnea (shortness of breath), and chest pain. Complications like cavitation, abscess formation, pleural effusion, or empyema might also appear in severe cases.
4. Disseminated Disease: The infection can spread via the bloodstream from its primary site of inoculation (lungs, gastrointestinal tract, or skin) and settle in various organs. Deep abscesses might form at the disseminated sites. Disseminated sites, apart from the central nervous system (CNS), show up as generalized non-specific symptoms. CNS involvement shows typical slow growth of the mass, with significant neurological manifestations including numbness and muscle weakness correlative to the affected region of the brain or the spinal cord. Other signs include meningitis-associated headache, neck stiffness, or altered mental status.
How to Diagnose Nocardiosis?
Laboratory Studies
The best way to diagnose nocardiosis is by bacterial culture with specimens obtained from the skin, purulent discharge, sputum, deep abscess, pleural aspirates, etc. Pertaining to its slow-growing nature, the specimen should be allowed to grow in the medium at the laboratory for about three to five days. Direct smears or histopathological staining may show the bacteria. In case of suspected dissemination or pulmonary nocardiosis, a blood sample should also be obtained for analysis. Blood cultures test positive for the bacteria in a small batch of patients. PCR, or polymerase chain reaction, is a highly sensitive and specific test for the detection of the exact causative species of Nocardia. The latest method of MALDI-TOF (matrix-assisted laser desorption ionization-time of flight mass spectrometry) is also used for species identification, but much study needs to be done to assess and improve its efficacy.
Imaging Studies
CT (computed tomography) and plain radiographs are quite functional in diagnosing pulmonary nocardiosis and tracking the course of the infection.
Radiographic studies may show:
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Irregular nodules that may cavitate.
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Reticulonodular or diffuse alveolar pulmonary infiltrates.
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Pulmonary abscess.
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Pleural effusion.
CNS involvement warrants an MRI (magnetic resonance imaging) study or CT. The obtained images may invariably show intracranial abscesses and contiguous structures that are characteristic of nocardiosis. Other systems with system-specific imaging should be studied with system-appropriate imaging.
Biopsy
This is another test that studies the disease under a microscope to analyze the pathognomic cell or tissue changes. A biopsy requires a skin sample or aspiration of deep abscesses. In pulmonary nocardiosis, bronchoalveolar lavage or transbronchial lung biopsy may be required if the bacterial culture studies fail.
Other Tests
CSF (cerebrospinal fluid) should be collected and tested in case of suspected or evident meningitis. CSF might be positive for neutrophilic pleocytosis, hypoglycorrhachia, and an elevated CSF protein level.
How to Treat Nocardiosis?
Antibiotic protocols are the mainstay of nocardiosis treatment. The condition requires a minimum of six months of antibiotic therapy, which on revaluation, may be extended for up to 12 months, especially if the CNS gets involved. Double-strength Trimethoprim-Sulfamethoxazole is the drug of choice for secondary prophylaxis. Biweekly or triweekly administration may be effective in preventing other opportunistic infections in immunocompromised patients. Ongoing immunosuppressive or immunomodulatory therapies need not be discontinued. Surgical interventions may be required to drain localized abscesses. Pulmonary infections with possible progression to pericarditis is a fatal complication that requires surgical drainage. Brain abscess should be first assessed for accessibility and then surgically drained, followed by a fortnight of antimicrobial therapy.
What Is the Prognosis of Nocardiosis?
The outcome is widely variable and is largely dependent on the organ affected, duration of infection, immunological constituency, and severity of the infection. Post-treatment cutaneous and soft tissue infections show better outcomes than pulmonary and disseminated systemic nocardiosis. The rate of cure of brain abscesses is less than 60 percent.
What Is the Differential Diagnosis of Nocardiosis?
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Bacterial pneumonia (bacterial lung infection).
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Cellulitis (fatal infection in deeper skin layers).
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Community-acquired pneumonia (pneumonia acquired from neighboring patients).
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Fungal pneumonia.
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Glioblastoma multiforme (type of aggressive brain cancer).
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Histoplasmosis (fungal infection from bat or bird dropping).
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Kaposi sarcoma (blood and lymph vessel cancer).
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Lung abscess.
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Mycobacterium avium complex (type of bacterial tuberculosis).
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Non-Hodgkin lymphoma (lymphatic system cancer).
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Parapneumonic pleural effusions (fluid accumulation in pleural space with pneumonia).
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Empyema thoracis (pus collection in pleural space).
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Pneumocystis jiroveci pneumonia (a type of fungal pneumonia).
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Sporotrichosis (infection by Sporothrix fungus).
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Tuberculosis (lung infection by Mycobacterium tuberculosis).
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Viral pneumonia.
What Are the Complications of Nocardiosis?
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Lung infection.
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Empyema.
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Brain abscess.
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Meningitis (inflammation of the meninges-nerve coatings).
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Osteomyelitis (bone infection).
Conclusion:
Nocardiosis is an opportunistic infection, the etiology of which is widely spread in the immediate environment. In healthy individuals, the infection may not cause any symptoms and go away asymptomatic. But the bacterial genus has the potential to create health havoc in immunocompromised individuals. Prophylactic therapy is available that can be included in the pharmacotherapeutic individuals in potentially risky patients to entirely avoid having to deal with these microscopic opportunists.
