Nocardiosis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

The clinical and radiographic findings in pulmonary, disseminated, and cutaneous nocardiosis are nonspecific. They may be mistaken for a variety of other bacterial infections, including actinomycosis and tuberculosis, as well as fungal infections and malignancies affecting the lungs, skin, and brain.[7]

Historical and physical features

Nocardiosis must be suspected in immunocompromised patients with subacute or chronic pneumonia, or in patients with central nervous system (CNS) or skin and soft tissue lesions. Alertness to the possibility of nocardiosis can expedite the diagnostic workup, especially in patients with predisposing factors. Symptoms of pulmonary disease are typically nonspecific and can include fever and cough with sputum production. Patients with CNS disease usually have one or more brain abscesses and so may present with focal neurologic signs of increased intracranial pressure (i.e., nausea, vomiting, headache, confusion, and reduced consciousness). Patients with cutaneous disease often have skin ulcers or abscesses.[43]

Laboratory testing

The diagnosis of nocardiosis requires isolation and identification of the organisms from a clinical specimen. Because Nocardia colonies may take up to 2 weeks to appear, it is important to notify the laboratory when infection is suspected. Measures can then be taken to optimize recognition and recovery of the organism. Nocardia can disseminate to virtually any organ, so clinical samples can vary. Because most cases are pulmonary, the most frequent samples are from sputum, bronchoalveolar lavage (BAL), or other respiratory specimens. Other samples may be from skin biopsies, aspiration from deep subcutaneous fluid collections, cerebrospinal fluid, and biopsy smears.[20]Nocardia is rarely seen as a contaminant in the laboratory, so each isolate must be carefully evaluated.[44] Serology is usually not useful, because no single serologic technique can detect all clinically relevant species. Moreover, antibody response is usually impaired in immunocompromised patients.[8]

Gram and acid-fast stains

Microscopic and macroscopic examination of specimens submitted for culture is the first step in providing a diagnosis.[8] Staining with modified acid-fast stain, and especially Gram stain, is particularly important to provide a rapid presumptive diagnosis while awaiting the results of the culture.[21][Figure caption and citation for the preceding image starts]: Expectorated sputum specimen: modified acid-fast staining showing Nocardia speciesFrom the collection of Dr Jorge Garbino [Citation ends].
Most Nocardia strains are acid-fast in direct smears if a weak acid is used for discoloration. Gram and modified acid-fast stains must be considered in the initial evaluation of a possible case of nocardiosis.
Samples may be collected again if the initial specimens are negative but there is a high suspicion of infection.
Tuberculosis can be differentiated because the mycobacterium does not stain well with either Gram or modified acid-fast stains and is microscopically different. Actinomyces can be differentiated from Nocardia as it is not detected by modified acid-fast stain.[7][Figure caption and citation for the preceding image starts]: Expectorated sputum specimen: Ziehl-Neelsen staining to compare the different morphology of Mycobacterium and NocardiaFrom the collection of Dr Jorge Garbino [Citation ends].

Cultures

Nocardia species can grow on most nonselective media used routinely for the culture of bacteria, fungi, and mycobacteria. In general, the colonies have a chalky-white or cotton ball appearance because of the presence of abundant aerial filaments.[20]
In specimens such as sputum that contain mixed flora, Nocardia colonies can easily be obscured by other bacteria that grow more rapidly. The colony yield can be increased by the use of selective media such as Thayer-Martin agar with antibiotics, but the suspicion of nocardiosis must be communicated to the laboratory to optimize recognition and recovery of the organism. Growth of Nocardia species may take 48 hours to several weeks, but typical colonies are usually seen after 3 to 5 days.[45]

Species typing

Once the microorganism has been isolated, multiple laboratory tests can be used to differentiate the species. Species can be initially identified by biochemical species typing, molecular techniques, or matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).
Species typing is essential because different species have different resistance profiles and this information is crucial to adjust antibiotic treatment.[8][46][47]

Other molecular diagnostics

PCR-based techniques can be used to identify Nocardia species on samples from BAL and other clinical specimens.[48][49]
Next-generation sequencing of clinical samples including tissue, BAL fluid, and blood is an emerging approach for the rapid diagnosis of nocardiosis, including species identification.[50][51]

Imaging

There is no specific radiologic pattern for pulmonary or disseminated nocardiosis. However, some radiographic features have been reported more frequently and can suggest the diagnosis.

Chest x-ray and computed tomography (CT) chest: multifocal consolidation, with the addition of cavitation in approximately one third of patients; pulmonary nodules; and pleural effusions.[21][52][53][Figure caption and citation for the preceding image starts]: Pulmonary nocardiosis: CT scan with nodular lesions in an immunosuppressed patientFrom the collection of Dr Jorge Garbino [Citation ends].
CT, or preferably magnetic resonance imaging, of the brain should always be performed to exclude neurologic involvement in immunocompromised patients with nocardiosis, or immunocompetent patients with pulmonary or disseminated disease.[43][54] Brain abscesses may mimic other conditions, such as malignancy, or bacterial or fungal infection.[55][Figure caption and citation for the preceding image starts]: Disseminated nocardiosis: CT scan with brain abscesses in an immunosuppressed patientFrom the collection of Dr Jorge Garbino [Citation ends].

Surgical biopsy

Although the diagnosis can frequently be confirmed with noninvasive samples such as sputum, surgical procedures are occasionally needed to obtain specimens and exclude or confirm Nocardia etiology. This may be particularly important for neurologic involvement in immunocompromised patients, in whom the spectrum of microorganisms can be broader than in immunocompetent patients.[38][54][55] If the diagnosis is uncertain, brain biopsy may be considered for patients with cerebral abscesses.[54][56][57]

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