Nocardiosis and Actinomycosis

Wael ElMaraachli and Antonino Catanzaro

INTRODUCTION

Nocardiosis and Actinomycosis are caused by bacteria in the genus Nocardia and the genus Actinomyces, respectively. These two organisms masquerade as fungi due to characteristic filamentous branching structures. They cause similar clinical syndromes that are nonspecific and diverse, and there is an inherent difficulty in cultivating either organisms; hence, their common presentations as masqueraders. Both organisms belong to the order Actinomycetales, but Nocardia is aerobic while Actinomyces is anaerobic.

NOCARDIOSIS

Microbiology and Epidemiology

Nocardia can be identified on Gram stain, with a typical appearance of delicate, Gram-positive, irregularly staining, beaded, branching filaments (hence, its previous misclassification as a fungus). It must be identified under oil immersion because of the extremely fine nocardial filaments (0.5–1.0 μm in diameter). The filaments can fragment easily into nondescript, coccobacillary forms. The organism is partially acid-fast due to the mycolic acid content of the wall.

Nocardia asteroides was formerly thought to be the most common species associated with human disease, but the group pathogenic to humans has been redefined as a complex that includes N. asteroides, N. farcinica, N. nova, and N. transvalensis. N. farcinica is more virulent than the others and more resistant to antimicrobials. It typically requires third-generation cephalosporins and tobramycin.

Nocardia species are not found in normal human flora. They are soil saprophytes, found worldwide in soil, decaying vegetable matter, and aquatic environments. They can become airborne, and inhalation is thought to be the most common mode of entry as evidenced by the observation that most infections involve the lung. Other modes of entry include ingestion and direct inoculation into the skin. There have been some reports of nosocomial transmission, but person-to-person transmission is generally not thought to occur.

The majority of patients with nocardial infection are immunocompromised (64% in one review). The most common causes of immunocompromise associated with nocardial infection are glucocorticoid therapy, malignancy, organ and hematopoietic stem cell transplantation, and HIV infection (especially when CD4 cell count is below 100 cells/μL). Chronic lung disease and alcoholism are also risk factors.

Clinical Manifestations

The sites of infection in nocardiosis, in decreasing frequency, are pulmonary, systemic (≥2 sites involved), central nervous system (CNS), and cutaneous. Unlike actinomycosis, pulmonary disease is the primary manifestation of nocardiosis in the majority of cases. Pulmonary infection can be acute, subacute, or a chronic suppurative infection with periods of remission and exacerbation. The most common symptoms are cough, purulent (occasionally bloody) sputum, chest pain, weight loss, high fever, chills, and night sweats.

Acute nocardial infection can appear as an isolated lung abscess or a bronchopneumonia that may lead to a lung abscess. Consolidation and large irregular nodules are common, and they may be cavitary. Masses and interstitial patterns also occur. Pleural involvement ranges from simple, uncomplicated effusion to empyema. Lymph nodes can be enlarged. Spread to other parts of the lung or chest wall rarely happens; however, sinus tracts and perforation of the chest wall can occur.

Chronic infection can appear as small abscesses or chronic fibronodular disease. The lesions may be confined to a small portion of the lungs or scattered throughout the lungs. The later presentation may mimic miliary tuberculosis.

Extrapulmonary clinical manifestations depend on the site of infection. Nocardia frequently disseminates hematogenously and commonly spreads to the CNS, causing meningitis or brain abscesses. For this reason, it is prudent for all patients with nocardiosis to have diagnostic brain imaging (unless they are immunocompetent and the infection is confined to the skin).

Chest imaging can demonstrate single or multiple nodules, lung masses (sometimes with cavitation), reticulonodular infiltrates, lobar consolidations, and pleural effusions.

Diagnosis

Diagnosis requires direct visualization or culture of Nocardia in clinical specimens. However, the organism can be difficult to detect. The yield is much higher when the specimens are obtained through invasive means (bronchoscopy, percutaneous lung aspiration, and open lung biopsy) than in expectorated specimens. Gram stain shows the typical delicate, Gram-positive, irregularly staining, beaded, branching filaments that may have fragmented into nondescript, coccobacillary forms. The organism is partially acid-fast and must be identified under oil immersion because of the extremely fine nocardial filaments (0.5–1.0 μm in diameter). It does not stain on hematoxylin–eosin and will be missed on typical tissue biopsies unless special stains are performed. In routine culture media, 5 to 21 days are required for growth, so the microbiology laboratory must be informed and a request made to keep the culture plates longer if Nocardia is suspected. Polymerase chain reaction testing on samples appears to be sensitive and specific but is not clinically available at most centers.

Treatment

Successful treatment of nocardiosis includes the use of appropriate antibiotics and, if necessary, surgical drainage. Trimethoprim–sulfamethoxazole (TMP-SMX) is still the treatment of choice for nocardiosis infection. However, variable susceptibilities are now being reported. As a result, in severe disease (some cases of pulmonary disease, and any cases of disseminated or CNS disease), it may be best to begin with intravenous therapy with TMP-SMX and another agent such as amikacin for disease outside the CNS, imipenem for CNS disease, and both amikacin and imipenem for disease that occurs in the CNS and in other organs. After 3 to 6 weeks of therapy, switching to oral therapy may be considered, based on susceptibility. Several potential alternative treatments have been used, such as minocycline, clarithromycin, amikacin, imipenem, meropenem, linezolid, third-generation cephalosporins such as ceftriaxone and cefotaxime, fluoroquinolones, and amoxicillin–clavulanate. Species identification and susceptibility testing are useful in choosing a successful alternative treatment. The duration of therapy is uncertain, but 6 to 12 months is usually necessary to prevent dissemination or recurrence. Immunosuppressed patients should be treated for a minimum of 12 months, and an ongoing suppressive regimen should be considered.

ACTINOMYCOSIS

Actinomycosis is most often caused by Actinomyces israelii, and less often by A. naeslundii/viscosus complex, A. odontolyticus, A. meyeri, and A. gerencseriae

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