Teaching Case

A middle-aged, 45-year-old male patient with longstanding history of Human Immunodeficiency Virus (HIV) infection and severe immunosuppression (4 CD+ cells/mmc) unresponsive to antiretroviral therapy, was hospitalised because of malaise, diarrhoea, weight loss and metabolic acidosis, without specific respiratory symptoms.

Initial chest radiographs (Fig. 1) disclosed a 3 cm right infraclavicular subpleural cavitary consolidation, confirmed HRCT with associated pleural adhesion, retraction and thickening (Fig. 2).
Negative results of tuberculin skin test, acute phase reactants, sputum culture and QuantiFERON™ assay did not confirm suspected tuberculosis. Empiric treatment was started with antituberculous and broad-spectrum antibiotics, including staphylococcal coverage: early radiographs after 3 weeks (Fig. 3) suggested initial regression with persistent cavitation. Radiographic follow-up at two months (Fig. 4) showed enlarging lesion with resolution of central cavity. Repeat HRCT (Fig. 5) confirmed growing, noncavitary mass with central hypodensity, satellite nodules, linear densities and peripheral “halo sign” ground-glass. Percutaneous aspirate excluded malignant changes, but failed to reveal causative organism.
Nocardia infection was diagnosed on the basis of bronchial lavage cultures and treated with cotrimoxazole plus linezolid. Three months after admission, chest radiographs (Fig. 6) and HRCT (Fig. 7) detected resolution of the pulmonary opportunistic lesion.

Pulmonary or systemic infection by Nocardia species is an uncommon, often severe opportunistic condition, increasingly recognised because of the growing number of immunosuppressed patients with reduced cellular immunity and improvements in laboratory techniques. Most cases occur in the setting of Human Immunodeficiency Virus (HIV), whereas in other patients predisposing factors include chronic obstructive lung disease, organ transplantation, antineoplastic chemotherapy, collagen vascular disease and corticosteroid treatment [1, 2].
Although with low incidence, Nocardia infections usually occur at an advanced stage of HIV disease with severe immunosuppression (mean CD4+ count 35 cells/mmc). Nocardia asteroides represents the most common (70% of cases) causative organism. Notably, nocardiosis may also develop during cotrimoxazole prophylaxis, because of drug resistance or infection by different Nocardia species [2, 3].
Nonspecific clinical manifestations indicate a subacute pneumonia, with malaise and possible respiratory failure, often suggesting Mycobacterium tuberculosis infection. The diagnosis is usually confirmed by sputum culture or bronchial lavage, and is usually delayed because of the very low prevalence, variable and nonspecific clinical features and radiologic findings, lack of serologic tests, difficulties and slowness of culture growth [3].
Chest radiographic appearances include lobar consolidations, large irregular nodules or solitary masses, or reticulonodular infiltrates: these abnormalities most commonly involve the upper lobes, are associated with cavitation in 62% of cases and with pleural effusion in one third of patients [4, 5].
CT confirms airspace consolidation/infiltrates or masses with internal low attenuation or cavitation, or multiple noncavitating nodules. AIDS patients are more likely to display a greater number of lesions and cavitations in 80% of cases [6, 7].
Although usually showing a chronic course, Nocardiosis is a life-threatening infection in severely immunocompromised patients, with mortality rates approaching 50% unless promptly diagnosed and treated with appropriate antibiotic therapy [1-3].
Awareness of Nocardiosis and a high clinical suspicion index should prompt its inclusion in the differential diagnosis of pulmonary consolidations or nodular lesions in immunocompromised or chronically ill patients, particularly those showing central hypoattenuation or cavitation, upper lobe infiltrates negative to tuberculous tests, or unresponsive to usual antibacterial or antituberculous treatment. Suspected Nocardia infection should be notified when requesting culture, to optimise its identification [4, 6, 7].