Nocardiosis

Nocardiosis is an infection caused by Nocardia species, which are aerobic, branching, weakly acid fast Gram positive bacteria found in soil and organic matter. It occurs predominantly in immunocompromised hosts, particularly those on prolonged corticosteroid therapy or with impaired cell mediated immunity.

Infection characteristically involves the lungs, with haematogenous dissemination to the central nervous system and skin. Relapse is common, so prolonged antimicrobial treatment is required.

Pathophysiology and risk groups

Infection is acquired through inhalation of organisms from soil or, less commonly, through direct cutaneous inoculation.

Cell mediated immunity is the principal host defence. This explains the strong association with prolonged corticosteroid therapy, solid organ and haematopoietic stem cell transplantation, HIV infection with low CD4 counts, and other causes of significant T cell dysfunction. A meaningful minority of cases occur in apparently immunocompetent hosts.

Pulmonary nocardiosis presents subacutely over weeks with cough, fever, weight loss and, on imaging, nodular or cavitary infiltrates. The radiographic appearance is non specific and often mimics tuberculosis, fungal infection or malignancy.

Central nervous system involvement occurs through haematogenous dissemination in a substantial proportion of pulmonary cases. It presents as single or multiple brain abscesses with headache, focal neurological deficit, seizure or altered consciousness.

Central nervous system involvement is often clinically silent, so actively screen with brain imaging in every patient diagnosed with pulmonary or disseminated disease.

Cutaneous nocardiosis arises from direct inoculation (traumatic wound contamination with soil) or as part of disseminated disease. It presents with nodular, ulcerative or abscess forming lesions, sometimes with a sporotrichoid pattern of spread along lymphatic channels.

Diagnosis requires culture of the organism from the relevant clinical specimen (sputum, bronchoalveolar lavage, abscess aspirate, tissue biopsy). Growth is slow, and culture can take one to two weeks.

While culture is pending, modified acid fast staining can give a rapid presumptive diagnosis by demonstrating beaded, branching, weakly acid fast filamentous organisms.

Species identification, increasingly performed using molecular methods, is important because antimicrobial susceptibility varies significantly between Nocardia species.

Perform brain imaging (computed tomography or, preferably, magnetic resonance imaging) in every patient with pulmonary or disseminated nocardiosis, whether or not neurological symptoms are present. Asymptomatic central nervous system involvement is common, and it significantly affects treatment duration.

High dose co trimoxazole (trimethoprim with sulfamethoxazole) is first line treatment. The dose is 15 mg per kg per day of the trimethoprim component, divided into two to four doses. Give it intravenously for severe or disseminated disease, then transition to oral therapy once clinically stable.

Use combination therapy for severe disease, central nervous system involvement, or significantly immunocompromised hosts. Add a carbapenem to co trimoxazole: imipenem 500 mg intravenously every 6 hours, or meropenem 2 g intravenously every 8 hours for central nervous system disease because of superior penetration.

Alternatively add amikacin (15 mg per kg per day divided into two or three doses, with therapeutic drug monitoring). Tailor the regimen once species identification and susceptibility results are available.

Linezolid 600 mg twice daily (oral or intravenous) is an effective alternative. It has reliable activity against essentially all Nocardia species and excellent central nervous system penetration. It is useful where sulfa allergy precludes co trimoxazole, or as part of combination therapy for severe disease.

Treatment is prolonged, so prolonged linezolid use requires monitoring for myelosuppression and peripheral neuropathy.

Duration is prolonged because of the propensity for relapse. The minimum is six months for pulmonary disease without central nervous system involvement in an immunocompetent host. Extend to twelve months for disseminated disease, central nervous system involvement, or ongoing significant immunosuppression. Some experts recommend even longer courses in the most severely immunocompromised patients.

Surgical drainage or excision is indicated for large or organised brain abscesses, significant cutaneous abscesses, or where diagnostic tissue is required and less invasive sampling has been non diagnostic.

Reduce immunosuppression where clinically feasible, as an important adjunct to antimicrobial therapy. Monitor closely for treatment response and for emergence of drug resistance or relapse.