Invasive Nocardiosis: Disease Presentation, Diagnosis and Treatment - Old Questions, New Answers?

Abstract

Nocardia spp. is an environmental filamentous Gram-positive bacterium that may cause infections in humans and, despite recent progress, many challenges remain regarding the management of nocardiosis. This review aims at describing most recently published data regarding the diagnosis, treatment and follow-up of patients with invasive nocardiosis. As nocardiosis mainly affects patients with cell-mediated immunity defects, a comprehensive workup is mandatory in case of invasive nocardiosis occurring in "apparently healthy patients". Indeed, invasive nocardiosis might reveal an unknown primary immunodeficiency or the presence of anti-GM-CSF autoantibodies. Even if the diagnosis of nocardiosis mostly relies on direct examination and bacterial culture, a genus-specific PCR may be used for the detection of Nocardia, when directly performed on a clinical sample. Brain imaging should always be performed, even in the absence of neurological symptoms. Cotrimoxazole (trimethoprim/sulfamethoxazole), linezolid, parenteral cephalosporins, carbapenems and amikacin may be used as initial antibiotics to treat nocardiosis. Cotrimoxazole or linezolid can be used as monotherapy in selected patients without brain involvement. Although treatment duration has historically been set to at least 6 months in the absence of central nervous system involvement, shorter durations (<120 days) seem to be associated with a favourable outcome.

Keywords: anti-GM-CSF autoantibodies; antibiotic susceptibility testing; brain imaging; cotrimoxazole; dissemination; molecular biology; opportunistic infection.

Figure 1

Workflow for identification of underlying disease favoring invasive nocardiosis.

Figure 2

Radiographic findings in patients with invasive nocardiosis. (A) Chest CT-scan of a sixty-year-old patient with chronic lymphocytic leukemia treated with ibrutinib who developed Nocardia pneumonia. (B and C) Twenty-one-year-old patient with chronic granulomatous disease who developed Nocardia pulmonary abscess with local extension to the ribs (white arrow). (D) Brain MRI of a forty-six-year-old cardiac transplant patient who developed Nocardia brain cerebral abscess (white arrowhead): ring-enhancing multilobulated lesion surrounded by edema causing a mass effect on the anterior ventricles. MRI, axial T1 after gadolinium injection.

Figure 3

Microbiological diagnosis of nocardiosis. (A) Direct examination of a bronchoalveolar lavage (BAL) after Gram staining revealing filamentous Gram-positive bacteria (white arrowhead). (B) Positive culture of the same BAL on blood agar plate.