Clinical Assessment of a Nocardia PCR-Based Assay for Diagnosis of Nocardiosis

Abstract

The diagnosis of nocardiosis, a severe opportunistic infection, is challenging. We assessed the specificity and sensitivity of a 16S rRNA Nocardia PCR-based assay performed on clinical samples. In this multicenter study (January 2014 to April 2015), patients who were admitted to three hospitals and had an underlying condition favoring nocardiosis, clinical and radiological signs consistent with nocardiosis, and a Nocardia PCR assay result for a clinical sample were included. Patients were classified as negative control (NC) (negative Nocardia culture results and proven alternative diagnosis or improvement at 6 months without anti-Nocardia treatment), positive control (PC) (positive Nocardia culture results), or probable nocardiosis (positive Nocardia PCR results, negative Nocardia culture results, and no alternative diagnosis). Sixty-eight patients were included; 47 were classified as NC, 8 as PC, and 13 as probable nocardiosis. PCR results were negative for 35/47 NC patients (74%). For the 12 NC patients with positive PCR results, the PCR assay had been performed with respiratory samples. These NC patients had chronic bronchopulmonary disease more frequently than did the NC patients with negative PCR results (8/12 patients [67%] versus 11/35 patients [31%]; P = 0.044). PCR results were positive for 7/8 PC patients (88%). There were 13 cases of probable nocardiosis, diagnosed solely using the PCR results; 9 of those patients (69%) had lung involvement (consolidation or nodule). Nocardia PCR testing had a specificity of 74% and a sensitivity of 88% for the diagnosis of nocardiosis. Nocardia PCR testing may be helpful for the diagnosis of nocardiosis in immunocompromised patients but interpretation of PCR results from respiratory samples is difficult, because the PCR assay may also detect colonization.

Keywords: Nocardia; PCR; immunocompromised hosts; nocardiosis; opportunistic infections.

FIG 1

Retrospective classification of the study patients. *, patients were excluded (n = 25) on the basis of no underlying condition favoring nocardiosis (n = 8), no proven alternative diagnosis or improvement at 6 months without anti-Nocardia treatment (n = 9), no clinical or radiological signs consistent with nocardiosis (n = 4), or positive microbiological cultures for Nocardia without PCR testing being performed (n = 4). **, antibiotic treatment for ≤14 days was allowed.

FIG 2

Clinical and radiological features in a series of 13 patients with probable nocardiosis. (A and B) Patient 1, multiple superficial and purple nodular skin lesions on both legs. (C) Patient 2, coronal enhanced computed tomography (CT) of the right leg, showing a muscle abscess of the thigh (white arrowhead, central low attenuation with peripheral enhancement). (D and E) Patient 3, axial enhanced lung CT (D), showing a right pulmonary mass (white star, central attenuation), and coronal enhanced CT of the right leg (E), showing a muscle abscess of the thigh (black arrowhead, central attenuation with peripheral enhancement). (F) Patient 4, axial nonenhanced lung CT, showing a right spiculated lung consolidation. (G) Patient 5, axial enhanced lung CT, showing a right pulmonary mass (white arrowhead, low density). (H) Patient 6, coronal enhanced lung CT, showing localized bronchiectasis with thin surrounding lung consolidation (white arrow). (I) Patient 7, axial enhanced abdominal CT, showing a subcutaneous abscess and lymph node involvement (black arrow). (J) Patient 8, coronal T2 fat-saturated magnetic resonance imaging of the legs, showing a subcutaneous abscess (black star, hyperintensity). (K) Patient 9, axial nonenhanced lung CT, showing a left apical lung mass (black arrowhead). (L) Patient 10, axial enhanced lung CT, showing a lung consolidation (black arrow) and diffuse ground-glass opacities (black arrowhead). (M) Patient 11, axial nonenhanced lung CT, showing a lung nodule (white arrow). (N) Patient 12, axial nonenhanced lung CT, showing a cavitated lung nodule (white arrowhead). (O and P) Patient 13, axial nonenhanced lung CT, showing bilateral involvement with excavation of 10 cm, micronodules, and lung consolidation.