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 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 PCR assay result for a clinical sample were included. Patients were classified as negative control (NC) (negative culture results and proven alternative diagnosis or improvement at 6 months without anti- treatment), positive control (PC) (positive culture results), or probable nocardiosis (positive PCR results, negative 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%]; = 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). PCR testing had a specificity of 74% and a sensitivity of 88% for the diagnosis of nocardiosis. 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.

Rapid Detection of Nocardia by Next-Generation Sequencing

“…Nocardia species are found worldwide in environments, and at least 33 of the total 80 more species have the ability to cause localized or systemic suppurative disease in human beings (Brown-Elliott et al, 2006). However, management of this rare infection is challenging, with mortality rates ranging from 20 o 30% in patients with disseminated infection, and up to 50% if there is central nervous system (CNS) involvement (Rouzaud et al, 2018).…”

Pathogenic Nocardia: A diverse genus of emerging pathogens or just poorly recognized?

“…Time taken from identifying symptoms to making a diagnosis can vary from 3 days to as much as 30 days [19][20][21]. The severity of an infection sometimes leads to administration of antimicrobial treatment prior to accurate diagnosis [22], causing some infections to go undiagnosed.…”

Nocardia spp.: A Rare Cause of Pneumonia Globally

“…has usually been considered evidence for infection, but some investigators have cited colonization only, particularly in patients with underlying bronchiectasis or CF 241,242 or when identified by PCR techniques. 40 Spanish investigators isolated Nocardia spp. in 40 subjects, 15 of whom were colonized without clinical infection; 20 had lung involvement and 5 had disseminated nocardiosis.…”

“…5,16,18,21 The diagnosis is often difficult, as the organism may take days to weeks to grow in culture. 37,38 Molecular biological techniques such as polymerase chain reaction (PCR) assays are more sensitive for diagnosis, and PCR and gene sequencing [39][40][41] also have greater accuracy for Nocardia species identification and have thus largely replaced conventional phenotypic laboratory procedures for determining species.…”