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From 23 SOTRs with nocardiosis, 2 had positive 1,3-β-D-glucan tests and both had alternative reasons for positive tests. 1,3-β-D-glucan does not appear to be useful for diagnosis of nocardiosis.
Keywords: 1,3-β-D-glucan; Fungitell; Nocardiosis; organ transplantation; diagnostic testing
To the Editor:
Solid organ transplant recipients (SOTR) are at risk for multiple opportunistic pathogens, including Nocardia. Nocardiosis has been associated with increased mortality among SOTRs, with multiple factors further increasing risk of poor outcomes.1,2 As such, there is a need to identify methods for faster diagnosis and earlier treatment initiation.
1,3-β-D-glucan (BDG), traditionally a marker of invasive fungal infection, has been detected in patients with nocardiosis.3,4 Subsequent in vitro studies have shown Nocardia isolates to have detectable BDG, raising the question of whether this assay could be a viable test for nocardiosis.3 However, several factors are known to cause clinical false-positive BDG results including use of intravenous immunoglobulin, intravenous albumin, and cellulose hemodialysis filter membranes.5 Furthermore, SOTRs are at risk for co-infection with fungal species that produce BDG, such as Candida and Aspergillus.
We evaluated a previously published cohort of SOTRs with nocardiosis,2 including those who underwent BDG testing from the serum or cerebrospinal fluid (CSF) within 7 days of Nocardia diagnosis. A positive BDG test was defined as ≥60 pg/mL. Alternative sources of positive BDG were also assessed.
From 125 total SOTRs with nocardiosis, 23 underwent serum BDG testing and 2 (8.7%) were positive (Table 1). One was a 57-year-old female pancreas transplant recipient with disseminated N. farcinica involving the lungs, brain, and muscle. The BDG value was 155 pg/mL. She had end-stage renal disease requiring intermittent hemodialysis and had recently received intravenous albumin. The second patient was a 56-year-old male heart transplant recipient with localized N. farcinica pulmonary infection. The BDG value was 381 pg/mL. This patient had also recently received intravenous albumin and had concomitant acute invasive pulmonary aspergillosis. There was only one patient with CSF BDG testing. This patient had disseminated N. otitidiscaviarum involving the lungs and brain whose serum and CSF BDG testing were both negative.
Table 1:
Characteristics of 23 solid organ transplant recipients with nocardiosis and 1,3-β-D-glucan testing
| Total Cohort (N=23) | |
|---|---|
| Age, y, median (IQR) | 61.0 (56.0, 66.5) |
| Male gender | 16 (69.6) |
| Race | |
| - American Indian or Alaska Native | 2 (8.7) |
| - Asian | 2 (8.7) |
| - Black or African American | 2 (8.7) |
| - White | 17 (73.9) |
| Ethnicity | |
| - Hispanic or Latino | 5 (21.7) |
| - Not Hispanic or Latino | 18 (78.3) |
| Time from transplantation, days, median (IQR) | 264.0 (136.5, 882.0) |
| Type of transplant | |
| - Heart | 4 (17.4) |
| - Kidney | 15 (65.2) |
| - Liver | 1 (4.3) |
| - Pancreas | 1 (4.3) |
| - Multiorgan | 2 (8.7) |
| Maintenance immunosuppression | |
| - Cyclosporine | 1 (4.3) |
| - Tacrolimus | 21 (91.3) |
| - Mycophenolate | 21 (91.3) |
| - Belatacept | 1 (4.3) |
| - Prednisone | 22 (95.7) |
| Hemodialysis dependency | 1 (4.3) |
| Disseminated infection† | 9 (39.1) |
| Site of infection‡ | |
| - Lung | 23 (100.0) |
| - Pleural space | 1 (4.3) |
| - CNS | 5 (21.7) |
| - Bloodstream | 3 (13.0) |
| - Skin | 1 (4.3) |
| - Other | 6 (26.1) |
| Nocardia Species | |
| - N. brasiliensis | 2 (8.7) |
| - N. cyriacigeorgica | 5 (21.7) |
| - N. farcinica | 8 (34.8) |
| - N. wallacei | 2 (8.7) |
| - Other§ | 6 (26.1) |
Data are n (%) unless otherwise specified.
Abbreviations: CNS, central nervous system; IQR, interquartile range; y, years.
Disseminated infection was defined as involvement of ≥2 noncontiguous organs, bloodstream involvement, or CNS involvement.
More than 1 site of infection possible per patient.
Other Nocardia species includes 1 each of N. abscessus, N. beijingensis, N. nova, N. otitidiscaviarum, N. paucivorans, and N. transvalensis/wallacei.
The present study shows a low rate of BDG positivity in SOTRs with nocardiosis. Both patients with positive results had either a concomitant invasive fungal infection or a recognized cause of elevated BDG levels in the absence of fungal infection. While case reports and small case series have previously reported SOTRs with nocardiosis and positive BDG, the described patients often had alternative causes of positive BDG testing or lack of a description of possible alternative sources of BDG elevation.3,4 Furthermore, while Nocardia species have been shown to cross-react with the BDG assay in an in vitro setting, it is less clear if this reactivity would be sufficient to be detected in a clinical setting.3
It remains possible that BDG detection differs by Nocardia species, site of infection, or severity of infection. Additionally, this study was performed retrospectively and without systematic BDG testing, and it remains possible that some patients with positive BDG did not undergo testing. However, based on present data, BDG seems unlikely to be a useful diagnostic tool for nocardiosis in SOTRs and positive BDG testing should prompt evaluation for invasive fungal infections and/or alternative sources of elevated BDG levels.
Funding
This project was supported by Grant Number UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Abbreviations:
- BDG
1,3-β-D-glucan
- CSF
Cerebrospinal fluid
- SOTR
Solid organ transplant recipients
Footnotes
Disclosures
All authors have no conflicts of interest to report.
References
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