Nocardia infections are rare, but potentially fatal conditions that are typically more problematic in patients with cell-mediated immunosuppression [
2], but may occasionally affect immunocompetent patients as well [
3].
Nocardia species is a ubiquitous, gram-positive, actinomycete saprophyte that lives in soil, organic matter and water. Human infection usually arises from direct inoculation of the skin or by inhalation. It is considered an opportunistic pathogen that affects patients with impaired cell-mediated immunity. Most of the patients with
Nocardia infection have predisposing factors, such as hematologic malignancies, treatment with corticosteroids, solid tumors, bone marrow or solid organ transplantation, HIV infection or chronic pulmonary or renal disease [
2]. The most common clinical presentation is subacute pneumonia with nodules, necrosis, cavitary disease, lung abscess, effusion, and/or empyema [
4‐
6]. Nocardial brain abscess is a rare clinical finding, most of which originate from a primary focus, such as the lungs, skin, or elsewhere in the body [
7]. Central nervous system involvement was recognized in over 44% of all cases of systemic nocardiosis [
8]. Moreover, nocardial brain abscess carries the highest mortality rate among all bacterial cerebral abscesses [
9].
Due to the nonspecific clinical and radiologic manifestations, including irregular nodules, cavitation, reticulonodular shadow, infiltration and pleural effusion, pulmonary nocardiosis is easily misdiagnosed as bacterial pneumonia, tuberculosis, mycosis or actinomycosis [
10]. Furthermore, nocardial brain abscess is often mistaken for aspergillosis, tuberculosis, or malignancy because of the similar clinical manifestations [
11]. Therefore, helpful diagnostic markers, such as Quantiferon test, cryptococcus antigen, galactomannan, and β-D-glucan (BDG) are very useful. BDG is a polysaccharide glucose polymer that is found in a broad range of commonly encountered fungal agents, including
Candida spp.,
Aspergillus spp., and
Pneumocystis jirovecii, with notable exception of cryptococci, zygomycetes, and
Blastomyces dermatitidis. BDG is helpful for the diagnosis of invasive fungal infections. This test is a chromogenic, quantitative enzyme immunoassay designed to detect BDG using purified, lysed amebocytes (Limulus amebocyte lysate). These cells contain components of the Limulus clotting cascade, including factors C and G, which initiate coagulation in the presence of bacterial lipopolysaccharide and BDG, respectively. By removing factor C from the lysate, the manufacturers limit activation of the cascade to BDG alone. However, false-positive results with certain hemodialysis filters [
12], fungal derived antibiotics [
13], immunoglobulins [
14],
Alcaligenes faecalis and
Stretococcus pneumoniae infection [
15], and bacteremia caused by
Pseudomonas aeruginosa [
16] have been described. Koncan et al. reported a case of
Nocardia abscessus brain abscess with BDG level that was elevated in the cerebrospinal fluid, but negative in serum [
1]. To our best knowledge, nocardial infection with high serum level of BDG has not been reported previously. Our case was the first English article about nocardial infection with elevated BDG level on serum. All known causes of false-positive BDG assay, including invasive fungal disease, hemodialysis treatment using cellulose membrane filter, and use of fungal-derived antibiotics and immunoglobulins, were not present in this patient. Metan et al. reported that clinical administration of intravenous ABPC/SBT caused false-positive BDG assay, although not statistically significant [
17]. On the other hand, Marty et al. reported that ABPC/SBT tested negative for BDG at the drug-infusate concentration or at maximum plasma concentration [
18]. In our patient, BDG level was examined 4 days after ABPC/SBT discontinuation; we think that ABPC/SBT administration did not cause a false-positive BDG assay. In this patient, because the bacterial suspension of the clinical isolate of
Nocardia farcinica was positive for BDG, environmental contamination was unlikely the cause of the positive serum BDG assay. We tested with BDG assay both a strain of
N. farcinica isolated from brain pus sample in this case and pure blood agr as negative control used Wako assay (Wako; Wako Pure Chemical Industries, Ltd., Tokyo, Japan). The positive cut off was 11 pg/ml. The strain was cultured on blood agr plate for 24 h at 37 °C. The bacteria were suspended in glucan free sterile saline and harvested by centrifugation (3000×g, 4 °C, 5 min). The organisms were resuspended in glucan free sterile saline and diluted from 1 × 10
8 to 2 × 10
8 CFU/ml as estimated by turbidimetry. Pure blood agar as negative control were always negative, but BDG levels of
N. farcinica were mildly elevated to about 20 pg/ml.
Pulmonary nocardiosis and nocardial brain abscess can be easily misdiagnosed clinically. Moreover, culture of
Nocardia species is difficult because of the slow growth of the bacteria and the presence of normal flora in the culture. Microbiologic diagnosis of nocardiosis and identification of nocardia clinical isolates by conventional methods are difficult and time-consuming [
19]. Additionally, cross-reactivity of
Nocardia species with serum BDG assay makes the diagnosis of nocardiosis difficult. Because BDG assay is widely used to diagnose invasive fungal infection, clinicians should take into consideration the fact that
Nocardia species may show cross-reactivity with BDG assay on serum. Clinicians should aim to detect the causative microbes without excessively depending on helpful serologic tests, such as BDG.