BACKGROUND: Recurrent respiratory infections are a leading cause of morbidity and mortality in persons with Cystic Fibrosis (pwCF). Recently, the emergence of Nocardia species as a potential pathogen in CF has raised questions about its role and management, as its clinical significance and the optimal patient management remain unclear in current clinical practice. This review explores the clinical implications of Nocardia species in patients with Cystic Fibrosis (pwCF) through a comprehensive literature review. Key objectives include assessing its impact on lung function, identifying colonization risk factors, and evaluating an appropriate treatment.
METHODS: The literature review, conducted until June 30, 2023, from databases like MEDLINE, PubMed, Embase, and Cochrane, included 16 articles involving 89 pwCF with Nocardia species isolation according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline recommendations. Articles reporting Nocardia prevalence and symptoms based on original data in adult and paediatric pwCF were included. All the retrieved studies were observational ones, thus, they were categorized by study type as case report and case series.
RESULTS: Overall 89 pwCF and Nocardia species isolation were included: 42 children and 47 adults. Where reported, we found these main following bacterial species: Nocardia asteroides (35%, 23/64), Nocardia farcinica (21%, 14/64), Nocardia tranvalensis (13%, 8/64) and Nocardia cyriacigeorgica (11%, 7/64). A co-infection was reported in 85% of patients (61/72). Of patients whose lung function was reported before and after Nocardia isolation, 23% (16/68) showed a decline in FEV1. Above all, 82 patients were treated at least once after isolation of Nocardia strain. In 93% (77/82) of cases, treatment was started immediately upon isolation. Antibiotic treatment was performed per os or intravenously depending on the clinical condition of the individual patient. Nocardia eradication was attempted in only 32 cases out of 82, and 78% (25/32) of these patients were successfully eradicated after one or more courses of antibiotics. Death was reported in 3 patients, 2 of which were children.
CONCLUSIONS: In general the isolation of the bacteria does not necessarily imply therapy, but patients need to be monitored closely to assess the possible occurrence of active infection. The treatment seems to be indicated in patients showing lung involvement with the possible appearance of pneumonia, pleural effusion, fever, cough, or a decrease in FEV1, as in the case that we described, or in patients undergoing pulmonary transplantation.

Few cases of primary Nocardial epidural abscesses have been reported in the literature over the past 50 years, with limited guidelines available for identification and management. Typically, cases involve a prior diagnosis of systemic Nocardiosis with resultant seeding of a disseminated infection to the spine. An adult with chronic low back pain and type 2 diabetes mellitus underwent three consecutive epidural steroid injections in an outpatient setting. The patient gradually developed diffuse bilateral lower extremity pain, acute urinary retention, and saddle paresthesia. Lumbar magnetic resonance imaging revealed central herniation with annular tear compressing the thecal sac and S1 nerve roots, a dorsal epidural hemorrhage, and an abscess causing severe canal stenosis at L4-L5 and L5-S1. The patient was treated with vancomycin, piperacillin-tazobactam, and methylprednisolone without improvement, ultimately requiring surgical decompression. Initial surgical cultures grew mycobacterium species prompting RIPE therapy. Symptoms continually worsened requiring repeat decompression. Final cultures grew Nocardia, which necessitated transition to linezolid and sulfamethoxazole/trimethoprim, resulting in clinical improvement. Nocardial infection is a rare cause of isolated epidural abscess that can complicate antibiotic selection, resulting in potentially delayed treatment and worsened clinical outcomes. This manuscript aims to elucidate this rare but essential caveat to epidural abscess management.

OBJECTIVE: The identification of anaerobes, Mycobacterium and Nocardia species, and moulds by MALDI-TOF-MS remains a challenge. This study aimed to evaluate the performance of MALDI-TOF in the identification of these organisms.
METHODS: A total of 382 strains, comprising 128 (33.5 %) anaerobes, 126(33.0 %) mycobacterial, 113(29.6 %), mycelial fungi, and 15(3.9 %) Nocardia species were evaluated by VITEK MS Version 3.0. The results were compared with the identification of the isolates by DNA sequence analysis. The DNA sequences used for analysis were the 16S rRNA for anaerobic bacteria, hsp65 gene for mycobacteria, whereas both 16S rRNA and hsp65 gene for Nocardia species, and internal transcribed spacer (ITS) and 28S rRNA gene\'s D1/D2 regions of fungi.
RESULTS: The VITEK-MS accurately identified 78.3 % (299/382) of the strains at the species, and 9.4 % (36/382) at the genus level. Misidentifications were observed in 3.9 % (15/382) isolates. Of isolates tested, 8.4 % (32/382) were not identified by the system, and 7.06 % (27/382) were not included in the IVD database.
CONCLUSIONS: An upgraded VITEK MS V3.0 database provides reasonably accurate and rapid identification of clinically relevant anaerobes, mycobacteria, Nocardia species, and moulds to the species level.

The identification of specialized metabolites isolated from microorganisms is urgently needed to determine their roles in treating cancer and controlling multidrug-resistant pathogens. Naphthoquinones act as anticancer agents in various types of cancers, but some toxicity indicators have been limited in their appropriate application. In this context, new isofuranonaphthoquinones (ifnq) that are less toxic to humans could be promising lead compounds for developing anticancer drugs. The aim of this study is to identify and characterize novel furanonaphthoquinones (fnqs) from Nocardia sp. CS682 and to evaluate their potential therapeutic applications. Analysis of the genome of Nocardia sp. CS682 revealed the presence of a furanonaphthoquinone (fnq) gene cluster, which displays a similar genetic organization and high nucleotide sequence identity to the ifnq gene cluster from Streptomyces sp. RI-77, a producer of the naphthoquinones JBIR-76 and JBIR-77. In this study, the overexpression of the Streptomyces antibiotic regulatory protein (SARP) in Nocardia sp. CS682DR (nargenicin gene-deleted mutant) explicitly produced new fnqs, namely, NOC-IBR1 and NOC-IBR2. Subsequently, the role of the SARP regulator was confirmed by gene inactivation using CRISPR-Cas9 and complementation studies. Furthermore, antioxidant, antimicrobial, and cytotoxicity assays were performed for the isolated compounds, and it was found that NOC-IBR2 exhibited superior activities to NOC-IBR1. In addition, a flexible methyltransferase substrate, ThnM3, was found to be involved in terminal methylation of NOC-IBR1, which was confirmed by in vitro enzyme assays. Thus, this study supports the importance of genome mining and genome editing approaches for exploring new specialized metabolites in a rare actinomycete called Nocardia.

A 77-year-old man with a history of left nephrectomy for renal cell carcinoma and partial hepatectomy for cholangiocarcinoma underwent 18F-FDG PET/CT for assessment of an irregular lung lesion. FDG-PET demonstrated development of an intensely avid spiculated left lower lobe pulmonary lesion and intensely avid left pulmonary hilar nodes, raising suspicion for a malignancy. Eleven days following the PET study, the patient was admitted to hospital with an altered mental state. CT brain revealed diffuse round hyperdensities within the brain parenchyma. Microbiology of the lung lesion was positive for Nocardia Beijingensis and he was subsequently diagnosed with disseminated nocardiosis.

In this study, a porous carbon derived from a metal-organic framework (PCMOF) as a target-responsive material functionalized with Nocardia particular antisense ssDNA oligonucleotide (ssDNA capture probe) was developed to construct a simple genosensor based on biogatekeeper strategy for sensitive detection of Nocardia in complex biological samples. The PCMOF with suitable pores volume was used to encapsulate electroactive dye methylene blue (MB), and the ssDNA capture probe was used as a gatekeeper to cap PCMOF. Without the presence of Nocardia target, the electrochemical signal of trapped MB was high. Upon adding the target, the hybridization of ssDNA capture probe and target led to the formation of a probe-target double-stranded (dsDNA) structure which dissociated from PCMOF and allowed MB molecules to be released. Therefore, the electrochemical signal of the genosensor decreased. The detection of Nocardia was accomplished by observing variations in the MB peak current intensity in a dose-dependent manner. For this genosensor, a linearity range from 10-18 to 10-7 M for synthetic ssDNA target and 10 to 108 copies/mL for two standard isolates, Nocardia farcinica PTCC 1309 and Nocardia brasiliensis ATCC 19296 as well as for clinical isolates (identified as Nocardia otitidiscaviarum) was observed, respectively. The detection limit (DL) values were 0.54 aM for synthetic ssDNA target and 5, 7, and 4 copies/mL for N. farcinica, N. brasiliensis, and N. otitidiscaviarum, respectively. This genosensor was also characterized by good specificity, reproducibility, and stability.

Nocardia exalbida, an uncommon Nocardia, was first identified in 2006. We herein report a 70-year-old man with pulmonary nocardiosis caused by N. exalbida after living-donor liver transplantation. We also review 11 previously reported cases of N. exalbida infections. To our knowledge, there are no case reports available on nocardiosis consequent to N. exalbida infection following transplantation, thus highlighting the importance of identifying bacterial species for the successful management of infection.

Nocardia keratitis is mostly seen in patients with alcoholism, malnutrition, or HIV. Its chronic waxing-and-waning course makes it difficult to diagnose. A 53-year-old male presented with pain and redness in his right eye for the past 3 weeks. The cornea had paracentral ulcer with stromal infiltrates and multiple satellite lesions giving wreath-like appearance suggestive of Nocardia. After corneal scraping, fortified amikacin, moxifloxacin, and cycloplegics were started. Gram stain revealed filamentous, branching Gram-positive bacteria and acid-fast on Ziehl-Neelsen stain confirming our clinical diagnosis. Ulcer completely resolved over 6 weeks. Thus, a high index of clinical suspicion which was further backed by microbiological confirmation aided in expedient management ensuring a successful outcome.

BACKGROUND: Nocardiosis is an unusual infection caused by aerobic gram-positive bacteria in the genus Nocardia. Infections resulting from Nocardia species are frequent in immunosuppressive patients. Weakened immune systems caused by human immunodeficiency virus infection, diabetes, cancer, and other conditions such as chronic lung disease, renal failure, etc, are the main risk factors for nocardiosis. Central nervous system (CNS) nocardiosis has been reported to represent ~2% of all and to be present in 15% to 50% of patients with systemic infection. The patient in our case had an isolated CNS nocardiosis caused by Nocardia terpenica infection, a rare reclassified Nocardia pathogen of CNS nocardiosis.
METHODS: We here present a 54-year-old Chinese male with a fever and headache for 15 days who showed positive meningeal irritation signs. Magnetic resonance imaging showed the right trigone of the lateral ventricular choroid plexitis and diffused leptomeningeal meningitis involving the bilateral cerebral hemisphere, cerebellar hemisphere, and brain stem. The patient was quickly diagnosed with CNS Nocardia infection by next-generation sequencing within 48 hours after admission. Meanwhile, the diagnosis was validated by Nocardia-positive staining in cerebral spinal fluid culturing. The patient was given trimethoprim-sulfamethoxazole, and his symptoms recovered after 3 days.
CONCLUSIONS: In this case, the clinical, radiological, and microbiological findings highlight the importance of suspecting Nocardia as the potential pathogen in patients with central nervous system inflammation of doubted immune incompetence. In addition, next-generation sequencing as an effective test is also highly recommended for suspicious CNS infection patients to perform a rapid diagnosis and treatment.

The genus Nocardia are gram-positive bacteria, many of which possess pathogenicity and infect human lungs, skin, brain, and other organs. Since research on the genus Nocardia has not progressed as rapidly as that on the genus Streptomyces, the genus Nocardia is considered a useful undeveloped resource for exploring natural products. On the other hand, when the genus Nocardia infects the human body, the strains are attacked by immune cells such as macrophages. Therefore, we suggested a new method for screening natural products by culturing the genus Nocardia in the presence of animal cells. In this review, we describe our recent results in searching for natural products from the genus Nocardia.