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Nocardia is a rare cause of ocular infections and most commonly occurs secondary to trauma. Systemic Nocardiosis may have ocular involvement in rare cases. We report a case of disseminated nocardiosis with orbital apex involvement and endophthalmitis in an immunocompromised patient. The patient presented with respiratory sepsis, and later developed complete ptosis and ophthalmoplegia in the left eye. This was on the background of treatment with high-dose prednisolone. Magnetic resonance imaging showed enhancement of the entire clivus, extending into the left orbital apex and cavernous sinus. The patient was initially treated empirically for CNS tuberculosis. Bronchoscopic cultures returned positive for Nocardia farcinica, and the patient was treated with trimethoprim/sulfamethoxazole and weaned off previous corticosteroids. [ABSTRACT FROM AUTHOR]

Background: Nocardia infections are rare infections in immunocompetent patients and occur mostly in immunocompromised individuals. Usually, nocardia affects skin, brain, and lungs, but in disseminated forms, which occurred mostly in immunocompromised patients, it can involve every organ. Nocardia sinusitis is extremely rare as our searches returned only a very few related studies. Case presentation: In this case report, we present, for the first time, a 55-year-old Iranian male patient diagnosed with chronic lymphocytic leukemia who was receiving chemotherapeutic drugs and developed a fever. Further laboratory tests and imaging revealed pansinusitis. Following rhinoendoscopy, the sinus mucosal biopsy pathology report showed sever inflammation accompanied by aggregation of filamentous thin-walled bacteria. The patient was treated with co-trimoxazole and meropenem. Following good clinical improvement the patient was discharged and advised to continue oral co-trimoxazole for 3 months. Conclusion: This case highlights that patients with febrile neutropenia should be assessed for rare infectious disease etiologies, especially those with chronic lymphocytic leukemia, as they have humeral immunodeficiency, and in the later stages of the disease, cellular immunodeficiency may also be involved. Therefore, a multisystem evaluation of patients with febrile neutropenia is necessary, particulary when no obvious source is identified in initial surveys, to uncover rare etiologies. [ABSTRACT FROM AUTHOR]

Background: Nocardia are widely present in nature and considered opportunistic pathogens. They can result in hematogenous spread infection through the ruptured skin or respiratory tract when the host's immune system is compromised. Currently, 119 species of Nocardia have been identified, with 54 capable of causing infections in humans. Nocardial brain abscesses are a rare intracranial lesion that accounts for only 2% of all brain abscesses, but have a mortality rate of 20–55%. This article reports a successfully cured case of mediastinal Nocardia infection with disseminated brain abscess. Case presentation: The patient presented with intermittent chills, shivering, and fever, with the highest temperature of 39˚C, accompanied by shoulder and back pain, dizziness, and headaches. A chest-enhanced computed tomography (CT) revealed multiple enhanced nodulars in the bilateral hilum and mediastinum. A head-enhanced CT revealed scattered multiple ring-enhanced nodules in both cerebral hemispheres and the left cerebrum, accompanied by extensive surrounding edema. The mediastinal puncture tissue culture confirmed the growth of Nocardia. After twice discussions with multidisciplinary team (MDT) to rule out the possibility of mediastinal and intracranial metastatic tumors, we promptly initiated treatment with a triple-drug antibiotic regimen consisting of imipenem/cilastatin sodium, linezolid dextrose, and Trimethoprim-sulfamethoxazole (TMP-SMX). The patient ultimately achieved complete remission. Conclusions: Mediastinal nocardiosis with disseminated brain abscesses is a rare condition that can be difficult to differentiate from brain metastases caused by lung cancer. Bacterial culture results, imaging features, and MDT discussions are crucial for accurate diagnosis and treatment. A triple-drug antibiotic regimen has been found to be effective in treatment with acceptable levels of toxicity. [ABSTRACT FROM AUTHOR]

A 2-y-old, intact female, mixed-breed dog was presented to the veterinary hospital with abdominal distension, anemia, and lethargy following a chronic history of nonspecific gastrointestinal signs. CBC and serum biochemistry revealed moderate nonregenerative anemia with neutrophilia, hypoalbuminemia, hyperglobulinemia, hypoglycemia, decreased urea and creatinine, and hypercholesterolemia. Abdominal radiographs and ultrasound revealed a large heterogeneous mesenteric mass and ascites. Abdominocentesis confirmed septic peritonitis with filamentous bacteria. Fine-needle aspiration of the mass yielded pyogranulomatous inflammation and hyphae. An exploratory laparotomy revealed a large cranial abdominal mass with granulomas present throughout the abdominal cavity. Due to the poor prognosis and disseminated disease, the owner elected euthanasia. Postmortem and histologic examinations detected intralesional mycetomas and bacterial colonies within the mesenteric masses. 16S ribosomal RNA gene PCR and sequencing using formalin-fixed, paraffin-embedded sections identified Nocardia yamanashiensis, Nocardioides cavernae, and Nocardioides zeicaulis. Fungal culture, PCR, and sequencing confirmed Scedosporium apiospermum. Our report highlights the importance of molecular methods in conjunction with culture and histologic findings for diagnosing coinfections caused by infrequent etiologic agents. Additionally, we provide a comprehensive literature review of Scedosporium apiospermum infections in dogs. [ABSTRACT FROM AUTHOR]

The aim of this study was to reveal diagnostic biomarkers of considerable importance for common pathogenic Nocardia, utilizing pan-genomic and comparative genome analysis to accurately characterize clinical Nocardia infections. In this study, complete or assembled genome sequences of common pathogenic Nocardia and closely related species were obtained from NCBI as discovery and validation sets, respectively. Genome annotation was performed using Prokka software, and pan-genomic analysis and extraction of Nocardia core genes were performed using BPGA software. Comparative genome analysis of these core genes with the validation-set gene sequences was then performed using BLAT, with a threshold of 30% amino acid coverage and identity, in order to distinguish specific core genes. Finally, candidate gene-specific primers were designed using Snapgene software and DNA samples were obtained from clinical Nocardia strains and closely related species for validation. The analysis identified eighteen core genes specific to Nocardia spp., four core genes specific to N. farcinica, and forty-six core genes specific to N. cyriacigeorgica. After rigorous clinical validation, one gene from Nocardia spp. and five genes from N. cyriacigeorgica were confirmed to have high specificity and therefore can be used as reliable biomarkers for accurate diagnosis of Nocardia infection. This pioneering research reveals diagnostic biomarkers of considerable significance, with the potential to substantially enhance the precise diagnosis of common pathogenic Nocardia infections, thereby laying the groundwork for innovative diagnostic methodologies in subsequent studies. [ABSTRACT FROM AUTHOR]

Background: Drug susceptibility testing (DST) for Nocardia spp. is essential to initiate effective antibiotic therapy. Currently, the only recommended technique is the determination of minimum inhibitory concentrations (MICs) by microdilution. This method can be tedious to perform, despite the availability of ready-to-use plates. Herein, the aim was to determine the critical inhibition diameters specific to Nocardia spp. Methods: MICs of 134 Nocardia isolates were determined by microdilution. Interpretative categories (Susceptible/Intermediate/Resistant) were determined using Clinical and Laboratory Standards Institute breakpoints. In parallel, disk diffusion DST was performed. Receiver-operating-characteristic (ROC) curves were constructed to determine the inhibition diameter value that best discriminated between susceptible and non-susceptible strains (intermediate/resistant). The category agreement (CA), the rate of major (maj) and very major (vmj) discrepancies between microdilution and disk diffusion method was calculated. Results: For tobramycin, the critical diameter of 19 mm (diameter ≤ 19 mm = resistant strain; diameter > 19 mm = susceptible strain) provided a CA of 98.5%, 0.0% vmj, and 2.9% maj discrepancies, reaching strictly the acceptable performance criteria defined by the U.S. Food and Drug Administration (FDA). For amikacin, the critical diameter of 25 mm (diameter ≤ 25 mm = resistant strain; diameter > 25 mm = susceptible strain) provided a CA of 98.5%, 0.0% vmj, and 1.5% maj discrepancies. For imipenem, excluding N. farcinica and N. cyriacigeorgica, the critical diameter of 29 mm (diameter ≤ 29 mm = resistant strain; diameter > 29 mm = susceptible strain), provided a CA of 98.6%, 0.0% vmj, and 0.0% maj discrepancies. Despite an estimated vmj rate 0.0%, the 95%-confident-interval exceeded the FDA criteria due to an insufficient number of amikacin/imipenem-resistant strains. For other tested antibiotics (ciprofloxacin, moxifloxacin, amoxicillin-clavulanate, ceftriaxone, cotrimoxazole, linezolid), the FDA criteria were not reached. Conclusions: Although the FDA criteria were mostly unmet, disk diffusion DST was suitable to accurately categorize Nocardia isolates into interpretative categories for the aminoglycosides and imipenem only, excluding species N. farcinica and N. cyriacigeorgica. [ABSTRACT FROM AUTHOR]

Introduction: In August 2023, hybrid sturgeons (Acipenser baerii♀×Acipenser schrenckii♂) cultured in Sichuan, China, showed infectious disease symptoms, including ulcers, liver and spleen nodules, and high mortality rates. Methods: Pathogenic bacteria were isolated from the liver of diseased sturgeons and analyzed for their phenotypic and molecular traits. Furthermore, iridovirus-specific TaqMan real-time PCR (RT-PCR) analyses were conducted. The histopathological characteristics were analyzed using paraffin sectioning and transmission electron microscopy (TEM). Transcriptome sequencing was performed to elucidate the impact of pathogen exposure and immune response profiles in infected sturgeon. Results: Pathogenic bacteria isolation and phylogenetic analyses of the 16S rRNA gene confirmed that the isolated bacteria clustered within the Nocardia seriolae group. The TaqMan RT-PCR assay was performed to detect the presence of white sturgeon iridovirus (WSIV), indicating a weakly positive signal. Histopathological examination revealed severe damage to various tissues, and a notable presence of bacteria was observed through acid-fast staining. Transmission electron microscopy analysis showed the presence of abundant bacteria and virus particles, indicating cellular invasion and subsequent damage. In summary, the disease in hybrid sturgeons was diagnosed as infection of N. seriolae and WSIV. To investigate the immune response of hybrid sturgeons to this infection, spleen transcriptomes were analyzed. Numerous immune-related genes and pathways, including the "Toll-like receptor", "B-cell receptor", and "T-cell receptor" signaling pathways, were altered in response to pathogenic threats. Significantly downregulated of key components of TCR and BCR signaling pathways, such as ZAP70 , BTK , and CD79A , suggested a temporary inhibition of these pathways critical for cellular immunity post-infection. Gene set enrichment analysis revealed significant suppression of the apoptosis signaling pathway and activation of autophagy and mitophagy signaling pathways following infection. Specifically, in the death receptor-mediated apoptosis signaling pathway, downregulation of TNFα , TRAIL , CASP6 , and CASP8 was observed, while several genes in the autophagy and mitophagy pathways showed upregulated expression post-infection. Discussion: We report the initial occurrence of N. seriolae infection in cultured sturgeons. These findings could provide a theoretical basis for diagnosing and preventing this disease, as well as enhance the understanding of host-pathogen interactions in fish. [ABSTRACT FROM AUTHOR]

Background: Nocardiosis is an opportunistic infection that has a low prevalence rate, its clinical manifestations are atypical and can be easily misdiagnosed as other diseases. The correct diagnosis and treatment are frequently delayed by various factors. In this case report, we present a pediatric patient with Neuromyelitis Optica Spectrum Disorders who developed Nocardia farcinica pneumonia complicated by pneumocystis jiroveci infection. Case presentation: An 8-year-old girl with chest pain and cough was admitted to the hospital. She suffered from Neuromyelitis Optica Spectrum Disorders and had been taking methylprednisolone and tacrolimus orally for 3 years. She was admitted to the hospital for tests and was diagnosed with acute pneumonia. Despite empiric antibiotic treatment, her condition gradually worsened. Respiratory distress developed, and she needed to use a ventilator for breathing. The symptoms she exhibited led us to suspect the presence of a tumor. Etiological tests later confirmed the co-infection of Nocardia farcinica and Pneumocystis jiroveci. After treatment, the child's lung infection eventually resolved. Conclusion: The Nocardia bacteria and Pneumocystis jiroveci are widely distributed in the environment, possess the capability of systemic dissemination, and exhibit significant resistance to specific treatments. Invasive sampling is frequently necessary for confirming their presence. Timely and accurate diagnosis as well as treatment play a crucial role in patient survival. [ABSTRACT FROM AUTHOR]

The zoonosis caused by Nocardia is increasing seriously. But commonly used antibiotic drugs often lead to resistance. N. seriolae dUTPase (NsdUTPase) plays a key role in the proliferation of Nocardia, and was regarded as a potent drug target. However, there was little report about the NsdUTPase inhibitors. In this study, we discovered a series of novel NsdUTPase inhibitors to fight against Nocardia. The first crystal structure of NsdUTPase was released, and a structure-based computational design was performed. Compounds 4b and 12b exhibited promising activities towards NsdUTPase (IC50 = 0.99 μM and 0.7 μM). In addition, they showed satisfied anti-Nocardia activity (MIC value ranges from 0.5 to 2 mg/L) and low cytotoxicity, which were better than approved drugs oxytetracycline and florfenicol. Molecular modelling study indicated that hydrophobic interaction might be the main contribution for ligand binding. Our results suggested that NsdUTPase inhibitors might be a useful way to repress Nocardia. [ABSTRACT FROM AUTHOR]

The typical clinical signs of Nocardia seriolae infection include white nodules, ranging from 0.1 to 10 mm in diameter, distributed across various internal organs. However, the structural composition of nodules of different sizes remains unexplored. In this study, natural cases of largemouth bass (Micropterus salmoides) were collected, and pathogenic bacteria were isolated and confirmed through a re-infection experiment. The isolated bacteria were identified as N. seriolae through 16S rRNA and gyrB gene sequencing. Healthy largemouth bass were infected with the isolate using an immersion infection and observed continuously over 56 days. Samples were successfully obtained from the incubation, prodromal, symptomatic, and convalescent phases, allowing for gross, histological, and ultrastructural observations of nodular lesion progression. Results demonstrated two types of nodular lesions: necrotic foci and granulomas. Macroscopically visible nodules larger than 1 mm, observed primarily in the liver, spleen, kidney, and muscle tissues of moribund fish, exhibited coagulative necrosis and were identified as the principal cause of mortality. Conversely, granulomas, with diameters less than 1 mm, were consistently present in the spleen, kidney, and liver during the symptomatic and convalescent phases. [ABSTRACT FROM AUTHOR]

Background: Development of brain abscess following solid organ transplantation is associated with significant morbidity and mortality. We undertook a descriptive study to evaluate the etiology, clinical manifestations, diagnosis, management, and outcomes of brain abscess in solid organ transplant (SOT) recipients at three major transplant centers in the United States. Methods: This is a retrospective study of adults with brain abscess following SOT between January 2000 and June 2021 at Mayo Clinic sites in Arizona, Minnesota, and Florida. Results: A total of 39 patients were diagnosed with a brain abscess following SOT. The most common pathogens were Nocardia sp. (24 cases, 61.5% [Nocardia farcinica, 37.5%]), followed by fungi (12 cases, 30.7% [Aspergillus sp., 83.3%]). The majority were kidney transplant recipients (59%). Median time to brain abscess diagnosis was 1.3 years (range, 29 days–12 years) after SOT; 10 of 12 patients (83%) with fungal brain abscess were diagnosed within 1 year after SOT. Twelve patients underwent brain biopsy for diagnosis (25% Nocardia vs. 50% fungal), eight (20.5%) underwent surgical resection of the abscess, and 31 (79.5%) received antimicrobial therapy alone. Median time to brain abscess resolution was 166 days for Nocardia and 356 days for fungal pathogens. Eleven of 39 patients (28.2%) died as a result of their brain abscess, including four of 24 patients (16%) with Nocardia and six of 10 patients (60%) with Aspergillus brain abscess. All‐cause mortality was 43.6%. Conclusion: Brain abscess remains an uncommon infectious complication following SOT. Nocardia and fungi accounted for 92% of pathogens in our cohort. Fungal brain abscess portends a poor prognosis. [ABSTRACT FROM AUTHOR]

Actinomycetoma, a neglected tropical disease affecting the skin and soft tissues, is primarily caused by filamentous bacteria including Nocardia species. Here, we report a healthy 56-year-old man who has a one-year history of nodular lesions with seropurulent discharge on his right knee. Despite negative initial tissue culture, the sulfur granules that were partially acid-fast and Gram-positive branching filamentous rods were revealed in the tissue section. Repeated investigation identified the rare pathogen Nocardia wallacei, using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and 16S ribosomal ribonucleic acid (rRNA) gene sequencing. The patient was successfully treated with a six-month course of trimethoprim-sulfamethoxazole. This report describes a rare case of actinomycetoma due to N. wallacei, highlighting the challenges in diagnosis and the importance of accurate pathogen identification for the successful management of infection. The current literature regarding the causative agent will also be discussed. [ABSTRACT FROM AUTHOR]

Abstract Background Disseminated nocardiosis is a rare and potentially fatal disease, with a higher incidence in immunocompromised patients, such as those living with human immunodeficiency virus (HIV) or hematological malignancies, including lymphoma. Information on Nocardia spp. infection in Venezuela is limited. Case presentation We present the case of a 62-year-old male patient, recently diagnosed with HIV, who exhibited prolonged fever and unintentional weight loss. Paraclinical tests revealed pancytopenia and a marked elevation of lactate dehydrogenase. Disseminated histoplasmosis was suspected, prompting a bone marrow (BM) aspirate. Culture and molecular studies for Histoplasma spp. and Mycobacterium tuberculosis in BM samples were negative. Antiretroviral therapy with tenofovir/lamivudine/dolutegravir was initiated, but the patient subsequently experienced clinical deterioration, including ascites, pericardial effusion, and respiratory failure. Post-mortem biopsy and immunohistochemistry identified non-Hodgkin’s lymphoma of B-cell lineage, and mycological culture of BM isolated Nocardia farcinica. Conclusion Disseminated nocardiosis may mimic histoplasmosis. Nocardia spp. infection should be considered in HIV patients, particularly in advanced stages of infection.

Nocardiosis, caused by various species of Nocardia, poses diagnostic and therapeutic challenges due to its diverse clinical presentations that often mimic other infections and malignancies. We present the case of a 72-year-old woman with a history of autoimmune hepatitis and diabetes mellitus (DM) who initially presented with fever, headaches, and confusion. Extensive investigations revealed an ischemic lesion in the central nervous system (CNS) attributed to vasculitis. Two months later, she returned with literal paraphasia, ocular symptoms (red eye and retro-orbital pain), and fever. Despite negative blood cultures, Nocardia cyriacigeorgica was isolated from vitreous humor and lung tissue, confirming the diagnosis of disseminated nocardiosis. A rigorous treatment regimen, including trimethoprim/sulfamethoxazole (TMP/SMX), Meropenem, and Linezolid, led to significant improvement. This case underscores the diagnostic complexity of Nocardiosis, emphasizing the need for early and precise diagnosis, multidisciplinary care, and prolonged treatment in severe cases. Further research is required to optimize therapeutic protocols, particularly in CNS-involved Nocardiosis.

Abstract Background Nocardiosis is a rare infectious disease, which is frequently underdiagnosed because of the distinct bacterial shape of the causative agent and its developmental history. The morphological analysis of bronchoalveolar lavage fluid can facilitate the detection of pathogenic bacteria by observing cellular–bacterial interactions. Case presentation An immunocompetent 67-year-old male patient of Asian ethnicity developed a cough without apparent cause 20 days earlier. We initially discovered mycobacteria that appeared to be Nocardia in the cytomorphological examination of bronchoalveolar lavage fluid, which was later determined to be Nocardia otitidiscaviarum through metagenomic next-generation sequencing and microbiological cultures. The patient was eventually diagnosed with Nocardia pneumonitis after other testing and clinical signs were considered. After anti-infective treatment, the patient improved and was discharged. Conclusion Several diagnostic approaches were used in this case, and the importance of cell morphology as an early screening method was emphasized for suspected Nocardia infection.

Nocardiosis is an opportunistic infection caused by Nocardia species (spp). Nocardia species are ubiquitous environmental saprophytes occurring in the soil, organic matter, and water. A 36-year-old, female, renal transplant recipient presented with cutaneous and cerebral symptoms of disseminated Nocardiosis. Prompt diagnosis and treatment of the case resulted in a favourable outcome. Nocardiosis is an important infection in transplant recipients, which should be diagnosed early so that appropriate therapy can be instituted. Keywords: Nocardia, oppurtunistic infections; renal transplant; solid organ transplant; disseminated nocardiosis

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.

Abstract Background Nocardiosis, despite its rarity and underreporting, is significant due to its severe impact, characterized by high morbidity and mortality rates. The development of a precise, reliable, rapid, and straightforward technique for identifying the pathogenic agent in clinical specimens is crucial to reduce fatality rates and facilitate timely antimicrobial treatment. In this study, we aimed to identify Nocardia spp. in clinical isolates, using MALDI-TOF MS as the primary method, with molecular methods as the gold standard. Clinical Nocardia isolates were identified using 16S rRNA/hsp65/gyrB/secA1/rpoB gene sequencing. Identification performance of the Bruker MALDI Biotyper 3.1 (V09.0.0.0_8468) and MBT Compass 4.1 (V11.0.0.0_10833) for Nocardia identification was evaluated. Results Seventy-six Nocardia isolates were classified into 12 species through gene sequencing. The MALDI Biotyper 3.1 (V09.0.0.0_8468) achieved 100% genus-level accuracy and 84.2% species accuracy (64/76). The MBT Compass 4.1 with the BDAL Database (V11.0.0.0_10833) improved species identification to 98.7% (75/76). The updated database enhanced species level identification with scores > 1.7, increasing from 77.6% (59/76) to 94.7% (72/76), a significant improvement (P = 0.001). The new and simplified extraction increased the proportion of strains identified to the species level with scores > 1.7 from 62.0% (18/29) to 86.2% (25/29) (P = 0.016). An in-house library construction ensured accurate species identification for all isolates. Conclusions The Bruker mass spectrometer can accurately identify Nocardia species, albeit with some variations observed between different database versions. The MALDI Biotyper 3.1 (V09.0.0.0_8468) has limitations in identifying Nocardia brasiliensis, with some strains only identifiable to the genus level. MBT Compass 4.1 (V11.0.0.0_10833) effectively addresses this shortfall, improving species identification accuracy to 98.7%, and offering quick and reliable identification of Nocardia. Both database versions incorrectly identified the clinically less common Nocardia sputorum as Nocardia araoensis. For laboratories that have not upgraded their databases and are unable to achieve satisfactory identification results for Nocardia, employing the new and simplified extraction method can provide a degree of improvement in identification outcomes.

Background: Nocardiosis is a rare infectious disease, which is frequently underdiagnosed because of the distinct bacterial shape of the causative agent and its developmental history. The morphological analysis of bronchoalveolar lavage fluid can facilitate the detection of pathogenic bacteria by observing cellular–bacterial interactions. Case presentation: An immunocompetent 67-year-old male patient of Asian ethnicity developed a cough without apparent cause 20 days earlier. We initially discovered mycobacteria that appeared to be Nocardia in the cytomorphological examination of bronchoalveolar lavage fluid, which was later determined to be Nocardia otitidiscaviarum through metagenomic next-generation sequencing and microbiological cultures. The patient was eventually diagnosed with Nocardia pneumonitis after other testing and clinical signs were considered. After anti-infective treatment, the patient improved and was discharged. Conclusion: Several diagnostic approaches were used in this case, and the importance of cell morphology as an early screening method was emphasized for suspected Nocardia infection. [ABSTRACT FROM AUTHOR]

N. neocaledoniensis is a very rare infectious pathogen that causes human disease, particularly in immunocompromised individuals. In this case report, we describe the successful diagnosis of N. neocaledoniensis in a patient confirmed by mNGS and the treatment of multiple skin abscesses due to N. neocaledoniensis infection. mNGS is an important diagnostic method complementary to routine bacterial culture and identification methods, especially for rare, novel, co-infected pathogens, and pathogens that are difficult to culture. This report may provide a reference for the clinical treatment and diagnosis of N. neocaledoniensis infection in humans. [ABSTRACT FROM AUTHOR]

Nocardiosis is a collective term for tissue and organ damage caused by Nocardia infection. Solid organ transplant recipients (SOTR) are at an increased risk of various pathogen infections, including Nocardia infection, due to immunosuppressive therapy which weakens their immune function. The diagnosis of nocardiosis has been challenging in the past. With the advent of molecular biology and other diagnostic methods, the diagnostic rate has significantly improved. Nocardia not only prone to cause necrotic pulmonary lesions but also invade other organs and tissues, such as intracranial infections and skin soft tissue infections, and can develop into systemic disseminated infections. For SOTR, nocardiosis is a potentially fatal disease with a fatality as high as 30%. Therefore, this article reviews the clinical characteristics of common nocardiosis in SOTR, new diagnostic technologies, and different anti-infective treatment strategies, aiming to provide a reference for the prevention and treatment of nocardiosis in clinical SOTR. [ABSTRACT FROM AUTHOR]

Nocardia is an emerging bacterial disease that often affects patients with compromised immune systems. As the number of patients undergoing solid organ transplants continues to rise, and as more cancer survivors are treated with long-term immune-modifying agents, corticosteroids, and immunosuppressive medications, organisms that typically pose no harm are becoming a public health concern. Carbapenems are usually a second-line therapy in the setting of Nocardia infections. We present the case of a patient who had an immunocompromised status and was diagnosed with Nocardia farcinica, which showed in vitro resistance to carbapenems. The symptoms were non-specific and had a common presentation with headache, fatigue, and a nonresponsive cough to usual cough drugs, although the infection was disseminated and had severe CNS and ocular involvement. The clinical course worsened when the carbapenem was withdrawn and markedly improved when it was re-administered, although the initial antibiogram showed resistance to carbapenems. Despite the observed in vitro resistance in the laboratory, the re-administration of carbapenems was beneficial, as both inflammatory markers and clinical status showed improvement. This was based on clinical judgment, which carefully evaluated the associated risks and benefits. Also, this raises the question of potential risks to develop real resistance to carbapenems of some Nocardia species, which could pose a significant challenge to healthcare. It could become a serious healthcare problem in the future and should prompt active environmental testing. [ABSTRACT FROM AUTHOR]

Purpose: Nocardia is emerging as a common and easily neglected cause of both healthcare- and occupation-associated infections worldwide, however, human vaccines for Nocardia prevention are not yet available. In this study, we aimed to evaluate the immunoprotective effect of the NFA47630 protein, a secreted protein abundant in the N. farcinica IFM10152 supernatant. Methods: Conservation and characteristics of nfa47630 were analyzed by PCR and bioinformatics. Then recombinant NFA47630 protein was cloned, expressed and purified for further antigenicity analysis. Subsequently, the ability to activate innate immunity was evaluated by examining the phosphorylation status of the MAPK signaling pathway and cytokine levels. Finally, the protective effect was evaluated on rNFA47630-immunized mice. Results: nfa47630 was conserved in N. farcinica strains with good antigenicity. The rNFA47630 protein was expressed under the optimal conditions of 0.2 mM IPTG, 28 °C, and it can be recognized by anti-N. farcinica and anti-N. cyriacigeorgica sera, but not anti-N. asteroids, anti-N. brasiliensis, anti-N. nova and anti-Mycobacterium bovis sera. It can upregulate the phosphorylation status of ERK, JNK, P38 and the cytokine levels of TNF-α, IL-10, IL-12, and IFN-γ. In addition, mice immunized with rNFA47630 protein exhibited higher antibody titers, greater bacterial clearance ability, milder organ infection, and higher survival rates than PBS-immunized mice. Conclusions: Our data demonstrate that NFA47630 is a potential vaccine candidate for defending against N. farcinica infection. [ABSTRACT FROM AUTHOR]

Nocardia farcinica is the most pathogenic Nocardia, which is easy to disseminate. It can be caused by trauma, and even lead to severe lung or central nervous system infection. This report covers a case of Nocardia brain abscess in an HIV patient, who underwent resection of the brain abscess, followed by anti-infective therapy with sulfamethoxazole and meropenem, and eventually made a good recovery. The mortality rate of Nocardia farcinica brain abscess has been attributed to the severity of the underlying disease, the difficulty in identifying the pathogen, and its inherent resistance to antibiotics, leading to inappropriate or late initiation of treatment. Medication should follow the principle of sufficient dosage and sufficient course of treatment. [ABSTRACT FROM AUTHOR]

Yellow nail syndrome (YNS) is a rare clinical syndrome characterized by nail bed changes, pulmonary involvement, and lymphatic drainage disorders. Pulmonary involvement usually manifests as bronchiectasis, bronchiolitis, and pleural effusion. There are few studies on yellow nail syndrome combined with opportunistic infection. Here, we report a case of clinically diagnosed YNS combined with Nocardia cyriacigeorgica infection and the course of treatment used, which can provide some useful information for clinicians to better understand this rare illness. [ABSTRACT FROM AUTHOR]

Mycetoma is currently considered as a neglected tropical disease. The incidence of mycetoma is unknown but most of the worldwide cases are present in the "mycetoma belt" including countries like Mexico, India, Senegal, and others. The treatment of mycetoma depends on the etiological agent responsible for the case. Treatment success reaches 60 to 90%; however, common treatment has been reported to be ineffective in some cases, due in part to resistance to the prescribed antibiotics. Therefore, it is necessary to develop new therapeutic options. In the past two decades, quinoxaline derivatives have shown relevance as antibacterial agents. Therefore, in this work, esters of quinoxaline 1,4-di-N-oxide derivatives were evaluated in vitro against the reference strain CECT-3052 from N. brasiliensis, six clinical isolates, and macrophages J774A.1 to determine their cytotoxicity and security index. Additionally, nine reference drugs were evaluated as controls. The results show that nine esters of quinoxaline 1,4-di-N-oxide derivatives had a minimum inhibitory concentration (MIC) < 1 µg/mL against the reference strain and four of them (N-05, N-09, N-11, and N-13) had an MIC < 1 µg/mL against the clinical isolates. Therefore, the scaffold quinoxaline 1,4-di-N-oxide could be used to develop new and more potent antinocardial agents. [ABSTRACT FROM AUTHOR]

The article discusses the impact of sulfonamide allergy labels on the risk of opportunistic infections after solid organ transplantation (SOT). SOT recipients with a sulfonamide allergy label were found to have an increased risk of Toxoplasma and Nocardia infections compared to those without the label. The study highlights the importance of reassessing sulfonamide allergy labels in SOT recipients to optimize prophylactic treatment and reduce the risk of opportunistic infections. Efforts should be made to identify safe delabeling strategies and promote the use of trimethoprim/sulfamethoxazole (TMP‐SMX) in eligible SOT recipients. [Extracted from the article]

The silkworm Nocardia infection model has been established as a useful animal model for screening the pathogenicity of Nocardia and evaluating the therapeutic effects of antimicrobial agents against Nocardia infection. No histopathological analysis of silkworms infected with Nocardia farcinica has yet been performed. In this study, we performed histological analyses on organs of silkworms infected with N. farcinica. One day after infection with N. farcinica, the organism developed a branching filamentous form from coccid cells in the hemolymph. In addition, we evaluated effective doses (ED50) values by treating infected silkworms with amikacin 30 seconds and 24 hours after infection and found that the ED50 values treated within 30 seconds and 24 hours after infection were 4.1 µg/larva and 5.6 µg/larva, respectively. Evaluation of treatment with amikacin against the infected silkworms was unaffected by the growth process form of Nocardia. These results suggest that the silkworm Nocardia infection model is a useful tool for evaluating the antimicrobial therapy in the growth process of the N. farcinica. [ABSTRACT FROM AUTHOR]

Background: Nocardiosis, a rare but serious infection caused by Grampositive, aerobic actinomycetes, primarily affects immunocompromised individuals. This report highlights an uncommon case of pulmonary nocardiosis in an immunocompetent patient leading to acute hypoxic respiratory failure. Case Presentation: A 45-year-old male gardener with no significant past medical history presented with acute dyspnea, pleuritic chest pain, fever, night sweats, and weight loss. Physical examination revealed respiratory distress and hypoxia. Imaging showed bilateral alveolar infiltrates and cavitary lesions. Sputum analysis identified Gram-positive branching filamentous bacteria, and Nocardia species were cultured. HIV test was negative. Management: The patient was admitted to the ICU and treated with high-flow oxygen therapy and empirical antibiotics (trimethoprim-sulfamethoxazole [TMP-SMX] and meropenem). Upon culture results, TMP-SMX was continued, and meropenem was discontinued. The patient showed significant improvement and was discharged on oral TMP-SMX for a six-month course. Discussion: This case underscores the importance of considering pulmonary nocardiosis in acute respiratory failure, even in immunocompetent patients. Early diagnosis and appropriate treatment are crucial for favorable outcomes. Conclusion: Pulmonary nocardiosis can cause severe respiratory symptoms in otherwise healthy individuals. Prompt recognition and treatment are essential to manage this potentially life-threatening condition effectively. [ABSTRACT FROM AUTHOR]

Nocardia spp., which belongs to one of the Nocardio-form filamentous bacteria, is usually surface hydrophobic and when overproduced attaches to the surface of bubbles under the action of surfactants, allowing the stable presence of foam on the surface of aeration tanks, leading to the occurrence of sludge-foaming events. Two novel phages, P69 and KYD2, were isolated from the environment, and their hosts were Nocardia transvalensis and Nocardia carnea, respectively. These two phages are Siphophages-like with long tails. An aeration tank pilot plant was constructed in the laboratory to simulate sludge foaming, and these two strains of phage were applied. Compared with the reactor not dosed with phage, the application of phage could reduce the host level in the reactor, resulting in the highest decrease in turbidity by more than 68% and sludge volume index by more than 25%. The time for surface foam disappearance was 9 h earlier than that of the control group (the group with the same concentration of Nocardia carnea but no bacteriophage applied), significantly improving water quality. The phage can effectively inhibit the propagation of Nocardia in the actual sludge-foaming event, control the sludge foaming, and improve the effluent quality. It provides a novel and relatively economical solution for controlling sludge foaming in sewage treatment plants in the future, shows that the phages have potential application value in the prevention and control of Nocardia, and provides another way to control the sludge-foaming event caused by the excessive reproduction of Nocardia in the future. [ABSTRACT FROM AUTHOR]

Background: Nocardia, a rare but potentially fatal pathogen, can induce systemic infections with diverse manifestations. This study aimed to investigate the tissue and organ damage caused by Nocardia farcinica (N. farcinica) in mice via different infection routes, evaluate the resulting host immune responses, and assess its invasiveness in brain tissue. Methods: BALB/c mice were infected with N. farcinica through intranasal, intraperitoneal, and intravenous routes (doses: 1 × 10^8, 1 × 10^7, 1 × 10^7 CFU in 50 µl PBS). Over a 7-day period, body temperature, weight, and mortality were monitored, and samples were collected for histopathological analysis and bacterial load assessment. Serum was isolated for cytokine detection via ELISA. For RNA-seq analysis, mice were infected with 1 × 107 CFU through three infection routes, after which brain tissue was harvested. Results: Intraperitoneal and intravenous N. farcinica infections caused significant clinical symptoms, mortality, and neural disruption in mice, resulting in severe systemic infection. Conversely, intranasal infection primarily affected the lungs without causing significant damage to other organs. Intraperitoneal and intravenous infections significantly increased serum cytokines, particularly TNF-α and IFN-γ. RNA-seq analysis of brains from intravenously infected mice revealed significant differential gene expression, whereas the intranasal and intraperitoneal routes showed limited differences (only three genes). The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the intravenous group were primarily related to immune processes. Conclusion: The study demonstrated that intravenous N. farcinica infection induces significant clinical symptoms, triggers an inflammatory response, damages multiple organs, and leads to systemic infections. [ABSTRACT FROM AUTHOR]

Background: Nocardiosis, despite its rarity and underreporting, is significant due to its severe impact, characterized by high morbidity and mortality rates. The development of a precise, reliable, rapid, and straightforward technique for identifying the pathogenic agent in clinical specimens is crucial to reduce fatality rates and facilitate timely antimicrobial treatment. In this study, we aimed to identify Nocardia spp. in clinical isolates, using MALDI-TOF MS as the primary method, with molecular methods as the gold standard. Clinical Nocardia isolates were identified using 16S rRNA/hsp65/gyrB/secA1/rpoB gene sequencing. Identification performance of the Bruker MALDI Biotyper 3.1 (V09.0.0.0_8468) and MBT Compass 4.1 (V11.0.0.0_10833) for Nocardia identification was evaluated. Results: Seventy-six Nocardia isolates were classified into 12 species through gene sequencing. The MALDI Biotyper 3.1 (V09.0.0.0_8468) achieved 100% genus-level accuracy and 84.2% species accuracy (64/76). The MBT Compass 4.1 with the BDAL Database (V11.0.0.0_10833) improved species identification to 98.7% (75/76). The updated database enhanced species level identification with scores > 1.7, increasing from 77.6% (59/76) to 94.7% (72/76), a significant improvement (P = 0.001). The new and simplified extraction increased the proportion of strains identified to the species level with scores > 1.7 from 62.0% (18/29) to 86.2% (25/29) (P = 0.016). An in-house library construction ensured accurate species identification for all isolates. Conclusions: The Bruker mass spectrometer can accurately identify Nocardia species, albeit with some variations observed between different database versions. The MALDI Biotyper 3.1 (V09.0.0.0_8468) has limitations in identifying Nocardia brasiliensis, with some strains only identifiable to the genus level. MBT Compass 4.1 (V11.0.0.0_10833) effectively addresses this shortfall, improving species identification accuracy to 98.7%, and offering quick and reliable identification of Nocardia. Both database versions incorrectly identified the clinically less common Nocardia sputorum as Nocardia araoensis. For laboratories that have not upgraded their databases and are unable to achieve satisfactory identification results for Nocardia, employing the new and simplified extraction method can provide a degree of improvement in identification outcomes. [ABSTRACT FROM AUTHOR]

Nocardia is widely distributed in the natural environment and typically cause opportunistic infections. However, it is important to note that the pathogenicity of different Nocardia species may vary significantly. Here we reported the first case of brain abscess caused by Nocardia beijingensis (N. beijingensis) infection in China. A 70-year-old male immunocompetent individual came to our hospital for treatment due to headache. After examination, it was found that he had a brain abscess caused by N. beijingensis. By utilizing a combination of surgical intervention and antibiotic therapy, the patient ultimately achieved full recovery. In addition, we isolated this strain and displayed its ultrastructure through scanning electron microscopy. The phylogenetic tree was analyzed by 16 S rRNA sequence. A literature review of N. beijingensis infections in all immunocompetent and immunocompromised patients was presented. It highlighted that abscess formation appears to be a common manifestation of N. beijingensis infection, and N. beijingensis has become an emerging pathogen in immunocompetent individuals. [ABSTRACT FROM AUTHOR]

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. Conclusion: 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. Strengths and limitations of this study: • A strength of this study is that it provides an updated systematic review on the management of Nocardia's isolation in patients with Cystic Fibrosis. By synthesising findings across all included studies we propose a therapeutic management algorithm. • This systematic review protocol follows the Joanna Briggs Institute, mixed-method systematic review protocol. • Limitations of the study is the paucity of randomised controlled trials and the heterogeneity among available publications. • There is potential for heterogeneity of published data, which may limit the conclusions that can be drawn from this study. [ABSTRACT FROM AUTHOR]

Introduction: Nocardia farcinica is an opportunistic bacterium that causes bovine mastitis and pulmonary, cutaneous, and central nervous system infections in humans. Bovine abortion caused by N. farcinica has been sporadically reported. The purpose of this study was to analyze the pathological findings of bovine abortions caused by N. farcinica in the Republic of Korea and determine the antimicrobial resistance and genotypical characteristics of N. farcinica isolates. Case presentation: Three cases of bovine abortions were submitted to the Animal and Plant Quarantine Agency for differential diagnosis. Grossly, one fetus showed severe lung consolidation following palpation of the entire lobes. Histologically, necrotizing granulomatous interstitial pneumonia was observed in all fetuses; a fetus with a gross lesion demonstrated necrotizing lymphadenitis in the mesenteric lymph nodes and necrotizing dermatitis in the ear. N. farcinica isolates were isolated from the abomasal contents and lungs of all fetuses. Finally, two cases were diagnosed as abortions due to N. farcinica, and one was diagnosed as an N. farcinica abortion coinfected with bovine viral diarrhea virus. According to the multilocus sequence analysis, all isolates were identified as N. farcinica and were determined to be genetically related to isolates from humans. Two N. farcinica isolates were resistant to trimethoprimsulfamethoxazole, which is recommended as the first treatment for human nocardial infections. Conclusion: This is the first pathological report of bovine abortion caused by N. farcinica in the Republic of Korea. Further studies are needed to phenotypically and genotypically characterize N. farcinica isolates with various sources and continuously monitor antimicrobial resistance patterns. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT Nocardia recovery from pulmonary samples is challenging due to the lack of a specific medium and the abundance of overgrown respiratory flora. This study aimed to compare the amoeba plate test (APT), an amoebic coculture with Acanthamoeba castellanii, with the axenic culture to recover Nocardia from pulmonary samples. Nocardia serial dilutions (n = 15 strains from seven species, concentrations ranging: 107–102 CFU/mL) in water and spiked overgrown sputa (n = 8) were simultaneously plated on agar with amoebic monolayer (APT) and without (control). Culture positivity rates, minimal growth concentrations, growth times, and abundance of flora overgrowth were compared for each condition. In water, Nocardia culture positivity rates were not significantly different between APT (86%, 30/35) and control (94%, 33/35; P = 0.246). In sputa, APT resulted in greater Nocardia growth (63%, 22/35 vs 37%, 13/35; P = 0.008). In addition, the elimination of interfering flora was more frequent using APT (34%, 12/35 vs 11%, 4/35; P = 0.01), and the overall abundance of flora was lower (median [interquartile range, IQR]: 1 [0–2] vs 3 [1-3]; P < 0.0001). The most grown species using APT were N. mexicana and N. otitidiscaviarum, whereas N. abscessus and N. nova were the most fastidious to grow under both conditions. This study reports Nocardia’s ability to grow in amoebic coculture, with some growth kinetic differences depending on the species, presumably implying their intra-amoebic multiplication. Furthermore, in APT, Nocardia recovery from overgrown sputa was greater, and flora decontamination was more effective. The present findings are strong arguments to implement APT as a complementary technique for Nocardia isolation from heavily contaminated samples.IMPORTANCEThe culture-proven diagnosis of Nocardiosis is challenging due to the difficulties in recovering Nocardia colonies from respiratory samples containing a complex polymicrobial flora. However, the isolation of Nocardia strains remains necessary to perform antibiotic susceptibility testing and adapt the antibiotic regimen of the patients. This study provides an innovative culture method based on a solid medium amoebic coculture, the amoeba plate test (APT), to cultivate Nocardia strains from clinical sputa samples. Nocardia grew across the APT amoebic monolayer. Moreover, the APT, which is already used in a reference center for the recovery of Legionella strains, exhibited good performances for Nocardia recovery and decontamination of interfering flora, thereby representing a promising second line tool to improve Nocardia culture.

AIM: Understanding the inhibitory role of bioactives from a novel Nocardia sp. against P. aeruginosa's Quorum-Sensing (QS) regulatory pathways and fabrication of effective foley catheters. BACKGROUND: P. aeruginosa‘s antimicrobial resistance is due to its biofilm formation, which reduces drug efficacy. Nocardia sp. has emerged as significant genus that produces bioactives with inhibitory effects on the biofilm. METHODS: Samples from a termite nest were used to isolate rare actinomycetes, which were tested to inhibit biofilm formation by the pathogen P. aeruginosa PAO1. Molecular interactions and regulatory effects were investigated using various techniques. RESULTS: The study details a new strain from the rare actinobacterial genus Nocardia sp., isolated from a termite nest known for its bioactive potential. The isolate's bioactive preparations inhibited P. aeruginosa biofilm formation by 86.4% without affecting growth. The significant compounds of the crude extract identified by GC-MS were docked against LasR, RhlR, and PQS (QS proteins), which showed high binding scores. The downregulation of QS system genes like lasA, lasB, rhlA, rhlB, and pqsA supports the idea that secondary metabolites act on the two main regulators of the QS. The bioactives also inhibited virulent factors viz., pyocyanin, pyoverdine, rhamnolipid, and proteases by 51.2, 81, 27.2 and 62.1%, respectively Finally, the bioactive preparation showed the potential to inhibit biofilm formation on catheters. CONCLUSIONS: The study indicates that Nocardia sp. produces compounds that can reduce biofilm formation in P. aeruginosa by targeting the QS-controlled pathogenicity. This research can benefit medical devices like catheters to resist contamination in clinical settings.

BACKGROUND: Nocardia are aerobic Gram-positive bacilli that can invade multiple organ systems, including the brain and lungs. It is most frequently found in patients who are immunocompromised. Invasive nocardial disease is a potentially life-threatening infection that can pose a diagnostic challenge. CASE PRESENTATION: Our case details a 76-year-old Indian woman with poorly-controlled diabetes mellitus admitted for confusion and falls. Imaging revealed intracranial abscesses and necrotic masses in the mediastinum and lungs. The suspected diagnosis was tuberculosis; however, she underwent extensive workup without a final diagnosis. Ultimately, a craniotomy with partial brain abscess resection was performed. Dura matter samples revealed Nocardia farcinica. CONCLUSIONS: This case illustrates the importance of considering Nocardia in patients with brain abscesses, particularly in those with immunocompromised states and demonstrates the diagnostic challenges that may arise in definitively making this diagnosis. Invasive procedures may be needed for diagnostic confirmation.

Li Zhang,1,&ast; Menglan Zhou,2,3,&ast; Ziran Wang,2,3,&ast; Hongqiong Zhu,4 Jing Lin,1,5 Minya Lu,2,3 Ying Ge,1 Yingchun Xu,2,3 Taisheng Li,1 Zhengyin Liu1 1Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal Diseases, Peking Union Medical College Hospital, Beijing, People’s Republic of China; 4Department of Infectious Disease, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 5Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengyin Liu, Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Number 1, Shuaifuyuan Road, Dongcheng District, Beijing, People’s Republic of China, Email zhengyinl@hotmail.comBackground: In China, due to the large population, infections caused by Nocardia may not be as rare. Unfortunately, there is still inadequate knowledge of the clinical impact caused by Nocardia. This study aimed to compare the clinical characteristics and treatment of localized and disseminated nocardiosis.Methods: The clinical and microbiological data of patients diagnosed with nocardiosis in a tertiary hospital in Beijing from July 2011 to July 2021 were collected and retrospectively analyzed.Results: Among the 54 nocardiosis cases, 34 cases were in the localized infection group, while 20 cases in the disseminated infection group. The proportion of patients with chronic structural lung disease was higher in the localized group (P=0.010). In contrast, patients with disseminated infections were more prone to receive long-term glucocorticoids and/or immunosuppressants (P=0.027). Pulmonary nodules were prominent features of imaging changes in patients with disseminated infections (P=0.027) whereas bronchial dilatation was more common in patients with localized infections (P=0.025). In addition, the disseminated group had longer average hospitalization days relative to the localized group (P=0.016), but there was no significant difference in mortality between them (P=0.942).Conclusion: There were differences in the clinical profiles between patients with localized and disseminated nocardiosis in terms of clinical presentation, infection site, radiological features, treatment, and prognosis. These findings may provide references for the management and treatment of patients with nocardiosis.Keywords: Nocardia, disseminated nocardiosis, immunosuppressive population

Abstract Background Nocardia is an ubiquitous soil organism. As an opportunistic pathogen, inhalation and skin inoculation are the most common routes of infection. Lungs and skin are the most frequent sites of nocardiosis. Testis is a highly unusual location for nocardiosis. Case presentation We report the case of an immunocompromised 75-year-old-man admitted for fever of unknown origin. He presented with skin lesions after gardening and was first suspected of Mediterranean spotted fever, but he did not respond to doxycycline. Then, physical examination revealed new left scrotal swelling that was compatible with a diagnosis of epididymo-orchitis. The patient’s condition did not improve despite empirical antibiotic treatment with the onset of necrotic scrotal abscesses requiring surgery. Nocardia brasiliensis yielded from the removed testis culture. High-dose trimethoprim-sulfamethoxazole and ceftriaxone were started. Multiple micro-abscesses were found in the brain and spinal cord on imaging studies. After 6 weeks of dual antibiotic therapy for disseminated nocardiosis, slight regression of the brain abscesses was observed. The patient was discharged after a 6-month course of antibiotics and remained relapse-free at that time of writing these lines. Trimethoprim-sulfamethoxazole alone is meant to be pursued for 6 months thereafter. We undertook a literature review on previously reported cases of genitourinary and urological nocardiosis; to date, only 36 cases have been published with predominately involvement of kidney, prostate and testis. Conclusions To the best of our knowledge, this is the first case of Nocardia brasiliensis simultaneously infecting skin, testis, brain and spinal cord in an immunocompromised patient. Knowledge on uncommon forms of nocardiosis remains scarce. This case report highlights the difficulty of diagnosing atypical nocardiosis and the importance of prompt bacteriological sampling in case of empirical antibiotics failure.

Abstract Background Nocardia species can affect both immunocompetent and immunocompromised people. Method This retrospective study, from 2009 to 2022, aims to compare the survival analyses of pulmonary nocardiosis in AIDS and non-AIDS patients in northeastern Thailand. Results A total of 215 culture-confirmed cases of pulmonary nocardiosis: 97 with AIDS and 118 without AIDS. The median CD4 count of AIDS patients was 11 cells/µL (range: 1–198), and 33% had concurrent opportunistic infections. 63.6% of 118 non-AIDS patients received immunosuppressive medications, 28.8% had comorbidities, and 7.6% had no coexisting conditions. Disseminated nocardiosis and pleural effusion were more prevalent among AIDS patients, whereas non-AIDS patients revealed more shock and respiratory failure. One hundred-fifty patients underwent brain imaging; 15 (10%) had brain abscesses. Patients with pulmonary nocardiosis have overall 30-day and 1-year mortality rates of 38.5% (95% CI: 32.3%, 45.4%) and 52.1% (95% CI: 45.6%, 58.9%), respectively. The Cox survival analysis showed that AIDS patients with disseminated nocardiosis had a 7.93-fold (95% CI: 2.61–24.02, p

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. [ABSTRACT FROM AUTHOR]

The present study was conducted to evaluate the effect of dietary Silphium perfoliatum L. on growth performance, immunity, intestinal health, and resistance against Nocardia seriolae of largemouth bass. Four dietary concentrations of S. perfoliatum L. were prepared: 0% (SPL0), 1% (SPL1), 2.5% (SPL2.5), and 5% (SPL5). After 60 d feeding, a challenge test was conducted by injecting N. seriolae intraperitoneally. The results showed that supplementing the diets with S. perfoliatum L. could promote the weight gain rate, specific growth rate, and feed intake. Meantime, S. perfoliatumL. could also enhance the activity of immunerelated enzymes and improve the expression of immune-related genes in the liver. Compared to the control group, S. perfoliatum L. improved intestinal morphology and reduced the abundance of harmful bacteria in intestinal microbiota. Importantly, supplementing the diets with S. perfoliatum L. protected largemouth bass from N. seriolae infection, resulting in a relative percent survival (RPS) of 24% (SPL1), 31.99% (SPL2.5), and 43.99% (SPL5). In conclusion, the present study showed that S. perfoliatum L. could boost growth performance, enhance immunity, promote intestinal health, and improve the ability of largemouth bass against N. seriolae infection. [ABSTRACT FROM AUTHOR]

Soil-dwelling Actinomycetes are a diverse and ubiquitous component of the global microbiome but largely lack genetic tools comparable to those available in model species such as Escherichia coli or Pseudomonas putida, posing a fundamental barrier to their characterization and utilization as hosts for biotechnology. To address this, we have developed a modular plasmid assembly framework, along with a series of genetic control elements for the previously genetically intractable Gram-positive environmental isolate Rhodococcus ruber C208, and demonstrate conserved functionality in 11 additional environmental isolates of Rhodococcus, Nocardia, and Gordonia. This toolkit encompasses five Mycobacteriale origins of replication, five broad-host-range antibiotic resistance markers, transcriptional and translational control elements, fluorescent reporters, a tetracycline-inducible system, and a counter-selectable marker. We use this toolkit to interrogate the carotenoid biosynthesis pathway in Rhodococcus erythropolis N9T-4, a weakly carotenogenic environmental isolate and engineer higher pathway flux toward the keto-carotenoid canthaxanthin. This work establishes several new genetic tools for environmental Mycobacteriales and provides a synthetic biology framework to support the design of complex genetic circuits in these species. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical characteristics of pulmonary tuberculosis patients complicated with infection of Nocardia farcinica aiming to improve the diagnosis and treatment the disease. Methods The clinical data of 22 cases of pulmonary tuberculosis complicated with Nocardia farcinica infection admitted to Guangzhou Chest Hospital from June 2020 to December 2023 were collected and the clinical manifestations, imaging, laboratory tests, treatment process, and disease outcomes were retrospectively analyzed. Results Among the 22 patients, there were 13 males and 9 females, aged 20 - 86 years, with a median age of 52 years. Common clinical manifestations included cough (22/22), sputum (21/22), and underlying diseases (13/22) . One case was positive for cerebrospinal fluid culture, and 21 cases were positive for sputum culture. The culture period was 5 - 26 days, with a median culture period of 18 days. The imaging manifestations were mainly plaques, plaques and cavities, and the lesions were spread in both lungs (17/22) and cavities (11/22) . After anti-tuberculosis treatment, the absorption of lung lesions in some patients was poor, and the absorption of the lesions was improved after anti-nocardia treatment. 8 cases were cured, 13 cases were improved and 1 case died. Conclusion The clinical symptoms of patients with pulmonary tuberculosis complicated with Nocardia farcinica were atypical, the culture period of Nocardia was long, and the imaging manifestations were similar to pulmonary tuberculosis, which is prone to misdiagnosis and missed diagnosis. For patients with poor response to anti-tuberculosis treatment and slow lesion absorption, the possibility of a concurrent Nocardia infection should be considered. [ABSTRACT FROM AUTHOR]