Case report: Pathology, antimicrobial resistance, and molecular characterization of bovine abortion cases caused by Nocardia farcinica in Korean native cattle.

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 trimethoprim-sulfamethoxazole, 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.

Activation of NF-κB/MAPK signaling and induction of apoptosis by salicylate synthase NbtS in Nocardia farcinica promotes neuroinflammation development.

Nocardia farcinica can cause a rare, yet potentially fatal, central nervous system infection. NbtS protein may be a key virulence factor in N. farcinica infection of the brain. In this study, we investigated the function of the virulence-associated factor NbtS in microglial cells in vitro and in infected mice in vivo. We explored the interactions between NbtS and microglial cells (BV2 and human microglial clone 3), revealing that NbtS activates the toll-like receptor 4-dependent MyD88-IRAK4-IRAK1 and MAPK/nuclear factor kappa B (NF-κB) pathways, significantly enhancing pro-inflammatory responses as indicated by increased levels of tumor necrosis factor alpha (TNF-α) and interleukin-1ß (IL-1ß), as measured by ELISA and quantitative PCR. Apoptosis was elevated in these cells, as shown by increased expression of Bax and caspase-3 and decreased Bcl-2 levels. The terminal deoxynucleotidyl transferase dUTP nick end labeling assay also confirmed the occurrence of apoptosis. In vivo, mice infected with an RS03155-deficient strain of N. farcinica exhibited higher survival rates and reduced brain inflammation, suggesting a pivotal role for the NbtS protein in the pathogenesis of Nocardia. Conservation of the RS03155 gene across Nocardia spp. was verified by PCR, and the immunogenic potential of NbtS was confirmed by Western blot analysis using sera from infected mice. These findings suggest that targeting NbtS may offer a novel therapeutic strategy against Nocardia infection. IMPORTANCE: The study presented in this article delves into the molecular underpinnings of Nocardia farcinica-induced neuroinflammation. By focusing on the salicylate synthase gene, RS03155, and its encoded protein, NbtS, we uncover a pivotal virulence factor that triggers a cascade of immunological responses leading to apoptosis in microglial cells. This research not only enhances our comprehension of the pathogenesis of Nocardia infections but also provides a potential therapeutic target. Given the rising importance of understanding host-microbe interactions within the context of the central nervous system, especially in immunocompromised individuals, the findings are of significant relevance to the field of microbiology and could inform future diagnostic and treatment modalities for Nocardia-associated neurological disorders. Our work emphasizes the need for continued research into the intricate mechanisms of microbial pathogenesis and the development of novel strategies to combat life-threatening infections.

A Diagnostic Challenge: A Case of Disseminated Nocardiosis Presenting With Generalized Lymphadenopathy in a Patient With Interleukin-12 Deficiency.

Deficiency in interleukin-12 (IL-12) can result in susceptibility to opportunistic infection, with IL-12 deficiency being a rare genetic cause. Nocardia farcinica is a gram-positive aerobic actinomycete that can cause disseminated and potentially lethal nocardiosis in immunocompromised patients. This report describes a 16-year-old male adolescent with IL-12 deficiency presenting with generalized lymphadenopathy due to disseminated Nocardia farcinica. The subject of our study is a male adolescent who exhibited clinical manifestations consistent with cholestasis. He underwent extensive workup for malignancy, suspecting cholangiocarcinoma initially. The workup turned out unremarkable, and later during his hospital stay, he deteriorated and required intensive care unit (ICU) admission, as he developed superior vena cava (SVC) syndrome from massive enlargement of mediastinal and cervical lymph nodes. During the patient's admission, it was found that he had a deficiency of interleukin-12 (IL-12). Later on, a blood culture revealed the presence of Nocardia farcinica species. Subsequently, the patient was initiated and improved drastically on an empirical antibiotic regimen consisting of amikacin, co-trimoxazole, meropenem, and moxifloxacin. Following that, the susceptibility results came out, and he was switched to oral co-trimoxazole and oral moxifloxacin as he no longer required inpatient care. This report highlights the importance of accurate diagnosis of causes of immunosuppression and early investigation, diagnosis, and management of potentially fatal opportunistic infections such as disseminated Nocardia farcinica.

Nocardia farcinica brain abscess with torque teno virus co-infection: A case report.

Background: Brain abscesses caused by Nocardia are rare and difficult to diagnose. Nocardia farcinica is among the most common species; however, the conventional diagnosis of N. farcinica infection consists of cerebrospinal fluid (CSF) and blood culture and Gram staining. These procedures prolong the time to diagnosis and initiating treatment. Case presentation: A 69-year-old woman with diabetes mellitus presented with headaches and dizziness persisting for 2 weeks, which was initially diagnosed as a brain abscess. Due to the unusual presentation and rapid progression of symptoms, she underwent surgical resection of the brain abscess. No pathogens were detected in blood or CSF cultures. However, metagenomic next-generation sequencing (mNGS) identified N. farcinica and Torque teno virus in pus extracted from the abscesses. The patient received appropriate antibiotic therapy and recovered fully without any residual neurological deficits. Conclusion: mNGS useful for prompt diagnosis and selection of antibiotic therapy for brain abscesses caused by Nocardia. Surgical intervention is necessary in some cases.

Bacteremia caused by Nocardia farcinica: a case report and literature review.

BACKGROUND: Nocardia farcinica is one of the most common Nocardia species causing human infections. It is an opportunistic pathogen that often infects people with compromised immune systems. It could invade human body through respiratory tract or skin wounds, cause local infection, and affect other organs via hematogenous dissemination. However, N. farcinica-caused bacteremia is uncommon. In this study, we report a case of bacteremia caused by N. farcinica in China. CASE PRESENTATION: An 80-year-old woman was admitted to Peking Union Medical College Hospital with recurrent fever, right abdominal pain for one and a half month, and right adrenal gland occupation. N. farcinica was identified as the causative pathogen using blood culture and plasma metagenomics next-generation sequencing (mNGS). The clinical considerations included bacteremia and adrenal gland abscess caused by Nocardia infection. As the patient was allergic to sulfanilamide, imipenem/cilastatin and linezolid were empirically administered. Unfortunately, the patient eventually died less than a month after the initiation of anti-infection treatment. CONCLUSION: N. farcinica bacteremia is rare and its clinical manifestations are not specific. Its diagnosis depends on etiological examination, which can be confirmed using techniques such as Sanger sequencing and mNGS. In this report, we have reviewed cases of Nocardia bloodstream infection reported in the past decade, hoping to improve clinicians' understanding of Nocardia bloodstream infection and help in its early diagnosis and timely treatment.

Overlapping infections of Mycobacterium canariasense and Nocardia farcinica in an immunocompetent patient: A case report.

BACKGROUND: Infections by non-tuberculous mycobacteria (NTM) have become more common in recent years. Mycobacterium canariasense (M. canariasense) was first reported as an opportunistic pathogen in 2004, but there have been very few case reports since then. Nocardia is a genus of aerobic and Gram-positive bacilli, and these species are also opportunistic pathogens and in the Mycobacteriales order. Conventional methods for diagnosis of NTM are inefficient. Metagenomic next-generation sequencing (mNGS) can rapidly detect many pathogenic microorganisms, even rare species. Most NTM and Nocardia infections occur in immunocompromised patients with atypical clinical symptoms. There are no previous reports of infection by M. canariasense and Nocardia farcinica (N. farcinica), especially in immunocompetent patients. This case report describes an immunocompetent 52-year-old woman who had overlapping infections of M. canariasense, N. farcinica, and Candida parapsilosis (C. parapsilosis) based on mNGS. CASE SUMMARY: A 52-year-old woman presented with a productive cough and chest pain for 2 wk, and recurrent episodes of moderate-grade fever for 1 wk. She received antibiotics for 1 wk at a local hospital, and experienced defervescence, but the productive cough and chest pain persisted. We collected samples of a lung lesion and alveolar lavage fluid for mNGS. The lung tissue was positive for M. canariasense, N. farcinica, and C. parapsilosis, and the alveolar lavage fluid was positive for M. canariasense. The diagnosis was pneumonia, and application of appropriate antibiotic therapy cured the patient. CONCLUSION: Etiological diagnosis is critical for patients with infectious diseases. mNGS can identify rare and novel pathogens, and does not require a priori knowledge.

A Rare Case Report of Disseminated Nocardia Farcinica Granulomatous Hepatitis and Clinical Management Experience.

Background: Nocardiosis is primarily an opportunistic infection affecting immunocompromised individuals, with a predilection for the lungs, brain, or skin in those with compromised immune function. Granulomatous hepatitis caused by Nocardia is a rare clinical manifestation. This study aims to provide a systematic overview of the clinical features of Nocardiosis caused by Nocardia farcinica, enhancing our understanding of this disease. Methods: We report a case of a 75-year-old male with no underlying diseases presenting with a history of "recurrent fever for more than 4 months", along with fatigue, poor appetite, and pleural and abdominal effusion. Despite treatment at multiple hospitals, the patient showed little improvement. Chest CT revealed chronic inflammation, small nodules, bilateral pleural effusion, and pleural thickening. Abdominal CT indicated multiple low-density lesions in the liver, multiple small calcifications, and abdominal effusion. Results: Liver biopsy suggested inflammatory changes, with focal granuloma formation. Metagenomic next-generation sequencing (mNGS) of liver tissue indicated Nocardia farcinica, leading to the final diagnosis of disseminated Nocardia farcinica granulomatous hepatitis. Conclusion: Nocardia infection is a rare disease primarily observed in immunocompromised patients but can also occur in those with normal immune function. The clinical and radiological features lack specificity; however, the utilization of mNGS technology enables rapid identification of the pathogenic microorganism. Nocardia farcinica is generally susceptible to sulfonamide drugs and amikacin, offering viable treatment options.

How an Antimicrobial Stewardship Team Treated a Nocardia farcinica-Associated Brain Abscess: A Case Report.

Nocardia species, which are ubiquitous in the environment, form lesions primarily in immunocompromised patients via oral or cutaneous infection. Some of these Nocardia species, such as N. farcinica, also infect the central nervous system via hematogenous dissemination, which rarely results in brain abscesses. Notably, N. farcinica is resistant to numerous antimicrobial drugs used in empirical therapy, necessitating the intervention of an infectious disease specialist. To date, no case of antimicrobial stewardship teams (ASTs) playing a central role in community hospitals without an infectious disease specialist has been reported. Here, we describe a case of N. farcinica-associated brain abscess in a small-to-medium-sized hospital with no infectious disease department or specialist, in which the AST assisted in the identification of the causative organism and in selecting appropriate therapeutic agents, ultimately leading to a cure. The patient was an 88-year-old man with a high fever. He had been taking prednisolone (10-15 mg/day) for approximately 1 year for pemphigoid. Considering the possibility of fever owing to bacteremia of cutaneous origin, ampicillin/sulbactam antimicrobial therapy at 6 g/day was initiated. A subsequent close examination led to the diagnosis of a brain abscess. Emergency abscess drainage was performed by a neurosurgeon, and postoperative antimicrobial combination therapy comprising ceftriaxone (4 g/day), vancomycin (2 g/day), and metronidazole (1,500 mg/day) was commenced. The AST suspected Nocardia infection earlier, but further testing was difficult to perform at this facility. Therefore, by requesting assistance from Nagoya University Hospital, we performed early bacterial identification by mass spectrometry and appropriate antimicrobial susceptibility testing by a custom panel on day 11. The patient was non-responsive to all the previously used antibiotics at the time of admission. On day 13 after admission, the patient was successfully treated with trimethoprim-sulfamethoxazole (TMP-SMX) and imipenem/cilastatin sodium, and the patient was cured. The AST can be as effective as an infectious disease specialist when a strong working relationship is established between the team and clinicians. Further, the activities of the AST can improve patient survival via active medical support in collaboration with attending physicians.

Infectious Diarrhea Caused by Nocardia farcinica in a 19-Month-Old Child.

Background: Nocardia farcinica, a pathogen known for its strong pathogenicity, is frequently implicated in skin, central nervous system, and lung infections among immunosuppressed hosts, while intestinal nocardiosis is rare. We report the case of infectious diarrhea caused by N. farcinica in a child. Case Presentation: A 19-month-old female child was admitted to the hospital with fever and diarrhea after the consumption of oranges. The etiological agent responsible for the diarrhea was identified through the examination of fecal smears using weak acid-fast staining and conducting fecal cultures. Whole-genome sequencing was employed to analyze the causative gene. Subsequent to a 5-day treatment regimen with amoxicillin-clavulanate at a dosage of 30 mg/kg every 12 hours, the child's condition improved significantly, leading to an uncomplicated discharge. Conclusion: This case illustrates the presence of intestine virulence factors in N. farcinica capable of causing diarrhea. The utilization of weak acid-fast staining in the examination of fecal smears is crucial for the accurate diagnosis of infectious diarrhea caused by Nocardia spp.

Exploring Nocardia's ecological spectrum and novel therapeutic frontiers through whole-genome sequencing: unraveling drug resistance and virulence factors.

Nocardia farcinica is the leading pathogen responsible for nocardiosis, a life-threatening infection primarily affecting immunocompromised patients. In this study, the genomic sequence of a clinically isolated N. farcinica sample was sequenced. Subsequently, the assembled genome was annotated to identify antimicrobial resistance and virulence genes, as well as plasmid and prophages. The analysis of the entire genome size was 6,021,225 bp, with a GC content of 70.78% and consists of 103 contigs and N50 values of 292,531 bp. The genome analysis revealed the presence of several antimicrobial resistance genes, including RbpA, mtrA, FAR-1, blaFAR-1, blaFAR-1_1, and rox. In addition, virulence genes such as relA, icl, and mbtH were also detected. The present study signifies that N. farcinica genome is pivotal for the understanding of antimicrobial resistance and virulence genes is crucial for comprehending resistance mechanism, and developing effective strategies to combat bacterial infections effectively, especially adhesins and toxins. This study aids in identifying crucial drug targets for combating multidrug-resistant N. farcinica in the future.

Nocardia farcinica abortion in a goat.

A female goat fetus was received by the Colorado State University-Veterinary Diagnostic Laboratory following an isolated abortion of twins by a reportedly healthy doe. Postmortem examination did not reveal any gross abnormalities. Histologic evaluation revealed pyogranulomatous and necrotizing bronchopneumonia with intracellular and extracellular gram-positive and non-acid-fast filamentous bacilli. Aerobic culture of the stomach contents and pooled lung and liver tissue yielded light growth of Nocardia sp., which was identified by MALDI-TOF MS and 16s rDNA sequencing as Nocardia farcinica.

Abdominal Abscesses Caused by Nocardia farcinica in an Immunocompromised Patient: A Case Report and Literature Review.

Nocardiosis is mainly an opportunistic infection that affects immunosuppressed individuals, with the most common manifestation being the pulmonary infection and cerebral abscesses. Abdominal abscesses caused by Nocardia is rare in diabetes patients. Here, we report a rare case of abdominal abscesses caused by Nocardia farcinica (N. farcinica) in a 56-year-old man with poorly controlled type 2 diabetes and prolonged use of corticosteroids for the treatment of secondary adrenal insufficiency. Abdominal CT suggested abdominal abscesses, and the culture of the abscess puncture fluid identified it as N. farcinica by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Treatment with a combination of trimethoprim-sulfamethoxazole (TMP-SMX) and imipenem/cilastatin (IPM/CS), along with surgical drainage and reduction in corticosteroid dosage, achieved successful outcomes in treating disseminated abdominal abscesses. Immunocompromised patients with unexplained fever, abdominal pain, and abdominal abscess should be suspected of Nocardia infection.

Brain Abscess Caused by Nocardia farcinica in a Young Immunocompetent Patient.

Cerebral nocardiosis is a rare opportunistic infectious disease that occurs mainly in immunocompromised hosts; however, immunocompetent patients may be affected too. It often results in the formation of intraparenchymal brain abscess, which represents only 2% of all cerebral abscesses. The overall mortality rate exceeds 20% in immunocompetent patients and 55% in immunocompromised patients. Bacteriological diagnosis is often confirmed only after the surgical excision of the abscess. Thus, the initiation of effective therapy is frequently delayed. Our goal is to highlight a diagnostic approach to cerebral nocardiosis in an immunocompetent patient with the purpose of accelerating the initiation of the appropriate therapy. We report a rare case of brain abscess caused by Nocardia farcinica in a 39-year-old male, a resident of New York City, USA, with a past medical history of intravenous (IV) drug use, who was admitted for altered mental status. The patient was cachectic and ill-appearing. Initial laboratory tests showed neutrophilic leukocytosis. Computed tomography (CT) of the head revealed a large ill-defined multilobulated mass of size 6 × 5 × 4.5 cm in the right cerebral hemisphere, which was confirmed with magnetic resonance imaging (MRI). The hospital course was complicated by the deterioration of mental status requiring endotracheal intubation. The patient underwent a right-sided hemicraniectomy; a wound culture identified Nocardia farcinica. The patient was started on intravenous (IV) Bactrim, which caused an allergic reaction. Thus, he was switched to IV imipenem-cilastatin. After E-test was performed, the patient was switched to oral linezolid. The initiation of targeted antibiotic therapy was crucial for the management of this patient and resulted in a good clinical outcome. In conclusion, cerebral nocardiosis, being an unusual and a potentially fatal infection, should be considered in the differential diagnosis of brain abscess even in immunocompetent hosts. Prompt bacteriological diagnosis helps to initiate a specific antimicrobial therapy. Long-term antimicrobial therapy and long-term follow-up are necessary to prevent relapse.

Disseminated Nocardia farcinica Infection and Treatment Response on F-18 Fludeoxyglucose Positron Emission Tomography Computed Tomography.

We report a rare case of nocardiosis with increased F-18 Fludeoxyglucose (F-18 FDG) uptake in widespread abscess foci of Nocardia farcinica infection in an immunocompromised patient on positron emission tomography computed tomography (PET/CT) imaging. A relatively infrequent cause of nocardiosis, N. farcinica is an opportunistic infection that may present with clinically aggressive disseminated disease. Whole-body F-18 FDG-PET/CT allows identifying the extent of disease, as well as monitoring response to therapy in patients with nocardiosis especially the disseminated form.

Evaluation of BACTEC MGIT 960 system for recovery of Nocardia from clinical specimens.

Nocardia spp. is an aerobic Gram-positive bacillus responsible for nocardiosis. Herein, we performed a retrospective study to evaluate the performance of BACTEC MGIT 960 system, in comparison with smear microscopy and blood agar plate (BAP) culture, to recover Nocardia from different clinical specimens. Furthermore, the inhibitory effect of antibiotics contained in MGIT 960 tube on Nocardia was also evaluated. The sensitivities for Nocardia recovery using smear microscopy, BAP culture, and MGIT 960 were 39.4% (54/137), 46.1% (99/215), and 81.3% (156/192), respectively. N. farcinica was the most detected species (60.4%, 136/225). In MGIT 960-recovered Nocardia strains, N. farcinica accounted for 76.9%. Furthermore, trimethoprim in MGIT 960 tube inhibited less N. farcinica growth than that of other Nocardia species, partially explaining why MGIT 960 recovered more N. farcinica from sputa. The current study demonstrated that MGIT 960 could recover Nocardia strains from heavily-contaminated samples if its components and antibiotics are redesigned.

Encephalic nocardiosis after mild COVID-19: A case report.

The COVID-19 pandemic and the associated post-acute sequelae of COVID-19 (PASC) have led to the identification of a complex disease phenotype that is associated with important changes in the immune system. Herein, we describe a unique case of Nocardia farcinica cerebral abscess in an individual with sudden immunodeficiency several months after mild COVID-19. Intravenous Bactrim and Imipenem were prescribed for 6 weeks. After this, a 12-month course of Bactrim and Clavulin was prescribed to be taken orally, given the N. farcinica infection at the level of the central nervous system. This case report highlights the need for future research into the pathophysiology of COVID-19 and PASC immune dysregulation in convalescent individuals. It also draws attention to the need for timely consideration of opportunistic infections in patients with a history of COVID-19.

Pulmonary nocardiosis with bloodstream infection diagnosed by metagenomic next-generation sequencing in a kidney transplant recipient: A case report.

BACKGROUND: Pulmonary nocardiosis is difficult to diagnose by culture and other conventional testing, and is often associated with lethal disseminated infections. This difficulty poses a great challenge to the timeliness and accuracy of clinical detection, especially in susceptible immunosuppressed individuals. Metagenomic next-generation sequencing (mNGS) has transformed the conventional diagnosis pattern by providing a rapid and precise method to assess all microorganisms in a sample. CASE SUMMARY: A 45-year-old male was hospitalized for cough, chest tightness and fatigue for 3 consecutive days. He had received a kidney transplant 42 d prior to admission. No pathogens were detected at admission. Chest computed tomography showed nodules, streak shadows and fiber lesions in both lung lobes as well as right pleural effusion. Pulmonary tuberculosis with pleural effusion was highly suspected based on the symptoms, imaging and residence in a high tuberculosis-burden area. However, anti-tuberculosis treatment was ineffective, showing no improvement in computed tomography imaging. Pleural effusion and blood samples were subsequently sent for mNGS. The results indicated Nocardia farcinica as the major pathogen. After switching to sulphamethoxazole combined with minocycline for anti-nocardiosis treatment, the patient gradually improved and was finally discharged. CONCLUSION: A case of pulmonary nocardiosis with an accompanying bloodstream infection was diagnosed and promptly treated before the dissemination of the infection. This report emphasizes the value of mNGS in the diagnosis of nocardiosis. mNGS may be an effective method for facilitating early diagnosis and prompt treatment in infectious diseases, which overcomes the shortcomings of conventional testing.

Otomastoiditis Caused by Nocardia Farcinica: A Case Report and Literature Review.

Nocardia farcinica usually infects people with impaired immune status and usually manifests in the lungs. Otomastoiditis caused by Nocardia infection is extremely rare, with only 4 cases reported to date. This report describes a case of otomastoid N. farcinica infection in an immunocompetent patient. The case was a 10-month-old immunocompetent infant who presented with an approximately 3-month history of right ear discharge for which treatment with various antibiotics had not resulted in significant improvement. Multiple cultures of secretions and pathologic examination failed to identify the causative organism. The patient then underwent right mastoidectomy. Finally, metagenomic next-generation sequencing identified the pathogen to be N. farcinica. The patient was infection-free at the 6-month follow-up but had developed labyrinthitis ossificans. Otomastoid Nocardia infection has characteristic clinical features, namely, formation of a large amount of granulation tissue and coexistence of bone destruction and new bone formation. Traditionally, Nocardia is challenging to diagnose. Metagenomic next-generation sequencing of lesions is helpful. Complete local debridement and free drainage are key to treatment.

Nocardia farcinica Pneumonia with Sepsis and a Bronchial Neoplasm in a Healthy Patient: A Case Report.

There are few reports on sepsis caused by infection with Nocardia in people with normal immune function, and there is no report on bronchial tumor caused by Nocardia. This paper describes a case of Nocardia farcinica pneumonia with sepsis and a bronchial neoplasm in a healthy patient.