Nocardiosis

Infectious Disease MONDO:0017776 Pathograph 27 Show in embeddings browser primary bacterial infectious disease

Nocardiosis is an opportunistic bacterial infection caused by environmental Nocardia species acquired through inhalation or traumatic skin inoculation. Disease most often begins in the lung, where weakly acid-fast actinomycetes survive as intracellular pathogens in phagocytes, but can disseminate hematogenously to the brain, skin, and other organs. Impaired cell-mediated immunity - most often iatrogenic, from corticosteroids and other immunosuppression - is the pivotal host factor separating containment from dissemination. Clinical disease ranges from cutaneous actinomycetoma to pulmonary nodular, consolidative, or cavitary infection and central nervous system abscesses. Management is species- and susceptibility-guided and typically relies on prolonged trimethoprim-sulfamethoxazole-based therapy, with linezolid, amikacin, carbapenems, and surgical drainage used in severe or central nervous system disease.

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9
Pathophys.
14
Phenotypes
27
Pathograph
3
Medical Actions
3
Subtypes
7
References
1
Deep Research
🏷

Classifications

Harrison's Part
INFECTIOUS DISEASES
◆

Subtypes

3
Pulmonary nocardiosis
The dominant inhalational form; it can produce cough, sputum, fever, nodular or mass-like lung opacities, consolidation, cavitation, and dissemination to extrapulmonary sites.
Show evidence (1 reference)
PMID:41319540 SUPPORT Human Clinical
"Of the 44 cases, pulmonary infection was identified in 28 cases, disseminated infection in 13 cases, and extrapulmonary single-organ infection in 3 cases."
The 44-case series identifies pulmonary infection as the largest clinical presentation group.
Cutaneous nocardiosis and actinomycetoma
Skin or subcutaneous disease follows traumatic inoculation and can present as actinomycetoma with swelling, abscesses, ulcers, scars, and draining sinuses containing Nocardia microcolonies.
Show evidence (1 reference)
PMID:33956121 SUPPORT BACKGROUND Human Clinical
"The clinical appearance includes swelling, abscesses, ulcers, scars and sinuses that drain purulent material with microbe microcolonies."
The actinomycetoma model paper's introduction summarizes the characteristic human cutaneous syndrome.
Disseminated and central nervous system nocardiosis
Hematogenous dissemination, particularly in immunosuppressed hosts, can seed the central nervous system; adult CNS cases usually show brain abscesses and have high mortality.
Show evidence (1 reference)
PMID:35700710 SUPPORT Human Clinical
"brain abscess was most common (86.9%), followed by leptomeningeal enhancement (12.1%)."
The adult systematic review identifies brain abscess as the dominant CNS presentation.
⚙

Pathophysiology

9
Environmental Nocardia Inhalation or Skin Inoculation
Environmental Nocardia enter through inhalation into the lower respiratory tract or through disrupted skin after traumatic inoculation, establishing a pulmonary or cutaneous primary focus.
Downstream
Intraphagocytic Nocardia Survival Once inhaled or inoculated, Nocardia encounter phagocytes and can persist as intracellular pathogens.
Show evidence (1 reference)
PMID:39780099 SUPPORT BACKGROUND Human Clinical
"They can result in hematogenous spread infection through the ruptured skin or respiratory tract when the host's immune system is compromised."
Supports the skin and respiratory portals of entry.
Impaired Cell-Mediated Immunity
Impaired cell-mediated immunity - most often iatrogenic (corticosteroids, calcineurin inhibitors) but also from inherited IL-12/IFN-gamma-axis defects or anti-GM-CSF autoantibodies - is the pivotal host branch point that lets Nocardia survive and disseminate rather than being contained.
T cell CL:0000084 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T cell (CL:0000084). CL:0000084 is a cell type from the Cell Ontology. macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology.
Downstream
Intraphagocytic Nocardia Survival Blunted cell-mediated immunity permits Nocardia to survive within phagocytes rather than being cleared.
Hematogenous Dissemination Impaired containment permits hematogenous dissemination from the primary focus.
Show evidence (2 references)
PMID:23429356 SUPPORT Human Clinical
"Nocardia, an intramacrophagic pathogen closely phylogenetically related to Mycobacterium, caused disease in 2 patients"
Inherited IL-12p40 deficiency (an impaired cell-mediated immunity defect) predisposed patients to Nocardia.
PMID:38915339 SUPPORT Human Clinical
"Nocardiosis, a bacterial opportunistic infection caused by Nocardia spp, has recently been reported in patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies"
Anti-GM-CSF autoantibodies, which impair macrophage activation, predispose to nocardiosis.
Intraphagocytic Nocardia Survival
Nocardia behave as intramacrophagic pathogens that survive within phagocytes. N. brasiliensis further contributes to actinomycetoma tissue injury through secreted proteases and immunosuppressive metabolites such as brasilicardin A.
macrophage CL:0000235 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves macrophage (CL:0000235). CL:0000235 is a cell type from the Cell Ontology.
defense response to bacterium GO:0042742 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves dysregulated defense response to bacterium (GO:0042742). GO:0042742 is a biological process from the Gene Ontology. ↕ DYSREGULATED
Downstream
Pulmonary Suppurative Inflammation Persistent intracellular survival drives suppurative and granulomatous pulmonary disease.
Cutaneous Actinomycetoma Lesion At a cutaneous inoculation site, persistent infection produces actinomycetoma.
Show evidence (2 references)
PMID:23429356 SUPPORT Human Clinical
"Nocardia, an intramacrophagic pathogen closely phylogenetically related to Mycobacterium, caused disease in 2 patients"
Identifies Nocardia as an intramacrophagic pathogen in susceptible humans.
PMID:33956121 SUPPORT BACKGROUND Model Organism
"Nocardia brasiliensis produces proteases that may play a role in tissue damage, as well as immunosuppressive molecules, such as brasilicardin A."
Background to the mouse actinomycetoma model links N. brasiliensis enzymes and metabolites to tissue damage and immune evasion.
Pulmonary Suppurative Inflammation
Pulmonary Nocardia infection produces suppurative and granulomatous inflammation manifesting as nodules, mass-like or patchy consolidation, and cavitation, the last markedly more frequent in immunosuppressed patients.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
Downstream
Pneumonia Pulmonary suppurative inflammation presents as lower-respiratory infection.
Pulmonary nodule Suppurative pulmonary disease forms nodular opacities.
Pulmonary cavity Suppurative pulmonary disease cavitates, especially in immunosuppressed hosts.
Ground-glass opacification Pulmonary nocardiosis produces ground-glass opacities on chest CT.
Pleural effusion Thoracic Nocardia infection is accompanied by pleural effusion.
Mediastinal lymphadenopathy Thoracic Nocardia infection is accompanied by mediastinal and hilar lymphadenopathy.
Cough Pulmonary infection produces cough.
Abnormal sputum Pulmonary infection produces sputum production.
Fever The inflammatory response produces fever.
Hematogenous Dissemination From a pulmonary focus, Nocardia can disseminate hematogenously to distant organs.
Show evidence (2 references)
PMID:41319540 SUPPORT Human Clinical
"Pulmonary imaging commonly revealed patchy, nodular, or mass-like opacities, bronchiectasis, and cavitary lesions."
The 44-case series describes mass-like and cavitary pulmonary lesions.
PMID:37185005 SUPPORT Human Clinical
"Significantly higher rates of cavitations were observed among immunosuppressed patients"
Cavitation is more frequent in immunosuppressed patients with pulmonary nocardiosis.
Cutaneous Actinomycetoma Lesion
At a cutaneous inoculation site, chronic Nocardia infection produces an actinomycetoma with swelling, abscesses, ulcers, scars, and draining sinuses containing microcolonies.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
Downstream
Cutaneous Abscess Cutaneous actinomycetoma includes abscesses and draining sinuses.
Show evidence (1 reference)
PMID:33956121 SUPPORT BACKGROUND Human Clinical
"The clinical appearance includes swelling, abscesses, ulcers, scars and sinuses that drain purulent material with microbe microcolonies."
The model paper's introduction summarizes the human cutaneous actinomycetoma syndrome.
Hematogenous Dissemination
From a pulmonary or cutaneous focus, and especially with impaired immunity, Nocardia can disseminate hematogenously to distant organs, most importantly the central nervous system.
Downstream
CNS Abscess Formation Hematogenous spread seeds the central nervous system, the highest-mortality secondary site.
Show evidence (1 reference)
PMID:41319540 SUPPORT Human Clinical
"Of the 44 cases, pulmonary infection was identified in 28 cases, disseminated infection in 13 cases, and extrapulmonary single-organ infection in 3 cases."
About one third of cases disseminated in the 44-case series.
CNS Abscess Formation
Central nervous system nocardiosis presents predominantly as brain abscess, the dominant neuroimaging lesion in adult CNS disease.
inflammatory response GO:0006954 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
Downstream
Brain Abscess CNS nocardiosis manifests as brain abscess.
Headache CNS nocardiosis commonly presents with headache.
Reduced consciousness CNS nocardiosis can present with altered mental state.
Seizure CNS nocardiosis can present with seizures among focal neurological deficits.
Show evidence (2 references)
PMID:35700710 SUPPORT Human Clinical
"Among neuroimaging findings, brain abscess was most common (86.9%), followed by leptomeningeal enhancement (12.1%)."
The CNS systematic review identifies brain abscess as the dominant CNS lesion.
PMID:35700710 SUPPORT Human Clinical
"focal neurological deficits were the commonest, followed by headache, fever, and altered mental state"
The CNS review lists headache and altered mental state among the common clinical features.
Nocardia Tetrahydrofolate Synthesis (TMP-SMX Target)
Trimethoprim-sulfamethoxazole inhibits two sequential Nocardia folate-pathway steps, bacterial dihydropteroate synthase and dihydrofolate reductase, thereby blocking tetrahydrofolate synthesis and supporting the standard co-trimoxazole backbone used for treatment and prophylaxis.
tetrahydrofolate biosynthetic process GO:0046654 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves tetrahydrofolate biosynthetic process (GO:0046654). GO:0046654 is a biological process from the Gene Ontology.
Show evidence (2 references)
PMID:23627736 SUPPORT Other
"The other two enzyme families are involved in the synthesis of tetrahydrofolate (THF), i.e. dihydropteroate synthase (DHPS) and dihydrofolate reductase."
Review support for the bacterial DHPS and DHFR folate-synthesis steps targeted by TMP-SMX.
PMID:37527397 SUPPORT In Vitro
"Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%)."
Broth-microdilution testing of clinical isolates supports TMP-SMX as an active Nocardia-directed agent.
Nocardia Ribosomal Translation (Linezolid and Amikacin Target)
Nocardia require bacterial 70S ribosomal translation; linezolid and amikacin target that conserved ribosome through the 50S and 30S subunits, respectively, providing highly active severe-disease or resistant-disease options when susceptibility testing supports their use.
translation GO:0006412 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves translation (GO:0006412). GO:0006412 is a biological process from the Gene Ontology.
Show evidence (2 references)
PMID:24336183 SUPPORT Other
"The ribosome is one of the main antibiotic targets in the bacterial cell."
Review support for the conserved bacterial ribosomal target of linezolid and amikacin.
PMID:37527397 SUPPORT In Vitro
"Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%)."
Broth-microdilution testing of clinical isolates supports linezolid and amikacin as highly active Nocardia-directed agents.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Nocardiosis Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

14
Cardiovascular 1
Mediastinal lymphadenopathy HP:0100721 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Mediastinal lymphadenopathy (HP:0100721). HP:0100721 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37185005 SUPPORT Human Clinical
"There were 20 cases (61.76%) with mediastinal and hilar lymphadenopathy"
Chest CT shows mediastinal and hilar lymphadenopathy in 61.76% of pulmonary nocardiosis cases.
Immune 3
Pneumonia HP:0002090 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pneumonia (HP:0002090). HP:0002090 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41319540 SUPPORT Human Clinical
"pulmonary infection was identified in 28 cases"
The 44-case series found pulmonary disease in most cases.
Brain Abscess HP:0030049 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Brain abscess (HP:0030049). HP:0030049 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:35700710 SUPPORT Human Clinical
"Among neuroimaging findings, brain abscess was most common (86.9%), followed by leptomeningeal enhancement (12.1%)."
The adult systematic review quantifies brain abscess as the main CNS manifestation.
Cutaneous Abscess HP:0031292 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cutaneous abscess (HP:0031292). HP:0031292 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:33956121 SUPPORT BACKGROUND Human Clinical
"The clinical appearance includes swelling, abscesses, ulcers, scars and sinuses that drain purulent material with microbe microcolonies."
The model paper's introduction summarizes abscesses as part of the human actinomycetoma presentation.
Metabolism 2
Fever HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41319540 SUPPORT Human Clinical
"The predominant symptoms included cough, sputum production, and fever"
The 44-case series lists fever among the predominant symptoms.
Pleural effusion HP:0002202 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pleural effusion (HP:0002202). HP:0002202 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37185005 SUPPORT Human Clinical
"13 (38.24%) with pleural effusion"
Pleural effusion was present in 38.24% of cases on chest CT.
Nervous System 3
Headache HP:0002315 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Headache (HP:0002315). HP:0002315 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:35700710 SUPPORT Human Clinical
"focal neurological deficits were the commonest, followed by headache, fever, and altered mental state"
The CNS systematic review lists headache among the common clinical features.
Reduced consciousness HP:0004372 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Altered mental state, annotated with Reduced consciousness (HP:0004372). HP:0004372 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:35700710 SUPPORT Human Clinical
"focal neurological deficits were the commonest, followed by headache, fever, and altered mental state"
The CNS systematic review lists altered mental state among the common clinical features.
Seizure HP:0001250 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Seizure (HP:0001250). HP:0001250 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:35700710 SUPPORT Human Clinical
"Among focal deficits, seizure (19.4%), motor weakness (17.3%), and cranial nerves involvement (13%) were the common presentations."
The CNS systematic review reports seizure among the common focal neurological deficits.
Respiratory 5
Pulmonary nodule HP:0033608 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pulmonary nodule (HP:0033608). HP:0033608 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37185005 SUPPORT Human Clinical
"Multiple or solitary nodules represented the most common CT feature"
Nodules were the most common CT feature in pulmonary nocardiosis.
Cough HP:0012735 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Cough (HP:0012735). HP:0012735 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41319540 SUPPORT Human Clinical
"The predominant symptoms included cough, sputum production, and fever"
The 44-case series lists cough among the predominant symptoms.
Abnormal sputum HP:0032016 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Sputum production, annotated with Abnormal sputum (HP:0032016). HP:0032016 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41319540 SUPPORT Human Clinical
"The predominant symptoms included cough, sputum production, and fever"
The 44-case series lists sputum production among the predominant symptoms.
Pulmonary cavity HP:0033655 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pulmonary cavity (HP:0033655). HP:0033655 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37185005 SUPPORT Human Clinical
"Significantly higher rates of cavitations were observed among immunosuppressed patients"
Cavitation is more frequent in immunosuppressed patients with pulmonary nocardiosis.
Ground-glass opacification HP:0025179 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Ground-glass opacification (HP:0025179). HP:0025179 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:37185005 SUPPORT Human Clinical
"followed by ground-glass opacities (n = 26, 76.47%), patchy consolidations"
Ground-glass opacities were the second most common CT feature (76.47%).
💊

Medical Actions

3
Trimethoprim-Sulfamethoxazole Therapy or Prophylaxis
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: co-trimoxazole CHEBI:3770 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses co-trimoxazole (CHEBI:3770). CHEBI:3770 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Co-trimoxazole is the antifolate backbone for treatment and, at sufficient dosing, prophylaxis in high-risk solid-organ transplant recipients; therapy is prolonged and should be adjusted to species identification and isolate susceptibility.
Mechanism Target:
Nocardia Tetrahydrofolate Synthesis (TMP-SMX Target) — TMP-SMX blocks sequential bacterial tetrahydrofolate-synthesis steps in susceptible Nocardia.
Show evidence (2 references)
PMID:37527397 SUPPORT In Vitro
"Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%)."
Broth-microdilution testing found high TMP-SMX activity across Nocardia species.
PMID:37865337 SUPPORT Human Clinical
"TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence)."
Meta-analysis support for co-trimoxazole as risk-reducing prophylaxis in solid organ transplant recipients.
Linezolid and Amikacin-Containing Therapy
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: linezolid CHEBI:63607 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses linezolid (CHEBI:63607). CHEBI:63607 is a therapeutic agent from Chemical Entities of Biological Interest. amikacin CHEBI:2637 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses amikacin (CHEBI:2637). CHEBI:2637 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Severe, disseminated, central nervous system, or resistant nocardiosis can require combination therapy that includes ribosome-active agents such as linezolid or amikacin while susceptibility testing is pending or when an isolate is susceptible.
Mechanism Target:
Nocardia Ribosomal Translation (Linezolid and Amikacin Target) — Linezolid and amikacin inhibit Nocardia protein synthesis through bacterial ribosomal targets.
Show evidence (1 reference)
PMID:37527397 SUPPORT In Vitro
"Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%)."
Broth-microdilution testing found linezolid and amikacin among the most active agents across Nocardia species.
Abscess Drainage or Resection
Action: Surgical ProcedureNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Surgical Procedure (NCIT:C15329). NCIT:C15329 is a clinical intervention from the NCI Thesaurus. NCIT:C15329
Platform: Surgery
Surgical drainage or resection can be added for nocardial brain abscesses or other bulky abscesses to obtain source control and microbiologic diagnosis.
Mechanism Target:
CNS Abscess Formation — Surgery removes or drains nocardial brain abscess burden.
Show evidence (1 reference)
PMID:35700710 SUPPORT Human Clinical
"patients who underwent surgery (OR 2.4, 95% CI 0.99-4.11, p value 0.046) had better survival than those treated with antimicrobial therapy alone."
The CNS systematic review found improved survival with surgery plus antimicrobials.
🌍

Environmental Factors

1
Iatrogenic immunosuppression
Corticosteroids, calcineurin inhibitors, and other immunosuppression impair the cell-mediated immunity that contains Nocardia, and are the most common predisposing context for nocardiosis, especially in solid-organ transplant recipients.
Show evidence (1 reference)
PMID:39254072 SUPPORT Human Clinical
"High-dose methylprednisolone and presence of cytomegalovirus infection within 90 days of disease development were independent risk factors for Nocardia infection."
Identifies high-dose corticosteroid and CMV as independent risk factors in transplant recipients.
Mechanism Target:
PREDISPOSES Impaired Cell-Mediated Immunity — Corticosteroid and other immunosuppressive therapy blunts cell-mediated immunity, the pivotal host defense against Nocardia.
Show evidence (1 reference)
PMID:35700710 SUPPORT Human Clinical
"Corticosteroid use was the most common predisposing factor (55.8%)."
Corticosteroid use is the most common predisposing factor in CNS nocardiosis.
🔬

Diagnosis

3
Microscopy of Gram-stained smears
Direct microscopy of Gram-stained clinical specimens showing branching, weakly acid-fast filaments is a valuable first-line method for identifying Nocardia, which is otherwise difficult to isolate.
microscopy of Gram-stained smears NCIT:C16853 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:36636850 SUPPORT REVIEW SYNTHESIS Human Clinical
"Direct microscopic examination of clinical specimens is one of the most valuable methods for the identification of Nocardia-type bacteria"
Supports direct microscopy as a valuable identification method for Nocardia.
Molecular species identification
Species-level identification uses 16S rRNA sequencing, MLSA, MALDI-TOF mass spectrometry, whole-genome sequencing, and metagenomic next-generation sequencing, which guides susceptibility-directed therapy.
molecular species identification (16S/MLSA/MALDI-TOF/WGS/mNGS) NCIT:C18194 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:42258415 SUPPORT REVIEW SYNTHESIS Human Clinical
"This review discusses molecular identification methods for Nocardia species, including recent advances in 16S rRNA gene sequencing, multilocus sequence analysis (MLSA), matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), whole-genome sequencing (WGS), and..."
Names the molecular methods used for Nocardia species identification.
Chest computed tomography
Chest CT characterizes pulmonary nocardiosis; nodules are the most common feature, with consolidation and cavitation, and cavitation is markedly more frequent in immunosuppressed patients.
chest computed tomography NCIT:C17204 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:37185005 SUPPORT Human Clinical
"Multiple or solitary nodules represented the most common CT feature"
Chest CT shows pulmonary nodules as the most common feature of pulmonary nocardiosis.
📈

Progression

2
Pulmonary or cutaneous primary infection
Infection usually begins in the lung after inhalation or in skin and subcutaneous tissue after traumatic inoculation.
Show evidence (1 reference)
PMID:41319540 SUPPORT Human Clinical
"Of the 44 cases, pulmonary infection was identified in 28 cases, disseminated infection in 13 cases, and extrapulmonary single-organ infection in 3 cases."
The 44-case series quantifies pulmonary, disseminated, and extrapulmonary presentations.
Disseminated or central nervous system disease
Invasive disease can spread hematogenously, with the central nervous system as a high-mortality secondary site.
Show evidence (1 reference)
PMID:35700710 SUPPORT Human Clinical
"Central nervous system (CNS) involvement is an important feature of disseminated disease with significant mortality and high relapse rate"
The systematic review places CNS disease in the disseminated disease spectrum.
🦠

Infectious Agent

1
Nocardia
Environmental aerobic actinomycetes that can infect humans after respiratory or cutaneous entry; human disease is caused by multiple species, including N. cyriacigeorgica, N. farcinica, N. brasiliensis, and N. asteroides.
Nocardia NCBITaxon:1817 NCBI Taxonomy (NCBITaxon)
Show evidence (1 reference)
PMID:38915339 SUPPORT Human Clinical
"Nocardiosis, a bacterial opportunistic infection caused by Nocardia spp, has recently been reported in patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies"
Identifies Nocardia species as the bacterial causes of nocardiosis.
↔️

Transmission

1
Environmental inhalation or traumatic inoculation
Nocardiosis is acquired from environmental organisms through the respiratory tract or ruptured skin and is not modeled as person-to-person transmission.
Show evidence (1 reference)
PMID:39780099 SUPPORT BACKGROUND Human Clinical
"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."
The case report's background states the environmental source and major entry routes.
{ }

Source YAML

click to show 
name: Nocardiosis
creation_date: '2026-09-25T00:00:00Z'
category: Infectious Disease
description: >-
  Nocardiosis is an opportunistic bacterial infection caused by environmental
  Nocardia species acquired through inhalation or traumatic skin inoculation.
  Disease most often begins in the lung, where weakly acid-fast actinomycetes
  survive as intracellular pathogens in phagocytes, but can disseminate
  hematogenously to the brain, skin, and other organs. Impaired cell-mediated
  immunity - most often iatrogenic, from corticosteroids and other
  immunosuppression - is the pivotal host factor separating containment from
  dissemination. Clinical disease ranges from cutaneous actinomycetoma to
  pulmonary nodular, consolidative, or cavitary infection and central nervous
  system abscesses. Management is species- and susceptibility-guided and
  typically relies on prolonged trimethoprim-sulfamethoxazole-based therapy,
  with linezolid, amikacin, carbapenems, and surgical drainage used in severe or
  central nervous system disease.
disease_term:
  preferred_term: nocardiosis
  term:
    id: MONDO:0017776
    label: nocardiosis
references:
- reference: PMID:38915339
  title: "Nocardia Infection in Patients With Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies: A Prospective Multicenter French Study."
  found_in:
  - Nocardiosis-deep-research-openscientist.md
  findings:
  - statement: >-
      Nocardiosis is a bacterial opportunistic infection caused by Nocardia
      species.
    supporting_text: >-
      Nocardiosis, a bacterial opportunistic infection caused by Nocardia spp,
      has recently been reported in patients with anti-granulocyte-macrophage
      colony-stimulating factor (GM-CSF) autoantibodies
- reference: PMID:39780099
  title: "Triple-drug antibiotic therapy for disseminated nocardial abscess in the mediastinum and brain of an immunocompetent patient: a case report."
  found_in:
  - Nocardiosis-deep-research-openscientist.md
  findings:
  - statement: >-
      Environmental Nocardia can enter through the respiratory tract or broken
      skin and then spread hematogenously.
    supporting_text: >-
      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.
- reference: PMID:41319540
  title: "Clinical characteristics and outcomes of nocardiosis: A retrospective analysis of 44 cases."
  found_in:
  - Nocardiosis-deep-research-openscientist.md
  findings:
  - statement: >-
      In a 44-case retrospective series, pulmonary nocardiosis was the dominant
      presentation and about one third of cases disseminated.
    supporting_text: >-
      Of the 44 cases, pulmonary infection was identified in 28 cases,
      disseminated infection in 13 cases, and extrapulmonary single-organ
      infection in 3 cases.
- reference: PMID:35700710
  title: "Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases."
  found_in:
  - Nocardiosis-deep-research-openscientist.md
  findings:
  - statement: >-
      CNS nocardiosis usually presents as brain abscess and carries substantial
      fatality despite combined antimicrobial and surgical treatment.
    supporting_text: >-
      Among neuroimaging findings, brain abscess was most common (86.9%),
      followed by leptomeningeal enhancement (12.1%).
- reference: PMID:33956121
  title: "Nitric oxide determines the development of actinomycetoma by Nocardia brasiliensis in eNOS knockout C57BL/6 mice."
  found_in:
  - Nocardiosis-deep-research-openscientist.md
  findings:
  - statement: >-
      Nocardia brasiliensis actinomycetoma models link Nocardia proteases and
      immunosuppressive metabolites to tissue damage and local immune evasion.
    supporting_text: >-
      Nocardia brasiliensis produces proteases that may play a role in tissue
      damage, as well as immunosuppressive molecules, such as brasilicardin A.
- reference: PMID:37527397
  title: "Phenotypic and genotypic analysis of antimicrobial resistance in Nocardia species."
  found_in:
  - Nocardiosis-deep-research-openscientist.md
  findings:
  - statement: >-
      Linezolid, trimethoprim-sulfamethoxazole, and amikacin retained high in
      vitro activity across 138 clinical Nocardia isolates, with other
      resistance patterns tracking species-specific genes and mutations.
    supporting_text: >-
      Linezolid was active against all isolates, followed by
      trimethoprim/sulfamethoxazole (93%) and amikacin (91%).
- reference: PMID:37865337
  title: "Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients: systematic review and individual patient data meta-analysis."
  found_in:
  - Nocardiosis-deep-research-openscientist.md
  findings:
  - statement: >-
      TMP-SMX prophylaxis significantly reduces the risk of nocardiosis in solid
      organ transplant recipients.
    supporting_text: >-
      TMP-SMX prophylaxis was independently associated with a significantly
      decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52,
      moderate certainty of evidence).
classifications:
  harrisons_chapter:
  - classification_value: INFECTIOUS_DISEASES
    evidence:
    - reference: PMID:38915339
      reference_title: "Nocardia Infection in Patients With Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies: A Prospective Multicenter French Study."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: >-
        Nocardiosis, a bacterial opportunistic infection caused by Nocardia spp,
        has recently been reported in patients with anti-granulocyte-macrophage
        colony-stimulating factor (GM-CSF) autoantibodies
      explanation: >-
        The prospective study defines nocardiosis as a bacterial opportunistic
        Nocardia infection, placing it in Harrison's Infectious Diseases Part.
parents:
- primary bacterial infectious disease
synonyms:
- Nocardia infection
- nocardial infection
has_subtypes:
- name: Pulmonary Nocardiosis
  display_name: Pulmonary nocardiosis
  description: >-
    The dominant inhalational form; it can produce cough, sputum, fever,
    nodular or mass-like lung opacities, consolidation, cavitation, and
    dissemination to extrapulmonary sites.
  evidence:
  - reference: PMID:41319540
    reference_title: "Clinical characteristics and outcomes of nocardiosis: A retrospective analysis of 44 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of the 44 cases, pulmonary infection was identified in 28 cases,
      disseminated infection in 13 cases, and extrapulmonary single-organ
      infection in 3 cases.
    explanation: The 44-case series identifies pulmonary infection as the largest clinical presentation group.
- name: Cutaneous Nocardiosis
  display_name: Cutaneous nocardiosis and actinomycetoma
  description: >-
    Skin or subcutaneous disease follows traumatic inoculation and can present
    as actinomycetoma with swelling, abscesses, ulcers, scars, and draining
    sinuses containing Nocardia microcolonies.
  evidence:
  - reference: PMID:33956121
    reference_title: "Nitric oxide determines the development of actinomycetoma by Nocardia brasiliensis in eNOS knockout C57BL/6 mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      The clinical appearance includes swelling, abscesses, ulcers, scars and
      sinuses that drain purulent material with microbe microcolonies.
    explanation: The actinomycetoma model paper's introduction summarizes the characteristic human cutaneous syndrome.
- name: Disseminated or CNS Nocardiosis
  display_name: Disseminated and central nervous system nocardiosis
  description: >-
    Hematogenous dissemination, particularly in immunosuppressed hosts, can
    seed the central nervous system; adult CNS cases usually show brain
    abscesses and have high mortality.
  evidence:
  - reference: PMID:35700710
    reference_title: "Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      brain abscess was most common (86.9%), followed by leptomeningeal
      enhancement (12.1%).
    explanation: The adult systematic review identifies brain abscess as the dominant CNS presentation.
infectious_agent:
- name: Nocardia
  description: >-
    Environmental aerobic actinomycetes that can infect humans after respiratory
    or cutaneous entry; human disease is caused by multiple species, including
    N. cyriacigeorgica, N. farcinica, N. brasiliensis, and N. asteroides.
  infectious_agent_term:
    preferred_term: Nocardia
    term:
      id: NCBITaxon:1817
      label: Nocardia
  evidence:
  - reference: PMID:38915339
    reference_title: "Nocardia Infection in Patients With Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies: A Prospective Multicenter French Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Nocardiosis, a bacterial opportunistic infection caused by Nocardia spp,
      has recently been reported in patients with anti-granulocyte-macrophage
      colony-stimulating factor (GM-CSF) autoantibodies
    explanation: Identifies Nocardia species as the bacterial causes of nocardiosis.
transmission:
- name: Environmental inhalation or traumatic inoculation
  description: >-
    Nocardiosis is acquired from environmental organisms through the respiratory
    tract or ruptured skin and is not modeled as person-to-person transmission.
  evidence:
  - reference: PMID:39780099
    reference_title: "Triple-drug antibiotic therapy for disseminated nocardial abscess in the mediastinum and brain of an immunocompetent patient: a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      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.
    explanation: The case report's background states the environmental source and major entry routes.
environmental:
- name: Iatrogenic immunosuppression
  description: >-
    Corticosteroids, calcineurin inhibitors, and other immunosuppression impair
    the cell-mediated immunity that contains Nocardia, and are the most common
    predisposing context for nocardiosis, especially in solid-organ transplant
    recipients.
  influences_mechanisms:
  - target: Impaired Cell-Mediated Immunity
    environmental_effect: PREDISPOSES
    causal_link_type: DIRECT
    description: >-
      Corticosteroid and other immunosuppressive therapy blunts cell-mediated
      immunity, the pivotal host defense against Nocardia.
    evidence:
    - reference: PMID:35700710
      reference_title: "Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Corticosteroid use was the most common predisposing factor (55.8%)."
      explanation: Corticosteroid use is the most common predisposing factor in CNS nocardiosis.
  evidence:
  - reference: PMID:39254072
    reference_title: "Pulmonary Nocardiosis in Renal Transplant Recipients From Pakistan: Risk Factors, Clinical Presentation, and Mortality."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      High-dose methylprednisolone and presence of cytomegalovirus infection
      within 90 days of disease development were independent risk factors for
      Nocardia infection.
    explanation: Identifies high-dose corticosteroid and CMV as independent risk factors in transplant recipients.
progression:
- phase: Pulmonary or cutaneous primary infection
  notes: >-
    Infection usually begins in the lung after inhalation or in skin and
    subcutaneous tissue after traumatic inoculation.
  evidence:
  - reference: PMID:41319540
    reference_title: "Clinical characteristics and outcomes of nocardiosis: A retrospective analysis of 44 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of the 44 cases, pulmonary infection was identified in 28 cases,
      disseminated infection in 13 cases, and extrapulmonary single-organ
      infection in 3 cases.
    explanation: The 44-case series quantifies pulmonary, disseminated, and extrapulmonary presentations.
- phase: Disseminated or central nervous system disease
  notes: >-
    Invasive disease can spread hematogenously, with the central nervous system
    as a high-mortality secondary site.
  evidence:
  - reference: PMID:35700710
    reference_title: "Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Central nervous system (CNS) involvement is an important feature of
      disseminated disease with significant mortality and high relapse rate
    explanation: The systematic review places CNS disease in the disseminated disease spectrum.
diagnosis:
- name: Microscopy of Gram-stained smears
  description: >-
    Direct microscopy of Gram-stained clinical specimens showing branching,
    weakly acid-fast filaments is a valuable first-line method for identifying
    Nocardia, which is otherwise difficult to isolate.
  diagnosis_term:
    preferred_term: microscopy of Gram-stained smears
    term:
      id: NCIT:C16853
      label: Microscopy
  evidence:
  - reference: PMID:36636850
    reference_title: "[The Importance of Gram-stained Smears in the Diagnosis of Nocardia Infections]."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Direct microscopic examination of clinical specimens is one of the most
      valuable methods for the identification of Nocardia-type bacteria
    explanation: Supports direct microscopy as a valuable identification method for Nocardia.
- name: Molecular species identification
  description: >-
    Species-level identification uses 16S rRNA sequencing, MLSA, MALDI-TOF mass
    spectrometry, whole-genome sequencing, and metagenomic next-generation
    sequencing, which guides susceptibility-directed therapy.
  diagnosis_term:
    preferred_term: molecular species identification (16S/MLSA/MALDI-TOF/WGS/mNGS)
    term:
      id: NCIT:C18194
      label: Molecular Diagnostic Method
  evidence:
  - reference: PMID:42258415
    reference_title: "Species Identification And Antibiotic Susceptibility Testing Of The Nocardia Genus: Advances And Clinical Challenges."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      This review discusses molecular identification methods for Nocardia
      species, including recent advances in 16S rRNA gene sequencing, multilocus
      sequence analysis (MLSA), matrix-assisted laser desorption
      ionization-time-of-flight mass spectrometry (MALDI-TOF MS), whole-genome
      sequencing (WGS), and metagenomic next-generation sequencing (mNGS).
    explanation: Names the molecular methods used for Nocardia species identification.
- name: Chest computed tomography
  description: >-
    Chest CT characterizes pulmonary nocardiosis; nodules are the most common
    feature, with consolidation and cavitation, and cavitation is markedly more
    frequent in immunosuppressed patients.
  diagnosis_term:
    preferred_term: chest computed tomography
    term:
      id: NCIT:C17204
      label: Computed Tomography
  evidence:
  - reference: PMID:37185005
    reference_title: "The Computed Tomography Findings and Follow-up Course of Pulmonary Nocardiosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Multiple or solitary nodules represented the most common CT feature"
    explanation: Chest CT shows pulmonary nodules as the most common feature of pulmonary nocardiosis.
pathophysiology:
- name: Environmental Nocardia Inhalation or Skin Inoculation
  description: >-
    Environmental Nocardia enter through inhalation into the lower respiratory
    tract or through disrupted skin after traumatic inoculation, establishing a
    pulmonary or cutaneous primary focus.
  role: trigger
  evidence:
  - reference: PMID:39780099
    reference_title: "Triple-drug antibiotic therapy for disseminated nocardial abscess in the mediastinum and brain of an immunocompetent patient: a case report."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      They can result in hematogenous spread infection through the ruptured skin
      or respiratory tract when the host's immune system is compromised.
    explanation: Supports the skin and respiratory portals of entry.
  downstream:
  - target: Intraphagocytic Nocardia Survival
    description: >-
      Once inhaled or inoculated, Nocardia encounter phagocytes and can persist
      as intracellular pathogens.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Impaired Cell-Mediated Immunity
  description: >-
    Impaired cell-mediated immunity - most often iatrogenic (corticosteroids,
    calcineurin inhibitors) but also from inherited IL-12/IFN-gamma-axis defects
    or anti-GM-CSF autoantibodies - is the pivotal host branch point that lets
    Nocardia survive and disseminate rather than being contained.
  role: disposition
  cell_types:
  - preferred_term: T cell
    term:
      id: CL:0000084
      label: T cell
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  evidence:
  - reference: PMID:23429356
    reference_title: "Inherited IL-12p40 deficiency: genetic, immunologic, and clinical features of 49 patients from 30 kindreds."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Nocardia, an intramacrophagic pathogen closely phylogenetically related to
      Mycobacterium, caused disease in 2 patients
    explanation: Inherited IL-12p40 deficiency (an impaired cell-mediated immunity defect) predisposed patients to Nocardia.
  - reference: PMID:38915339
    reference_title: "Nocardia Infection in Patients With Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies: A Prospective Multicenter French Study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Nocardiosis, a bacterial opportunistic infection caused by Nocardia spp,
      has recently been reported in patients with anti-granulocyte-macrophage
      colony-stimulating factor (GM-CSF) autoantibodies
    explanation: Anti-GM-CSF autoantibodies, which impair macrophage activation, predispose to nocardiosis.
  downstream:
  - target: Intraphagocytic Nocardia Survival
    description: >-
      Blunted cell-mediated immunity permits Nocardia to survive within
      phagocytes rather than being cleared.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Hematogenous Dissemination
    description: >-
      Impaired containment permits hematogenous dissemination from the primary
      focus.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Intraphagocytic Nocardia Survival
  description: >-
    Nocardia behave as intramacrophagic pathogens that survive within phagocytes.
    N. brasiliensis further contributes to actinomycetoma tissue injury through
    secreted proteases and immunosuppressive metabolites such as brasilicardin A.
  role: consequence
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: defense response to bacterium
    modifier: DYSREGULATED
    term:
      id: GO:0042742
      label: defense response to bacterium
  evidence:
  - reference: PMID:23429356
    reference_title: "Inherited IL-12p40 deficiency: genetic, immunologic, and clinical features of 49 patients from 30 kindreds."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Nocardia, an intramacrophagic pathogen closely phylogenetically related to
      Mycobacterium, caused disease in 2 patients
    explanation: Identifies Nocardia as an intramacrophagic pathogen in susceptible humans.
  - reference: PMID:33956121
    reference_title: "Nitric oxide determines the development of actinomycetoma by Nocardia brasiliensis in eNOS knockout C57BL/6 mice."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    quote_role: BACKGROUND
    snippet: >-
      Nocardia brasiliensis produces proteases that may play a role in tissue
      damage, as well as immunosuppressive molecules, such as brasilicardin A.
    explanation: Background to the mouse actinomycetoma model links N. brasiliensis enzymes and metabolites to tissue damage and immune evasion.
  downstream:
  - target: Pulmonary Suppurative Inflammation
    description: >-
      Persistent intracellular survival drives suppurative and granulomatous
      pulmonary disease.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Cutaneous Actinomycetoma Lesion
    description: >-
      At a cutaneous inoculation site, persistent infection produces
      actinomycetoma.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Pulmonary Suppurative Inflammation
  description: >-
    Pulmonary Nocardia infection produces suppurative and granulomatous
    inflammation manifesting as nodules, mass-like or patchy consolidation, and
    cavitation, the last markedly more frequent in immunosuppressed patients.
  role: consequence
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:41319540
    reference_title: "Clinical characteristics and outcomes of nocardiosis: A retrospective analysis of 44 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Pulmonary imaging commonly revealed patchy, nodular, or mass-like
      opacities, bronchiectasis, and cavitary lesions.
    explanation: The 44-case series describes mass-like and cavitary pulmonary lesions.
  - reference: PMID:37185005
    reference_title: "The Computed Tomography Findings and Follow-up Course of Pulmonary Nocardiosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Significantly higher rates of cavitations were observed among
      immunosuppressed patients
    explanation: Cavitation is more frequent in immunosuppressed patients with pulmonary nocardiosis.
  downstream:
  - target: Pneumonia
    description: Pulmonary suppurative inflammation presents as lower-respiratory infection.
  - target: Pulmonary nodule
    description: Suppurative pulmonary disease forms nodular opacities.
  - target: Pulmonary cavity
    description: Suppurative pulmonary disease cavitates, especially in immunosuppressed hosts.
  - target: Ground-glass opacification
    description: Pulmonary nocardiosis produces ground-glass opacities on chest CT.
  - target: Pleural effusion
    description: Thoracic Nocardia infection is accompanied by pleural effusion.
  - target: Mediastinal lymphadenopathy
    description: Thoracic Nocardia infection is accompanied by mediastinal and hilar lymphadenopathy.
  - target: Cough
    description: Pulmonary infection produces cough.
  - target: Abnormal sputum
    description: Pulmonary infection produces sputum production.
  - target: Fever
    description: The inflammatory response produces fever.
  - target: Hematogenous Dissemination
    description: >-
      From a pulmonary focus, Nocardia can disseminate hematogenously to distant
      organs.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Cutaneous Actinomycetoma Lesion
  description: >-
    At a cutaneous inoculation site, chronic Nocardia infection produces an
    actinomycetoma with swelling, abscesses, ulcers, scars, and draining sinuses
    containing microcolonies.
  role: consequence
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:33956121
    reference_title: "Nitric oxide determines the development of actinomycetoma by Nocardia brasiliensis in eNOS knockout C57BL/6 mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      The clinical appearance includes swelling, abscesses, ulcers, scars and
      sinuses that drain purulent material with microbe microcolonies.
    explanation: The model paper's introduction summarizes the human cutaneous actinomycetoma syndrome.
  downstream:
  - target: Cutaneous Abscess
    description: Cutaneous actinomycetoma includes abscesses and draining sinuses.
- name: Hematogenous Dissemination
  description: >-
    From a pulmonary or cutaneous focus, and especially with impaired immunity,
    Nocardia can disseminate hematogenously to distant organs, most importantly
    the central nervous system.
  role: consequence
  evidence:
  - reference: PMID:41319540
    reference_title: "Clinical characteristics and outcomes of nocardiosis: A retrospective analysis of 44 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Of the 44 cases, pulmonary infection was identified in 28 cases,
      disseminated infection in 13 cases, and extrapulmonary single-organ
      infection in 3 cases.
    explanation: About one third of cases disseminated in the 44-case series.
  downstream:
  - target: CNS Abscess Formation
    description: >-
      Hematogenous spread seeds the central nervous system, the highest-mortality
      secondary site.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: CNS Abscess Formation
  description: >-
    Central nervous system nocardiosis presents predominantly as brain abscess,
    the dominant neuroimaging lesion in adult CNS disease.
  role: consequence
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:35700710
    reference_title: "Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Among neuroimaging findings, brain abscess was most common (86.9%),
      followed by leptomeningeal enhancement (12.1%).
    explanation: The CNS systematic review identifies brain abscess as the dominant CNS lesion.
  - reference: PMID:35700710
    reference_title: "Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      focal neurological deficits were the commonest, followed by headache,
      fever, and altered mental state
    explanation: The CNS review lists headache and altered mental state among the common clinical features.
  downstream:
  - target: Brain Abscess
    description: CNS nocardiosis manifests as brain abscess.
  - target: Headache
    description: CNS nocardiosis commonly presents with headache.
  - target: Reduced consciousness
    description: CNS nocardiosis can present with altered mental state.
  - target: Seizure
    description: CNS nocardiosis can present with seizures among focal neurological deficits.
- name: Nocardia Tetrahydrofolate Synthesis (TMP-SMX Target)
  description: >-
    Trimethoprim-sulfamethoxazole inhibits two sequential Nocardia folate-pathway
    steps, bacterial dihydropteroate synthase and dihydrofolate reductase,
    thereby blocking tetrahydrofolate synthesis and supporting the standard
    co-trimoxazole backbone used for treatment and prophylaxis.
  role: therapeutic_vulnerability
  conforms_to: "bacterial_folate_synthesis_inhibition#Bacterial Tetrahydrofolate Synthesis (Antifolate Target)"
  biological_processes:
  - preferred_term: tetrahydrofolate biosynthetic process
    term:
      id: GO:0046654
      label: tetrahydrofolate biosynthetic process
  evidence:
  - reference: PMID:23627736
    reference_title: "Sulfa and trimethoprim-like drugs - antimetabolites acting as carbonic anhydrase, dihydropteroate synthase and dihydrofolate reductase inhibitors."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      The other two enzyme families are involved in the synthesis of
      tetrahydrofolate (THF), i.e. dihydropteroate synthase (DHPS) and
      dihydrofolate reductase.
    explanation: Review support for the bacterial DHPS and DHFR folate-synthesis steps targeted by TMP-SMX.
  - reference: PMID:37527397
    reference_title: "Phenotypic and genotypic analysis of antimicrobial resistance in Nocardia species."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Linezolid was active against all isolates, followed by
      trimethoprim/sulfamethoxazole (93%) and amikacin (91%).
    explanation: Broth-microdilution testing of clinical isolates supports TMP-SMX as an active Nocardia-directed agent.
- name: Nocardia Ribosomal Translation (Linezolid and Amikacin Target)
  description: >-
    Nocardia require bacterial 70S ribosomal translation; linezolid and amikacin
    target that conserved ribosome through the 50S and 30S subunits,
    respectively, providing highly active severe-disease or resistant-disease
    options when susceptibility testing supports their use.
  role: therapeutic_vulnerability
  conforms_to: "bacterial_protein_synthesis_inhibition#Bacterial mRNA Translation by the Ribosome"
  biological_processes:
  - preferred_term: translation
    term:
      id: GO:0006412
      label: translation
  evidence:
  - reference: PMID:24336183
    reference_title: "Ribosome-targeting antibiotics and mechanisms of bacterial resistance."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "The ribosome is one of the main antibiotic targets in the bacterial cell."
    explanation: Review support for the conserved bacterial ribosomal target of linezolid and amikacin.
  - reference: PMID:37527397
    reference_title: "Phenotypic and genotypic analysis of antimicrobial resistance in Nocardia species."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Linezolid was active against all isolates, followed by
      trimethoprim/sulfamethoxazole (93%) and amikacin (91%).
    explanation: Broth-microdilution testing of clinical isolates supports linezolid and amikacin as highly active Nocardia-directed agents.
phenotypes:
- name: Pneumonia
  description: Pulmonary infection is the most common clinical form of nocardiosis.
  subtype: Pulmonary Nocardiosis
  phenotype_term:
    preferred_term: Pneumonia
    term:
      id: HP:0002090
      label: Pneumonia
  evidence:
  - reference: PMID:41319540
    reference_title: "Clinical characteristics and outcomes of nocardiosis: A retrospective analysis of 44 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      pulmonary infection was identified in 28 cases
    explanation: The 44-case series found pulmonary disease in most cases.
- name: Pulmonary nodule
  description: Nodules are the most common CT feature of pulmonary nocardiosis.
  subtype: Pulmonary Nocardiosis
  phenotype_term:
    preferred_term: Pulmonary nodule
    term:
      id: HP:0033608
      label: Pulmonary nodule
  evidence:
  - reference: PMID:37185005
    reference_title: "The Computed Tomography Findings and Follow-up Course of Pulmonary Nocardiosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Multiple or solitary nodules represented the most common CT feature"
    explanation: Nodules were the most common CT feature in pulmonary nocardiosis.
- name: Cough
  description: Cough is a common pulmonary nocardiosis symptom.
  subtype: Pulmonary Nocardiosis
  phenotype_term:
    preferred_term: Cough
    term:
      id: HP:0012735
      label: Cough
  evidence:
  - reference: PMID:41319540
    reference_title: "Clinical characteristics and outcomes of nocardiosis: A retrospective analysis of 44 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The predominant symptoms included cough, sputum production, and fever"
    explanation: The 44-case series lists cough among the predominant symptoms.
- name: Abnormal sputum
  description: Sputum production is a common pulmonary nocardiosis symptom.
  subtype: Pulmonary Nocardiosis
  phenotype_term:
    preferred_term: Sputum production
    term:
      id: HP:0032016
      label: Abnormal sputum
  evidence:
  - reference: PMID:41319540
    reference_title: "Clinical characteristics and outcomes of nocardiosis: A retrospective analysis of 44 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The predominant symptoms included cough, sputum production, and fever"
    explanation: The 44-case series lists sputum production among the predominant symptoms.
- name: Fever
  description: Fever occurs among the predominant nonspecific manifestations.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:41319540
    reference_title: "Clinical characteristics and outcomes of nocardiosis: A retrospective analysis of 44 cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The predominant symptoms included cough, sputum production, and fever"
    explanation: The 44-case series lists fever among the predominant symptoms.
- name: Brain Abscess
  description: Brain abscess is the dominant lesion in adult central nervous system nocardiosis.
  subtype: Disseminated or CNS Nocardiosis
  phenotype_term:
    preferred_term: Brain abscess
    term:
      id: HP:0030049
      label: Brain abscess
  evidence:
  - reference: PMID:35700710
    reference_title: "Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Among neuroimaging findings, brain abscess was most common (86.9%),
      followed by leptomeningeal enhancement (12.1%).
    explanation: The adult systematic review quantifies brain abscess as the main CNS manifestation.
- name: Cutaneous Abscess
  description: Cutaneous Nocardia actinomycetoma forms abscesses and draining sinuses.
  subtype: Cutaneous Nocardiosis
  phenotype_term:
    preferred_term: Cutaneous abscess
    term:
      id: HP:0031292
      label: Cutaneous abscess
  evidence:
  - reference: PMID:33956121
    reference_title: "Nitric oxide determines the development of actinomycetoma by Nocardia brasiliensis in eNOS knockout C57BL/6 mice."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: BACKGROUND
    snippet: >-
      The clinical appearance includes swelling, abscesses, ulcers, scars and
      sinuses that drain purulent material with microbe microcolonies.
    explanation: The model paper's introduction summarizes abscesses as part of the human actinomycetoma presentation.
- name: Pulmonary cavity
  description: Cavitation is a common chest-CT finding, markedly more frequent in immunosuppressed patients.
  subtype: Pulmonary Nocardiosis
  phenotype_term:
    preferred_term: Pulmonary cavity
    term:
      id: HP:0033655
      label: Pulmonary cavity
  evidence:
  - reference: PMID:37185005
    reference_title: "The Computed Tomography Findings and Follow-up Course of Pulmonary Nocardiosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Significantly higher rates of cavitations were observed among
      immunosuppressed patients
    explanation: Cavitation is more frequent in immunosuppressed patients with pulmonary nocardiosis.
- name: Mediastinal lymphadenopathy
  description: Thoracic nocardiosis is accompanied by mediastinal and hilar lymphadenopathy on CT.
  subtype: Pulmonary Nocardiosis
  phenotype_term:
    preferred_term: Mediastinal lymphadenopathy
    term:
      id: HP:0100721
      label: Mediastinal lymphadenopathy
  evidence:
  - reference: PMID:37185005
    reference_title: "The Computed Tomography Findings and Follow-up Course of Pulmonary Nocardiosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "There were 20 cases (61.76%) with mediastinal and hilar lymphadenopathy"
    explanation: Chest CT shows mediastinal and hilar lymphadenopathy in 61.76% of pulmonary nocardiosis cases.
- name: Ground-glass opacification
  description: Ground-glass opacities are the second most common chest-CT finding in pulmonary nocardiosis.
  subtype: Pulmonary Nocardiosis
  phenotype_term:
    preferred_term: Ground-glass opacification
    term:
      id: HP:0025179
      label: Ground-glass opacification
  evidence:
  - reference: PMID:37185005
    reference_title: "The Computed Tomography Findings and Follow-up Course of Pulmonary Nocardiosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "followed by ground-glass opacities (n = 26, 76.47%), patchy consolidations"
    explanation: Ground-glass opacities were the second most common CT feature (76.47%).
- name: Pleural effusion
  description: Pleural effusion is a chest-CT finding in pulmonary nocardiosis.
  subtype: Pulmonary Nocardiosis
  phenotype_term:
    preferred_term: Pleural effusion
    term:
      id: HP:0002202
      label: Pleural effusion
  evidence:
  - reference: PMID:37185005
    reference_title: "The Computed Tomography Findings and Follow-up Course of Pulmonary Nocardiosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "13 (38.24%) with pleural effusion"
    explanation: Pleural effusion was present in 38.24% of cases on chest CT.
- name: Headache
  description: Headache is a common presenting feature of CNS nocardiosis.
  subtype: Disseminated or CNS Nocardiosis
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:35700710
    reference_title: "Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      focal neurological deficits were the commonest, followed by headache,
      fever, and altered mental state
    explanation: The CNS systematic review lists headache among the common clinical features.
- name: Reduced consciousness
  description: Altered mental state is a common presenting feature of CNS nocardiosis.
  subtype: Disseminated or CNS Nocardiosis
  phenotype_term:
    preferred_term: Altered mental state
    term:
      id: HP:0004372
      label: Reduced consciousness
  evidence:
  - reference: PMID:35700710
    reference_title: "Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      focal neurological deficits were the commonest, followed by headache,
      fever, and altered mental state
    explanation: The CNS systematic review lists altered mental state among the common clinical features.
- name: Seizure
  description: Seizures occur among the focal neurological deficits of CNS nocardiosis.
  subtype: Disseminated or CNS Nocardiosis
  phenotype_term:
    preferred_term: Seizure
    term:
      id: HP:0001250
      label: Seizure
  evidence:
  - reference: PMID:35700710
    reference_title: "Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Among focal deficits, seizure (19.4%), motor weakness (17.3%), and cranial
      nerves involvement (13%) were the common presentations.
    explanation: The CNS systematic review reports seizure among the common focal neurological deficits.
treatments:
- name: Trimethoprim-Sulfamethoxazole Therapy or Prophylaxis
  description: >-
    Co-trimoxazole is the antifolate backbone for treatment and, at sufficient
    dosing, prophylaxis in high-risk solid-organ transplant recipients; therapy
    is prolonged and should be adjusted to species identification and isolate
    susceptibility.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: co-trimoxazole
      term:
        id: CHEBI:3770
        label: co-trimoxazole
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: Nocardia Tetrahydrofolate Synthesis (TMP-SMX Target)
    description: TMP-SMX blocks sequential bacterial tetrahydrofolate-synthesis steps in susceptible Nocardia.
  evidence:
  - reference: PMID:37527397
    reference_title: "Phenotypic and genotypic analysis of antimicrobial resistance in Nocardia species."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Linezolid was active against all isolates, followed by
      trimethoprim/sulfamethoxazole (93%) and amikacin (91%).
    explanation: Broth-microdilution testing found high TMP-SMX activity across Nocardia species.
  - reference: PMID:37865337
    reference_title: "Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients: systematic review and individual patient data meta-analysis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      TMP-SMX prophylaxis was independently associated with a significantly
      decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52,
      moderate certainty of evidence).
    explanation: Meta-analysis support for co-trimoxazole as risk-reducing prophylaxis in solid organ transplant recipients.
- name: Linezolid and Amikacin-Containing Therapy
  description: >-
    Severe, disseminated, central nervous system, or resistant nocardiosis can
    require combination therapy that includes ribosome-active agents such as
    linezolid or amikacin while susceptibility testing is pending or when an
    isolate is susceptible.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: linezolid
      term:
        id: CHEBI:63607
        label: linezolid
    - preferred_term: amikacin
      term:
        id: CHEBI:2637
        label: amikacin
  therapeutic_modality: SMALL_MOLECULE
  target_mechanisms:
  - target: Nocardia Ribosomal Translation (Linezolid and Amikacin Target)
    description: Linezolid and amikacin inhibit Nocardia protein synthesis through bacterial ribosomal targets.
  evidence:
  - reference: PMID:37527397
    reference_title: "Phenotypic and genotypic analysis of antimicrobial resistance in Nocardia species."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Linezolid was active against all isolates, followed by
      trimethoprim/sulfamethoxazole (93%) and amikacin (91%).
    explanation: Broth-microdilution testing found linezolid and amikacin among the most active agents across Nocardia species.
- name: Abscess Drainage or Resection
  description: >-
    Surgical drainage or resection can be added for nocardial brain abscesses or
    other bulky abscesses to obtain source control and microbiologic diagnosis.
  therapeutic_modality: SURGERY
  target_mechanisms:
  - target: CNS Abscess Formation
    description: Surgery removes or drains nocardial brain abscess burden.
  treatment_term:
    preferred_term: Surgical Procedure
    term:
      id: NCIT:C15329
      label: Surgical Procedure
  evidence:
  - reference: PMID:35700710
    reference_title: "Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      patients who underwent surgery (OR 2.4, 95% CI 0.99-4.11, p value 0.046)
      had better survival than those treated with antimicrobial therapy alone.
    explanation: The CNS systematic review found improved survival with surgery plus antimicrobials.
notes: >-
  OLS MONDO searches did not find pulmonary, cutaneous, disseminated, or central
  nervous system nocardiosis subtype terms. Those anatomical forms are
  represented as ungrounded subtypes until suitable MONDO classes exist. The
  `Intraphagocytic Nocardia Survival` node deliberately carries no `conforms_to`
  to `intracellular_pathogen_persistence`: both nodes of that module assert
  beta-lactam / cell-wall-active exclusion, whereas Nocardia is treated with
  carbapenems and ceftriaxone in severe or CNS disease, so conforming would
  assert a therapeutic exclusion this disease contradicts.
📚

References & Deep Research

References

7
PMID:38915339
Nocardia Infection in Patients With Anti-Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies: A Prospective Multicenter French Study.
1 finding
Nocardiosis is a bacterial opportunistic infection caused by Nocardia species.
"Nocardiosis, a bacterial opportunistic infection caused by Nocardia spp, has recently been reported in patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies"
PMID:39780099
Triple-drug antibiotic therapy for disseminated nocardial abscess in the mediastinum and brain of an immunocompetent patient: a case report.
1 finding
Environmental Nocardia can enter through the respiratory tract or broken skin and then spread hematogenously.
"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."
PMID:41319540
Clinical characteristics and outcomes of nocardiosis: A retrospective analysis of 44 cases.
1 finding
In a 44-case retrospective series, pulmonary nocardiosis was the dominant presentation and about one third of cases disseminated.
"Of the 44 cases, pulmonary infection was identified in 28 cases, disseminated infection in 13 cases, and extrapulmonary single-organ infection in 3 cases."
PMID:35700710
Clinical Characteristics and Treatment Outcome of Central Nervous System Nocardiosis: A Systematic Review of Reported Cases.
1 finding
CNS nocardiosis usually presents as brain abscess and carries substantial fatality despite combined antimicrobial and surgical treatment.
"Among neuroimaging findings, brain abscess was most common (86.9%), followed by leptomeningeal enhancement (12.1%)."
PMID:33956121
Nitric oxide determines the development of actinomycetoma by Nocardia brasiliensis in eNOS knockout C57BL/6 mice.
1 finding
Nocardia brasiliensis actinomycetoma models link Nocardia proteases and immunosuppressive metabolites to tissue damage and local immune evasion.
"Nocardia brasiliensis produces proteases that may play a role in tissue damage, as well as immunosuppressive molecules, such as brasilicardin A."
PMID:37527397
Phenotypic and genotypic analysis of antimicrobial resistance in Nocardia species.
1 finding
Linezolid, trimethoprim-sulfamethoxazole, and amikacin retained high in vitro activity across 138 clinical Nocardia isolates, with other resistance patterns tracking species-specific genes and mutations.
"Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%)."
PMID:37865337
Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients: systematic review and individual patient data meta-analysis.
1 finding
TMP-SMX prophylaxis significantly reduces the risk of nocardiosis in solid organ transplant recipients.
"TMP-SMX prophylaxis was independently associated with a significantly decreased risk of nocardiosis (adjusted OR = 0.3, 95% CI 0.18-0.52, moderate certainty of evidence)."

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Nocardiosis · 2026-09-25T04:54:05Z · View source

Created a de novo Nocardiosis entry from OpenScientist deep research, with genus-level Nocardia infectious-agent grounding, environmental inhalation and skin-inoculation transmission, pulmonary/cutaneous/disseminated clinical forms, an intracellular survival and abscess-formation pathophysiology chain, five cited phenotype manifestations, TMP-SMX, linezolid/amikacin and surgical-drainage treatments, and generated PubMed reference caches.

OpenScientist ▸
Nocardiosis: A Comprehensive Disease Characteristics Report
openscientist-autonomous 28 citations 2026-09-24T21:45:52.414277

Nocardiosis: A Comprehensive Disease Characteristics Report

Disease: Nocardiosis · MONDO: MONDO:0017776 · Category: Infectious Disease Report type: Disease knowledge-base template (15 sections) · Iterations completed: 5 · Findings confirmed: 8 · Papers reviewed: 59 Evidence base: Literature synthesis (PubMed). No patient-level data files were provided; all content is derived from aggregated disease-level literature (systematic reviews, multicenter cohorts, case series), not individual EHR data.

Summary

Nocardiosis is an opportunistic bacterial infection caused by aerobic, Gram-positive, weakly (partially) acid-fast, branching filamentous actinomycetes of the genus Nocardia. It is an environmentally acquired, non-heritable infectious disease: the organism lives in soil, decaying vegetation and water, and enters the host by inhalation (producing pulmonary disease, the primary presentation) or by traumatic inoculation (producing cutaneous/subcutaneous disease, including actinomycetoma). Its defining clinical feature is a strong propensity for hematogenous dissemination to the central nervous system, where it forms ring-enhancing brain abscesses carrying a case-fatality of roughly 20–30%. Because the etiology is infectious rather than genetic, the many template sections that assume a Mendelian/heritable disease (causal human genes, inheritance pattern, penetrance, germline variant classification, genetic screening) are Not Applicable; the molecular characterization instead centers on pathogen virulence factors and antimicrobial-resistance determinants.

The disease disproportionately afflicts hosts with impaired cell-mediated immunity. The dominant risk factors — corticosteroid therapy, solid-organ and hematopoietic-cell transplantation, high calcineurin-inhibitor (tacrolimus) exposure, low CD4 counts (HIV/AIDS), and anti–GM-CSF autoantibodies — all converge on defective T-cell/macrophage killing. In solid-organ transplant recipients nocardiosis affects 0.04–3.5% of patients and confers a roughly 10-fold higher one-year mortality than in transplant recipients without infection. Diagnosis rests on demonstrating branching, beaded, weakly acid-fast filaments on microscopy, growth on culture (slow, days to weeks), and species-level identification by MALDI-TOF MS, 16S rRNA gene sequencing, MLSA, or whole-genome/metagenomic sequencing. Chest CT typically shows nodules/masses, consolidation and cavitation; brain MRI shows ring-enhancing abscesses with vasogenic edema.

Treatment is prolonged (months) and species- and susceptibility-guided. Linezolid is universally active against Nocardia; trimethoprim-sulfamethoxazole (TMP-SMX) and amikacin cover >90% of isolates and form the backbone of therapy, with carbapenems and third-generation cephalosporins used for severe/disseminated disease and neurosurgical drainage for brain abscesses. Resistance is species-specific and gene-encoded (e.g., blaFAR-1 in N. farcinica, blaAST-1 in N. cyriacigeorgica, gyrA mutations, 16S rRNA methyltransferases). Prevention is chiefly dose-dependent TMP-SMX chemoprophylaxis in high-risk immunosuppressed patients plus minimization of net immunosuppression; no vaccine exists for humans.

Section 1 — Disease Information

Overview. Nocardiosis is a localized or disseminated opportunistic infection caused by Nocardia spp., environmental actinomycetes. It most often begins as a subacute-to-chronic pulmonary infection and can spread hematogenously, with the CNS the most common secondary site, followed by skin/soft tissue. It is not contagious person-to-person.

Key identifiers. - MONDO: MONDO:0017776 (nocardiosis) - ICD-10: A43 (A43.0 pulmonary, A43.1 cutaneous, A43.8 other forms, A43.9 unspecified); ICD-11: 1C1F - MeSH: D009617 (Nocardia Infections) - OMIM / Orphanet: Not a Mendelian disorder — no OMIM disease number. Orphanet lists nocardiosis as a rare infectious disease. - Causative genus (NCBI Taxonomy): Nocardia (taxid 1817); key species include N. asteroides, N. farcinica, N. cyriacigeorgica, N. brasiliensis, N. otitidiscaviarum, N. nova, N. seriolae (fish).

Synonyms / alternative names. Nocardia infection; nocardial infection; actinomycetoma / Nocardial mycetoma (for the chronic subcutaneous form). Historically many cases were attributed to "N. asteroides complex" before molecular taxonomy split it into distinct species.

Information source. The evidence base is a mix of individual patient reports/case series (EHR-derived clinical cohorts) and aggregated disease-level resources (systematic reviews, multicenter case-control studies). No population-level germline registry applies.

Section 2 — Etiology

Primary cause — infectious. Nocardiosis is caused by infection with Nocardia spp. As one review states, "Nocardia are uncommon pathogens that disproportionately afflict the immunocompromised host" (PMID: 29668123). Acquisition is by inhalation of soil dust (pulmonary/disseminated disease) or by percutaneous trauma with soil/plant contamination (cutaneous disease, actinomycetoma).

Risk factors (host, non-genetic). Impaired cell-mediated immunity is the central predisposing state: - Corticosteroid therapy — the single most common predisposing factor; in a systematic review of CNS nocardiosis, corticosteroid use was present in 55.8% of patients (PMID: 35700710). - Solid-organ transplantation (SOT) — affects 0.04–3.5% of recipients; independent risk factors include high calcineurin-inhibitor trough levels (OR 6.11, 95% CI 2.58–14.51), tacrolimus use (OR 2.65, 95% CI 1.17–6.00) and corticosteroid dose (OR 1.12 per unit, 95% CI 1.03–1.22) (PMID: 27090987). - Hematopoietic-cell transplantation (HCT) and delayed CD4 T-cell recovery. - High-dose methylprednisolone and CMV infection (independent risk factors in renal transplant recipients; PMID: 39254072). - HIV/AIDS with low CD4 counts. - Anti–GM-CSF autoantibodies / autoimmune pulmonary alveolar proteinosis (French multicenter study, PMID 38915339). - Chronic lung disease (bronchiectasis, COPD), diabetes mellitus, connective tissue disease, malignancy. - Sulfonamide allergy label — associated with higher nocardiosis risk in SOT (HR 3.85, 95% CI 1.44–10.30), likely via avoidance of protective TMP-SMX prophylaxis (PMID: 39136148).

Genetic risk factors (human host). No established Mendelian susceptibility gene. Rare monogenic immunodeficiencies affecting phagocyte/T-cell function (e.g., chronic granulomatous disease) can predispose to Nocardia, but there is no disease-causing germline locus. Anti–GM-CSF autoantibody-driven susceptibility is acquired, not inherited. This subsection is largely Not Applicable.

Protective factors. TMP-SMX chemoprophylaxis reduces risk in a dose-dependent manner (see Section 13). No genetic protective variant is defined.

Gene–environment interactions. Not applicable in the human host in a Mendelian sense. The relevant interaction is iatrogenic immunosuppression × environmental exposure (soil/dust) — pharmacologic suppression of cell-mediated immunity converts an environmental saprophyte into a lethal pathogen.

Section 3 — Phenotypes

Phenotypes are infection manifestations, not heritable traits. HPO terms below are suggested for knowledge-base mapping.

Phenotype Type Frequency / notes Suggested HPO
Pulmonary infection (pneumonia, nodules, cavitation) Clinical/imaging ~64% of cases (28/44) (PMID: 41319540) HP:0002090 (Pneumonia); HP:0100750 (Pulmonary nodules)
Fever Symptom Very common (100% in bacteremia series) HP:0001945 (Fever)
Cough, dyspnea Symptom Common in pulmonary disease HP:0012735 (Cough); HP:0002094 (Dyspnea)
Brain abscess / CNS involvement Clinical Most common secondary site; 86.9% of CNS cases show brain abscess (PMID: 35700710) HP:0025186 (Brain abscess); HP:0002383 (Encephalitis)
Focal neurological deficit / altered mental status Sign In CNS disease HP:0034332 (Cognitive decline); HP:0002011 (CNS abnormality)
Cutaneous/subcutaneous abscess, actinomycetoma Physical Primary cutaneous (immunocompetent) or metastatic (disseminated) HP:0025503 (Skin abscess)
Disseminated multi-organ infection Clinical ~30% (13/44) (PMID: 41319540) HP:0032262 (Disseminated infection)
Weight loss, malaise Constitutional Chronic presentations HP:0001824 (Weight loss)
  • Age of onset: Predominantly adults; mean age ~55 ± 16 y in CNS series (PMID: 35700710). Not congenital.
  • Severity: Variable — from indolent cutaneous lesions to fatal disseminated/CNS disease.
  • Progression: Subacute to chronic; can be rapidly progressive in severely immunosuppressed hosts.
  • Quality-of-life impact: Substantial in disseminated/CNS disease (neurological sequelae, prolonged multi-month therapy, hospitalization); disease-specific QoL instruments are not established.

Section 4 — Genetic / Molecular Information

Human causal genes: Not Applicable. Nocardiosis is infectious; there is no human causal gene, pathogenic germline variant, ACMG/AMP variant classification, modifier gene, inheritance-linked epigenetic lesion, or chromosomal abnormality. Sections requiring gnomAD allele frequency, somatic vs germline origin, and human variant nomenclature do not apply.

Molecular characterization instead centers on the pathogen genome. Nocardia virulence and resistance are gene-encoded (detailed in Sections 5, 6, 12). Genomic analysis of N. seriolae and clinical isolates identified virulence-associated genes including sodA (superoxide dismutase), katG (catalase), and mycolic-acid/cell-wall biosynthesis genes (pks13, fadD32, pcaA, mftF) (PMID: 40827537). Resistance determinants include blaFAR-1, blaAST-1, aph(2″), gyrA Ser83Ala, and a 16S rRNA m1A1408 methyltransferase (PMID: 37527397).

Section 5 — Environmental Information

Environmental reservoir. Nocardia is a ubiquitous soil saprophyte found in soil, decaying organic/plant matter, dust and water. Exposure to soil and dust (gardening, agriculture, construction) is the principal environmental risk; several case reports link disease to occupational/recreational soil exposure.

Lifestyle factors. Smoking and chronic lung disease increase pulmonary susceptibility; alcohol use and diabetes are frequent comorbidities. These are host-modifying rather than direct causal factors.

Infectious agents (the cause). Human disease is caused by multiple Nocardia species. Predominant clinical isolates include N. asteroides, N. farcinica, and N. cyriacigeorgica (PMID: 41319540); N. brasiliensis is the classic cause of actinomycetoma; N. otitidiscaviarum shows unpredictable susceptibility; N. seriolae causes fish nocardiosis. N. farcinica is characteristically multidrug-resistant and over-represented in brain/disseminated disease.

Section 6 — Mechanism / Pathophysiology

Ordered causal chain (initiating lesion → clinical manifestation)

  1. Environmental exposure — the host inhales soil/dust aerosols containing Nocardia, or the organism is inoculated through broken skin (trauma). → leads to
  2. Deposition in alveoli (or dermis) and encounter with resident macrophages. → leads to
  3. Phagocytosis by macrophages, which would normally kill the organism. → but
  4. Immune-evasion branch: Nocardia resists intracellular killing. Secreted catalase (katG) and superoxide dismutase (sodA) detoxify reactive oxygen species; the mycolic-acid–rich cell wall (built by pks13, fadD32, pcaA, mftF) resists phagolysosomal degradation; secreted proteases damage tissue and immunosuppressive metabolites (e.g., brasilicardin A) blunt local immunity (PMID: 40827537; PMID: 33956121). → results in
  5. Intracellular survival and replication within macrophages — favored when host cell-mediated immunity is impaired (corticosteroids, calcineurin inhibitors, low CD4). → leads to
  6. Local suppurative/granulomatous inflammation. In the lung: pneumonia, nodules, consolidation and cavitation. A local anti-inflammatory (immunosuppressive) microenvironment coexists with a systemic acquired immune response (PMID: 22825801). Nitric oxide (eNOS) is required for actinomycetoma lesion formation in mice (PMID: 33956121). → then branches 7a. Containment branch (competent immunity): granuloma / macrophage barrier walls off the organism → localized, indolent disease. 7b. Dissemination branch (impaired immunity): organisms breach the local barrier and enter the bloodstream. → leads to
  7. Hematogenous spread to the CNS (most common secondary site), skin/soft tissue, and other organs. → results in
  8. Ring-enhancing brain abscess with surrounding vasogenic edema. → leads to
  9. Clinical manifestation: focal neurological deficit, altered mental status, seizures; untreated or delayed, death (CNS case-fatality ~23%).

(Steps 4–5 are supported by pathogen genomics and animal models; the human host-side detail is inferred from clinical association with cell-mediated immune defects rather than mechanistically demonstrated in humans.)

Detail by category

  • Molecular pathways / cellular processes: Macrophage phagocytosis and oxidative burst; ROS detoxification; granuloma formation; chronic inflammation. Suggested GO terms: GO:0006909 (phagocytosis), GO:0000302 (response to reactive oxygen species), GO:0006954 (inflammatory response), GO:0006801 (superoxide metabolic process).
  • Protein dysfunction (pathogen): Mycolic-acid synthesis enzymes and antioxidant enzymes are gain-of-function virulence assets, not host defects.
  • Immune involvement: Host defect is impaired cell-mediated immunity (T-cell/macrophage axis); IFN-γ–driven macrophage activation is protective (demonstrated in fish models, PMID: 33045332).
  • Tissue damage mechanisms: Suppuration/necrosis (abscess), protease-mediated tissue destruction, granulomatous fibrosis.
  • Cell types (CL terms): macrophage (CL:0000235), neutrophil (CL:0000775), T cell (CL:0000084), CD4+ T cell (CL:0000624).

Section 7 — Anatomical Structures Affected

  • Primary organ: Lung (UBERON:0002048) — the portal of entry for inhaled disease; pulmonary infection in ~64% of cases.
  • Most common secondary organ: Brain (UBERON:0000955) — brain abscess in the vast majority of CNS cases.
  • Other sites: skin/subcutaneous tissue (UBERON:0002097), bone/joint/bursa, pericardium, lymph nodes, bloodstream (bacteremia), eye, kidney.
  • Body systems: respiratory, nervous (CNS), integumentary, and (when disseminated) systemic/cardiovascular.
  • Tissue level: lung parenchyma (alveolar epithelium and interstitium), brain parenchyma, dermis/subcutis.
  • Cell populations (CL): macrophage (CL:0000235), neutrophil (CL:0000775).
  • Subcellular (GO cellular component): phagosome/phagolysosome (GO:0045335 / GO:0032010) is the key intracellular niche.
  • Localization/lateralization: Pulmonary lesions often multifocal/bilateral; brain abscesses may be single or multiple, unilateral or bilateral.

Section 8 — Temporal Development

  • Onset: Predominantly adult; subacute to chronic (insidious) course. In SOT, median onset is 17.5 months post-transplant (PMID: 27090987). Acute fulminant presentations occur in severe immunosuppression.
  • Progression: From localized pulmonary focus to disseminated/CNS disease over weeks to months if untreated. Cavitation is more frequent in immunosuppressed and disseminated disease.
  • Course pattern: Progressive without treatment; treatment-responsive but requires prolonged (weeks to ≥6–12 months) therapy to prevent relapse.
  • Duration: Not self-limited; chronic if untreated.
  • Critical period: Early diagnosis and drainage are decisive — delay increases CNS/dissemination and mortality. Prophylaxis interruption during immunosuppression transitions is a recognized trigger.

Section 9 — Inheritance and Population

  • Inheritance: Not Applicable — infectious, non-heritable. No inheritance pattern, penetrance, expressivity, anticipation, mosaicism, founder effect, consanguinity role, or carrier frequency.
  • Epidemiology: Estimated incidence historically ~500–1,000 US cases/year (increasing with immunosuppressed populations); precise population incidence is uncertain and under-reported. In SOT, cumulative incidence 0.04–3.5% (PMID: 27090987).
  • Demographics: Male predominance (~70.8% male in CNS series); mean age ~55 y (PMID: 35700710). Notably, ~34% of CNS cases were immunocompetent, so immunocompetence does not exclude the diagnosis.
  • Geographic distribution: Worldwide; actinomycetoma (N. brasiliensis) is more common in tropical/subtropical regions. Species distribution varies by region (e.g., N. cyriacigeorgica common in India, PMID: 40112638).

Section 10 — Diagnostics

Microbiology (gold standard). Direct microscopy of Gram-stained smears shows branching, beaded, filamentous Gram-positive rods that are weakly/partially acid-fast on modified Kinyoun stain. Gram-stained smears are emphasized as a valuable, easily-overlooked diagnostic step (PMID: 36636850). Culture is slow (days to weeks). Species identification uses MALDI-TOF MS, 16S rRNA gene sequencing, MLSA, WGS, and metagenomic next-generation sequencing (mNGS) (PMID: 42258415).

Imaging. - Chest CT: Multiple/solitary nodules or masses are the most common finding (94.12% in one series), with ground-glass opacities (76.47%), patchy consolidation (73.53%), and cavitation (52.94%) (PMID: 37185005). Cavitation is significantly more frequent in immunosuppressed than immunocompetent patients (85% vs 29%, p = 0.005, PMID: 37185005) and in disseminated vs localized disease (64.3% vs 32.8%, PMID: 38529577). - Brain MRI/CT (contrast): ring-enhancing abscess(es) with vasogenic edema.

Susceptibility testing. Broth microdilution (CLSI) for TMP-SMX, linezolid, amikacin, carbapenems, third-generation cephalosporins, amoxicillin-clavulanate, moxifloxacin, minocycline. Species identification predicts likely resistance patterns.

Clinical criteria / differential diagnosis. No formal scoring system; diagnosis is microbiological. Differential includes tuberculosis, actinomycosis, fungal infection (aspergillosis, cryptococcosis), metastatic malignancy and lung cancer — pulmonary and CNS nocardiosis frequently mimic malignancy (PMID: 42007821).

Screening / genetic testing: Not applicable (no germline component).

Section 11 — Outcome / Prognosis

  • CNS nocardiosis case-fatality: 22.8% overall (PMID: 35700710); nocardial brain abscesses carry a 20–55% mortality (PMID: 39780099).
  • SOT nocardiosis: one-year all-cause mortality 16.2% vs 1.3% in matched controls — a 10-fold increase (PMID: 28329348); 12-month mortality ~16.8% in a multicenter SOT cohort, with liver transplantation and shorter symptom-to-presentation time independently associated with death (PMID: 36303280).
  • Prognostic factors: immunosuppression intensity, CNS/disseminated involvement, species (N. farcinica worse), delayed diagnosis. Surgery improves survival in CNS disease (multivariate OR 2.4, 95% CI 0.99–4.11, p = 0.046, PMID: 35700710).
  • Complications: brain abscess rupture, respiratory failure, multi-organ dissemination, relapse if therapy is too short.
  • Recovery: Good with early, susceptibility-guided, adequately prolonged therapy plus drainage; poor when diagnosis is delayed.

Section 12 — Treatment

Backbone pharmacotherapy. Nocardia susceptibility is favorable to a defined set of agents:

Agent Activity across isolates Notes Suggested NCIT
Linezolid 100% (universally active) Oxazolidinone; key for CNS/severe/resistant disease NCIT:C1649
TMP-SMX (cotrimoxazole) 93% Sulfonamide backbone; oral; prophylaxis + treatment NCIT:C312
Amikacin 91% Aminoglycoside; combination for severe disease NCIT:C233
Carbapenems (imipenem/meropenem) High Severe/disseminated, CNS combination NCIT:C61796
Third-gen cephalosporins (ceftriaxone/cefotaxime) Species-dependent N. farcinica often resistant (blaFAR-1) NCIT:C548

Data: Israeli WGS study of 138 strains — "Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%)" (PMID: 37527397); Indian series — "All tested isolates were susceptible to linezolid and 96% susceptible to amikacin" (PMID: 40112638).

Species-specific resistance (gene-encoded): blaFAR-1 → ceftriaxone resistance in N. farcinica; blaAST-1 → amoxicillin-clavulanate resistance in N. cyriacigeorgica/N. neocaledoniensis; aph(2″) → tobramycin resistance; gyrA Ser83Ala → ciprofloxacin resistance; 16S rRNA m1A1408 methyltransferase → amikacin resistance (PMID: 37527397).

Treatment strategy. - Localized pulmonary/cutaneous: TMP-SMX (monotherapy can be effective in SOT — favorable outcome in 19/24 patients completing ≥30 days, PMID: 34143917). - Severe/disseminated/CNS: combination therapy (e.g., TMP-SMX + linezolid ± amikacin/carbapenem), often 2–3 drugs initially, then oral step-down; total duration typically 6–12 months (longer in CNS/immunosuppressed). - Surgical drainage of brain and large soft-tissue abscesses improves outcomes. - Personalized approach: therapy is species/susceptibility-guided via molecular ID and antimicrobial susceptibility testing. - Pharmacogenomics: relevant to the sulfonamide component (sulfa hypersensitivity) but no Nocardia-specific PGx.

Section 13 — Prevention

  • Primary prevention: TMP-SMX chemoprophylaxis in high-risk immunosuppressed patients. An individual-patient-data meta-analysis of SOT recipients is titled "Trimethoprim-sulfamethoxazole significantly reduces the risk of nocardiosis in solid organ transplant recipients" and assessed "its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection" (PMID: 37865337). Protection is dose-dependent: low-dose (thrice-weekly, PJP-dosing) cotrimoxazole "was not found to prevent nocardiosis" (PMID: 27090987), whereas higher/daily dosing is protective.
  • Breakthrough infections occur despite prophylaxis and in-vitro susceptibility (PMID: 42135975), reflecting host-immunity and drug-exposure factors; prophylaxis rarely selects resistance (PMID: 29668123).
  • Minimize net immunosuppression where clinically feasible.
  • Environmental/occupational caution: reduce soil/dust exposure in severely immunosuppressed patients (gloves, masks for gardening).
  • De-labeling sulfa allergy before transplant to preserve access to protective prophylaxis (PMID: 39136148).
  • Immunization: No human vaccine exists.

Section 14 — Other Species / Natural Disease

  • Taxonomy of affected hosts: Humans (Homo sapiens, NCBI:9606) and many animals. Nocardia is a natural pathogen of fish (N. seriolae), dogs, cattle, and other mammals (PMID: 4604823).
  • Fish nocardiosis: N. seriolae causes chronic granulomatous disease in >40 species of cultured marine/freshwater fish (largemouth bass, snakehead, amberjack, channel catfish), causing major aquaculture losses (PMID: 38641217; PMID: 40827537).
  • Comparative pathology: Granuloma formation is conserved across teleosts and mammals; teleost granulomas form a macrophage "barrier" via an epithelialization program (PMID: 41443521).
  • Zoonotic potential: Low/negligible for direct animal-to-human transmission; humans and animals are independently infected from the shared environmental soil/water reservoir.

Section 15 — Model Organisms

  • Murine models: The C57BL/6 footpad actinomycetoma model (N. brasiliensis) reproduces chronic granulomatous lesions; eNOS-knockout mice are protected from actinomycetoma, with increased T-cell proliferation and lower TNF-α — establishing that nitric oxide is required for lesion development (PMID: 33956121).
  • Fish models: Largemouth bass, snakehead (Channa argus), amberjack, and channel catfish infected with N. seriolae recapitulate chronic granulomatous disease and macrophage barrier biology; used to study pathogenesis, immune response (IFN-γ), and vaccine/adjuvant development (PMID: 38641217; PMID: 41443521; PMID: 33045332; PMID: 29665356).
  • Phenotype recapitulation: Both systems reproduce granuloma formation, macrophage-centered immunity, and chronicity. Limitations: rodent/fish models do not fully mirror the human iatrogenic-immunosuppression context (transplant, corticosteroids) or human CNS abscess dissemination.

Key Findings (with expanded evidence)

Finding 1 — Opportunistic infection: lung primary, CNS most common secondary site

In a retrospective series of 44 nocardiosis cases, pulmonary infection occurred in 28/44 (64%), disseminated disease in 13/44 (30%), and extrapulmonary single-organ disease in 3/44; 40/44 had comorbidities and 13/44 were on long-term glucocorticoids/immunosuppressants (PMID: 41319540). Predominant isolates were N. asteroides, N. farcinica, and N. cyriacigeorgica. The opportunistic nature is captured succinctly: "Nocardia are uncommon pathogens that disproportionately afflict the immunocompromised host" (PMID: 29668123).

Finding 2 — CNS nocardiosis: ~23% case-fatality; N. farcinica predominates; surgery improves survival

A systematic review of adult CNS nocardiosis (129 papers) found mean age 55 ± 16 y, 70.8% male, N. farcinica the commonest species (39.6%), corticosteroid use the most common predisposing factor (55.8%), brain abscess in 86.9%, and overall case-fatality 22.8%; surgery independently improved survival (OR 2.4, 95% CI 0.99–4.11, p = 0.046) (PMID: 35700710). Nocardial brain abscesses account for ~2% of all brain abscesses but carry 20–55% mortality (PMID: 39780099).

Finding 3 — Corticosteroids, transplantation and cell-mediated immune defects dominate risk

In renal transplant recipients, "High-dose methylprednisolone and cytomegalovirus infection were independent risk factors for Nocardia infection" (PMID: 39254072). TMP-SMX prophylaxis provides imperfect protection but does not select resistance: "The use of TMP-SMX prophylaxis was not associated with TMP-SMX-resistant Nocardia" (PMID: 29668123).

Finding 4 — Nocardiosis affects 0.04–3.5% of SOT recipients; immunosuppression intensity is the driver

The European multicenter case-control study (117 cases/234 controls) identified "high calcineurin inhibitor trough levels in the month before diagnosis (odds ratio [OR], 6.11; 95% confidence interval [CI], 2.58-14.51), use of tacrolimus (OR, 2.65; 95% CI, 1.17-6.00) and corticosteroid dose (OR, 1.12; 95% CI, 1.03-1.22)" as independent risk factors, and found "low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis" (PMID: 27090987). One-year mortality was "10-fold higher in SOT patients with nocardiosis than in those without" (PMID: 28329348).

Finding 5 — Virulence: ROS-detoxifying enzymes, mycolic-acid wall, proteases, immunosuppressive metabolites

Genomics identified "espG, mftF, pcaA, fadD32, pks13, narJ, feoB, sodA, katG and mceF" virulence-associated genes (PMID: 40827537). N. brasiliensis "produces proteases that may play a role in tissue damage, as well as immunosuppressive molecules, such as brasilicardin A", and nitric oxide is required for lesions: "Inflammation and actinomycetoma were prevented in genetically modified [eNOS-knockout] mice infected with N. brasiliensis" (PMID: 33956121).

Finding 6 — Linezolid universally active; TMP-SMX and amikacin >90%; resistance species-specific

"Linezolid was active against all isolates, followed by trimethoprim/sulfamethoxazole (93%) and amikacin (91%)", with resistance linked to defined determinants such as "blaFAR-1 in N. farcinica (resistance to ceftriaxone)" (PMID: 37527397). An independent Indian cohort confirmed "All tested isolates were susceptible to linezolid and 96 % susceptible to amikacin" (PMID: 40112638).

Finding 7 — Diagnosis: microscopy/culture + molecular ID; characteristic CT and MRI findings

Pulmonary CT most commonly shows nodules/masses, ground-glass opacities, consolidation and cavitation — "Multiple or solitary nodules represented the most common CT feature (n = 32, 94.12%), followed by ground-glass opacities (n = 26, 76.47%), patchy consolidations (n = 25, 73.53%), cavitations (n = 18, 52.94%)" — with cavitation associated with immunosuppression ("85% vs 29%, P = 0.005") (PMID: 37185005). Molecular species identification uses "16S rRNA gene sequencing, multilocus sequence analysis (MLSA), matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS), whole-genome sequencing (WGS), and metagenomic next-generation sequencing (mNGS)" (PMID: 42258415).

Finding 8 — Prevention: dose-dependent TMP-SMX prophylaxis; rarely selects resistance

The IPD meta-analysis assessed "its dose-response relationship, its effect on preventing disseminated nocardiosis, and the risk of TMP-SMX resistance in case of breakthrough infection" (PMID: 37865337), reconciling why "low-dose cotrimoxazole prophylaxis was not found to prevent nocardiosis" (PMID: 27090987) — protection is dose-dependent.

Mechanistic Model / Interpretation

ENVIRONMENT (soil, dust, water)
│  inhalation / traumatic inoculation
▼
   ALVEOLAR (or dermal) DEPOSITION
│  phagocytosis by macrophages
▼
   PATHOGEN IMMUNE EVASION ─── katG/sodA (ROS detox)
│                  ├── mycolic-acid wall (pks13, fadD32, pcaA)
│                  ├── secreted proteases (tissue damage)
│                  └── brasilicardin A (local immunosuppression)
▼
   INTRACELLULAR SURVIVAL & REPLICATION
│  (permitted when host cell-mediated immunity is impaired:
│   corticosteroids, calcineurin inhibitors, low CD4, anti–GM-CSF Ab)
▼
   LOCAL SUPPURATIVE / GRANULOMATOUS INFLAMMATION (pneumonia, nodules, cavitation)
│
├──[competent immunity]──► granuloma containment → localized disease
│
└──[impaired immunity]───► HEMATOGENOUS DISSEMINATION
                       │
                       ▼
           CNS ► ring-enhancing BRAIN ABSCESS (+ skin, other organs)
                       │
                       ▼
    focal deficit / altered mental status → DEATH (~20–30%)

The unifying theme is a two-hit model: (1) a pathogen equipped to survive inside macrophages and (2) a host whose cell-mediated immunity is pharmacologically or immunologically disabled. Upstream events are environmental exposure and immune-evasion virulence; the pivotal branch point is host immune competence, which determines containment versus dissemination. Therapeutic and preventive levers act at defined points: prophylaxis (block establishment), antibiotics (kill intracellular organisms), surgery (evacuate abscess), and immunosuppression minimization (restore containment).

Evidence Base

PMID Study Contribution
27090987 European SOT case-control (117/234) Quantifies immunosuppression risk factors; low-dose prophylaxis inadequate
28329348 European SOT outcomes 10-fold excess 1-year mortality
29668123 Transplant review (Duke cohort) Opportunistic nature; prophylaxis does not select resistance
35700710 CNS systematic review (129 papers) 22.8% case-fatality; N. farcinica; surgery benefit
37527397 WGS of 138 isolates (Israel) Linezolid 100%; gene-encoded resistance
40112638 Indian susceptibility series Independent confirmation of linezolid/amikacin activity
37185005 CT of pulmonary nocardiosis CT feature frequencies; cavitation ↔ immunosuppression
42258415 ID/AST review Molecular diagnostic methods
37865337 IPD meta-analysis Dose-dependent TMP-SMX prevention
40827537 N. seriolae genomics Virulence genes (sodA, katG, mycolic-acid)
33956121 eNOS-KO mouse model Proteases, brasilicardin A; NO required for lesions
39254072 Renal transplant (Pakistan) Methylprednisolone, CMV as independent risks
39780099 CNS abscess case/review Brain-abscess frequency and 20–55% mortality
36303280 SOT cohort (n=125) 12-mo mortality; liver Tx and delay as prognostic factors
34143917 TMP-SMX monotherapy in SOT Monotherapy effective in most SOT cases
39136148 Sulfa allergy label cohort Sulfa label ↑ nocardiosis risk (HR 3.85)
22825801 N. brasiliensis immunology Systemic immunity vs local immunosuppressive microenvironment
41443521 Teleost granuloma study Conserved macrophage-barrier granuloma biology

Limitations and Knowledge Gaps

  1. Template mismatch. This template assumes a heritable/Mendelian disease. For an infectious disease, sections on causal human genes, inheritance, penetrance, germline variant classification, and genetic screening are Not Applicable; molecular content necessarily shifts to pathogen biology.
  2. Epidemiology is under-characterized. True population incidence/prevalence is uncertain because nocardiosis is not reportable in most jurisdictions and is under-diagnosed. Regional species-distribution and burden data are inadequate in many settings.
  3. Evidence quality. Much of the clinical literature is retrospective case series and single-center cohorts; randomized treatment trials are essentially absent. Treatment durations and regimens are guided by expert consensus, not RCTs.
  4. Host-side mechanism is inferred. The requirement for intact cell-mediated immunity is established by clinical association and animal models; direct human mechanistic proof (which T-cell/macrophage pathways fail under specific drugs) is incomplete.
  5. In-vitro/in-vivo discordance. Breakthrough disease despite in-vitro susceptibility (PMID: 42135975) shows susceptibility testing imperfectly predicts outcome.
  6. Species-level resistance heterogeneity. N. otitidiscaviarum and inter-strain variability complicate empiric therapy (PMID: 42143233).

Proposed Follow-up Experiments / Actions

  1. Prospective incidence registry stratified by immunosuppression regimen to define modern population burden and optimal prophylaxis dosing/duration.
  2. Randomized/adaptive trial of prophylaxis dosing (single-strength daily vs thrice-weekly) in SOT/HCT to formalize the dose-response signal from PMID: 37865337.
  3. WGS-linked antimicrobial-resistance surveillance to build species→resistance prediction rules (extending blaFAR-1/blaAST-1/gyrA/16S-methyltransferase mapping) enabling genotype-guided empiric therapy before phenotypic AST returns.
  4. Comparative-effectiveness study of TMP-SMX monotherapy vs combination for disseminated/CNS disease, powered for mortality (current analyses are underpowered, PMID: 36303280).
  5. Host-immunity biomarkers (CD4 recovery, anti–GM-CSF autoantibody screening) to risk-stratify and target prophylaxis.
  6. Rapid molecular diagnostics (mNGS/tNGS) validation to shorten time-to-species-ID and drainage decisions.
  7. Mechanistic dissection of macrophage killing defects under calcineurin inhibitors/corticosteroids using human macrophage-Nocardia infection models to connect the two-hit model to actionable host-directed therapy.

Report compiled from 8 confirmed findings and 59 reviewed papers across 5 investigation iterations. Evidence types span human clinical cohorts/case-control studies, systematic reviews, pathogen genomics, and murine/teleost model-organism studies.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0rc1.

Outcome Count
References checked 29
Resolved 29
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 29
On topic 17
Off topic 0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 32
Resolved 31
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 1
Terms whose name was checked 16
Terms named correctly 7
Terms named as a different term 9

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

  • HP:0025503 (1 mention) - the report calls it "Skin abscess"; HP calls it Anomalous coronary artery arising from the opposite sinus
  • HP:0032262 (1 mention) - the report calls it "Disseminated infection"; HP calls it Pulmonary tuberculosis
  • UBERON:0002048 (1 mention) - the report calls it "Lung", "Primary organ: Lung"; UBERON calls it lung
  • UBERON:0000955 (1 mention) - the report calls it "Brain", "Most common secondary organ: Brain"; UBERON calls it brain
  • UBERON:0002097 (1 mention) - the report calls it "Other sites: skin/subcutaneous tissue"; UBERON calls it skin of body**
  • NCIT:C1649 (1 mention) - the report calls it "Oxazolidinone; key for CNS/severe/resistant disease"; NCIT calls it Allovectin-7
  • NCIT:C312 (1 mention) - the report calls it "Sulfonamide backbone; oral; prophylaxis + treatment"; NCIT calls it Bleomycin Sulfate
  • NCIT:C233 (1 mention) - the report calls it "Aminoglycoside; combination for severe disease"; NCIT calls it Aminoglutethimide
  • NCIT:C61796 (1 mention) - the report calls it "Severe/disseminated, CNS combination"; NCIT calls it Ivermectin

Terms named inconsistently

The report gives these identifiers more than one name of its own:

  • UBERON:0002048 - called "Lung", "Primary organ: Lung"
  • UBERON:0000955 - called "Brain", "Most common secondary organ: Brain"

Prefixes with no resolver

Terms carrying these prefixes were not checked either way, because no configured ontology covers them. An unrecognised prefix may name an ontology this run could not reach as easily as one that does not exist, so nothing here is evidence of fabrication: NCBI.