Nocardia/Nocardiosis

Nocardia is a branching, filamentous, gram-positive bacilli. It is partially acid fast due to the presence of mycolic acids in the cell wall. Nocardia is a ubiquitous soil organism that most commonly affects immunocompromised patients. Nocardia is transmitted via inhalation of aerosolized bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview or less commonly, via direct contact with wounds. Nocardia causes opportunistic infections, primarily pulmonary infections ( pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia, abscess, or cavitary lesions), which may spread to form brain abscesses. In immunocompetent patients, Nocardia can cause a cutaneous infection. Treatment for nocardiosis is with trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim–sulfamethoxazole and/or surgical intervention as indicated.

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Classification

Microbiology flowchart gram-positive bacteria classification

Gram-positive bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview:
Most bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thick layer of peptidoglycan retain the crystal violet stain utilized in Gram staining but are not affected by the safranin counterstain. These bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview appear as purple-blue on the stain, indicating that they are gram positive. The bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview can be further classified according to morphology (branching filaments, bacilli, and cocci in clusters or chains) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The cocci can also be further identified. Staphylococci can be narrowed down on the basis of the presence of the enzyme coagulase and on their sensitivity to the antibiotic novobiocin. Streptococci are grown on blood agar and classified on the basis of which form of hemolysis they employ (α, β, or γ). Streptococci are further narrowed on the basis of their response to the pyrrolidonyl-β-naphthylamide (PYR) test, their sensitivity to specific antimicrobials (optochin and bacitracin), and their ability to grow on sodium chloride (NaCl) media.

Image by Lecturio. License: CC BY-NC-SA 4.0

General Characteristics

Nocardia

  • General characteristics:
    • Structure:
      • Branching, filamentous rods
      • Filaments fragment readily into coccobacillary forms.
    • Gram stain: gram positive
    • Other stain(s): weakly acid fast due to mycolic acids in the cell wall
    • Enzyme produced: urease positive, catalase positive
    • Spore formation: non-spore forming
    • Oxygen requirement: obligate aerobe
  • Culture medium: grows on most ordinary laboratory media (such as blood agar) 
  • Nocardiosis (disease caused):
    • Frequently an opportunistic infection, manifesting as a pulmonary or disseminated disease.
    • Localized disease occurs, and usually presents as a cutaneous syndrome.
Stain nocardia species

This slide with gram-positive aerobic Nocardia asteroides reveals chains of bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology: Overview among aerial mycelia.

Image by Lecturio.

Clinically relevant species

  • Nocardia asteroides (N. asteroides) has been divided based antimicrobial susceptibility patterns:
    • N. abscessus complex
    • N. brevicatena-paucivorans complex
    • N. nova complex
    • N. transvalensis complex
    • N. farcinica
    • N. cyriacigeorgica
  • Nocardia brasiliensis (N. brasiliensis)

Epidemiology

  • Incidence of nocardiosis: 500–1,000 cases per year in the United States
  • Infection affects men > women
  • All ages are susceptible to infection.

Related videos

Pathogenesis

Reservoir and transmission

  • Reservoir(s): soil, decaying organic matter, water
  • Transmission:
    • Inhalation:
      • Primary route of exposure
      • Mainly with N. asteroides, causing pulmonary disease
    • Environmental exposure through trauma or wound contamination:
      • Mainly with N. brasiliensis 
      • Infections affect the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and lymph nodes.

Virulence

  • Mechanisms of Nocardia spp:
    • Resistance to phagocytosis: when bacterial growth is in log phase
    • Resistance to hydrolysis: If phagocytosis occurs, the fusion of the phagosome and lysosome is stopped.
    • Resistance to antimicrobial action of neutrophils:
      • Superoxide dismutase from the cell surface
      • Increased catalase 
  • N. farcinica:
    • More virulent than other species
    • With antimicrobial resistance
    • Associated with disseminated infection
  • L forms:
    • Microbial variants without a structurally intact cell wall
    • Found to persist in animal models (in cerebrospinal fluid)
    • Believed to be related to relapse or development of neurologic signs even after treatment

Disease process

  • Nocardia is introduced after a local injury to the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin and infection occurs:
    • In immunocompetent patients: remains localized
    • In immunocompromised patients: with potential to spread to other organs
  • Pleuropulmonary nocardiosis: 
    • Infection follows after inhalation of contaminated aerosolized droplets. 
    • Majority of patients are immunocompromised.
Pathogenesis of nocardia

Pathogenesis of Nocardia:
Left: Inhaled organisms colonize the oropharynx and are passively aspirated into the lower airways, resulting in necrosis and abscess formation (in immunocompromised patients).
Right: Environmental exposure and contamination of wounds lead to wound infections or granulomatous lesions.

Image by Lecturio.

Host risk factors

  • Frequently the immunocompromised, particularly with impaired cell-mediated immunity:
    • Human immunodeficiency virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology: Overview (HIV) syndrome: usually in patients with < 250 CD4+ T lymphocytes T lymphocytes T cells, also called T lymphocytes, are important components of the adaptive immune system. Production starts from the hematopoietic stem cells in the bone marrow, from which T-cell progenitor cells arise. These cells migrate to the thymus for further maturation. T Cells/μL
    • Transplant recipients 
    • Chronic glucocorticoid use
    • Chronic immunosuppression
    • Malignancy
  • Others:
    • Alcoholism
    • Diabetes
    • Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD)
    • Inflammatory bowel disease

Clinical Presentation

Pulmonary nocardiosis

  • Predominant clinical presentation
  • Presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, night sweats, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, weight loss, cough, chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain, weight loss 
  • Seen mostly in the immunocompromised
  • Chest X-ray/computed tomography (CT) scan: infiltrates, cavitary lesions, abscess, or pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
  • May mimic tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis but with negative purified protein derivative (PPD) test
Copd and nocardia spp

Computed tomography (CT) scan imaging of the lung in a patient with chronic obstructive pulmonary disease and Nocardia infection:
A: right upper lobar consolidation
B: computed tomography images after 12 days, showing cavitary consolidation and ground glass opacity

Image: “ COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD) and Nocardia spp.” by the Department of Respiratory Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China. License: CC BY 4.0.

Disseminated nocardiosis

  • 2 or more non-contiguous sites are affected.
  • Infections may spread to the central nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System (CNS), causing brain abscesses.
  • Slow-growing mass(es) causing headaches, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, and neurologic deficits
  • Signs of meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis may be present.
Disseminated central nervous system nocardiosis

Magnetic resonance imaging (MRI) with contrast showing multiple abscesses (arrows): The patient has disseminated CNS nocardiosis, with bilateral involvement of the brain. Multiple ring lesions with surrounding edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema are shown.

Image: “45-year-old male” by the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China. License: CC BY 3.0.

Cutaneous nocardiosis

  • Commonly from N. brasiliensis
  • Occurs after trauma (gardening, surgery, animal bite)
  • Affects even the immunocompetent
  • Chronic, slowly progressing lesions
  • Presentation:
    • Primary cutaneous infection: 
      • Cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis or a single/multiple erythematous nodule(s) at the site of trauma
      • May drain purulent material
    • Lymphocutaneous nocardiosis: 
      • Cutaneous infection with lymphadenitis, possibly ulcerating and/or draining purulent material 
      • Similar to how Sporothrix schenckii infection presents (thus also called “sporotrichoid nocardiosis”)
    • Mycetoma: 
      • Progressive and chronic deep skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin infection 
      • May extend to the fascia, muscle, and bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Structure of Bones
      • May cause deformities and sinus tracts
      • May be a form of disseminated infection in immunocompromised patients
Nocardia brasiliensis infection

Image of cutaneous nocardiosis: fluctuant, purulent, and crusted nodule noted in a patient receiving long-term immunosuppressive therapy. Tissue cultures revealed N. brasiliensis.

Image: “Lesional skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin” by Alison M. Fernandes et al. License: CC BY 4.0.

Diagnosis and Management

Diagnosis

  • Culture: 
    • Grows on ordinary laboratory media after 3 to 5 days incubation in air
    • Specimens: sputum, pus, spinal fluid, or biopsy material
  • Microscopic examination: filamentous rods, with beading and branching morphology
  • Imaging studies are dictated by the clinical presentation:
    • Chest X-ray/CT scan of the chest: in pulmonary nocardiosis
    • CT scan of the brain/MRI: in patients with neurologic symptoms
Nocardia brain biopsy

Nocardia (white arrow) as found on a brain biopsy

Image: “Nocardia as found on a brain biopsy” by Doc James. License: Public domain, edited by Lecturio.

Management

  • Trimethoprim-sulfamethoxazole
  • Newer β-lactams (imipenem, meropenem, cefotaxime) may be effective.
  • Surgical drainage for abscess

Comparisons

Actinomyces Actinomyces Actinomyces is an anaerobic, gram-positive, branching, filamentous rod. Actinomyces israelii is the most common species involved in human disease. The organism is commonly found as part of the normal flora in the oral cavity, gastrointestinal tract, and reproductive tract. Actinomyces/Actinomycosis and Nocardia

Table: Gram-positive, branching, filamentous rods that must be distinguished
Differentiating factors Actinomyces Actinomyces Actinomyces is an anaerobic, gram-positive, branching, filamentous rod. Actinomyces israelii is the most common species involved in human disease. The organism is commonly found as part of the normal flora in the oral cavity, gastrointestinal tract, and reproductive tract. Actinomyces/Actinomycosis Nocardia
Oxygen requirement Anaerobic Aerobic
Acid-fast stain Not acid fast Acid fast (partially)
Reservoir/habitat Normal oral, gastrointestinal, and reproductive flora Found in soil, water, decaying organic matter
Infections caused
  • Orofacial abscesses, associated with dental caries or facial trauma
  • Sinus tracts
  • Pelvic inflammatory disease Pelvic inflammatory disease Pelvic inflammatory disease (PID) is defined as a polymicrobial infection of the upper female reproductive system. The disease can affect the uterus, fallopian tubes, ovaries, and adjacent structures. Pelvic inflammatory disease is closely linked with sexually transmitted diseases, most commonly caused by Chlamydia trachomatis, Neisseria gonorrhoeae, and Gardnerella vaginalis. Pelvic Inflammatory Disease
  • Pulmonary infection in immunocompromised patients (can spread hematogenously and cause brain abscesses)
  • Cutaneous lesions in immunocompetent patients
Management Treatment with penicillin Treatment with trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim-sulfamethoxazole
Treatment mnemonic: SNAP (sulfonamides-Nocardia, Actinomyces Actinomyces Actinomyces is an anaerobic, gram-positive, branching, filamentous rod. Actinomyces israelii is the most common species involved in human disease. The organism is commonly found as part of the normal flora in the oral cavity, gastrointestinal tract, and reproductive tract. Actinomyces/Actinomycosis-penicillin)

Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium and Nocardia

Table: Acid-fast rods comparison
Differentiating factors Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium Nocardia
Oxygen requirement Aerobic Aerobic
Spore formation Non-spore forming Non-spore forming
Acid-fast stain Acid fast Partially acid fast
Structure Straight or slightly curved rods Branching filamentous rods
PPD* test PPD* positive PPD* negative
*PPD: purified protein derivative

Differential Diagnosis

  • Sporotrichosis: infection caused by Sporothrix schenckii. Lymphocutaneous infection is the most common form and presents like cutaneous nocardiosis (inoculation of soil through the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin with erythematous, nodular lesion(s) along lymphatic channels). Culture of aspirated material helps distinguish the organisms.
  • Mycobacterial infection: pulmonary infection from Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis (M. tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis) also presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, night sweats, weight loss, cough, hemoptysis Hemoptysis Hemoptysis is defined as the expectoration of blood originating in the lower respiratory tract. Hemoptysis is a consequence of another disease process and can be classified as either life threatening or non-life threatening. Hemoptysis can result in significant morbidity and mortality due to both drowning (reduced gas exchange as the lungs fill with blood) and hemorrhagic shock. Hemoptysis, and dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea. Both are acid-fast organisms, but Nocardia is only partially acid fast and is seen as a branching rod (resembling fungal hyphae). Recent infection with M. tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis results in a positive PPD test.
  • Brain metastasis: Both brain metastasis and CNS nocardiosis present insidiously and imaging may show multiple lesions in one or both cerebral hemispheres. History helps in diagnosing these conditions; disseminated nocardiosis usually comes from a lung infection. Pulmonary investigation with imaging and cultures also help differentiate nocardiosis.

References

  1. Beaman, B., Black, C., Doughty, F., & Beaman, L. (1985) Role of superoxide dismutase and catalase as determinants of pathogenicity of Nocardia asteroides: importance in resistance to microbicidal activities of human polymorphonuclear neutrophils. Infect Immun. 1985 Jan;47(1):135-41. doi: 10.1128/IAI.47.1.135-141.
  2. Filice, G.A. (2018). Nocardiosis. In Jameson, J., Fauci, A.S., Kasper, D.L., Hauser, S.L., Longo, D.L., & Loscalzo, J. (Eds.), Harrison’s Principles of Internal Medicine, 20e. McGraw-Hill. 
  3. Kurdgelashvili, G. (2018). Nocardiosis. Medscape. Retrieved 25 Nov 2020, from https://emedicine.medscape.com/article/224123-overview
  4. Long, S., Prober, C., & Fischer, M. (2018). Nocardia species. Principles and Practice of Pediatric Infectious Diseases. (5th ed, p. 812). Elsevier, Inc.
  5. Riedel, S., Hobden, J.A., Miller, S., Morse, S.A., Mietzner, T.A., Detrick, B., Mitchell, T.G., Sakanari, J.A., Hotez, P., & Mejia, R. (Eds.) (2019). Aerobic non–spore-forming gram-positive bacilli: Corynebacterium Corynebacterium Corynebacteria are gram-positive, club-shaped bacilli. Corynebacteria are commonly isolated on tellurite or Loeffler's media and have characteristic metachromatic granules. The major pathogenic species is Corynebacterium diphtheriae, which causes a severe respiratory infection called diphtheria. Corynebacterium, Listeria Listeria Listeria spp. are motile, flagellated, gram-positive, facultative intracellular bacilli. The major pathogenic species is Listeria monocytogenes. Listeria are part of the normal gastrointestinal flora of domestic mammals and poultry and are transmitted to humans through the ingestion of contaminated food, especially unpasteurized dairy products. Listeria Monocytogenes Infections, Erysipelothrix, Nocardia, and related pathogens. Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28e. McGraw-Hill. 
  6. Ryan, K.J. (Ed.) (2017). Actinomyces Actinomyces Actinomyces is an anaerobic, gram-positive, branching, filamentous rod. Actinomyces israelii is the most common species involved in human disease. The organism is commonly found as part of the normal flora in the oral cavity, gastrointestinal tract, and reproductive tract. Actinomyces/Actinomycosis and Nocardia. Sherris Medical Microbiology, 7e. McGraw-Hill. 
  7. Spellman, D., Sexton, D., & Mitty, J. (2019). Microbiology, epidemiology and pathogenesis of nocardiosis. UpToDate. Retrieved 25 Nov 2020, from https://www.uptodate.com/contents/microbiology-epidemiology-and-pathogenesis-of-nocardiosis

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