Actinomyces/Actinomycosis

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. The disease is caused when the organism is displaced even by minor trauma or procedure, allowing the organism to move beyond the mucosal barrier. Reaching areas of low oxygen leads to the organism’s multiplication. Actinomyces is associated with cervicofacial infection, which forms draining sinus tracts. Actinomyces can also affect the thoracic, abdominal, and pelvic areas. Drainage or infected tissue may have the characteristic yellow sulfur granules associated with Actinomyces. Management is with long-term penicillin and surgery, if needed.

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Classification

Gram-positive bacteria:
Most bacteria 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 appear as purple-blue on the stain, making them gram positive. The bacteria 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 based on the presence of the enzyme coagulase and on their sensitivity to the antibiotic novobiocin. Streptococci are grown on blood agar and classified based on which form of hemolysis they employ (a, b, or g). Streptococci are further narrowed based on 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.

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General Characteristics

Actinomyces

  • General characteristics:
    • Structure: branching, filamentous rods/bacilli
    • Gram stain: gram-positive
    • Other stain(s): not acid-fast
    • Spore formation: non-spore–forming (differentiates Actinomyces from fungi)
    • Oxygen requirement: anaerobe
  • Culture medium: same as for other anaerobes
  • Actinomycosis (disease-caused): 
    • Chronic suppurative and granulomatous infection
    • Associated with abscess formation with interconnecting sinus tracts
    • Sulfur granules:
      • Characteristic finding 
      • Microcolonies of the bacteria with yellow color (no sulfur) and peripheral clubs
      • Found embedded in tissue elements

Clinically relevant species

  • A. israelii (most common)
  • A. gerencseriae
  • A. naeslundii
  • A. viscosus
  • A. odontolyticus
  • A. meyeri

Histopathological changes of brain abscess due to A. naeslundii bacteria (in silver stain). Branching bacilli are noted.

Image: “Actinomyces naeslundii 01” by CDC/Dr. Lucille Georg. License: Public Domain

Epidemiology

  • Men > women
  • Higher prevalence in low socioeconomic areas and in those with poor dental hygiene
  • Use of intrauterine device (IUD) has increased incidence in women.

Pathogenesis

Reservoir and transmission

Reservoir:

  • Normal flora of:
    • Oral cavity
    • Reproductive tract
    • Gastrointestinal (GI) tract

Transmission:

  • Trauma displaces the organism.
  • Breaching the mucosal barrier and moving to areas with low oxygen (anaerobic environment) facilitate its multiplication.

Risk factors

  • Poor oral hygiene 
  • Gingivitis
  • Dental surgery
  • Dental trauma
  • IUD use
  • Alcoholism
  • Malnutrition
  • Malignancy and related local tissue damage (from the disease or from radiation treatment)
  • Diabetes
  • Osteonecrosis of the jaw due to bisphosphonates

Pathophysiology

  • The bacteria take advantage of the mucosal break, invading neighboring tissues.
  • Once Actinomyces infection is established, inflammatory response follows (suppurative and granulomatous). 
  • Infection spreads by creating sinuses that contain sulfur granules; these may drain into the surface. 
  • Infections occur near the usual reservoir.
  • Pulmonary infections occur, from direct extension of the oropharyngeal source or by aspiration of oral and GI secretions.

Pathogenesis of Actinomyces
When there is a breakdown of the mucosal barrier, Actinomyces from the oropharynx (which goes to respiratory areas), GI tract, and reproductive tract cause infection and spread to contiguous tissues while creating sinus tracts.

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Clinical Presentation

Cervicofacial disease

  • Most common presentation
  • Oral/facial abscesses in the jaw (“lumpy jaw”), draining through sinus tracts 
  • Commonly affects the maxilla, cheek, and lower jaw
  • Forms characteristic yellow sulfur granules in pus or tissues:
    • Resemble grains of sand
    • Bacterial microcolonies
  • May extend to other tissues, bones, and lymph nodes
  • Manifestations:
    • Trismus and difficulty chewing
    • Pain occurs with compression of neighboring structures.
  • Often associated with dental caries, extractions, or jaw trauma

Thoracic actinomycosis

  • Transmission: 
    • Aspiration of oropharyngeal secretions
    • Introduction of bacteria via esophageal injury
    • Direct extension from neck or abdomen
    • Hematogenous spread
  • Presents as subacute pulmonary infection: fever, cough with sputum
  • Lung parenchyma: may have cavitations, which can form sinus tracts
  • These tracts can go through the chest wall or invade the ribs.

Abdominal actinomycosis

  • From a ruptured appendix/bowel or an ulcer
  • Patient may have had prior abdominal surgery.
  • Presents with fever, change in bowel habits, abdominal pain, weight loss
  • Extension can affect any intraabdominal organ.

Pelvic actinomycosis

  • In patients with an IUD
  • May present as lower abdominal pain and vaginal discharge
  • May cause pelvic abscesses

Diagnosis and Management

Diagnosis

  • Culture: 
    • Culture media and techniques: same as for other anaerobes 
    • Prolonged incubation (sometimes takes 7–21 days to appear)
    • Specimen(s): 
      • Pus (from draining sinuses)
      • Sputum
      • Specimens of tissue (with yellow-orange, microscopic sulfur granules)
    • In some cases, Actinomyces is seen on Pap smear.
      • If symptomatic of infection: IUD is removed and sent for culture.
      • If without symptoms: Patient is educated on symptoms to watch for and IUD is left in place.
  • Microscopic examination of sulfur granule: composed of tissue elements and branching actinomycotic filaments (club-shaped at the periphery)
  • Imaging studies:
    • Computed tomography (CT) scan of the abdomen: shows site and extent of the disease in abdominal infection
    • CT of the chest:
      • Evaluates thoracic infection
      • Shows mass with central areas of low attenuation and ring-like rim enhancement 
      • Cavities also may be seen.
    • Pelvic ultrasound: 
      • Obtained when patients present with symptoms of pelvic inflammatory disease
      • Look for abscess

Osteonecrosis of the jaw associated with Actinomyces
(a) Hematoxylin and eosin staining of an aggregate composed of filaments, so-called sulfur granules (#). These granules macroscopically appear as yellow granules surrounded by neutrophilic granulocytes (*) and a necrotic bone trabecula (+, magnification x 100).
(b) The granules (#) stain periodic-acid Schiff (PAS)–positive (magnification x 200).
(c) High magnification elucidates the filamentous structure (#, sun-ray morphology) of the organisms (magnification x 400).
(d) Typical growth pattern of Actinomyces spp. in microbiological culture.

Image: “The association of medication-related osteonecrosis of the jaw with Actinomyces spp. infection” by Scientific Reports. License: CC BY 4.0

Management

  • Prolonged penicillin treatment 
    • Mild disease: 2–6 months
    • Severe disease: 6–12 months
  • Alternatives for penicillin-allergic patients: clindamycin or erythromycin
  • Surgical incision and drainage may be required.
  • Removal of IUD 

Comparison

Two clinically relevant gram-positive, branching, filamentous rods that must be distinguished:

Differentiating factorsActinomycesNocardia
Oxygen requirementAnaerobicAerobic
Acid-fast stainNot acid-fastAcid-fast (partially)
Reservoir/habitatNormal oral, GI, and reproductive floraFound in soil, water, decaying organic matter
Infections caused
  • Orofacial abscesses, associated with dental caries or facial trauma
  • Sinus tracts
  • Pelvic inflammatory disease
  • Pulmonary infection in immunocompromised patients (can spread hematogenously and cause brain abscesses)
  • Cutaneous lesions in immunocompetent patients
ManagementPenicillinTrimethoprim-sulfamethoxazole

Mnemonic:

 SNAP (Sulfonamides-Nocardia, ActinomycesPenicillin)

Differential Diagnosis

  • Appendicitis: presents with abdominal pain and tenderness, mostly in the right lower quadrant. Computed tomography scan can help diagnose appendicitis. Abdominal actinomycosis can occur if appendicitis is complicated with rupture.
  • Odontogenic abscess/infection: arises after dental extraction or from an infected tooth. Infections are often polymicrobial; most common bacteria are Streptococcus viridians, Peptostreptococcus, and Staphylococcus. Culture will differentiate the organisms.
  • Pelvic inflammatory disease: the more common bacteria involved in this disease are Chlamydia trachomatis and Neisseria gonorrhoeae. Infections from both organisms are sexually transmitted. Actinomycosis is often associated with IUD use.

References

  1. Riedel S, Hobden JA, et al (Eds.) (2019). Infections caused by anaerobic bacteria. In Jawetz, Melnick, & Adelberg’s Medical Microbiology (28th ed.) McGraw-Hill. 
  2. Russo TA. (2018). Actinomycosis. In Jameson J, Fauci AS, et al (Eds.), Harrison’s Principles of Internal Medicine (20th ed.) McGraw-Hill.
  3. Ryan KJ (Ed.) (2017). Actinomyces and nocardia. In Sherris Medical Microbiology (7th ed.) McGraw-Hill.
  4. Sharma S, Hashmi M, Valentino D. (2020). Actinomycosis. StatPearls. Retrieved Nov 25, 2020, from https://www.ncbi.nlm.nih.gov/books/NBK482151/
  5. Valour F, Sénéchal A, et al (2014). Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist, 7, 183–197. https://dx.doi.org/10.2147%2FIDR.S39601

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