Actinomyces/Actinomycosis

Classification

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 Fungi Fungi belong to the eukaryote domain and, like plants, have cell walls and vacuoles, exhibit cytoplasmic streaming, and are immobile. Almost all fungi, however, have cell walls composed of chitin and not cellulose. Fungi do not carry out photosynthesis but obtain their substrates for metabolism as saprophytes (obtain their food from dead matter). Mycosis is an infection caused by fungi. Mycology: Overview)
  • 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 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 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

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 Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries
• Malignancy and related local tissue damage (from the disease or from radiation treatment)
• Diabetes
• Osteonecrosis of the jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint due to bisphosphonates Bisphosphonates Bisphosphonates are pyrophosphate analogs most well-known for treating osteoporosis by preventing bone loss. Bisphosphonates end in the suffix "-dronate" or "-dronic acid" (e.g., alendronate, risedronate, pamidronate) and bind to hydroxyapatite crystals in bone, inhibiting osteoclast-induced bone resorption. Bisphosphonates

Pathophysiology

• 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 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.

Clinical Presentation

Cervicofacial disease

• Most common presentation
• Oral/facial abscesses in the jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint (“lumpy jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint”), draining through sinus tracts 
• Commonly affects the maxilla, cheek, and lower jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint
• 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 Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain occurs with compression of neighboring structures.
• Often associated with dental caries, extractions, or jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint trauma

Thoracic actinomycosis

• Transmission: 
  • Aspiration of oropharyngeal secretions
  • Introduction 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 via esophageal injury
  • Direct extension from neck or abdomen
  • Hematogenous spread
• Presents as subacute pulmonary infection: 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, cough with sputum
• Lung parenchyma: may have cavitations, which can form sinus tracts
• These tracts can go through the chest wall Chest wall The chest wall consists of skin, fat, muscles, bones, and cartilage. The bony structure of the chest wall is composed of the ribs, sternum, and thoracic vertebrae. The chest wall serves as armor for the vital intrathoracic organs and provides the stability necessary for the movement of the shoulders and arms. 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 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, 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 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
    • Look for abscess

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:

Mnemonic:

 SNAP (Sulfonamides-Nocardia, Actinomyces–Penicillin)

Differential Diagnosis

• Appendicitis Appendicitis Appendicitis is the acute inflammation of the vermiform appendix and the most common abdominal surgical emergency globally. The condition has a lifetime risk of 8%. Characteristic features include periumbilical abdominal pain that migrates to the right lower quadrant, fever, anorexia, nausea, and vomiting. 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 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 are Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus viridians, Peptostreptococcus, and Staphylococcus Staphylococcus Staphylococcus is a medically important genera of Gram-positive, aerobic cocci. These bacteria form clusters resembling grapes on culture plates. Staphylococci are ubiquitous for humans, and many strains compose the normal skin flora. Staphylococcus. Culture will differentiate the organisms.
• Pelvic inflammatory disease: the more common 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 involved in this disease are Chlamydia Chlamydia Chlamydiae are obligate intracellular gram-negative bacteria. They lack a peptidoglycan layer and are best visualized using Giemsa stain. The family of Chlamydiaceae comprises 3 pathogens that can infect humans: Chlamydia trachomatis, Chlamydia psittaci, and Chlamydia pneumoniae. Chlamydia trachomatis and Neisseria Neisseria Neisseria is a genus of bacteria commonly present on mucosal surfaces. Several species exist, but only 2 are pathogenic to humans: N. gonorrhoeae and N. meningitidis. Neisseria species are non-motile, gram-negative diplococci most commonly isolated on modified Thayer-Martin (MTM) agar. Neisseria gonorrhoeae. Infections from both organisms are sexually transmitted. Actinomycosis is often associated with IUD use.