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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.

Last updated: Dec 29, 2023

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Classification

Microbiology flowchart gram-positive bacteria 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, indicating that they are 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 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

Actinomyces

  • General characteristics:
    • Structure: branching, filamentous rods Filamentous rods Nocardia/Nocardiosis/ bacilli Bacilli Shigella
    • Gram stain Gram stain Klebsiella: gram-positive Gram-Positive Penicillins
    • Other stain(s): not acid-fast
    • Spore Spore The reproductive elements of lower organisms, such as bacteria; fungi; and cryptogamic plants. Microsporidia/Microsporidiosis formation: non-spore–forming (differentiates Actinomyces from fungi Fungi A kingdom of eukaryotic, heterotrophic organisms that live parasitically as saprobes, including mushrooms; yeasts; smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi, commonly known as molds, refer to those that grow as multicellular colonies. Mycology)
    • Oxygen requirement: anaerobe
  • Culture medium: same as for other anaerobes Anaerobes Lincosamides
  • Actinomycosis Actinomycosis Infections with bacteria of the genus actinomyces. Tetracyclines (disease-caused):
    • Chronic suppurative and granulomatous infection
    • Associated with abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease 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 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
Actinomyces naeslundii

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 Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency in low socioeconomic areas and in those with poor dental hygiene
  • Use of intrauterine device (IUD) has increased incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in women.

Related videos

Pathogenesis

Reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli and transmission

Reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli:

  • 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 Gingivitis Inflammation of gum tissue (gingiva) without loss of connective tissue. Chédiak-Higashi Syndrome
  • Dental surgery
  • Dental trauma
  • IUD use
  • Alcoholism Alcoholism A primary, chronic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. The disease is often progressive and fatal. It is characterized by impaired control over drinking, preoccupation with the drug alcohol, use of alcohol despite adverse consequences, and distortions in thinking, most notably denial. Each of these symptoms may be continuous or periodic. Wernicke Encephalopathy and Korsakoff Syndrome
  • 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 Malignancy Hemothorax and related local tissue damage (from the disease or from radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma treatment)
  • Diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
  • 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: Anatomy 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 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 Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease occur near the usual reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli.
  • Pulmonary infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease occur, from direct extension Extension Examination of the Upper Limbs of the oropharyngeal source or by aspiration of oral and GI secretions.
Pathogenesis of actinomyces

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.

Image by Lecturio.

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: Anatomy (“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: Anatomy”), draining through sinus tracts 
  • Commonly affects the maxilla Maxilla One of a pair of irregularly shaped bones that form the upper jaw. A maxillary bone provides tooth sockets for the superior teeth, forms part of the orbit, and contains the maxillary sinus. Skull: Anatomy, 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: Anatomy
  • Forms characteristic yellow sulfur granules in pus or tissues:
    • Resemble grains of sand
    • Bacterial microcolonies
  • May extend to other tissues, bones, and lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy
  • Manifestations:
    • Trismus Trismus Spasmodic contraction of the masseter muscle resulting in forceful jaw closure. This may be seen with a variety of diseases, including tetanus, as a complication of radiation therapy, trauma, or in association with neoplastic conditions. Tetanus and difficulty chewing
    • Pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways occurs with compression Compression Blunt Chest Trauma 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: Anatomy trauma

Thoracic actinomycosis Actinomycosis Infections with bacteria of the genus actinomyces. Tetracyclines

  • Transmission:
  • 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: Anatomy or invade the ribs Ribs A set of twelve curved bones which connect to the vertebral column posteriorly, and terminate anteriorly as costal cartilage. Together, they form a protective cage around the internal thoracic organs. Chest Wall: Anatomy.

Abdominal actinomycosis Actinomycosis Infections with bacteria of the genus actinomyces. Tetracyclines

  • From a ruptured appendix Appendix A worm-like blind tube extension from the cecum. Colon, Cecum, and Appendix: Anatomy/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 Abdominal Pain Acute Abdomen, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Extension Extension Examination of the Upper Limbs can affect any intraabdominal organ.

Pelvic actinomycosis Actinomycosis Infections with bacteria of the genus actinomyces. Tetracyclines

Diagnosis and Management

Diagnosis

  • Culture:
    • Culture media and techniques: same as for other anaerobes Anaerobes Lincosamides 
    • Prolonged incubation Incubation The amount time between exposure to an infectious agent and becoming symptomatic. Rabies Virus (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 Pap smear Cytological preparation of cells collected from a mucosal surface and stained with Papanicolaou stain. Cervical Cancer Screening.
      • 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 Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast with central areas of low attenuation and ring-like rim enhancement 
      • Cavities also may be seen.
    • Pelvic ultrasound:
      • Obtained when patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 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 Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
Osteonecrosis of the jaw associated with actinomyces

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 Penicillin Rheumatic Fever treatment
    • Mild disease: 2–6 months
    • Severe disease: 6–12 months
  • Alternatives for penicillin-allergic patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship: clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides or erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides
  • Surgical incision and drainage Incision And Drainage Chalazion may be required.
  • Removal of IUD 

Comparison

Two clinically relevant gram-positive Gram-Positive Penicillins, branching, filamentous rods Filamentous rods Nocardia/Nocardiosis that must be distinguished:

Differentiating factors Actinomyces Nocardia Nocardia 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 or less commonly, via direct contact with wounds. Nocardia/Nocardiosis
Oxygen requirement Anaerobic Aerobic
Acid-fast stain Acid-Fast Stain Meningitis in Children Not acid-fast Acid-fast (partially)
Reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli/habitat Normal oral, GI, and reproductive flora Found in soil, water, decaying organic matter
Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease 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 immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (can spread hematogenously and cause brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification abscesses)
  • Cutaneous lesions in immunocompetent patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
Management Penicillin Penicillin Rheumatic Fever Trimethoprim-sulfamethoxazole

Mnemonic:

 SNAP (Sulfonamides-Nocardia, ActinomycesPenicillin)

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 Abdominal Pain Acute Abdomen and tenderness, mostly in the right lower quadrant Right lower quadrant Anterior Abdominal Wall: Anatomy. Computed tomography scan can help diagnose 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. Abdominal actinomycosis Actinomycosis Infections with bacteria of the genus actinomyces. Tetracyclines can occur if 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 is complicated with rupture.
  • Odontogenic abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease/infection: arises after dental extraction or from an infected tooth. Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease 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 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 Peptostreptococcus A genus of gram-positive, anaerobic, coccoid bacteria that is part of the normal flora of humans. Its organisms are opportunistic pathogens causing bacteremias and soft tissue infections. Perianal and Perirectal Abscess, 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 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: 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 involved in this disease are Chlamydia trachomatis Chlamydia trachomatis Type species of Chlamydia causing a variety of ocular and urogenital diseases. Chlamydia and Neisseria gonorrhoeae Neisseria gonorrhoeae A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of gonorrhea. Neisseria. Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease from both organisms are sexually transmitted. Actinomycosis Actinomycosis Infections with bacteria of the genus actinomyces. Tetracyclines 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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