Harrison's Practice

Actinomycosis

Definition

  • Indolent, slowly progressive infection caused by anaerobic or microaerophilic bacteria, primarily of the genus Actinomyces, which colonize the mouth, colon, and vagina
  • Clinical presentations are myriad and include:
    • Oral–cervicofacial disease
    • Thoracic disease
    • Abdominal disease
    • Pelvic disease
    • Central nervous system (CNS) disease
    • Musculoskeletal and soft-tissue infection
    • Disseminated disease

Epidemiology

  • Age
    • Occurs throughout life
    • Peak incidence in the middle decades
  • Sex
    • Men have a 3-fold higher incidence of infection than do women, possibly because of:
      • Poorer dental hygiene
      • More frequent trauma
  • The decreased incidence since the preantibiotic era may be associated with:
    • Improved dental hygiene
    • Early initiation of antimicrobial treatment

Risk Factors

  • Local infection susceptibility
    • Foreign bodies: intrauterine contraceptive devices (IUCDs)
      • Rarely develops when the IUCD has been in place for < 1 year
      • Risk increases with time.
    • Poor dental hygiene
    • Neoplasia and/or radiation therapy causing local tissue damage
    • Trauma
    • Ulcerative mucosal infections due to:
      • Herpes simplex virus
      • Cytomegalovirus
  • Abnormal host immune defenses due to:
    • HIV infection
    • Chemotherapy
    • Transplantation
    • Diabetes
    • Poor nutrition
  • Failure to seek or lack of access to health care

Etiology

  • The bacteria causing actinomycosis are part of the normal oral flora and are often cultured from the bronchi, GI tract, and female genital tract.
  • Most common cause of infection: A. israelii
  • Established but less common causes: A. naeslundii, A. odontolyticus, A. viscosus, A. meyeri, A. gerencseriae, Propionibacterium propionicum
  • Increasing data support the following as additional causes of human actinomycosis: A. europaeus, A. neuii, A. radingae, A. graevenitzii, A. turicensis, A. cardiffensis, A. houstonensis, A. hongkongensis, and A. funkei.
  • Virtually all actinomycotic infections are polymicrobial.
    • The contribution of other species to the pathogenesis of actinomycosis is uncertain.
    • Common co-infecting organisms
      • Actinobacillus actinomycetemcomitans
      • Eikenella corrodens
      • Enterobacteriaceae
      • Species of Fusobacterium, Bacteroides, Capnocytophaga, Staphylococcus, and Streptococcus
  • A critical step in the development of actinomycosis is disruption of the mucosal barrier.
    • Local infection may ensue.
    • Once established, actinomycosis spreads contiguously in a slowly progressive manner, ignoring tissue planes.
    • Infection may then develop at virtually any site in the body.
  • A hallmark of actinomycosis is the characteristic chronic indolent phase, manifested by:
    • Lesions that usually appear as single or multiple indurations
    • Central necrosis consisting of neutrophils and sulfur granules (an in vivo matrix of bacteria, calcium phosphate, and host material; virtually diagnostic of actinomycosis)
    • Fibrotic walls of the mass, typically described as "wooden"
    • Over time, sinus tracts to the skin, adjacent organs, or bone
    • Rarely, distant hematogenous seeding
  • Foreign bodies (e.g., IUCDs) appear to facilitate infection.

Symptoms & Signs

Oral–cervicofacial disease

  • Most common
  • Soft-tissue swelling, abscess, or mass lesion, often mistaken for neoplasm
  • The angle of the jaw is generally involved.
    • Otitis, sinusitis, and canaliculitis can develop.
  • Pain, fever, and leukocytosis are variably reported.
  • Contiguous extension to the cranium, cervical spine, or thorax is a potential sequela.

Thoracic disease

  • Usually follows an indolent progressive course, with involvement of pulmonary parenchyma and/or pleural space
  • Chest pain
  • Fever
  • Weight loss
  • Cough (when present, variably productive)
  • Pulmonary lesions suggestive of actinomycosis
    • May cross fissures or pleura
    • May involve the mediastinum, contiguous bone, or chest wall
    • May be associated with a sinus tract
  • Mediastinal infection is uncommon.
    • Usually arising from thoracic extension
    • Rarely resulting from perforation of the esophagus, from trauma, or from head and neck or abdominal disease
  • Rare: primary endocarditis, isolated disease of the breast

Abdominal disease

  • Months or years usually pass after inciting events, such as:
    • Appendicitis
    • Diverticulitis
    • Peptic ulcer disease
    • Foreign-body perforation
    • Bowel surgery
    • IUCD-associated pelvic disease
  • Usually presents as:
    • Abscess
    • Mass
    • Mixed lesion, often fixed to underlying tissue and mistaken for a tumor
  • Symptoms that mimic inflammatory bowel disease
    • Sinus tracts to the abdominal wall, to the perianal region, or between the bowel and other organs
  • Recurrent disease or a wound or fistula that fails to heal
  • Hepatic infection
    • Usually presents as single or multiple abscesses or masses
  • Urogenital tract infection
    • All levels of the urogenital tract can be infected.
    • Renal disease presents as pyelonephritis and/or renal and perinephric abscess.
    • Bladder involvement may result in:
      • Ureteral obstruction
      • Fistulas to bowel, skin, uterus

Pelvic disease

  • Most commonly in association with IUCDs
  • Can present months after device is removed
    • Symptoms typically indolent
    • Fever
    • Weight loss
    • Abdominal pain
    • Abnormal vaginal bleeding or discharge
  • Endometritis commonly progresses to pelvic masses or a tubo-ovarian abscess.
  • A "frozen pelvis," mimicking cancer or endometriosis, can develop by the time of recognition.

CNS disease

  • Rare
  • Single or multiple brain abscesses (most common)
  • Meningitis
  • Epidural or subdural space infection
  • Cavernous sinus syndrome

Musculoskeletal and soft-tissue infection

  • Skin, subcutaneous tissue, muscle, and bone (with periostitis or acute or chronic osteomyelitis), involved alone or in various combinations
  • Frequent cutaneous sinus tracts
  • Extremity infection uncommon; usually results from trauma

Disseminated disease

  • Rarely results in multiple organ infections
  • Lungs and liver most frequently affected
  • Presentation: multiple nodules mimicking disseminated cancer
  • Clinical presentation may be surprisingly indolent.

Differential Diagnosis

Diagnostic Approach

  • Diagnostic challenge
    • Has been called "the most misdiagnosed disease"
    • Has been said that "no disease is so often missed by experienced clinicians"
  • Myriad clinical presentations, but 3 that should prompt consideration:
    • Combination of chronicity, progression across tissue boundaries, and mass-like features (mimicking cancer, with which it is often confused)
    • Development of a sinus tract, which may spontaneously resolve and recur
    • Refractory or relapsing infection after a short course of therapy, since cure requires prolonged treatment
  • Oral–cervicofacial disease
    • Actinomycosis should be considered with any mass lesion or relapsing infection in the head and neck.
  • Diagnosis requires aspiration/biopsy (with or without CT or ultrasonographic guidance) or surgery to obtain clinical material for examination and culture.
    • Most commonly diagnosed by microscopic identification of sulfur granules (matrix of bacteria, calcium phosphate, and host material) in pus or tissues
    • Sulfur granules can occasionally be grossly identified from draining sinus tracts or pus.
    • Microbiologic identification is often precluded by prior antibiotic therapy or failure to perform appropriate cultures.
      • For optimal yield, avoidance of even a single dose of antibiotics is mandatory.

Laboratory Tests

  • Nonspecific laboratory testing
    • Leukocytosis variably present
  • Specific laboratory studies
    • Microscopic tissue examination
      • Identification of sulfur granules (an in vivo matrix of bacteria, calcium phosphate, and host material) in pus or tissues
      • Occasionally, granules can be grossly identified from draining sinus tracts or pus.
    • Microbiologic identification of actinomycetes
      • Often precluded by prior administration of antibiotics or failure to perform appropriate cultures (i.e., incubation under strict anaerobic conditions for at least 14 days)
      • For optimal yield, avoid any use of antibiotics.
      • Primary isolation requires 5–7 days but may take as long as 2–4 weeks.
      • Because these organisms are components of the normal oral and genital tract flora, their identification in sputum, bronchial washings, and cervicovaginal secretions is of little significance in the absence of sulfur granules.
    • Immunofluorescence testing (available through the Centers for Disease Control and Prevention) is a faster diagnostic alternative to culture for:
      • A. israelii
      • A. naeslundii
      • P. propionicum

Imaging

  • Thoracic disease
    • Radiographic appearance
      • Mass lesion or pneumonia
    • CT
      • Central areas of low attenuation and ring-like rim enhancement
      • Cavitary disease or hilar adenopathy
      • Pleural thickening, effusion, or empyema in > 50% of cases
      • Rarely, pulmonary nodules or endobronchial lesions
      • Pulmonary lesions may cross fissures or pleura.
      • Pulmonary lesions may involve the mediastinum, contiguous bone, or chest wall or may be associated with a sinus tract.
  • Abdominal disease
    • CT
      • Enhancement is most often heterogeneous, and adjacent bowel is thickened.
      • Sinus tracts to the abdominal wall, to the perianal region, or between the bowel and other organs
  • CNS disease
    • CT
      • Abscess usually appears as a ring-enhancing lesion with a thick wall that may be irregular or nodular.

Diagnostic Procedures

  • Aspiration or biopsies (with or without CT or ultrasonographic guidance) to obtain clinical material for diagnosis
    • Tissue examination reveals acute or chronic inflammatory granulation tissue, infiltration by inflammatory cells, and dense surrounding fibrosis.
    • Sulfur granules (an in vivo matrix of bacteria, calcium phosphate, and host material) are usually sparse; multiple biopsy samples may be required.

Treatment Approach

  • High doses of antimicrobial agents for a prolonged period
    • Therapy must be individualized.
    • If therapy is extended beyond the point of resolution of measurable disease, the risk of relapse is minimized.
  • Many co-isolates are pathogens, and a regimen covering these organisms during the initial treatment course is reasonable.
  • Medical therapy alone should be attempted before combined medical-surgical therapy is undertaken, even in extensive disease.
    • In most cases, surgery can be avoided or a less extensive procedure used.
      • Valuable in sparing critical organs, such as the bladder or reproductive organs in women of child-bearing age
    • For well-defined abscess, percutaneous drainage combined with medical therapy
    • If infection is in a critical location (e.g., the epidural space, CNS) or if therapy fails, surgery may be appropriate.

Specific Treatments

General guidelines

  • Controlled evaluations have not been performed.
  • Dosing regimens require individualization according to the site and extent of infection.
  • As a general rule, the following guidelines are required for cure of most serious infections and bulky disease.
    • Parenteral administration of the maximal antimicrobial dose for 2–6 weeks
    • Subsequent oral therapy, for a total duration of 6–12 months
  • Less extensive disease, particularly in the oral-cervicofacial region
    • A shorter course may suffice. [1]
  • For IUCD-associated disease
    • In the presence of symptoms that cannot otherwise be accounted for, remove the IUCD and consider a 14-day course of empirical treatment for possible early pelvic actinomycosis.

Widely accepted treatments

  • Agents for which there is extensive successful clinical experience
    • Penicillin: 18–24 mU/d, given in divided doses IV every 4 hours; 1–2 g/d in divided doses PO every 6 hours
    • Amoxicillin: 1.5 g/d, given in divided doses PO every 8 hours
    • Erythromycin: 2–4 g/d, given in divided doses IV every 6 hours; 1–2 g/d in divided doses PO every 6 hours
    • Tetracycline: 1–2 g/d, given in divided doses PO every 6 hours
    • Doxycycline: 200 mg/d IV or PO every 12–24 hours
    • Minocycline: 200 mg/d IV or PO every 12 hours
    • Clindamycin: 2.7 g/d, given in divided doses IV every 8 hours; 1.2–1.8 g/d in divided doses PO every 6–8 hours

Agents with anecdotal success

  • Dosing is not given because there is no accepted standard.

Agents to avoid

Agents predicted to be efficacious on the basis of in vitro activity

Monitoring

  • CT and MRI should be used to monitor the response of disease to therapy.
  • Women with IUCDs
    • Prudent to remove IUCD if symptoms cannot be accounted for, whether or not organisms are detected
      • If advanced disease is excluded, initiate a 14-day course of empirical treatment for possible early pelvic actinomycosis.
    • Detection of Actinomyces-like organisms or immunofluorescence-positive organisms in the absence of symptoms
      • Education of the patient
      • Close follow-up but not removal of IUCD unless an equally suitable means of contraception can be agreed on

Complications

  • General
    • Abscess formation
    • Sinus tract formation
    • Periostitis
    • Osteomyelitis
  • Oral–cervicofacial disease
    • Contiguous extension to cranium, cervical spine, or thorax
  • Thoracic disease
    • Empyema
    • Mediastinal infection
  • Abdominal disease
    • Fistulas/sinus tract to abdominal wall, perianal region, between bowel and other organs
    • Ureteral obstruction
  • Pelvic disease
    • Frozen pelvis
  • CNS disease
    • Meningitis

Prognosis

  • Relapse is common if antimicrobial therapy is discontinued prematurely.
  • Prognosis is generally good with appropriate antimicrobial therapy.
    • Refractory disease has been described in patients with HIV infection.

Prevention

  • Good oral hygiene

ICD-9-CM

  • 039.9 Actinomycotic infections of unspecified site
  • 039._ Actinomycotic infections, (specific site specified by fourth digit)

Internet Sites

References

  1. Sudhakar SS, Ross JJ: Short-term treatment of actinomycosis: two cases and a review. Clin Infect Dis 38:444, 2004  [PMID:14727221]

General Bibliography

  • Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 29-1993. A 54-year-old man with a mass in the thigh and a mass in the lung. N Engl J Med 329:264, 1993  [PMID:8316271]
  • Choi J et al: Optimal duration of IV and oral antibiotics in the treatment of thoracic actinomycosis. Chest 128:2211, 2005  [PMID:16236876]
  • Hennrikus EF, Pederson L: Disseminated actinomycosis. West J Med 147:201, 1987  [PMID:3660783]
  • Hsieh MJ et al: Thoracic actinomycosis. Chest 104:366, 1993  [PMID:8339619]
  • Kayikcioglu F et al: Actinomyces infection in female genital tract. Eur J Obstet Gynecol Reprod Biol 118:77, 2005  [PMID:15596277]
  • Kim TS et al: Thoracic actinomycosis: CT features with histopathologic correlation. AJR Am J Roentgenol 186:225, 2006  [PMID:16357406]
  • Lakshmana Kumar YC, Javherani R: Primary hepatic actinomycosis. Trans R Soc Trop Med Hyg 11:868,2005
  • Manfredi R et al: Progressive intractable actinomycosis in patients with AIDS. Scand J Infect Dis 27:405, 1995  [PMID:8658080]
  • Miller M, Haddad AJ: Cervicofacial actinomycosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85:496, 1998  [PMID:9619663]
  • Pulverer G, Schütt-Gerowitt H, Schaal KP: Human cervicofacial actinomycoses: microbiological data for 1997 cases. Clin Infect Dis 37:490, 2003  [PMID:12905132]
  • Smego RA, Foglia G: Actinomycosis. Clin Infect Dis 26:1255, 1998  [PMID:9636842]
  • Smith AJ et al: Antimicrobial susceptibility of Actinomyces species with 12 antimicrobial agents. J Antimicrob Chemother 2:407, 2005
  • Spagnuolo PJ, Fransioli M: Intrauterine device-associated actinomycosis simulating pelvic malignancy. Am J Gastroenterol 75:144, 1981  [PMID:7234838]
  • This topic is based on Harrison’s Principles of Internal Medicine, 17th edition, chapter 156, Actinomycosis by TA Russo.

PEARLS

  • Consider actinomycosis in any patient who has a chronic process associated with a mass progressing across tissue boundaries, a sinus tract (which may resolve and recur), or a refractory or relapsing course of infection that responds incompletely to a short course of antibiotic therapy.
  • Consider actinomycosis in any patient with an IUCD and symptoms referable to the pelvic region without other explanation.
  • Avoid empirical antibiotic treatment before tissue sampling so as to increase the chances of growing the infecting organism in culture.
  • Isolation of these organisms from cultures of the areas they normally colonize (the GI, respiratory, or genital tracts), in the absence of sulfur granules or other tissue pathology, is of no clear significance.
  • Treatment with a long course of appropriate antibiotics is required for cure.

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Actinomycosis
Last updated: August 24, 2009
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