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Author: Jorge M Quinonez, MD, Medical Director of Pediatrics, Chief Medical Officer, Family Health Centers of South West Florida, Inc

Jorge M Quinonez is a member of the following medical societies: American Academy of Pediatrics and Infectious Diseases Society of America

Editors: Itzhak Brook, MD, MSc, Professor, Department of Pediatrics, Georgetown University School of Medicine; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Mark R Schleiss, MD, American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota School of Medicine; Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine; Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Author and Editor Disclosure

Synonyms and related keywords: actinomycosis, actinophytosis, lumpy jaw, Actinomyces, Actinomyces israelii, A israelii, Actinomyces naeslundii, A naeslundii, Actinomyces odontolyticus, A odontolyticus, Actinomyces viscosus, A viscosus, Actinomyces meyeri, A meyeri, infections of the oral region, infections of the cervicofacial region, cervicofacial actinomycosis, thoracic actinomycosis, abdominal actinomycosis, pelvic actinomycosis, Actinobacillus actinomycetemcomitans, Eikenella corrodens, Fusobacterium, Bacteroides, Capnocytophaga, Staphylococcus, Streptococcus, Enterococcus

pulmonary infection, appendicitis, diverticulitis, tonsillitis, mastoiditis, otitis, periostitis, osteomyelitis, pneumonia, tuberculosis, tracheoesophageal fistulas, pericarditis, myocarditis, endocarditis, typhoid fever, amebic dysentery, intrauterine contraceptive device, pneumonitis, pleural effusion

Background

Actinomycosis is a chronic bacterial disease. Localized swelling with suppuration, abscess formation, tissue fibrosis, and draining sinuses characterize this disease. Gram-positive, pleomorphic non–spore-forming, non–acid-fast anaerobic or microaerophilic bacilli of the genus Actinomyces and the order Actinomycetales cause actinomycosis. Actinomyces are very closely related to Nocardia species; both were once considered to be fungal organisms.

Infections of the oral and cervicofacial regions are the most commonly recognized infections; however, the thoracic region, abdominopelvic region, and the CNS are also frequently involved. Actinomyces israelii, Actinomyces naeslundii, Actinomyces odontolyticus, Actinomyces viscosus, and Actinomyces meyeri most frequently cause human actinomycosis. Actinomyces gerencseriae may also cause disease in humans. Three former Centers for Disease Control and Prevention (CDC) coryneform bacteria now have been added to the Actinomyces group and are thought to be potential causes for disease; these include Actinomyces neuii,1 Actinomyces radingae, and Actinomyces turicensis. Actinomyces radicidentis, a recently described species, has been isolated with polymerase chain reaction from patients with endodontic infections.2

Actinomyces species grow well in enriched media with brain-heart infusion and may be aided in growth by an atmosphere of 6-10% ambient carbon dioxide. They grow best at 37°C. Colonies can appear at 3-7 days, but, to ensure that no growth is missed, observe cultures for 21 days.

Propionibacterium propionicus and related species of bacteria can also cause actinomycosislike disease. Other bacteria that are frequently isolated from clinical specimens concomitantly with Actinomyces in human infection include Actinobacillus actinomycetemcomitans, Eikenella corrodens, and species of Fusobacterium, Bacteroides, Capnocytophaga, Staphylococcus, Streptococcus, and Enterococcus.

Pathophysiology

Actinomyces species that cause human disease are not found in nature but are normal flora of the oropharynx, GI tract, and female genital tract. This is not an exogenous infection; therefore, no person-to-person spread of the pathogen occurs.

In general, Actinomyces species, being members of the normal flora, are agents of low pathogenicity and require disruption of the mucosal barrier to cause disease. Oral and cervicofacial diseases are commonly associated with dental procedures, trauma, oral surgery, or dental sepsis. Pulmonary infections usually arise after aspiration of oropharyngeal or GI secretions. GI infection frequently follows loss of mucosal integrity, such as with surgery, appendicitis, diverticulitis, trauma, or foreign bodies. Numerous reports have linked the use of intrauterine contraceptive devices to the development of actinomycosis of the female genital tract.3 The presence of a foreign body in this setting appears to trigger infection.

Other bacterial species that often are copathogens to Actinomyces species may aid spread of infection by inhibiting host defenses and reducing local oxygen tension. Once the organism is established locally, it spreads to surrounding tissues in a progressive manner, leading to a chronic, indurated, suppurative infection often with draining sinuses and fibrosis. In tissues, Actinomyces grow in microscopic or macroscopic clusters of tangled filaments surrounded by neutrophils. When visible, these clusters are pale yellow and exude through sinus tracts; they are called sulfur granules. This is not an exclusive finding of actinomycosis, and its absence does not rule out the diagnosis. Other conditions, such as eumycetoma and nocardiosis, have been linked to the production of sulfur granules.

Frequency

United States

The disease is uncommon. Studies in the Cleveland area in the 1970s showed incidence to be about 1 per 300,000 persons.

International

Studies in Germany and the Netherlands in the 1960s showed incidence of 1 per 100,000 persons. No data are available on the incidence of disease in developing nations.

Sex

A male-to-female infection ratio of 3:1 is encountered in most series. Unconfirmed explanations for this comprise poorer oral hygiene and augmented oral trauma in males.

Age

Infection can develop in individuals of all ages; however, it is rare in the pediatric population and in patients older than 60 years. Most cases are encountered in individuals in the mid decades of life.



History

History is specific to the type of actinomycosis infection encountered.

  • Cervicofacial actinomycosis
    • This is the most common and recognized presentation of the disease.
    • Actinomyces species are commonly present in high concentrations in tonsillar crypts and gingivodental crevices. Many patients have a history of poor dentition, oral surgery or dental procedures, or trauma to the oral cavity.
    • Chronic tonsillitis, mastoiditis, and otitis are also important risk factors for actinomycosis.
    • Periostitis or osteomyelitis can develop if the infection extends to facial and maxillary bones. The mandible appears to be one of the most common osteomyelitis sites.
    • Meningitis can also develop if the process extends into the cranial bones through sinus tracts.
  • Thoracic actinomycosis
    • Diagnosis of this condition requires a high index of suspicion.
    • The most common route for infection is aspiration of oropharyngeal or GI secretions.
    • Patients may have a history or risk factors for aspiration.
    • Other less common routes of infection include extensions from cervicofacial disease or spread from the abdomen and, rarely, dissemination through blood from other sites of infection.
    • The most common clinical presentation is a chronic, indolent, slowly progressing pneumonia with or without pleural involvement. Patients present with a productive cough, fever, chest pain, and weight loss. The condition can mimic tuberculosis or malignancy.
    • The disease can spread to the mediastinum and cause tracheoesophageal fistulas, pericarditis, myocarditis, or endocarditis.
    • Posterior mediastinal involvement can lead to vertebral infection with bone destruction or disease of paraspinal muscles and soft tissues.
  • Abdominal actinomycosis
    • Abdominal actinomycosis is the most covert and indolent of all forms of the disease.
    • Diagnosis is rarely suspected or made on clinical grounds. Usually, the laboratory or the pathologist provides diagnosis.
    • The infection usually develops after GI mucosal integrity is broken from surgical procedures or trauma, although, on many occasions, the inciting conditions may not be apparent.
    • Conditions such as typhoid fever, amebic dysentery, and the presence of foreign bodies, such as chicken and fish bones, have precluded the development of actinomycosis.
    • Appendicitis with perforation is the most common predisposing event, and, as a result, right-sided abdominal infection is far more common than left-sided abdominal infection. The inciting event can precede the diagnosis by months to years.
    • Patients present with nonspecific symptoms and findings, such as fever, weight loss, diarrhea or constipation, and abdominal pain. Extension to the perirectal space is not uncommon and these patients present with defecation symptoms.
    • Hepatic, renal, and splenic disseminations are uncommon complications of abdominal actinomycosis.
  • CNS disease
    • Clinical features are indistinguishable from those of other infections of the CNS.
    • The findings in those patients without meningeal involvement are typically those of a space-occupying lesion with focal neurologic defects and increased intracranial pressure.
    • The specific signs and symptoms are attributed to the anatomic location of the abscess, empyema, or actinomycoma.
    • Patients with chronic meningitis have an indolent picture that is no different from other chronic meningitides with headaches, low toxicity, and subtle neurologic findings dominating the picture.
  • Pelvic actinomycosis
    • This condition is extremely rare in the pediatric population and is almost exclusively is observed in patients who present with prolonged use of intrauterine contraception devices, usually for longer than 2 years.
    • Pelvic actinomycosis may develop from extension of intestinal infection, commonly from indolent ileocecal disease.
    • Patients present with an indolent history of vaginal discharge, abdominal or pelvic pain, menorrhagia, fever, weight loss, and prolonged use of an intrauterine contraceptive device.

Physical

Physical findings are specific to the type of actinomycosis infection encountered.

  • Cervical actinomycosis
    • Patients may present with an acute form of disease characterized by the formation of a painful pyogenic abscess with trismus and fistulas that drain the characteristic sulfur containing granules.
    • More commonly, patients present with a painless indurated mass at the angle of the jaw or submandibular region with 1 or several draining sinus tracts that discharge sulfur granules.
    • Although infection of the mandible is the most often encountered presentation, include actinomycosis in the differential of any mass lesion encountered in the head and neck regions.
  • Thoracic actinomycosis
    • Specific clinical or radiologic findings are not recognized.
    • Physical examination reveals diffuse rales and rhonchi. Decreased breath sounds can be appreciated if a pleural empyema is present.
    • The patient appears chronically ill.
    • Radiographic findings have the appearance of pneumonitis or a mass lesion, and, frequently, a pleural effusion is present.
    • Hilar adenopathy can often be observed.
    • Extension to adjacent tissues with involvement of chest wall muscles and soft tissues may lead to the formation of sinus tracts extending to the skin. This finding should always raise the possibility of actinomycosis.
  • Abdominal actinomycosis
    • An abscess or a hard, firm mass fixed to underlying tissue can be palpated in all quadrants, more commonly in the right lower quadrant.
    • Sinus tracts that extend to the abdominal wall or perirectal tissues may be found sporadically. Patients experience localized or diffuse abdominal tenderness.
    • Hepatomegaly and jaundice can be found with liver involvement. Appearance of symptoms is indolent, and the patient may have had symptoms for months before seeking attention.
  • Pelvic disease: Upon physical examination, a pelvic mass can be felt on the adnexa and a vaginal or cervical discharge can be observed with speculum examination.

Causes

Predisposing risk factors are specific to the type of infection encountered.

  • Cervicofacial actinomycosis
    • Poor dental hygiene
    • Oral surgery
    • Dental work
    • Oral trauma
    • Chronic mastoiditis
    • Chronic otitis
    • Chronic tonsillitis
  • Thoracic actinomycosis
    • Any risk factor for aspiration
    • Alcohol or drug intoxication
    • Altered mental status
    • Neurologically devastated patients
  • Abdominal actinomycosis
    • Previous GI surgery
    • Perforation of the bowel, appendix, or colon
    • Abdominal trauma
    • Foreign bodies
    • Typhoid fever
    • Amebic dysentery
  • CNS actinomycosis
    • Prior Actinomyces infection at a distant site, such as lungs, abdomen, or pelvis
    • Extension from contiguous source, such as cervicofacial actinomycosis, paranasal infection, or middle ear infection
  • Pelvic actinomycosis
    • Prolonged use of intrauterine contraception devices
    • Spread from intestinal infection



Tuberculosis

Other Problems to be Considered

Cervical actinomycosis

Bacterial abscess of oral cavity
Neoplasia
Bacterial osteomyelitis of mandible

Thoracic actinomycosis

Tuberculosis
Nocardiosis
Bronchogenic carcinoma
Mesothelioma
Lymphoma
Lung abscess
Histoplasmosis
Blastomycosis

Abdominal actinomycosis

Intestinal tuberculosis
Ameboma
Regional enteritis
Carcinoma of the cecum

CNS actinomycosis

Intracranial neoplasia
Tuberculous meningitis
Chronic meningitis
Histoplasma capsulatum
Cryptococcus neoformans
Blastomyces dermatitidis

Pelvic actinomycosis

Intrapelvic neoplasia
Endometriosis



Lab Studies

Microbiologic identifications of the organisms that cause actinomycosis are uncommon. Diagnosis usually relies on the clinical picture and the presence of sulfur granules either observed macroscopically or microscopically. No serologic test or skin test for actinomycosis is available. Actinomyces is usually part of the normal flora; its presence on sputum samples, bronchial washings, or cervicovaginal secretions is not enough to make the diagnosis. Polymerase chain reaction has been used for diagnosis in some research laboratories.

  • Gram stain
    • Gram stain is more sensitive than culture.
    • Actinomyces are identified as gram-positive rods that are non–acid fast in diphtheroidal arrangement.
  • Hematoxylin-eosin stain of sulfur granules - Basophilic masses with a radiating border of eosinophilic terminal clubs
  • Culture
    • Tissue, pus, or sulfur granules are ideal.
    • Use anaerobic transport media.
    • No prior use of antibiotics is imperative.
    • Brain and heart infusion blood agar is cultured anaerobically or enriched with carbon dioxide.
    • Growth is in 5-7 days and may take 2-4 weeks.
  • Other useful stains
    • Grocott-Gomori methenamine-silver nitrate stain
    • P-aminosalicylic acid
    • Goodpasture stain
    • Brown-Brenn stain

Imaging Studies

  • CT scanning of the involved area is useful in differentiating between an inflammatory mass and a tumor.4
  • Abdominal and pelvic ultrasonographic studies have been used for diagnosing masses that may be due to actinomycosis.
  • Chest radiography in thoracic actinomycosis may provide some idea of the degree of pulmonary and pleural involvement; however, diagnosing the disease on the basis of radiographic findings alone is impossible.

Procedures

  • Fine-needle aspiration, biopsy, CT scanning, or ultrasound-guided aspirations and biopsies can be successfully used to retrieve clinical materials for diagnosis.

Histologic Findings

  • Histologic diagnosis is difficult because many specimens contain only a few sulfur granules.
  • The use of a specific monoclonal antibody conjugated with fluorescein is a useful alternative that allows rapid identification by direct staining of clinical materials even after they have been fixed in formalin.



Medical Care

  • In patients whose actinomycosis is not critical, the option to treat medically along with prolonged courses of antibiotics is an acceptable alternative.
  • A combined medical-surgery approach is frequently needed for complicated disease, especially when thoracic, abdominal, or CNS disease is present.
  • The duration of therapy is prolonged and should be extended well beyond resolution of symptoms to decrease the likelihood of recurrence.

Surgical Care

  • Surgery is indicated for resection of necrotic tissue, debulking of large masses, sinus tract excision, incision and drainage of empyemas, and abscesses and bone curettage.
  • Surgery alone is not curative, and the use of prolonged courses of antibiotics is always required.

Consultations

  • Pediatric surgeon
  • Pediatric infectious diseases specialist
  • Ear, nose, and throat specialist
  • Dentist and/or maxillofacial surgeon
  • Gynecologist



Drug Category: Antibiotics

For most complicated cases, 4-6 wk of intravenous penicillin G followed by 6-12 months of oral penicillin V is indicated. For patients with penicillin allergy, clindamycin, ceftriaxone, chloramphenicol, and tetracyclines are good alternatives. Parenteral and oral combinations of these drugs have been successful. Because co-infection with A actinomycetemcomitans is common, covering for this organism when present is important, especially in patients who are critically ill. Actinomycosis is susceptible to third-generation cephalosporins, rifampin, trimethoprim-sulfamethoxazole, ciprofloxacin, tetracyclines, and chloramphenicol.

Drug NamePenicillin G (Pfizerpen)
DescriptionFirst-line drug. Used for IV courses of 4-6 wk. Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.
Adult DoseCervicofacial actinomycosis: 1-6 million U/d IV divided q6h
Other types of actinomycosis: 10-20 million U/d IV divided q6h
Pediatric Dose250,000-400,000 U/kg/d IV divided q6h
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsSerum sickness; neutropenia with large and prolonged doses; interstitial nephritis; hypokalemia with large doses; GI disturbances

Drug NamePenicillin V potassium (Beepen-VK, Betapen-VK, Pen-Vee K)
DescriptionFirst-line drug to be used as follow-up on previous parenteral therapy.
Adult Dose250-500 mg PO q6h
Pediatric Dose25-50 mg/kg/d PO divided tid/qid
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsUse caution with impaired renal function; do not use with nausea, vomiting, gastroparesis, or intestinal hypermotility

Drug NameClindamycin (Cleocin)
DescriptionSecond-line drug. Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Adult Dose150-450 mg/dose PO q6-8h; not to exceed 1.8 g/d
600-1200 mg/d IV/IM divided q6-8h
Pediatric Dose25-30 mg/kg/d PO divided q6-8h; not to exceed 1.8 g/d
25-40 mg/kg/d IV divided q6-8h
ContraindicationsDocumented hypersensitivity; regional enteritis, ulcerative colitis, hepatic impairment, antibiotic-associated colitis
InteractionsIncreases duration of neuromuscular blockade, induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsAdjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis

Drug NameChloramphenicol (Chloromycetin)
DescriptionSecond-line drug. The PO form is unavailable in the United States. Only use when no other alternatives are available. Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis.
Adult Dose250-750 mg PO q6h
1 g IV q6h
Pediatric Dose50-100 mg/kg/d PO/IV divided q6h
ContraindicationsDocumented hypersensitivity; do not use for trivial infections or when not indicated; do not use as a prophylactic agent
InteractionsConcurrent administration with barbiturates, chloramphenicol serum levels may decrease while barbiturate levels may increase causing toxicity; manifestations of hypoglycemia may develop with sulfonylureas; rifampin may reduce serum chloramphenicol levels, presumably through hepatic enzyme induction; may increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in toxicity; chloramphenicol levels may be increased or decreased
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsObtain baseline blood studies followed by periodic blood studies during treatment; suspend therapy on appearance of leukopenia, reticulocytopenia, anemia, or thrombocytopenia; avoid repeated courses; avoid concurrent use with other bone marrow suppressive agents; extreme precaution when using in term or premature newborns

Drug NameCeftriaxone (Rocephin)
DescriptionSecond-line drug. Arrests bacterial growth by binding to one or more penicillin binding proteins.
Adult Dose1-2 g IV qd or divided bid; not to exceed 4 g/d
Pediatric Dose50-75 mg/kg/d IV qd or divided bid
ContraindicationsDocumented hypersensitivity
InteractionsProbenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity
PregnancyB - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
PrecautionsAdjust dose in renal impairment; caution in breastfeeding women or patients allergic to penicillin; reports of ultrasonographic gallbladder changes

Drug NameTetracycline HCl (Sumycin)
DescriptionSecond-line drug. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s).
Adult Dose250-500 mg PO q6h
Pediatric Dose<8 years: Contraindicated
>8 years: 25-50 mg/kg/d PO divided q6-12h
ContraindicationsDocumented hypersensitivity; do not use in children <8 y; severe hepatic dysfunction
InteractionsBioavailability decreases with antacids that contain aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsPhotosensitivity may develop with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (second half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may develop with outdated tetracyclines



Further Outpatient Care

  • Observe patients for a prolonged period because the potential for relapse is significant. Emphasize compliance with prolonged courses of antibiotics to prevent recurrences.

Deterrence/Prevention

  • The practice of good oral and dental hygiene may reduce the possibility of developing actinomycosis.
  • No measure absolutely prevents the disease.
  • Explain to female patients about the possibility of actinomycosis when intrauterine or intravaginal devices are used.

Prognosis

  • The use of high doses and prolonged courses of antibiotics has dramatically altered the prognosis of this disease.
  • Patients who present late in the disease process tend to have a poor outcome.

Patient Education

  • Education on good oral hygiene practices is extremely valuable in preventing actinomycosis.
  • Educate female patients using intrauterine contraceptive devices on the possibility of developing actinomycosis.



Medical/Legal Pitfalls

  • Failure to warn female patients about the possibility of developing actinomycosis before placing an intrauterine contraceptive device
  • Failure to include actinomycosis in the differential diagnosis of patients with chronic abdominal symptoms, particularly those who have had previous surgery

Special Concerns

Always consider actinomycosis in patients of all ages who present with the following conditions:

  • Poor oral hygiene
  • Clinical setting for possible aspiration
  • Previous oral and GI surgery
  • Female patients using intrauterine contraceptive devices



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Actinomycosis excerpt

Article Last Updated: Jun 27, 2008