AUTHOR AND EDITOR INFORMATION

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Background

Actinomycosis is a subacute-to-chronic bacterial infection caused by filamentous, gram-positive, anaerobic-to-microaerophilic bacteria that are not acid fast. It is characterized by contiguous spread, suppurative and granulomatous inflammation, and formation of multiple abscesses and sinus tracts that may discharge sulfur granules. The most common clinical forms of actinomycosis are cervicofacial (ie, lumpy jaw), thoracic, and abdominal. In women, pelvic actinomycosis is possible.

Pathophysiology

Actinomycetes are prominent among the normal flora of the oral cavity but less prominent in the lower gastrointestinal tract and female genital tract. As these microorganisms are not virulent, they require a break in the integrity of the mucous membranes and the presence of devitalized tissue to invade deeper body structures and cause human illness.

Furthermore, actinomycosis generally is a polymicrobial infection, with isolates numbering as many as 5-10 bacterial species. Establishment of human infection may require the presence of such companion bacteria, which participate in the production of infection by elaborating a toxin or enzyme or by inhibiting host defenses. These companion bacteria appear to act as copathogens that enhance the relatively low invasiveness of actinomycetes. Specifically, they may be responsible for the early manifestations of the infection and for treatment failures.

Once infection is established, the host mounts an intense inflammatory response (ie, suppurative, granulomatous), and fibrosis may develop subsequently. Infection typically spreads contiguously, frequently ignoring tissue planes and invading surrounding tissues or organs. Ultimately, the infection produces draining sinus tracts. Hematogenous dissemination to distant organs may occur in any stage of the infection, whereas lymphatic dissemination is unusual.

Cervicofacial actinomycosis

Cervicofacial actinomycosis is the most common manifestation, comprising 50-70% of reported cases. Infection typically occurs following oral surgery or in patients with poor dental hygiene. This form of actinomycosis is characterized in the initial stages by soft-tissue swelling of the perimandibular area. Direct spread into the adjacent tissues occurs over time, along with development of fistulas (sinus tracts) that discharge purulent material containing yellow (ie, sulfur) granules. Invasion of the cranium or the bloodstream may occur if the disease is left untreated.

Thoracic actinomycosis

Thoracic actinomycosis accounts for 15-20% of cases. Aspiration of oropharyngeal secretions containing actinomycetes is the usual mechanism of infection. Occasionally, thoracic actinomycosis may result from the introduction of organisms via esophageal perforation, by direct spread from an actinomycotic process of the neck or abdomen, or via hematogenous spread from a distant lesion. Thoracic actinomycosis commonly presents as a pulmonary infiltrate or mass, which, if left untreated, can spread to involve the pleura, pericardium, and chest wall, ultimately leading to the formation of sinuses that discharge sulfur granules.

Actinomycosis of the abdomen and pelvis

Actinomycosis of the abdomen and pelvis accounts for 10-20% of reported cases. Typically, patients have a history of recent or remote bowel surgery (eg, perforated acute appendicitis, perforated colonic diverticulitis following trauma to the abdomen) or ingestion of foreign bodies (eg, chicken or fish bones), during which actinomycetes is introduced into the deep tissues. The ileocecal region is involved most frequently, and the disease presents classically as a slowly growing tumor. Diagnosis is usually established postoperatively, following exploratory laparotomy for a suspected malignancy. Involvement of any abdominal organ, including the abdominal wall, can occur by direct spread, with eventual formation of draining sinuses. Actinomycosis of the pelvis most commonly occurs by the ascending route from the uterus in association with intrauterine contraceptive devices (IUCDs). In such cases, an IUCD has been in place for an average of 8 years.

Frequency

United States

Actinomycosis is a rare infection. During the 1970s, the reported annual incidence in the Cleveland area was 1 case per 300,000. Improved dental hygiene and widespread use of antibiotics for various infections probably have contributed to the declining incidence of this disease.

International

Actinomycosis occurs worldwide, with likely higher prevalence rates in areas with low socioeconomic status and poor dental hygiene.

Mortality/Morbidity

The availability of antibiotics has greatly improved the prognosis for all forms of actinomycosis. At present, cure rates are high and neither deformity nor death is common.

Race

No racial predilection exists.

Sex

For unknown reasons, men are affected more commonly than women, with the exception of pelvic actinomycosis. The reported male-to-female ratio is 3:1.

Age

Actinomycosis can affect people of all ages, but the majority of cases are reported in young to middle-aged adults (aged 20-50 y).

CLINICAL

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• Cervicofacial actinomycosis (ie, lumpy jaw)
• • History of dental manipulation or trauma to the mouth, poor oral hygiene, dental caries, or periodontal disease; may arise following local tissue damage caused by neoplasm or radiation treatment
  • Painless or occasionally painful soft-tissue swelling involving the submandibular or perimandibular region; over time, multiple sinuses drain pus containing sulfur granules; tendency to remit and recur
  • Reddish or bluish discoloration of the skin overlying the lesion
  • Chewing difficulties (ie, with involvement of mastication muscles)
• Thoracic actinomycosis
• • History of aspiration (Risk factors include seizure disorder, alcoholisms, and poor dental hygiene.)
  • Dry or productive cough, occasionally blood-streaked sputum, shortness of breath, chest pain
  • Fever, weight loss, fatigue, anorexia
• Abdominal actinomycosis
• • History of abdominal surgery, perforated viscus, mesenteric vascular insufficiency, or ingestion of foreign bodies (eg, fish or chicken bones)
  • Nonspecific symptoms: The most common nonspecific symptoms are as follows:
  • • Low-grade fever
    • Weight loss
    • Fatigue
    • Change in bowel habits
    • Vague abdominal discomfort
    • Nausea
    • Vomiting
    • Sensation of a mass
• Pelvic actinomycosis
• • History of IUCD
  • Lower abdominal discomfort, abnormal vaginal bleeding or discharge

Physical

• Cervicofacial actinomycosis
• • Patients present with nodular lesion(s), usually located at the angle of the jaw. These gradually increase in size and number (ie, multiple abscesses), and ultimately form sinuses that open onto the cheek or submandibular area. Sulfur granules may be seen in the exudate.
  • Nodules may be tender in the initial stages, but typically they are nontender and woody hard in the later stages.
  • Lymphadenopathy typically is absent.
  • Trismus is present if the mastication muscles are involved.
  • Fever is variably present.
• Thoracic actinomycosis
• • Fever, cachexia, abnormal breath sounds, cough (dry or productive of purulent sputum), hemoptysis
  • Sinus tracts with drainage from the chest wall (ie, pleurocutaneous fistula)
• Abdominal actinomycosis
• • Scar(s) from antecedent abdominal surgery
  • Low-grade fever and cachexia (variably present)
  • Mass most often located in the right lower quadrant, less frequently in the left lower quadrant; mass typically firm-to-hard in consistency, nontender, often fixed to underlying tissue
  • Sinus tracts with drainage from either the abdominal wall (ie, peritoneocutaneous fistula) or the perianal region
• Pelvic actinomycosis
• • Pelvic mass
  • Menometrorrhagia
  • Other manifestations, as in abdominal actinomycosis

Causes

Actinomycosis is caused by gram-positive filamentous bacteria that do not form spores and are not acid-fast. They belong to the order of Actinomycetales, family Actinomycetaceae, genus Actinomyces. Members of the genera Propionibacterium, Actinobaculum, and Bifidobacterium may cause similar clinical syndromes. These bacteria grow slowly in anaerobic-to-microaerophilic conditions, forming colonies with a characteristic molar tooth appearance. The most common isolated species are Actinomyces israeli and Actinomyces gerencseriae, Actinomyces turicensis, Actinomyces radingae, Actinomyces europaeus, followed by Actinomyces naeslundii, Actinomyces odontolyticus, Actinomyces viscosus, Actinomyces meyeri, and Propionibacterium propionicum.

In addition to these microorganisms, almost all actinomycotic lesions contain so-called companion bacteria. The most important of these bacteria is Actinobacillus actinomycetemcomitans, followed by Peptostreptococcus, Prevotella, Fusobacterium, Bacteroides, Staphylococcus, and Streptococcus species, and Enterobacteriaceae, depending on the location of actinomycotic lesions. These companion bacteria appear to magnify the low pathogenic potential of actinomycetes.

DIFFERENTIALS

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Other Problems to be Considered

Abdominal mass
Epidural abscess

WORKUP

Section 5 of 11  

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Lab Studies

• CBC count: Anemia and mild leukocytosis are common.
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are often elevated.
• Chemistry results usually are normal, with the exception of a frequently elevated alkaline phosphatase level in hepatic actinomycosis.
• Organism cultures
• • Because actinomycosis is difficult to diagnose on the basis of the typical clinical features, direct identification and/or isolation of the infecting organism from a clinical specimen or from sulfur granules is necessary for definitive diagnosis in most cases.
  • Acceptable specimen material is obtained from draining sinuses, deep needle aspirate, or biopsy specimens; swabs, sputum, and urine specimens are unacceptable or inappropriate.
  • Prompt transport of the specimens to the microbiology laboratory is necessary for optimal isolation of actinomycete organisms, preferably in an anaerobic transport device.
  • A Gram-stained smear of the specimen may demonstrate the presence of beaded, branched, gram-positive filamentous rods, suggesting the diagnosis.
  • Cultures should be placed immediately under anaerobic conditions and incubated for 48 hours or longer; the isolation and definitive identification of actinomycetes may require 2-3 weeks.
  • Nucleic acid probes and polymerase chain reaction (PCR) methods are being developed for more rapid and more accurate identification.
  • Antimicrobial susceptibility testing is not indicated in the management of actinomycosis, partly because of their predictable antibiogram.
• The preliminary diagnosis of actinomycosis also can be made by examining sulfur granules. Granules should be crushed between 2 slides, stained with 1% methylene-blue solution, and examined microscopically for features characteristic of actinomycetes.
• Serologic diagnosis: Current serologic tests have no role in diagnosing actinomycosis.
• Papanicolaou test: The relationship between a Papanicolaou test result that is positive for actinomycetelike organisms and the eventual development of pelvic actinomycosis is not clear.

Imaging Studies

• Chest x-ray films
• • A chest x-ray film may disclose a poorly defined mass or pneumonitis or cavitary lesion, with or without pleural involvement; hilar adenopathy is uncommon.
  • The presence of a masslike lesion that extends across fissures or pleura, invades into the adjacent chest wall or thoracic vertebrae, or causes local destruction of the ribs or sternum suggests thoracic actinomycosis.
• CT scans (irrespective of the anatomic area of involvement) usually reveal an infiltrative mass with focal areas of decreased attenuation that enhance with contrast. This infiltrative mass has a tendency to invade surrounding tissues; surrounding lymphadenopathy is uncommon.

Procedures

• CT scan or ultrasound-guided fine-needle aspiration and/or biopsy have been used successfully to obtain clinical material for diagnosis.
• Surgery (eg, thoracotomy with open lung biopsy, exploratory laparotomy) may be required for diagnostic purposes.

Histologic Findings

Actinomycosis is characterized by a mixed suppurative and granulomatous inflammatory reactions, connective tissue proliferation, and the presence of sulfur granules. The sulfur granules are almost pathognomonic for this infection, although similar findings have been reported with Nocardia brasiliensis, Streptomyces madurae, and Staphylococcus aureus presenting as botryomycosis. The granules are approximately 0.1-1 mm in diameter and may be seen with the naked eye as yellowish particles.

Microscopically, the granules manifest a cauliflowerlike shape at low magnification; at higher magnification (X100), when the particle has been pressed between slide and cover slip, a clump of filamentous actinomycete microcolonies surrounded by polymorphonuclear neutrophils (PMNs) can be observed. Gram stain renders these microcolonies visible as gram-positive, intertwined branching filaments, with radially arranged, peripheral hyphae. Coexisting with them are the companion bacteria, which are gram-positive and gram-negative cocci and rods. Image 1 and Image 2 are representative photomicrographs.

TREATMENT

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Medical Care

In most cases, antimicrobial therapy is the only treatment required, although surgery can be an adjunct in selected cases. Penicillin G is the drug of choice for treating an infection caused by actinomycetes.

Surgical Care

Attempt to cure actinomycosis, including extensive disease, with aggressive antimicrobial therapy alone initially. Surgical therapy may include incision and drainage of abscesses, excision of sinus tracts and recalcitrant fibrotic lesions, decompression of closed-space infections, and interventions aimed at relieving obstruction (eg, when actinomycotic lesions compress the ureter).

Consultations

• Interventional radiology
• Surgery
• Infectious diseases

Diet

No specific dietary precautions are indicated.

Activity

Patients may be active to the degree tolerated.

MEDICATION

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High-dose penicillin, administered over a prolonged period, is the cornerstone of therapy for actinomycosis. The risk of actinomycetes developing penicillin resistance appears to be minimal. Lack of a clinical response to penicillin usually indicates the presence of resistant companion bacteria, which may require modification of the antibiotic regimen (ie, addition of an agent that is active against these copathogens).

Antibiotics that possess no activity against Actinomyces species include metronidazole, aminoglycosides, aztreonam, co-trimoxazole (TMP-SMX), and penicillinase-resistant penicillins (eg, methicillin, nafcillin, oxacillin, cloxacillin) and cephalexin. The data concerning the fluoroquinolones (ciprofloxacin, gatifloxacin and moxifloxacin) are insufficient.

Drug Category: Antibiotics

Therapy must cover all likely pathogens in the context of this clinical setting.

FOLLOW-UP

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Further Inpatient Care

• Obtain imaging studies and percutaneous diagnostic studies to allow more expedient diagnosis of actinomycosis.
• Place a peripherally inserted central catheter (PICC) for administration of intravenous antibiotics.
• Arrange outpatient intravenous antibiotic therapy.
• If the patient's condition is failing penicillin therapy, consider broadening the antimicrobial spectrum to cover the potentially uncultured companion bacteria.

Further Outpatient Care

• Follow up on outpatient intravenous antibiotic programs, and switch patients to oral antibiotic therapy. Prolonged antibiotic therapy is often required.
• Use CT scans and magnetic resonance imaging to monitor the response to therapy.

In/Out Patient Meds

• Discharge patients taking oral antibiotics.

Transfer

• If a CT scanner or interventional radiology is not available, transfer to a facility with these services.

Deterrence/Prevention

• Maintenance of good oral hygiene and adequate regular dental care are important.
• Patients and physicians alike should be aware of the increased risk of infection associated with insertion of IUCD.

Complications

• Osteomyelitis of the mandible, ribs, and vertebrae
• CNS disease, including brain abscess; chronic meningitis; actinomycetoma; cranial, epidural, and subdural infection; and spinal epidural infection
• Endocarditis
• Hepatic actinomycosis
• Disseminated actinomycosis

Prognosis

• When actinomycosis is diagnosed early and treated with appropriate antibiotic therapy, the prognosis is excellent.
• The more advanced and complicated actinomycotic forms require aggressive antibiotic and surgical therapy for optimal outcome; however, deaths can occur despite such therapy.

Patient Education

• Because actinomycosis is an endogenous infection, no risk of person-to-person transmission exists.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• Failure to make a timely diagnosis: To minimize delays in diagnosis, actinomycosis should be considered in the differential diagnosis of any inflammatory lesion of subacute or long-term nature.
• Failure to determine ineffectiveness of antibiotic therapy

MULTIMEDIA

Section 10 of 11  

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• Workup
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• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Actinomycosis in the endometrial tissue, low-power view. Image courtesy of Paul Gibbs, MD.
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Media file 2:  Actinomycosis in the endometrial tissue, high-power view. Image courtesy of Paul Gibbs, MD.
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REFERENCES

Section 11 of 11

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• Differentials
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Article Last Updated: Apr 14, 2006