Actinomycosis 

Updated: Jul 24, 2018
Author: Jason F Okulicz, MD, FACP, FIDSA; Chief Editor: Michael Stuart Bronze, MD 

Overview

Background

Actinomycosis is a subacute-to-chronic bacterial infection caused by filamentous, gram-positive, non–acid-fast, anaerobic-to-microaerophilic bacteria. 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.

For additional information on actinomycosis, see the articles Actinomycosis (dermatology focus), Actinomycosis (pediatrics focus), and Actinomycosis (ophthalmology focus).

Pathophysiology

Actinomycetes are prominent among the normal flora of the oral cavity but less prominent in the lower gastrointestinal tract and female genital tract. Because 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 to cause human illness.

Furthermore, actinomycosis is generally 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 actinomycosis and for treatment failures.

Once infection is established, the host mounts an intense inflammatory response (ie, suppurative, granulomatous), and fibrosis may then follow. 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 actinomycosis, whereas lymphatic dissemination is unusual.

Cervicofacial actinomycosis

Cervicofacial actinomycosis is the most common type of the infection, comprising 50-70% of reported cases. This infection typically occurs following oral surgery or in patients with poor dental hygiene. Cervicofacial 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 granules with a yellow sulfurlike appearance (termed 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 results 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, these 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 are introduced into the deep tissues. The ileocecal region is involved most frequently, and the disease typically presents 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. Pelvic actinomycosis most commonly ascends 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.

Epidemiology

Frequency

United States

Actinomycosis is rare. During the 1970s, the reported annual incidence of actinomycosis in the Cleveland area was 1 case per 300,000 persons. Improved dental hygiene and widespread use of antibiotics for various infections have probably 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 of all forms of actinomycosis. At present, cure rates are high, and neither deformity nor death is common.

Race

Actinomycosis has no racial predilection.

Sex

For unknown reasons, actinomycosis is more common in men than in women (male-to-female ratio, 3:1), with the exception of pelvic actinomycosis.

Age

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

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.

 

Presentation

History

Cervicofacial actinomycosis

Cervicofacial actinomycosis (ie, lumpy jaw) may have the following features:

  • 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 by osteonecrosis of the jaw or maxilla due to radiation treatment or bisphosphonate use[1, 2, 3, 4]

  • 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

Thoracic actinomycosis may have the following features:

  • History of aspiration (Risk factors include seizure disorder, alcoholism, and poor dental hygiene.)

  • Dry or productive cough, occasionally blood-streaked sputum, shortness of breath, chest pain

  • Fever, weight loss, fatigue, anorexia

Abdominal actinomycosis

Abdominal actinomycosis may have the following features:

  • History of abdominal surgery, perforated viscus, mesenteric vascular insufficiency, or ingestion of foreign bodies (eg, fish or chicken bones)

  • Nonspecific symptoms; the most common 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

Pelvic actinomycosis may have the following features:

  • History of IUCD

  • Lower abdominal discomfort, abnormal vaginal bleeding or discharge

Physical

Cervicofacial actinomycosis

Patients with cervicofacial actinomycosis 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 are typically nontender and woody hard in the later stages.

Lymphadenopathy is typically absent.

Trismus is present if the mastication muscles are involved.

Fever is variably present.

Thoracic actinomycosis

Findings may include the following:

  • 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

Findings may include the following:

  • 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

Findings may include the following:

  • Pelvic mass

  • Menometrorrhagia

  • Other manifestations, as in abdominal actinomycosis

Causes

Actinomycosis is caused by filamentous, gram-positive, non–acid-fast, non–spore-forming bacteria. They belong to the order of Actinomycetales, family Actinomycetaceae, genus Actinomyces. The continued development of advanced molecular methods has led to the identification of additional Actinomyces species isolated from human material, with a total of 25 Actinomyces and Actinomyces-like organisms emerging as potential causes of infection at various body sites.[5] Members of the genera Propionibacterium, Actinobaculum, and Bifidobacterium may cause similar clinical syndromes. Actinomyces organisms grow slowly in anaerobic-to-microaerophilic conditions, forming colonies with a characteristic molar tooth appearance. The most common isolated species are Actinomyces israeli, Actinomyces gerencseriae, Actinomyces turicensis, Actinomyces radingae, and 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.

Complications

See the list below:

  • 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

 

DDx

 

Workup

Laboratory Studies

CBC count

Anemia and mild leukocytosis are common.

Erythrocyte sedimentation rate and C-reactive protein

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels are often elevated.

Chemistry

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 based on 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 actinomycetes, 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 of actinomycosis.

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.

Sulfur granules

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 that is positive for actinomycetelike organisms and the eventual development of pelvic actinomycosis is unclear.

The prevalence of smears positive for Actinomyces organisms in women who use IUCDs is approximately 7%.[6]

Because of the lack of sensitivity and specificity and low positive predictive value, the prognostic significance of detecting Actinomyces organisms is minimal in the absence of concomitant symptoms.[6]

Imaging Studies

Chest radiography

A chest radiograph may reveal 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 scanning

CT scanning (irrespective of the anatomic area of involvement) usually reveals an infiltrative mass with focal areas of decreased attenuation that enhance with contrast. This infiltrative mass tends 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 of actinomycosis.

Surgery (eg, thoracotomy with open lung biopsy, exploratory laparotomy) may be required for diagnostic purposes.

Histologic Findings

Actinomycosis is characterized by mixed suppurative and granulomatous inflammatory reactions, connective-tissue proliferation, and the presence of sulfur granules. The sulfur granules are nearly pathognomonic for actinomycosis, although similar findings have been reported with infections caused by 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. The images below are representative photomicrographs.

Actinomycosis in the endometrial tissue, low-power Actinomycosis in the endometrial tissue, low-power view. Image courtesy of Paul Gibbs, MD.
Actinomycosis in the endometrial tissue, high-powe Actinomycosis in the endometrial tissue, high-power view. Image courtesy of Paul Gibbs, MD.
 

Treatment

Medical Care

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

Parenteral antibiotics are administered initially via PICC line, with transition to oral agents.

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). In a case series of 23 patients with abdominal actinomycosis, approximately 50% of patients required emergency surgery for symptoms of peritonitis.[7]

Consultations

See the list below:

  • Interventional radiologist

  • Surgeon

  • Infectious diseases specialist

Diet

No specific dietary precautions are indicated in patients with actinomycosis.

Activity

Patients with actinomycosis may be active to the degree tolerated.

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.

Long-Term Monitoring

Follow up on outpatient intravenous antibiotic programs and switch patients to oral antibiotic therapy. Prolonged antibiotic therapy is often required.

Use CT scanning and MRI to monitor the response to therapy.

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 penicillin therapy is failing, consider broadening the antimicrobial spectrum to cover the potentially uncultured companion bacteria.

Transfer

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

 

Medication

Medication Summary

High-dose penicillin administered over a prolonged period (6 months to 1 year) is the cornerstone of therapy for actinomycosis. These recommendations were developed at a time when patients with actinomycosis typically presented late in the course of illness with large lesions, often receiving intermittent antibiotic therapy. In addition, modern imaging modalities were not available to monitor therapy. Success with shorter courses of therapy (< 6 mo) has been reported, especially in cervicofacial actinomycosis.[8] Ultimately, the treatment duration should be tailored to the individual patient based on clinical and radiographic response. Patients should be monitored more closely if shorter treatment durations are considered.

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), penicillinase-resistant penicillins (eg, methicillin, nafcillin, oxacillin, cloxacillin), and cephalexin. The data concerning the fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) are limited; however, treatment success has been cited in case reports.[9, 10]

Antibiotics

Class Summary

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

Penicillin G (Pfizerpen, Bicillin)

DOC for treatment of actinomycosis. Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

Penicillin VK (Pen-Vee K, V-Cillin-K)

DOC for treatment of actinomycosis. Interferes with synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

Doxycycline (Bio-Tab, Doryx, Vibramycin)

For nonpregnant patients with penicillin allergy. Inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Clindamycin (Cleocin)

Alternative in patients allergic to penicillin. Lincosamide agent that inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Drawback is lack of coverage against some companion bacteria.

Amoxicillin/clavulanic acid (Augmentin)

Drug combination that can be used alone in mild to moderately severe cases of actinomycosis; covers both pathogenic actinomycetes and companion bacteria, which frequently are resistant to penicillin.

Ceftriaxone (Rocephin)

Covers both pathogenic actinomycetes and companion bacteria, which frequently are resistant to penicillin. Useful in moderately severe to severe forms of cervicofacial and thoracic actinomycosis. Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms. Arrests bacterial growth by binding to penicillin-binding proteins.

Imipenem/cilastatin (Primaxin)

Covers both pathogenic actinomycetes and companion bacteria, which frequently are resistant to penicillin. Useful in moderately severe to severe forms of abdominal and pelvic actinomycosis.

 

Questions & Answers

Overview

What is actinomycosis?

What is the pathophysiology of actinomycosis?

What is the pathophysiology of cervicofacial actinomycosis?

What is the pathophysiology of thoracic actinomycosis?

What is the pathophysiology of actinomycosis of the abdomen and pelvis?

What is the prevalence of actinomycosis in the US?

What is the global prevalence of actinomycosis?

What is the mortality and morbidity associated with actinomycosis?

What is the racial predilection of actinomycosis?

What are the sexual predilections of actinomycosis?

Which patient groups have the highest prevalence of actinomycosis?

What is the prognosis of actinomycosis?

What is the risk of person-to-person transmission of actinomycosis?

Presentation

Which clinical history findings are characteristic of thoracic actinomycosis?

Which clinical history findings are characteristic of abdominal actinomycosis?

Which clinical history findings are characteristic of pelvic actinomycosis?

Which clinical history findings are characteristic of cervicofacial actinomycosis?

Which physical findings are characteristic of cervicofacial actinomycosis?

Which physical findings are characteristic of thoracic actinomycosis?

Which physical findings are characteristic of abdominal actinomycosis?

Which physical findings are characteristic of pelvic actinomycosis?

What causes actinomycosis?

What are complications of actinomycosis?

DDX

What are the differential diagnoses for Actinomycosis?

Workup

Which findings on CBC count suggest actinomycosis?

Which findings of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels suggests actinomycosis?

Which chemistry results suggest actinomycosis?

What is the role of organism cultures in the diagnosis of actinomycosis?

What is the role of sulfur granules in the diagnosis of actinomycosis?

What is the role of serologic testing in the diagnosis of actinomycosis?

What is the role of a Papanicolaou test in the diagnosis of actinomycosis?

What is the role of chest radiography in the diagnosis of actinomycosis?

What is the role of CT scanning in the diagnosis of actinomycosis?

What is the role of invasive procedures in the diagnosis of actinomycosis?

Which histologic findings are characteristic of actinomycosis?

Treatment

How is actinomycosis treated?

What is the role of surgery in the treatment of actinomycosis?

Which specialist consultations may be beneficial to patients with actinomycosis?

Which dietary modifications are used in the treatment of actinomycosis?

Which activity modifications are used in the treatment of actinomycosis?

How is actinomycosis prevented?

What is included in long-term monitoring of actinomycosis?

What is included in inpatient care for actinomycosis?

When is patient transfer indicated for the treatment of actinomycosis?

Medications

What is the role of medications in the treatment of actinomycosis?

Which medications in the drug class Antibiotics are used in the treatment of Actinomycosis?