- Thin, branching (filamentous or beaded) Gram-positive bacillus [Fig 1].
- Microaerophilic grows best anaerobically.
- VERY fastidious, often does not grow in culture.
- Agents: A. israelii, A. naeslundii, A. odontolyticus, A. viscosus, A. meyer, Propionibacterium propionicum and A. gereneseriae.
- Virtually all cases are mixed infections with other bacteria, including Eikenella corrodens, Bacteroides spp, S. aureus, Streptococcus spp., Aggregatibacter actinomycetemcomitans, and/or Fusobacterium sp.
- Normal flora of mouth, gut, and genital tract.
- Diagnosis is often made by histopathology -- not by culture, even when suspected.
- Nearly always part of a mixed infection, especially with flora such as Aggregatibacter (ex Actinobacillus) actinomycetemcomitans, Eikenella corrodens, Bacteroides spp, S. aureus, Streptococcus spp.
- Actinomyces spp. reside on mucosal surfaces and gain access to deeper tissues via surgical procedures, trauma, etc., disrupting the mucosal barrier.
- The main niche is the oral cavity/pharynx. Also, in GI (distal esophagus), GU tract.
- Actinomyces spp. infection may advance through tissue planes with no respect for anatomical barriers.
- Slowly progressing infection, often with granulomatous features categorized according to the body site.
- Orocervical: most common form.
- Risk factors: alcohol, smoking, poor dentition.
- Thoracic: through aspiration, hematogenous or direct spread.
- May present with empyema, chest wall abscess
- Abdominal actinomycosis associated with surgical procedures or IAI.
- Pelvic actinomycosis associated with IUDs.
- Orocervical: most common form.
- Characteristic chronic lesion: dense fibrosis ("woody"), draining sinus with "sulfur granules" [Fig 2] that contain colonies of Actinomyces [Fig 3].
- Diagnosis: characteristic Gram stain (filamentous or beaded branching rods) in tissue or sulfur granule with radiating Gram-positive bacilli seen on histopathology or exudate or in culture.
- Recovery is important if from typically uncontaminated sources, e.g., uncontaminated tissue, needle aspirates, OR detection of typical sulfur granules, etc.
- Otherwise, Actinomyces may be part of routine oral or GI flora and not represent a true pathogen.
- Suspicion may be raised upon imaging studies that show infection crossing tissue planes (e.g., empyema crossing into the chest wall).
- The main differential is Nocardia [see Table Comparison with Nocardia]. It looks similar upon Gram staining, but Nocardia spp. are weakly AFB positive upon this stain and is usually a disease of an immunocompromised host.
- Lesions of actinomycosis are often mistaken for tumor, especially in the lung, abdomen or bone.
Agents of actinomycosis
N. asteroides complex and other species
Filamentous or beaded/branching, Gram-positive bacillus
Filamentous Gram-positive bacillus
Mouth, GI or GU flora
Previously healthy or co-morbidities (e.g., diabetes), poor dentition
Decreased cell-mediated immunity
Occasionally strikes immunocompetent
Indurated tissue, fistula or sinus track with sulfur granules
Indurated with sulfur granules
Subacute to Indolent
Penicillin G, ampicillin/amoxicillin, antipseudomonal PCNs, most cephalosporins, macrolides, tetracycline, imipenem, clindamycin
SITES OF INFECTION
- Oral cervicofacial: characteristic "lumpy jaw" with loss of temporomandibular jaw angle by swelling [Fig 4].
- This is the most common and classical presentation.
- It usually evolves over months. Infections are usually polymicrobial and may include abscess formation.
- Risk factors: poor oral hygiene, heavy alcohol use, and smoking.
- Also seen associated with:
- Osteonecrosis of the jaw related to bisphosphonate therapy.
- Osteoradionecrosis (necrosis associated with irradiation of the head and neck)
- Pelvic infection: classically, IUD-associated, with IUD in place > 1 yr.
- Presents with prolonged abdominal pain, vaginal bleeding or discharge and fever.
- Ddx: tumor, endometritis, tubo-ovarian abscess, endometriosis.
- Organisms may be present in cervical smears but do not represent infection.
- Thoracic: pneumonia or mass lesion +/- cavity or hilar adenopathy.
- May cross anatomical boundaries to the mediastinum, pleura, bone, or chest wall [Fig 5].
- Often confused with malignancy.
- Intra-abdominal: abscess or mass lesion. Follows invasive procedures or as a complication of appendicitis.
- Musculoskeletal: lesions in either muscle, bone or (rarely) joint.
- Cardiac: endocarditis (The "A" of HACEK is Actinobacillus actinomycetemcomitans, now known as Aggregatibacter actinomycetemcomitans.)
- CNS: meningitis (rare), encephalitis (rare), brain abscess
- Disseminated infection: rare.
- Infections associated with foreign bodies (periprosthetic infections).
- The unique features of actinomycosis are the mass lesions, often indurated "woody hard," expand slowly without limitation by anatomical boundaries, sinus tracts, and drainage "sulfur granules."
- The typical course is indolent; tumors are often suspected, and signs of infection may or may not be present (fever, elevated ESR, leukocytosis).
- The pathogen is infrequently recovered even with careful anaerobic methods, but the "sulfur granules" in drainage is often considered indicative.
- Characteristic lesions are indurated, often "woody hard," and extend by sinus tracks by direct spread through contiguous tissue without respect for anatomical boundaries.
- Imaging with CT or US often shows mass lesions and is not infrequently mistaken for neoplasms.
- Microscopic exam of biopsies, CT-guided aspirates or drainage: may show characteristic "sulfur granules" (Gram-positive filamentous branching rods radiating from a central core). Still, it may lack Gram stain evidence and show granulomatous changes, necrosis or acute and chronic inflammation.
- Culture: challenging due to normal flora contamination, prior antibiotic therapy and the fastidious characteristics of this bacterium that are often difficult to retrieve in the microbiology laboratory.
- Specimens containing Actinomyces from superficial infections should be interpreted cautiously as organisms are part of normal flora. Correlate with the clinical picture.
- Penicillin G 18-24mil units IV/d x 2-6 wks, then amoxicillin 500-750mg PO three times a day/four times a day x 6-12 mos until sufficient resolution.
- Oral therapy alone may be adequate; no high-quality trials exist to compare treatment approaches or duration.
- The need to treat co-pathogens is unclear.
- Doxycycline 100mg twice daily IV x 2-6 wks if not able to take orals, then 100mg PO twice daily x 6-12mos.
- Erythromycin 500mg PO four times a day x 6-12 mos.
- Other agents (limited data): clarithromycin, azithromycin, imipenem, cefotaxime, piperacillin/tazobactam, clindamycin, and ceftriaxone.
- Many clinicians use ceftriaxone for once-daily convenience; however, with C. difficile risks, PCN G may be preferred.
- Not active: metronidazole, TMP/SMX, ceftazidime, aminoglycosides, oxacillin, fluoroquinolones.
- Response to appropriate antibiotic therapy is usually slow; very long courses are required to achieve resolution and prevent relapse.
- Surgery: usually reserved for suspected neoplasm, to establish a diagnosis, lesion in a vital area (epidural, CNS, etc.), large mass or unresponsiveness to treatment.
- Surgical procedures: debulking, excision of fistula tracts, abscess drainage.
Selected Drug Comments
Neither cefotaxime nor ceftriaxone was usually selected for Actinomyces infection, but the limited experience is quite good. The main reason for selection is the perceived need to treat other pathogens; these drugs are reasonable in this context.
A good drug for actinomycosis - good in vitro activity and a limited but very favorable published experience in vivo. As with penicillin - it needs high doses and a long course. High risk for C diff., so PCN is usually preferred.
A good drug for actinomycosis. The agents are susceptible, and clinical experience seems good. An advantage is the availability of oral and parenteral forms. Some clinicians will start therapy with high IV doses of penicillin or clindamycin and use doxycycline for a prolonged oral maintenance phase.
A good drug for actinomycosis. The published experience includes anecdotal cases with large thoracic lesions that resolved.
This drug won’t work. Actinomyces are not susceptible in vitro. This means Actinomycetes are probably not true anaerobes.
Penicillin G: standard drug for actinomycosis. Need high doses given IV to penetrate a very fibrotic and dense lesion. The course must be long to achieve resolution and prevent relapse.
Preferred by some to penicillin G for parenteral therapy. For OPAT, the drug is less stable and needs to be kept refrigerated or mixed just before administration, so typically, Penicillin G is selected.
Preferred drug for oral treatment--either initially for mild-moderate infections or maintenance therapy after the initial parenteral course.
- Duration depends on the site of infection and clinical response.
- The disease is "actinomycosis" caused by one of six Actinomyces agents, most commonly A. israelii.
- SUSPECT: characteristic lesion (hard, chronic inflammatory mass [+/- sinus tracts] passing through tissue planes) and micro (Gram stain ID culture often negative).
- A newly recognized entity is associated with osteonecrosis of the mandible.
- Most abx are active except metronidazole.
- Resistance varies by species. A. turicensis and A. europaeus are the most resistant.
Basis for recommendation
- Wong VK, Turmezei TD, Weston VC. Actinomycosis. BMJ. 2011;343:d6099. [PMID:21990282]
Comment: The disease is defined by location. Cervicofacial is most common, then thoracic and abdominopelvic. Path -- crosses tissue planes and causes sinus tracts. It often mimics tumors and other infections with its imaging and clinical features. Treatment is a long course of antibiotics.
- Skuhala T, Vukelić D, Desnica B, et al. Unusual presentations of actinomycosis: a case series and literature review. J Infect Dev Ctries. 2021;15(6):892-896. [PMID:34242202]
Comment: Four unusual cases out of 15 at two institutions: subcutaneous actinomycotic abscess, actinomycosis of the stomach with underlying non-Hodgkin lymphoma, sepsis due to Actinomyces neslundii originated from chronic asymptomatic periapical tooth abscesses and actinomycosis of the distal part of the penile shaft.
- Tippett E, Goyal N, Guy S, et al. Actinomyces spp. bloodstream and deep vein thrombus infections in people who inject drugs. Infection. 2019;47(3):479-482. [PMID:30406927]
Comment: A rare cause of infection in PWID, but endocarditis, septic pulmonary emboli or thrombophlebitis, soft tissue abscesses and prosthetic joint infections are described. In this series, blood cultures were positive in three patients.
- Steininger C, Willinger B. Resistance patterns in clinical isolates of pathogenic Actinomyces species. J Antimicrob Chemother. 2016;71(2):422-7. [PMID:26538502]
Comment: In vitro data is often hard to come by with this organism. Organisms are almost always susceptible to beta-lactam antibiotics (without the need for beta-lactamase inhibitors), tetracyclines and vancomycin.
- Moskowitz SM, Shailam R, Mark EJ. CASE RECORDS of the MASSACHUSETTS GENERAL HOSPITAL. Case 25-2015. An 8-Year-Old Girl with a Chest-Wall Mass and a Pleural Effusion. N Engl J Med. 2015;373(7):657-67. [PMID:26267626]
Comment: Case report of an 8-year-old patient with pneumonia complicated by empyema necessitatis. Culture yielded A. israelii and A. actinomycetccomitans. Treatment was drainage and doxycycline for one year.
- Könönen E, Wade WG. Actinomyces and related organisms in human infections. Clin Microbiol Rev. 2015;28(2):419-42. [PMID:25788515]
Comment: Comprehensive overview of the significance of Actinomyces in human infections.
- Han JY, Lee KN, Lee JK, et al. An overview of thoracic actinomycosis: CT features. Insights Imaging. 2013;4(2):245-52. [PMID:23242581]
Comment: CT anatomical features: parenchymal, bronchiectatic, endobronchial and extrapulmonary.
- von Graevenitz A. Actinomyces neuii: review of an unusual infectious agent. Infection. 2011;39(2):97-100. [PMID:21340579]
Comment: Different than the usual actino--aerobic growth, microscopic morphology (no branching), and the types and location of infections. Abscesses and infected atheromas are the most frequent types of infections, followed by infected skin structures, endophthalmitis, and bacteremias, including endocarditis. This organism appears to have susceptibility profile similar to other members.
- Song JU, Park HY, Jeon K, et al. Treatment of thoracic actinomycosis: A retrospective analysis of 40 patients. Ann Thorac Med. 2010;5(2):80-5. [PMID:20582172]
Comment: Review of 40 cases of thoracic actinomycosis -- 17 had immediate surgery due to hemoptysis or concern for cancer. Antibiotic therapy for the other 23 was successful in 18 (78%); 5 failed and required surgery. The antibiotic failures received these drugs on an average of 10 months, but those who responded showed improvement within two months.
- Maki K, Shinagawa N, Nasuhara Y, et al. Endobronchial actinomycosis associated with a foreign body--successful short-term treatment with antibiotics--. Intern Med. 2010;49(13):1293-6. [PMID:20606362]
Comment: Case report of endobronchial actinomyces associated with a fish bone swallowed 28 months before detection.
- Yi F, Prasad S, Sharkey F, et al. Actinomycotic infection of the abdominal wall mimicking a malignant neoplasm. Surg Infect (Larchmt). 2008;9(1):85-9. [PMID:18363472]
Comment: Case report -- abdominal wall mass treated with long course of penicillin for actinomycosis. Due to poor response the patient had surgical excision which the authors noted is indicated for suboptimal response or a malignant process cannot be ruled out.
- Hall V. Actinomyces--gathering evidence of human colonization and infection. Anaerobe. 2008;14(1):1-7. [PMID:18222714]
Comment: Review of recent evidence that actinomycosis is a significant factor in infected osteoradionecrosis and bisphosphonate-associated osteonecrosis of jaws. A. graevenitzii may be the causative agent. Diagnosis is based on histopathology.
- Akhan SE, Dogan Y, Akhan S, et al. Pelvic actinomycosis mimicking ovarian malignancy: three cases. Eur J Gynaecol Oncol. 2008;29(3):294-7. [PMID:18592800]
Comment: Three cases were initially diagnosed as pelvic malignancy and treated surgically. The review noted the association with IUD, the mistake of aggressive surgery for presumed malignancy and the diagnosis based on histopathology
- Hansen T, Kunkel M, Springer E, et al. Actinomycosis of the jaws--histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis. Virchows Arch. 2007;451(6):1009-17. [PMID:17952459]
Comment: Authors reviewed archived material for actinomycosis of jaws and found bisphosphonate-associated osteonecrosis (BON) in 60% and infected osteoradionecrosis (IORN) in 36%. All cases showed actinomyces colonies in bone. PCR indicated A. israeli in 7 of 7 decalcified tissue specimens.
- Yildiz O, Doganay M. Actinomycoses and Nocardia pulmonary infections. Curr Opin Pulm Med. 2006;12(3):228-34. [PMID:16582679]
Comment: Authors call attention to the common features of actinomyces and nocardiosis - both often cause chronic lung disease that simulates lung cancer or TB.
- Kim TS, Han J, Koh WJ, et al. Thoracic actinomycosis: CT features with histopathologic correlation. AJR Am J Roentgenol. 2006;186(1):225-31. [PMID:16357406]
Comment: Chronic pulmonary actinomycosis typically presents as a segmental consolidation with frequent cavity formation. A broncholith can be secondarily infected, resulting in endobronchial actinomycosis, often with distal obstructive pneumonia.
- Sarkonen N, Könönen E, Eerola E, et al. Characterization of Actinomyces species isolated from failed dental implant fixtures. Anaerobe. 2005;11(4):231-7. [PMID:16701573]
Comment: Actinomycetes were the most common bacteria on failed dental implants -A. odontolyticus > A. naeslundii = A. viscosus > A. israelii; A. georgiae, A. geroneseriae and A. graevenitzii were rare.
- Smith AJ, Hall V, Thakker B, et al. Antimicrobial susceptibility testing of Actinomyces species with 12 antimicrobial agents. J Antimicrob Chemother. 2005;56(2):407-9. [PMID:15972310]
Comment: Eighty-seven strains tested to 12 antibiotics. All were sensitive to penicillin, ampicillin and beta-lactam/beta-lactamase inhibitors. All were resistant to ciprofloxacin. Linezolid showed good activity.
- Sudhakar SS, Ross JJ. Short-term treatment of actinomycosis: two cases and a review. Clin Infect Dis. 2004;38(3):444-7. [PMID:14727221]
Comment: The authors argue that treatment may be < 6 months based on their experience with two cases (esophageal and cervicofacial).
- Pulverer G, Schütt-Gerowitt H, Schaal KP. Human cervicofacial actinomycoses: microbiological data for 1997 cases. Clin Infect Dis. 2003;37(4):490-7. [PMID:12905132]
Comment: In these 1997 cases, the predominant species were A. israelii (41%), A. gerencseriae (27%), A. naeslundii (9%), A. odontolyticus (1%), and P. propionicum (1%).
- Lee IJ, Ha HK, Park CM, et al. Abdominopelvic actinomycosis involving the gastrointestinal tract: CT features. Radiology. 2001;220(1):76-80. [PMID:11425976]
Comment: The authors review 18 cases. GI lesions showed concentric or eccentric bowel wall thickening; 17 pts had a pelvic or peritoneal mass with a mean diameter of 3.2cm adjacent to the involved bowel. Clinical features included abd pain, fever, leukocytosis & long-term IUD use.
- Mardis JS, Many WJ. Endocarditis due to Actinomyces viscosus. South Med J. 2001;94(2):240-3. [PMID:11235043]
Comment: This is the third reported case of A. viscosus endocarditis, although many cases involving other Actinomyces have been reported. All cases have involved natural valves, and there appears to be a high frequency of embolic lesions.
- Cheon JE, Im JG, Kim MY, et al. Thoracic actinomycosis: CT findings. Radiology. 1998;209(1):229-33. [PMID:9769836]
Comment: A review of 22 cases resulted in the following definition of typical CT findings: chronic segmental air-space consolidation that contains low-attenuation areas with peripheral enhancement or adjacent pleural thickening.
- Holmberg K. Diagnostic methods for human actinomycosis. Microbiol Sci. 1987;4(3):72-8. [PMID:2484673]
Comment: Diagnostic methods include 1) cultivation of the microbe (which is hard to do); 2) typical appearance on gram stain, especially with sulfur granules; and 3) fluorescent antibody (FA) stains that are available for 4 of the 6 agents of actinomycosis.
- Valicenti JF, Pappas AA, Graber CD, et al. Detection and prevalence of IUD-associated Actinomyces colonization and related morbidity. A prospective study of 69,925 cervical smears. JAMA. 1982;247(8):1149-52. [PMID:7057605]
Comment: A survey of 69,925 women with pap smear screened for actino with FA stain for A. israelii showed the prevalence in those with IUD use was 1.6-5.3%; it was never found in the absence of an IUD. It should be noted that the rates of A. israelii with IUDs were high, but the rate of pelvic actinomycosis was much lower.
Pulmonary thoracic actinomyces eroding through chest wall; Source: PG Auwaerter MD
Sulfur granules from chest wall sinus tract
Source: PG Auwaerter MD
Sulphur granules (microscopic)
Colonies of actinomyces make up sulphur granules.
Source: CDC/ Dr. Richard L. Levin, Greater Southeast Community Hospital, Washington, D.C.; Dr. V.R. Dowell
Gram-positive, beaded and branching rods (magnification 1125x) characteristic of actinomyces. Specimen from jaw area, often organisms may not grow in laboratory. Source: CDC/ Dr. Lucille Georg
Actonomycosis causing jaw swelling
Actinomycosis causing chronic swelling and a sinus tract.
Source: CDC/Dr. Thomas F. Sellers/Emory University 1963