Actinomyces
MICROBIOLOGY
- Thin, branching (filamentous or beaded) Gram-positive bacillus [Fig 1].
- Microaerophilic, grow best anaerobically.
- VERY fastidious, often does not grow in culture.
- Agents: A. israelii, A. naeslundii, A. odontolyticus, A. viscosus, A. meyer and 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, genital tract.
- Diagnosis is often made by histopathology -- not by culture, even when suspected.
CLINICAL
- Nearly always part of a mixed infection, especially with flora such as Actinobacillus actinomycetemcomitans, Eikenella corrodens, Bacteroides spp, S. aureus, Streptococcus spp.
- Slowly progressing infection, often with granulomatous features categorized according to the body site (orocervical, thoracic, abdominopelvic).
- Characteristic chronic lesion: dense fibrosis ("woody"), draining sinus with "sulfur granules" [Fig 2] that contain colonies of actinomyces [Fig 3].
- Infection may advance through tissue planes with no respect for anatomical boundaries.
- 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 important if from normally uncontaminated sources, e.g., uncontaminated tissue, needle aspirates, OR detection of typical sulfur granules, etc.
- Otherwise, Actinomyces may be part of normal oral or GI flora and not represent a true pathogen.
- Main differential is Nocardia [see Table Comparison with Nocardia]. Looks similar on Gram stain, but Nocardia spp. are weakly AFB, and is usually disease of an immunocompromised host.
- Lesions of actinomycosis are often mistaken for a tumor, especially in lung, abdomen or bone.
Actinomyces | ||
Agents: | Agents of actinomycosis | N. asteroides complex and other species |
Gram stain: | Filamentous or beaded/branching, Gram positive bacillus | Filamentous Gram positive bacillus |
Modified AFB: | Negative | Positive (weakly) |
Source: | Mouth, GI or GU flora | Soil |
Typical Hosts: | Previously healthy or co-morbidities (e.g., diabetes), poor dentition | Decreased cell mediated immunity Occasionally strikes immunocompetant |
Clinical features: | Indurated tissue, fistula or sinus track with sulfur granules | Indurated with sulfur granules |
Course: | Indolent | Subacute to Indolent |
Rx: | Penicillin G, ampicillin/amoxicillin, antipseudomonal PCNs, most cephalosporins, macrolides, tetracycline, imipenem, clindamycin |
SITES OF INFECTION
General
- Oral cervico-facial: characteristic "lumpy jaw" with loss of temporomandibular angle of jaw by swelling.
- This is the most common and classical presentation.
- Usually evolves over months. Infections usually polymicrobial and may include abscess formation.
- Risk factors: poor oral hygiene, heavy alcohol use, and smoking have been associated with this form of actinomycosis.
- Osteonecrosis of jaw: post chemotherapy, radiation therapy or post-bisphosphonate--sometimes associated.
- 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.1`
- Organisms may be present in cervical smears, does not represent infection.
- Thoracic: pneumonia or mass lesion +/- cavity or hilar adenopathy.
- May cross anatomical boundaries to mediastinum, pleura, bone, or chest wall [Fig 4].
- Often confused with malignancy.
- Intra-abdominal: abscess or mass lesion. Follows invasive procedure or as 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
Classic Presentation
- The unique features of actinomycosis are the mass lesions that are 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, 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.
Diagnosis
- 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 are 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), but may lack Gram stain evidence and just show granulomatous changes, necrosis or acute and chronic inflammation.
- Culture: challenging due to normal flora contamination, prior antibiotic therapy and/or the fastidious characteristics of this bacterium that are often difficult to retrieve in the microbiology laboratory.
TREATMENT
Antibiotics
- Preferred:
- 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.
- The need to treat co-pathogens is unclear.
- Alternatives:
- 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 to prevent relapse.
Surgery
- Surgery: usually reserved for suspected neoplasm, to establish diagnosis, lesion in vital area (epidural, CNS, etc.), large mass or unresponsiveness to treatment.
- Surgical procedures: debulking, excision of fistula tracts, abscess drainage.
Selected Drug Comments
Drug | Recommendation |
Neither cefotaxime nor ceftriaxone are usually selected for Actinomyces infection but the limited experience is quite good. Main reason for selection is perceived need to treat other pathogens; in this context these drugs are reasonable. | |
Good drug for actinomycosis - good in vitro activity and a limited but very favorable published experience in vivo. As with penicillin - need high doses and long course. | |
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 totally resolved. For CNS involvement, it may be preferred to give meropenem, but experience with that drug is less. | |
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, drug is less stable and needs to be keep refrigerated or mixed just prior to administration, so typically Penicillin G is selected. | |
Preferred drug for oral treatment--either initially for mild-moderate infections, or maintenance therapy after initial parenteral course. |
FOLLOW UP
- Use of high-dose abx and long duration of antibiotics justified by tradition and perceived need for penetration into dense fibrotic tissue.
OTHER INFORMATION
- 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 being the most resistant.
Basis for recommendation
- Wong VK, Turmezei TD, Weston VC. Actinomycosis. BMJ. 2011;343:d6099. [PMID:21990282]
Comment: Disease is defined by location Cervicofacial is most common, then thoracic and abdominopelvic. Path -- crosses tissue planes and causes sinus tracts. Often mimcs tumor and other infections by imaging and clinical features. Treatment is long course of antibiotics.
References
- Tippett E, Goyal N, Guy S, et al. Actinomyces spp. bloodstream and deep vein thrombus infections in people who inject drugs. Infection. 2018. [PMID:30406927]
Comment: Rare cause of infection in PWID, but endocarditis, septic pulmonary emboli or thrombophlebitis, soft tissue abscesses and prosthetic joint infections described. In this series, blood cultures were positive in three of the four 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 bywith this organism. Organisms is almost always susceptible to beta-lactam antibiotics (without 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 8 year old patient with pneumonia complicated by empyema necessitatis. Culture yielded A. israelii and A. actinomycetccomitans. Treatment was drainage and doxycycline for 1 year.
- 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, endocbronchial and extrapulmonary.
Rating: Important - 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 susceptiblity 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 to 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 2 months.
Rating: Important - 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 actimnomyces associated with a fish bone swallowed 28 months prior to 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.
Rating: Important - 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 major factor in infected osteoradionecrosis and bisphosphonate-associated osteonecrosis of jaws. A. graevenitzii may be the causative agent. Diagnosis is based on histopathology.
Rating: Important - 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: 3 cases 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 review archived material for actinomycosis of jaws and found bisphosphonate-associated osteonecrosis (BON) in 60% and infected osteoradiionecrosis (IORN) in 36%. All cases showed actinomyces colonies in bone. PCR indicated A israeli in 7 of 7 decalcified tissue specimens.
Rating: Important - 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.
- 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: 87 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.
Rating: Important - 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.
- 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 on the basis of their experience with two cases (esophageal and cervicofacial).
Rating: Important - 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%).
Rating: Important - 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. viscosusendocarditis, although a large number of cases involving other species of 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: 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.
- Heffner JE. Pleuropulmonary manifestations of actinomycosis and nocardiosis. Semin Respir Infect. 1988;3(4):352-61. [PMID:3062727]
Comment: Review of thoracic actinomycosis which is very similar in clinical features for pulmonary nocardiosis. The organisms look identical on gram stain, but actino is not a disease of the compromised host, is not weakly acid fast, will not respond to sulfonamides and may produce typical sulfur granules. Other diagnostic considerations in chronic inflammatory lung infections are TB, MOTT, endemic fungi and cryptococcosis as well as cancer & lymphomas.
- 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.
Rating: Important - Wohlgemuth SD, Gaddy MC. Surgical implications of actinomycosis. South Med J. 1986;79(12):1574-8. [PMID:3787296]
Comment: Reviews role of surgery - most cases respond to long courses of abx initially given IV. Main role of surgery is to establish dx, drain abscess, excise inflammatory masses that are near vital areas, debulk lesions that are unresponsive to abx.
Rating: Important - 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 was high, but the rate of pelvic actinomycosis was much lower.
Rating: Important
Media
Pulmonary Actinomyces
Pulmonary thoracic actinomyces eroding through chest wall; Source: PG Auwaerter MD
Sulfur granules
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 |
Actinomyces (microscopic)
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
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