- ICD-10-CM A42.9 Actinomycosis, unspecified
Actinomycosis most commonly presents as a cervicofacial infection, accounting for approximately 50% of all actinomycosis cases. Actinomyces can cause preseptal cellulitis, orbital cellulitis, canaliculitis, conjunctivitis, keratitis, and endophthalmitis. Actinomyces israelii was first described by Kruse in 1896, and now there are 49 species of actinomyces identified. There are 26 species, such as Actinomycetes meyeri, Actinomyces nueii, Actinomyces turicensus, that have been known to cause human infections. Actinomyces israelii has been documented to cause keratitis, canaliculitis, and endophthalmitis, and orbital actinomycosis among other infections. Actinomyces nueii has been documented to cause endophthalmitis and can cause preseptal cellulitis.
Risk factors for orbital actinomycosis include immunosuppression, HIV/AIDS, poor dental hygiene, dental caries, dental extractions, gingivitis, gingival trauma, diabetes, irradiation, and malnutrition. A large case series has found that men were three times more likely to get actinomycosis infections than women.
Actinomyces is a non-spore-forming, branching gram-positive bacteria that are strict or facultative anaerobes ranging from diphtheroidal to coccoid filaments. Actinomyces is normally found in oral flora. Yellow sulfur granules are classically seen in infected tissue but not in vitro. Sulfur granules do not actually contain any sulfur material.
Actinomyces is not considered an opportunistic organism; however, they will often affect areas of mucosal compromise or tissue injury in the head and neck areas. Commonly, oral maxillofacial trauma or dental caries are preceding events that lead to infection. The spread of Actinomyces is through hematogenous spread secondary to direct contact.
Other predisposing factors include gingivitis or gingival trauma, diabetes mellitus, immunosuppression including HIV/AIDS, malnutrition, local tissue damage caused by neoplastic disease or irradiation, osteonecrosis of the jaws
Orbital actinomycosis can be diagnosed based on a combination of clinical presentation, signs, symptoms, imaging, biopsy, histology, gene sequencing and culture results. Definitive diagnosis is usually done with a positive culture result.
Orbital actinomycosis usually is a slowly progressive, chronic, nontender, indurated mass that progresses to abscesses, fistulae, and draining sinus tracts. The history can also be a rapidly progressive, acute suppurative infection that forms an abscess.
It is recommended to perform a thorough ophthalmology and orbital exam. The exam should include best-corrected visual acuity (BCVA), pupillary function, intraocular pressure, color vision, visual field evaluation, extraocular motility, presence of pain, facial sensation, slit lamp biomicroscopy, dilated fundus exam, orbital auscultation, and exophthalmometry.
Signs and Symptoms
The presentation of Actinomyces follows two general patterns: (1) chronic, slowly progressive mass that can form abscesses, fistulas, and sinus tracts (2) less commonly it can be an acute process that presents as a suppurative infection with progression to abscess.
- Lesions with overlying discoloration of skin including blue or red appearance (often confused with cellulitis)
- Sinus tracts that express yellow exudate characteristic of sulfur granules
Symptoms include the following: 
- Pain if there is compression of adjacent structures including the tongue
- Fever and other constitutional symptoms (fatigue, malaise)
- Lymphadenopathy is seen later in disease course
Clinicians should be aware of uncommon complications of Actinomyces including osteomyelitis. In addition, Actinomyces has been identified as source of peri-implantitis associated with dental implant and osteonecrosis of the jaw secondary to bisphosphonate use.
Orbital Actinomycosis can mimic a number of other conditions, including malignancy. Therefore, it requires a high degree of clinical suspicion to make the diagnosis. Furthermore, cervicofacial actinomycosis often initially responds to a short course of broad spectrum antibiotics leading to further difficulty in definitive diagnosis.
- Culture → performed through needle aspiration and incubation of minimum 14 days is recommended.
- Histological diagnosis → several biopsy specimens from various locations improve probability of diagnosis in addition to a series of biopsies. Biopsy shows granulation tissue with neutrophil infiltration, macrophages, plasma cells, lymphocytes, and surrounding fibrosis.
- Fluorescent-conjugated Monoclonal antibody.
- Molecular → PCR with 16s rRNA gene probes, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) 
- Serology → Not a reliable test 
The differential diagnosis can include other orbital infections, orbital inflammatory disorders, and orbital neoplasia.
- Orbital bacterial infections: preseptal cellulitis, orbital cellulitis, abscess, syphilis, mycobacteria
- Orbital fungal infections: aspergillosis, mucormycosis, blastomycosis, coccidiomycosis, histoplasmosis
- Orbital inflammatory disorders: Sarcoidosis, granulomatosis with polyangiitis, nonspecific orbital inflammation, Graves' ophthalmopathy, polyarteritis nodosa, collagen vascular disorders
- Orbital neoplasia: primary tumor, metastasis, lymphoma, lacrimal gland tumor, leukemia
The treatment of orbital actinomycosis consists mainly of antibiotic therapy. Surgical intervention in the form of debridement or fistula excision may be necessary in some cases that are more severe or refractory to medical management. The duration of antibiotic treatment depends on the initial burden of disease, performance of surgical resection/debridement, and the patient’s response to treatment.
The mainstay of treatment consists of penicillin, often given parenterally for an extended duration. Other parental options include ceftriaxone. Oral amoxicillin may be appropriate in milder cases. No randomized control trials have been performed for the treatment of orbital actinomycosis. The recommendation of penicillin comes from small case series that have demonstrated success, as well as in vitro susceptibility testing. Penicillin is given in high doses because of the need to obtain effective concentration in the infected tissues.
Aminoglycosides, metronidazole, aztreonam, trimethoprim-sulfamethoxazole, penicillinase-resistant penicillins (eg, nafcillin, oxacillin), cephalexin, ceftazidime, and antifungal drugs are not active against these organisms and should not be used for therapy
Medical follow up
While mild cases may respond well to antimicrobials with or without surgical debridement, a multi-disciplinary approach is often necessary for more extensive or refractory cases. It may be prudent to involve the services of oculoplastic surgery, otolaryngology, ophthalmology, infectious disease and neurosurgery depending on the extent of the infection
Surgical interventions should also be considered if medical treatment is not effective. Local debridement can reduce the formation of scar tissue and also reduce the duration of antibiotics needed and can shorten the disease course. Drainage of abscesses, excision of sinus tracts, fistulas, and necrotic tissues may also be necessary for severe cases of infection. Repeat debridements or excision may be necessary in some cases. A case series by Payoong et al demonstrated that 8 out of 10 ocular actinomycosis cases required surgical intervention. Imaging may be used to monitor the disease process, and follow-up until complete resolution of actinomycosis after surgery is recommended.
Actinomyces has a high potential for relapse, thus prolonged antibiotic treatment is the preferred approach to prevent recurrence of the disease, along with close follow-up to monitor for resolution. There are also rare case reports of Tolosa-Hunt syndrome due to actinomyces involvement in the cavernous sinus.
Patients with orbital actinomycosis can have no residual complications with excellent prognosis if treated in a timely manner. However, reports range from 0% to 28% mortality rate depending on location of actinomycosis infection, time until diagnosis, and time until treatment, with central nervous system disease having the worst outcomes. Therefore, it is imperative to diagnose and treat actinomycosis early for the best outcomes.
- Könönen E, Wade WG. Actinomyces and Related Organisms in Human Infections. Clinical Microbiology Reviews. 2015;28(2):419-442.
- Payoong P, Saetiew N, Putcharoen O, Suankratay C. Orbital and pulmonary actinomycosis: the first case report and literature review. Case Rep Infect Dis 2018; 2018:4759807
- Mehrotra N, Baidya A, Brijwal M, Aggarwal R, Chaudhry R. Actinomycosis of eye: Forgotten but not uncommon. Anaerobe. 2015;35(Pt B):1-2. doi:10.1016/j.anaerobe.2015.06.001
- Fulmer NL, Neal JG, Bussard GM, Edlich RF. Lacrimal canaliculitis. Am J Emerg Med. 1999;17(4):385-386. doi:10.1016/s0735-6757(99)90093-1
- Kruse W. 1896. Systematik der Streptothricheen und Bakterien, p 48–96. In Flugge C. (ed), Die Mikroorganismen, 3rd ed, vol 2Vogel, Leipzig, Germany.
- Gajdács M, Urbán E, Terhes G. Microbiological and Clinical Aspects of Cervicofacial Actinomyces Infections: An Overview. Dent J (Basel). 2019 Sep 1;7(3):85. doi: 10.3390/dj7030085. PMID: 31480587; PMCID: PMC6784480.
- Gómez-Garcés José Luis, Burillo A, Gil Y, Sáez-Nieto Juan A. Soft Tissue Infections Caused by Actinomyces neuii , a Rare Pathogen. Journal of Clinical Microbiology. 2010;48(4):1508-1509. doi:10.1128/jcm.02139-09.
- Zelyas N, Gee S, Nilsson B, Bennett T, Rennie R. Infections Caused byActinomyces neuii: A Case Series and Review of an Unusual Bacterium. Canadian Journal of Infectious Diseases and Medical Microbiology. 2016;2016:1-7.
- Kolm I, Aceto L, Hombach M, Kamarshev J, Hafner J, Urosevic-Maiwald M. Cervicofacial actinomycosis: a long forgotten infectious complication of immunosuppression - report of a case and review of the literature. Dermatol Online J. 2014;20(5):22640. Published 2014 May 16.
- Khadka P, Koirala S. Primary cutaneous actinomycosis: a diagnosis consideration in people living with HIV/AIDS. AIDS Res Ther. 2019;16(1):16. Published 2019 Jul 30. doi:10.1186/s12981-019-0232-4
- Feder HM Jr. Actinomycosis manifesting as an acute painless lump of the jaw. Pediatrics. 1990;85(5):858-864.
- Wong VK, Turmezei TD, Weston VC. Actinomycosis. BMJ. 2011;343:d6099. Published 2011 Oct 11. doi:10.1136/bmj.d6099
- Lerner P. I. The lumpy jaw. Cervicofacial actinomycosis. Infectious disease clinics of North America, 1988;2(1), 203–220.
- Belmont, M. J., Behar, P. M., & Wax, M. K. Atypical presentations of actinomycosis. Head & neck, 1999;21(3), 264–268.
- Jacobs RF, Schutze GE. Actinomycosis. In: Nelson Textbook of Pediatrics, 16th ed, Behrman RE (Ed), WB Saunders, Philadelphia 2000. p.823.
- Schaal KP, Beaman BL. Clinical significance of actinomycetes. In: The Biology of the Actinomycetes, Goodfellow M, Mordarski M, Williams ST (Eds), Academic Press, New York 1983. Vol 389.
- Burns, B. V., al-Ayoubi, A., Ray, J., Schofield, J. B., & Shotton, J. C. Actinomycosis of the posterior triangle: a case report and review of the literature. The Journal of laryngology and otology, 1997;111(11), 1082–1085.
- Kaplan, I., Hirshberg, A., Shlomi, B., Platner, O., Kozlovsky, A., Ofec, R., & Schwartz-Arad, D. The importance of histopathological diagnosis in the management of lesions presenting as peri-implantitis. Clinical implant dentistry and related research, 2015;17 Suppl 1, e126–e133.
- Anavi-Lev, K., Anavi, Y., Chaushu, G., Alon, D. M., Gal, G., & Kaplan, I. Bisphosphonate related osteonecrosis of the jaws: clinico-pathological investigation and histomorphometric analysis. Oral surgery, oral medicine, oral pathology and oral radiology, 2013;115(5), 660–666.
- Peabody JW Jr, Seabury JH. Actinomycosis and nocardiosis. A review of basic differences in therapy. Am J Med 1960; 28:99
- Lo Muzio, L., Favia, G., Lacaita, M., De Lillo, A., Scully, C., Napoli, A., Lo Russo, L., & Maiorano, E. The contribution of histopathological examination to the diagnosis of cervico-facial actinomycosis: a retrospective analysis of 68 cases. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology, 2014;33(11), 1915–1918.
- Smego, R. A., Jr, & Foglia, G. Actinomycosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 1998;26(6), 1255–1263.
- Kuyama, K., Fukui, K., Ochiai, E., Maruyama, S., Iwadate, K., Saku, T., & Yamamoto, H. Identification of the actinomycete 16S ribosomal RNA gene by polymerase chain reaction in oral inflammatory lesions. Oral surgery, oral medicine, oral pathology and oral radiology. 2013;116(4), 485–491.
- De Vreese, K., & Verhaegen, J. Identification of coryneform Actinomyces neuii by MALDI-TOF MS: 5 case reports and review of literature. Acta clinica Belgica. 2013;68(3), 210–214.
- Brook I. Actinomycosis: diagnosis and management. South Med J 2008; 101:1019–23
- Valour F, Sénéchal A, Dupieux C, et al. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist. 2014;7:183-197. Published 2014 Jul 5. doi:10.2147/IDR.S39601
- Martin MV. The use of oral amoxycillin for the treatment of actinomycosis. A clinical and in vitro study. Br Dent J. 1984;156(7):252-254. doi:10.1038/sj.bdj.4805331
- Lerner PI. Susceptibility of pathogenic actinomycetes to antimicrobial compounds. Antimicrob Agents Chemother. 1974;5(3):302-309. doi:10.1128/AAC.5.3.302
- Smith AJ, Hall V, Thakker B, Gemmell CG. Antimicrobial susceptibility testing of Actinomyces species with 12 antimicrobial agents. J Antimicrob Chemother. 2005;56(2):407-409. doi:10.1093/jac/dki206
- Gajdács M, Urbán E, Terhes G. Microbiological and Clinical Aspects of Cervicofacial Actinomyces Infections: An Overview. Dentistry Journal. 2019;7(3):85. doi:10.3390/dj7030085.
- Pagliani L, Campi L, Cavallini G, M: Orbital Actinomycosis Associated with Painful Ophthalmoplegia. Ophthalmologica 2006;220:201-205. doi: 10.1159/000091767
- Acevedo F, Baudrand R, Letelier LM, Gaete P. Actinomycosis: a great pretender. Case reports of unusual presentations and a review of the literature. Int J Infect Dis. 2008;12(4):358-362. doi:10.1016/j.ijid.2007.10.006