Actinomyces

Etiology and Epidemiology

Almost 50 species of Actinomyces have been identified using 16S ribosomal RNA sequencing, with more than half these species associated with human infection. Actinomyces israelii is the predominant species causing human actinomycosis. Other species associated with infection include, but are not limited to, Actinomyces odontolyticus, A. meyeri, A. naeslundii, A. gerencseriae, and A. viscosus.

Although actinomycosis occurs worldwide, it is a rare infection. Accordingly, knowledge regarding the epidemiology of actinomycosis is limited to case reports and case series. Based on these reports, this infection appears to affect people of all ages, with no predilection for a particular race, season, or occupation. The infection rate may be higher among males, possibly related to increased trauma or poorer dental hygiene. In a review of 85 cases of actinomycosis, 27% were in persons <20 yr old, and 7% were among children <10 yr old. The youngest patient in this series was 28 days old. Risk factors in children include trauma, dental caries, debilitation, and poorly controlled diabetes mellitus. Although actinomycosis is not a common opportunistic infection, disease has been associated with corticosteroid use, leukemia, renal failure, congenital immunodeficiency diseases, and HIV infection.

Pathogenesis

The 3 most common sites of Actinomyces infection are, in order of frequency, cervicofacial, abdominal and pelvic, and thoracic regions, although infection may involve any organ in the body. Actinomycosis typically follows a breach in the local cutaneous or mucosal barrier, such as after a traumatic injury or surgery. Other medical interventions can result in mucosal barrier injuries and predispose to infection, such as the association between intrauterine devices and pelvic actinomycosis. Involvement of the thoracic region has been postulated to present after an aspiration event in patients with poor dentition or a recent dental procedure or after aspiration of a foreign body. Notably, more than one third of patients do not have an identifiable antecedent event that would explain the onset of actinomycosis.

The hallmark of actinomycosis is contiguous spread that fails to respect tissue or fascial planes. Sites of infection show dense cellular infiltrates and suppuration that form many interconnecting abscesses and sinus tracts. These abscesses and sinus tracts may be followed by cicatricial healing from which the organism spreads by burrowing along fascial planes, causing deep, communicating, scarred sinus tracts.

Diagnosis

The presence of sulfur granules on macroscopic or microscopic evaluation of involved tissue is highly suggestive of a diagnosis of actinomycosis. On macroscopic appearance, the sulfur granules are typically yellow, accounting for their name, but may be white, gray, or brown. These granules microscopically can appear on hematoxylin-eosin or Gomori methenamine silver stains as a mass of gram-positive branching filamentous rods surrounded by the host immune response inclusive of polymorphonuclear neutrophils and a milieu of eosinophilic staining inert material often referred to as the Splendore-Hoeppli phenomenon . Notably, one species, A. meyeri , is nonbranching. Nocardia is indistinguishable from Actinomyces on Gram stain, but Nocardia stains with the modified acid-fast stain, contrasting with Actinomyces .

Although highly suggestive of actinomycosis, sulfur granules often are not present, and thus additional testing is necessary to make the diagnosis. Patients with actinomycosis in the absence of sulfur granules are typically diagnosed by culturing the organism from tissue procured from the involved site. Cultures on brain-heart infusion agar incubated at 37°C (98.6°F) anaerobically (95% nitrogen and 5% carbon dioxide) and a separate set incubated aerobically reveal organisms within the lines of streak at 24-48 hr. A. israelii colonies appear as loose masses of delicate, branching filaments with a characteristic spider-like growth. Colonies of other species, such as A. naeslundii and A. viscosus may have similar growth characteristics. Unfortunately, even under these conditions, it can be challenging to grow Actinomyces, and the yield of different culturing techniques can vary by species. Additionally, conventional biochemical testing for speciation is complex and may result in misclassification of an organism. The evolution of diagnostic tools such as 16S rRNA sequence analysis and matrix-assisted laser desorption/ionization (MALDI) time of flight (TOF) mass spectrometry has improved the accuracy of speciation of cultured organisms and highlighted the potential for detection of Actinomyces directly from the involved tissue without culture.

Importantly, actinomycosis is usually, if not always, polymicrobial in nature. In a large study of >650 cases, infection with Actinomyces was identified in pure culture in only 1 case and was usually identified with other endogenous flora, most notably members of the HACEK group, which includes Aggregatibacter (formerly Haemophilus ) aphrophilus, Aggregatibacter (formerly Actinobacillus ) actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae. A. actinomycetemcomitans is a fastidious, gram-negative bacillus that is part of the oral flora and has been implicated as a pathogen in periodontal disease. Other bacterial species frequently isolated concomitantly in human actinomycosis include Fusobacterium, Bacteroides, Capnocytophaga, and aerobic and anaerobic streptococci.

CT or MRI of the involved area is often employed in the initial patient evaluation. No pathognomonic radiographic findings exist for actinomycosis, but the identification of a process that invades across tissue planes and ignores anatomic boundaries can be highly suggestive of actinomycosis. Furthermore, radiographic imaging can be helpful to establish the extent of the infectious process, guide subsequent diagnostic and therapeutic interventions, and monitor for resolution of infection.