Version July 2025
INTRODUCTION —
Actinomycosis is an infection characterized by abscess formation, induration, draining sinus tracts, fistulae, and tissue fibrosis. It can mimic several other conditions, particularly malignancy and granulomatous disease. Cervicofacial involvement is the most common manifestation of actinomycosis, accounting for 50 percent of all cases, while abdominal, thoracic, pelvic, and central nervous system actinomycosis occur less frequently [1,2].
The microbiology, pathophysiology, epidemiology, clinical sites of infection, and diagnosis of actinomycosis will be reviewed here. Treatment of actinomycosis is discussed separately. (See "Treatment of actinomycosis".)
DISTINGUISHING CHARACTERISTICS —
Actinomycosis has two unique characteristics that distinguish it from other infections. The presence of either of these findings should prompt immediate suspicion of actinomycosis. (See 'When to suspect actinomycosis' below.)
Spread across tissue planes — A hallmark of actinomycosis is the tendency to spread without regard for anatomical barriers (including tissue planes or lymphatic drainage). This is often noted on imaging where a mass is seen aggressively crossing anatomic tissue planes (image 1).
Formation of sulfur granules — Actinomyces spp are noted for forming characteristic sulfur granules in infected tissue but not in vitro. The term "sulfur granule" is a misnomer, reflecting only the yellow color of the granule in pus, since they are not composed of any sulfur at all. The granules are actually discrete macroscopic grains of hard consistency, 100 to 1000 mcm in diameter, often visible to the naked eye or by microscopy with low magnification (10x) (picture 1). They are composed of an internal tangle of mycelial fragments and a radiating arrangement of eosinophilic peripheral clubs.
These sulfur granules represent colonies of Actinomyces spp and are characterized by a zone of granulation tissue surrounding one or more oval eosinophilic granules. Beaded or filamentous, non–acid-fast, gram-positive bacilli radiate from these granules (picture 1) [3].
However, not all Actinomyces species form sulfur granules (eg, A. odontolyticus), and a peripheral fringe of clubs may be absent in certain instances, such as in a tonsillar crypt infection in which there is a minimal surrounding tissue reaction [1,4].
Similar granules may also be formed by other microorganisms, notably Nocardia brasiliensis and Streptomyces madurae (both can cause mycetoma), as well as Staphylococcus aureus (a cause of botryomycosis), Monosporium spp, Cephalosporium spp, and Aspergillus spp. These other granules are best distinguished by an absence of peripheral clubs, which appear to be specific to Actinomyces species. Additionally, Actinomyces spp and Arachnia spp generally can be differentiated from other gram-positive anaerobes by means of growth rate (slow), by catalase production (negative, except A. viscosus), and by gas-liquid chromatographic detection of acetic, lactic, and succinic acids produced in peptone-yeast-glucose broth.
MICROBIOLOGY —
Actinomycosis is caused by branching gram-positive bacteria belonging to the order Actinomycetales, family Actinomycetaceae, genus Actinomyces [4].
●General characteristics – Actinomyces spp are non-spore-forming, non-acid fast, strict or facultative anaerobes with a variable cellular morphology, ranging from diphtheroid to coccoid filaments (picture 2). Actinomyces spp are fastidious organisms that require an enriched medium (such as brain-heart infusion broth) for growth. Incubation at 37°C with 6 to 10 percent carbon dioxide provides optimal growth conditions. It takes 3 to 10 or more days to grow them in culture. Some species, such as A. israelii, A. gerencseriae, Pseudopropionibacterium propionicum (previously classified as an Actinomyces spp), and a few strains of A. naeslundii appear as "molar tooth" colonies on agar or as "bread-crumb" colonies suspended in broth media.
●Species implicated in human disease – Human actinomycosis is primarily caused by Actinomyces israelii. With improved and novel microbiologic detection methods, several novel species (eg, Actinomyces neuii, Actinomyces meyeri) are increasingly recognized in human infections [1]. At least 49 different Actinomyces species have been described [5], of which more than 26 have been associated with disease in humans, including A. odontolyticus, A. naeslundii, A. meyeri, A. viscosus, A. funkei, A. gerencseriae, A. pyogenes, A. urogenitalis, A. georgiae, and A. graevenitzii [6-10]. Genomic diversity has been reported with some Actinomyces spp, such as A. naeslundii [11]. Other implicated species include Pseudopropionibacterium propionicus (initially named Actinomyces propionicus) as well as the coryneform bacteria, Actinomyces neuii, A. radingae, and A. turicensis [6,11,12].
●Part of normal human flora – Actinomyces spp are part of the normal flora of the oral cavity, intestinal tract, and female genital tract.
●Presence in polymicrobial infections – Most actinomycotic infections are polymicrobial, involving other aerobic and anaerobic bacteria. In one study of more than 650 cases of actinomycosis, Actinomyces spp were not isolated in pure culture in a single case [13]. Aggregatibacter (Actinobacillus) actinomycetemcomitans and Haemophilus aphrophilus were the most common co-isolates in this study. Other bacteria frequently isolated along with Actinomyces spp include Eikenella corrodens, Fusobacterium, Bacteroides, Capnocytophaga, Staphylococcus, Streptococcus, and Enterococcus [6,14]. However, the significance of these coexisting bacteria in the pathogenesis of actinomycosis remains unclear [15].
●Distinguishing features from fungi – The name actinomycosis literally translates as "ray fungus" and reflects its characteristic filamentous, fungal-like appearance in infected tissues. However, Actinomyces spp are true bacteria with filaments much narrower than fungal hyphae. While actinomycotic filaments readily fragment into bacillary forms, tubular hyphae of molds never fragment and exhibit distinct branching patterns. Another distinguishing feature between Actinomyces and fungi is the method of reproduction, which occurs by binary fission in Actinomyces spp and not by spore formation or budding as in fungi [4].
PATHOGENESIS —
Actinomyces spp are commensal flora of the oral cavity, intestinal tract, and female genital tract [16]. Disease occurs when there is a breach in the mucosal barrier and the bacteria can invade into deeper tissues [17]. As the infection progresses, granulomatous tissue, extensive reactive fibrosis and necrosis, abscesses, draining sinuses, and fistulas are formed [18].
Disease occurs almost exclusively by direct invasion and rarely by hematogenous spread. Almost all actinomycotic lesions contain so-called co-pathogens or companion bacteria (eg, other anaerobes, Staphylococcus spp, Streptococcus spp, Enterobacterales). These co-pathogens assist in the spread of infection by inhibiting host defenses and reducing local oxygen tension. After the organism is established locally, it spreads to surrounding tissues. The spread is in a progressive manner, leading to a chronic, indurated, suppurative infection often with draining sinuses and fibrosis.
Actinomyces spp grow in microscopic or macroscopic clusters of tangled filaments surrounded by neutrophils, leading to purulent lesions with sinus tracts draining a pale, yellow discharge. The pale, yellow discharge is composed of purulent loculations (clusters of plasma cells, multinucleated giant cells, and foamy macrophages) that contain "sulfur granules" (clusters of Actinomyces organisms). The center of such clusters is often positive for basophil-staining with congregation of eosinophils which takes in the form of pear-shaped "clubs." Each purulent loculation contains one to six "sulfur granules" and up to 50 loculations can be present in each lesion. The granule is stabilized by a protein-polysaccharide complex and mineralized by host calcium phosphate [4]. Some experts suggest that the protein-polysaccharide complex provides a mechanism of resistance to phagocytic activity by the host. (See 'Formation of sulfur granules' above.)
Person-to-person transmission of actinomycetes can occur rarely via human bites or fist fight trauma.
EPIDEMIOLOGY —
Actinomyces are found as normal flora in various mammal including humans, primates, and cattle pigs. They are not found in the environment. Actinomycosis is a relatively rare condition but has a worldwide distribution with no predilection for age, race, season, or occupation [13,19]. However, it is two to four times more common in men [17,18,20-22]. The annual incidence rate of actinomycosis is reported to be approximately about 0.3 cases per million people per year [23].
Predisposing factors to developing actinomycosis include [24-27]:
●Diabetes mellitus (14 percent of cases)
●Immunosuppression (14 percent of cases)
●Malnutrition
●Local tissue damage or inflammation (eg, tissue trauma, dental procedures, gingivitis, irradiation, osteonecrosis, poor oral hygiene; 71 percent of cases)
CLINICAL MANIFESTATIONS
Course of illness — Actinomycosis can present with variable signs and symptoms, but it usually evolves in one of two distinct patterns:
●Chronic, slowly-progressive infection (more common) – non-tender, indurated mass that slowly evolves into multiple abscesses, fistulae, and draining sinus tracts.
●Acute suppurative infection (less common) – rapidly progresses to abscess formation.
Signs and symptoms — Actinomycosis can be difficult to diagnose and can take weeks or months to cause symptoms after infection. The time it takes to diagnose actinomycosis depends on the type of specimen and the incubation period needed to recover the bacteria [28]. In one study, the median diagnosis time frame from the onset of first symptoms was 30 days (with a range of 20 to 157 days) [28]. Actinomycosis is distinguished by its propensity to form painless purulent abscesses and multiple draining sinus tracts that evolve with time into fistulae and lead to extensive tissue fibrosis. These characteristic lesions usually develop slowly, over weeks to months, with adherence to overlying skin that confers a bluish or reddish appearance. This is often mistaken for cellulitis but, in fact, more likely represents venous congestion. Over time, sinus tracts invariably form on the skin surface or mucosa, eventually erupting to express a thick yellow or serous exudate, which yields the characteristic sulfur granules [4] (see 'Formation of sulfur granules' above). An inflammatory cicatricial scarring is one of the more noticeable long-term sequelae [24]. As the infection continues, it spreads to adjacent structures (without regard for anatomic barriers), causing additional localizing symptoms (eg, pain from tissue compression, trismus in cervicofacial disease, dyspnea in thoracic disease) and further tissue fibrosis [19,29].
Fatigue and malaise are commonly present, and fever occurs in over 50 percent of cases [19,28,29].
Laboratory and imaging findings — There are no laboratory findings that are specific to actinomycosis. Anemia, mild leukocytosis, and an elevated sedimentation rate are relatively common.
Imaging findings vary based on which organ system is involved, but typically demonstrate the presence of a mass within the surrounding structures, visualization of abscesses, and its spread across tissue planes [30]. The masses often appear solid with focal low-attenuation areas or cystic with thickened walls (image 1). Nevertheless, these findings are non-specific and are often mistaken for malignancy initially.
Because this infection spreads directly across tissue planes, regional lymphadenopathy is rare until quite late in the disease course [31]. This is in contrast to tumors which typically present with notable regional lymphadenopathy. (See 'Differential diagnosis' below.)
Sites of clinical infection — The orocervicofacial area is most common site of infection (40 to 60 percent), followed by abdominopelvic (25 to 35 percent), thoracopulmonary (20 to 25 percent), and cutaneous regions (3 to 5 percent) [32,33]. Infection at other sites is uncommon but has been reported in both central nervous system (CNS) and ocular regions.
Orocervicofacial disease — Actinomyces spp are normal constituents of the oral flora within gingival crevices and tonsillar crypts and are particularly prevalent in periodontal pockets, dental plaques, and on carious teeth [4]. Most cases of cervicofacial actinomycosis are of odontogenic origin.
Pain and trismus are the most common clinical symptoms of cervicofacial actinomycosis. The symptoms often present as disproportionate to the local (visible) inflammation. Fistulization from the perimandibular region is the most easily recognized manifestation of cervicofacial actinomycosis [4].
Orocervicofacial actinomycosis may involve almost any tissue or structure surrounding the upper or lower mandible and the oral cavity. However, the mandible itself is consistently the most commonly identified site of infection [4]. In one study of 317 patients reported from Cologne between 1952 and 1975, the presenting sites were identified below [34]. Improved dental hygiene and widespread use of antibiotics have likely contributed to the declining incidence of this disease [35].
●Mandible – 53.6 percent
●Cheek – 16.4 percent
●Chin – 13.3 percent
●Submaxillary ramus and angle – 10.7 percent
●Upper jaw – 5.7 percent
●Mandibular joint – 0.3 percent
While direct bony invasion is decidedly uncommon, periostitis and posttraumatic osteomyelitis occurred in 11.7 percent of cases in this study [34]. Rarely, actinomycosis may also present as severe periodontitis [36], peri-implantitis with dental implant failure [37,38], development of fistulae, suppurative and granulomatous lesions on the skin of the face [39], and bisphosphonate-related osteonecrosis of the jaw [33,40]. Although most cases of cervicofacial actinomycosis are of odontogenic origin, primary infections have been reported in various structures within the head and neck, often quite remote from any potential periodontal source. In particular, actinomycosis involving the scalp, tongue, maxillary sinus, ethmoid sinus, larynx, thyroid gland, thyroidectomy incision site, and lungs have all been reported [29,33,41-44].
Thoracopulmonary disease — Thoracic infections usually occur following aspiration of bacteria from the oropharynx, especially in patients with dental disease or poor dentition and/or oral hygiene. Rarely, thoracic disease occurs following esophageal perforation, by direct extension from another location such as the neck or an abdominal site, or hematogenous spread [41,45]. Other thoracic presentations include breast involvement in a form that may resemble malignancy or the form of recurrent abscesses. Infection of breast prosthesis has also been described [46].
●Clinical presentation – Patients often present with a history of slowly developing infection of both the lung and pleura. The most common symptoms are fever, weight loss, shortness of breath, chest pain, productive cough, and hemoptysis. Most patients have a history of underlying lung disease. Because of the indolent nature of the infection, many patients present in the later stages of disease, when extension of the infection through tissue planes has already occurred.
●Complications – The infection often spreads from pneumonic focus across lung fissures to involve the pleura and the chest wall, with eventual fistula formation and drainage containing sulfur granules [47]. The mediastinum, pericardium, and myocardium may also rarely be affected. Pericarditis or endocarditis are uncommon but can occur through direct extension or spread through the blood [48,49].
The infection can also spread to the mediastinum. Anterior mediastinal involvement can present as a mass or a superior vena cava syndrome [50]. Posterior mediastinal infection can cause an esophageal fistula, and involve the vertebral, paraspinous muscle, and the soft tissues. Vertebral involvement of transverse processes can include the posterior ends of the ribs. However, collapsed vertebra and narrowing of the disk space are rare (in contrast to tuberculosis where this is common). Typical vertebral involvement includes bone destruction along with new bone formation which manifests itself as honeycomb or saw-toothed like appearance on radiography [51].
●Radiographic findings – Radiographic studies can show involvement of any of the lung lobes. Computed tomography (CT) scan is most useful in detecting cavitary formation. Small lung cavities can be seen in over half of these patients [52]. The pulmonary lesion is either a mass lesion or pneumonitis, sometimes with pleural involvement. Extension to the chest wall with destruction of adjacent bones can be present. Although not common, hilar adenopathy can also be present. Air bronchogram within a mass lesion can be indicative of actinomycosis or another non-malignant process. Pleural effusion without any other findings can also occur. Pleural thickening, effusion, or emphysema are common [53]. Since the clinical presentation and radiological manifestations are often non-specific, thoracopulmonary actinomycosis can often mimic malignancy. In a retrospective review of 37 cases of histologically confirmed pulmonary actinomycosis from a large metropolitan center, 57 percent were initially diagnosed as lung cancer [54].
Abdominopelvic disease — Abdominal actinomycosis is more common than pelvic actinomycosis.
●Abdominal actinomycosis – Intestinal actinomycosis usually occurs following a breach in the intestinal mucosal barrier, such as that following recent abdominal surgery, trauma, neoplasia, or a perforated viscus [22]. Actinomycotic abscesses can also present in the abdomen following cholecystectomy complicated by spilled gallstones during gallbladder removal [55,56]. Because of the slow growth characteristics of these pathogens, such patients may present months to years after cholecystectomy.
The appendix and ileocecal region are the most common sites involved [32,57]. The infection is characterized by a chronic, indolent course with symptoms such as fever, fatigue, weight loss, and abdominal pain. Physical findings may include a palpable mass, visible sinus tracts, or fistulas. The disease tends to remain localized as the infection spreads contiguously, disregarding tissue planes. Lymphadenopathy is not a common clinical finding [58]. Hematogenous dissemination is also rare [18,32].
Radiographic findings are nonspecific in abdominal actinomycosis and typically show a solid mass abutting adjacent structures. Barium enema may show luminal narrowing, extrinsic compression, or fistulization.
Colonoscopic findings are varied and include normal or thickened-appearing mucosa, colitis, ulceration, a nodular lesion, or a button-like elevation of an inverted appendiceal orifice (picture 3) [57,59-63]. The main differential diagnoses at endoscopy include neoplasia, Crohn's disease, and tuberculosis. Endoscopic biopsies occasionally allow a preoperative diagnosis to be made when characteristic histologic findings are found [57,64]. (See 'Establishing a diagnosis' below.)
●Pelvic actinomycosis – Pelvic actinomycosis is rare; this condition typically arises after a breach in the mucosal barrier, such as following recent surgery and/or a procedure. The most common symptoms are pelvic pain and vaginal bleeding [65]. Many patients are initially mistaken for having tubo-ovarian abscess or neoplasm prior to the diagnosis of actinomycosis. There have been multiple reports of abdominopelvic actinomycosis associated with the use of intrauterine contraceptive devices [16,21,22,66,67]. In a systematic review of pelvic actinomycosis, an intrauterine device (IUD) was found in half of all cases [68]. (See "Intrauterine contraception: Candidates and device selection".)
●Hepatic actinomycosis – Hepatic actinomycosis is rare [58]. When it does occur, it tends to present with non-specific symptoms, such as fever, abdominal pain, weight loss, and malaise. Imaging typically shows one or more hepatic lesions. Diagnosis tends to be made on histopathology of biopsied liver tissue.
Other sites of infection — Although cervicofacial, thoracic, and abdominopelvic disease make up the majority of Actinomyces spp infections, other sites of infection can occasionally occur.
●Central nervous system disease – CNS actinomycosis is extremely rare. It can be caused by contiguous spread from cervicofacial infection or by hematogenous spread from other sites of infection, such as the lungs or the abdomen [68]. However, in many cases, another site of infection cannot be identified. Recent dental procedures, head trauma/surgery, and ear infections are risk factors for CNS actinomycosis. The most common symptom is presence of focal neurological deficits, followed by headache, fever, and altered mental status. In a systematic review of 118 patients with CNS actinomycosis, brain abscess was identified in 55 percent, most commonly involving the frontal and parietal lobes [68]. Leptomeningeal enhancement, subdural empyema, and ventriculitis were the other predominant neuroimaging findings. Overall mortality rate was 11 percent. Patients who underwent surgery in addition to antimicrobial therapy had a better survival rate compared to those who received antimicrobial therapy alone. (See "Treatment of actinomycosis", section on 'Surgical management in select cases'.)
●Bacteremia – Isolated bacteremia due to Actinomyces spp is rare. Isolation of Actinomyces spp in the bloodstream should prompt an aggressive search for another site of infection. If no other site of infection is found after a careful clinical assessment and no evidence of systemic infection is present, the isolated bacteremia may be due to transient translocation of bacteria from a disruption in mucosal barrier [69] and may not require antimicrobial therapy. This is more likely to occur with the use of advanced diagnostic techniques like 16S polymerase chain reaction (PCR) and MALDI-TOF MS, which can identify the organisms more accurately than traditional standard techniques.
Endocarditis due to Actinomyces spp is extremely rare but can occur in patients who inject drugs [70].
DIAGNOSIS —
Actinomycosis is a difficult disease to diagnose prior to microbiologic or histopathologic confirmation due to its rarity, nonspecific symptoms, and imitation of more common conditions such as malignancy, Crohn's disease (abdominal actinomycosis), tuberculosis, and other granulomatous infections (eg, endemic fungal infections, nocardiosis). (See 'Differential diagnosis' below.)
When to suspect actinomycosis — Actinomycosis should be suspected in any patient presenting with indolent, constitutional symptoms and with fistulas, sinus tracts, and/or masses that are spreading to adjacent structures without regard to tissue planes. Additional factors that increase suspicion for actinomycosis include presence of "sulfur granules" on cytology and temporary improvement in symptoms with a short course of antibiotics. If actinomycosis is suspected, antibiotics should be avoided, when possible, until a specimen is obtained to optimize detection.
Approach to diagnosis
Obtain specimens for testing — In order to test for actinomycosis, we obtain blood cultures as well as any fluid or tissue from any present mass, fistula, or sinus tract and send to microbiology and pathology labs for testing. The most appropriate specimens for submission are pus, sulfur granules, tissue, or fluid. In one study, 18 percent of actinomycosis cases were diagnosed based on positive blood cultures [28]. Swabs, sputum, and stool samples should be avoided due to high likelihood of contamination from commensal flora [6,71]. Pulmonary samples for diagnosing actinomycosis include those from fiberoptic bronchoscopy especially for endobronchial disease, and culture of bronchoalveolar lavage washings or lung biopsy. In some cases, open resection may be necessary, especially if malignancy cannot be ruled out. If actinomycosis is suspected pre-operatively, the aim should be to conserve as much lung as possible. Intraoperative frozen section analysis can help decide the extent of resection [41].
Sending specimens for testing — All collected specimen samples should be sent to the microbiology laboratory for gram stain, aerobic and anaerobic culture, and an AFB stain; as well as the pathology laboratory for hematoxylin-eosin staining as well as special staining with Grocott-Gomori-methenamine stain [4,6].
The specimen should be expeditiously transported to the laboratory in media supportive of anaerobic growth. The clinical microbiology laboratory should be notified that actinomycosis is suspected so specimens can be incubated under strict anaerobic or at least microaerophilic conditions for at least 14 to 21 days to allow adequate detection [4,6,21]. The pathologist should also be alerted to the suspected diagnosis, as special stains may be needed to identify the organism. The choice of method often depends on the clinical presentation, location of the lesion, and available expertise.
Establishing a diagnosis — Definitive diagnosis requires isolation and identification of pathogen on either culture or histopathology [32]. Presence of Actinomyces spp on culture or histology of a usually sterile specimen (eg, lung tissue) is indicative of actinomycosis. Isolation of Actinomyces spp on a non-sterile site specimen (eg, sputum, stool) warrants further evaluation to determine whether the patient has actinomycosis. Factors such as the patient's clinical presentation, risk factors, and response to treatment (or lack thereof) should be considered when determining whether an Actinomyces isolate represents true infection or colonization/contamination. (See 'Incidental finding on culture or histology' below.)
●Microbiologic testing – The presence, in pus or tissue specimens, of non-acid-fast, gram-positive organisms with filamentous branching is very suggestive of actinomycosis. Often, beaded or filamentous, non–acid-fast, gram-positive bacilli can be seen on gram stain radiating from the edge of a sulfur granule (picture 1) [3]. Culture is more specific, but the diagnosis is confirmed by culture in less than 50 percent of suspected cases [18,32].
Negative cultures can occasionally be false negatives, especially when the patient has received antibiotics in the past seven to ten days.
Although Actinomyces spp do not stain acid-fast, this feature helps distinguish it from Nocardia spp, which, apart from staining positive for acid-fast, are indistinguishable from Actinomyces spp on Gram stain.
●Histopathology testing – Actinomyces spp are best visualized using the Grocott methenamine silver (GMS) stain, however other special stains, including p-aminosalicylic acid, MacCallen-Goodpasture, and Brown-Brenn stains are reasonable options as well.
On hematoxylin and eosin staining, tissue sections typically reveal acute or chronic inflammatory granulation tissue with infiltration by neutrophils, foamy macrophages, plasma cells and lymphocytes, and surrounding dense fibrosis. Healing lesions tend to demonstrate profound fibrosis, even avascular in nature, often in proximity to areas of acute suppuration [4].
Sulfur granules can occasionally be seen, but their absence on histology does not rule out actinomycosis. Chronic, long-standing actinomycosis may present with significant fibrosis and detection of "sulfur granules" may be difficult, requiring testing of multiple tissue sections [72,73]. Often, a series of biopsies is required to confirm a pathologic diagnosis [4,31,74].
●If testing is negative but suspicion remains – If both microbiologic and histologic testing are negative for Actinomyces spp (particularly in the setting of prior antibiotic therapy) but actinomycosis is suspected based on the clinical presentation, molecular techniques may be helpful in identifying the causative pathogen. In particular, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF) or 16S rRNA gene sequencing may be useful in identification of Actinomyces spp [75]. Nucleic acid probes are being developed for more rapid and accurate identification of Actinomyces spp [76-78].
●Diagnostic tests of limited utility
•Monoclonal antibody staining – Specific staining using fluorescent-conjugated monoclonal antibody (FA) has been shown to improve the identification of various Actinomyces species, even in mixed infections and after fixation in formalin [6]. An additional advantage is the ability to define single filaments in granulation tissue. Despite their potential, these techniques are not readily available to most clinical microbiology laboratories.
•Serology – Serology does not appear to be a practical or reliable diagnostic tool. While agglutinins and complement-fixing antibodies appear in the serum of some patients with actinomycosis, they may represent cross-reactivity due to other disease processes, particularly tuberculosis [79]. Rapid serodiagnosis by the detection of specific antibodies using immunoelectrophoresis or monospecific antigens is under development, but these are not widely available for clinical use [79].
Incidental finding on culture or histology — Often, actinomycosis is not suspected and instead incidentally found on tissue biopsy staining or culture [74]. Isolation of Actinomyces spp from pathology or culture of a tissue biopsy sample is usually indicative of actinomycosis but could occasionally be due to normal flora colonization [80]. In such cases, the clinical presentation of the patient, the specific Actinomyces species, and location of specimen sample should be considered. Colonization is more likely when the organism species is known for its low pathogenicity in humans, the clinical presentation of the patient is not consistent with actinomycosis, and the specimen was obtained from a non-sterile site (eg, vaginal tract, oral mucosa). True infection is more likely when the organism species is known to cause human disease (eg, A. israelii), the clinical presentation is typical for actinomycosis, and the specimen was obtained from a sterile site that should not be colonized with Actinomyces spp (eg, lung tissue).
DIFFERENTIAL DIAGNOSIS —
Actinomycosis is a great mimicker of other conditions, particularly malignancy and granulomatous disease, such as mycobacterial and Nocardia spp infections [4]. The differential diagnosis of a solid mass spreading across tissue planes with or without associated abscesses and purulent draining sinus tracts includes the following:
●Malignancy – A mass due to actinomycosis cannot be distinguished from malignancy on imaging. Often Actinomyces spp are detected on culture or histopathology incidentally during workup for malignancy. This is because as actinomycosis progresses with repeated courses of antibiotic therapy, the fibrotic and "woody" induration often comes to resemble a malignant process. The presence of regional lymphadenopathy is more suggestive of malignancy as actinomycosis rarely presents with regional lymphadenopathy. Additionally, malignant lesions should not respond at all to antimicrobial therapy while actinomycosis lesions do partially respond. Positron emission tomography-computed tomography (PET-CT) is not useful for differentiating actinomycosis from malignancy due to enhanced metabolic regions in both conditions [54,81].
●Nocardiosis – Nocardia species belong to the same order as Actinomyces spp, thus infections caused by these microbes may be at times difficult to distinguish from one another. Nocardia brasiliensis can also form similar "sulfur" nodules. Nocardiosis tends to affect the lungs, brain, and/or skin and is less likely to involve the abdomen, thoracic cavity outside of the lungs, and the cervicofacial area. Additionally, Nocardia spp stain acid-fast while Actinomyces spp do not. (See "Nocardia infections: Epidemiology, clinical manifestations, and diagnosis", section on 'Clinical manifestations'.)
●Mycobacterial infections (including tuberculosis) – Mycobacteria also belong to the same order as Actinomyces spp and can be difficult to distinguish. The chronic nature of actinomycosis can resemble indolent mycobacterial infections, such as tuberculosis (TB), especially when cavity formation occurs in thoracic infections. Both also form granulomas that can be seen on histopathology. The acid-fast stain and culture can differentiate between Actinomyces spp and mycobacteria as mycobacteria stain acid-fast while Actinomyces spp do not. Additionally, mycobacteria are much less likely to cross tissue planes when expanding. (See "Overview of nontuberculous mycobacterial infections", section on 'Spectrum of clinical syndromes' and "Diagnosis of pulmonary tuberculosis in adults" and "Abdominal tuberculosis", section on 'Diagnosis' and "Central nervous system tuberculosis: An overview", section on 'Forms of disease' and "Tuberculosis disease in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Diagnosis'.)
●Other causes specific to site of infection – Other differential diagnoses may be considered depending on the site affected. Abdominal actinomycosis is often diagnosed in patients suspected of having Crohn's disease and thoracic actinomycosis can sometimes be mistaken for blastomycosis, which can also destroy adjacent ribs posteriorly but rarely forms sinuses. (See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults", section on 'Diagnostic evaluation' and "Clinical manifestations and diagnosis of blastomycosis", section on 'Diagnosis'.)
Similar "sulfur" granules may be formed by other microorganisms (eg, Nocardia brasiliensis, Streptomyces madurae, Staphylococcus aureus). Differentiation between these based on morphology of the granules is discussed above. (See 'Formation of sulfur granules' above.)
SPECIAL POPULATIONS
Children — Actinomycosis is rare in infants and children. Cervicofacial actinomycosis involving the submandibular region and appendiceal actinomycosis are the most common presentations in this population [82,83]. In the latter presentation, a pseudotumorous mass in the region of the appendix is often observed. Congenital lesions involving a dermoid cyst or pyriform sinus have also been reported [82]. Because of its rarity, the diagnosis of actinomycosis in children should arouse suspicion of an underlying immunodeficiency state, particularly chronic granulomatous disease [13,84].
Pregnant individuals — Actinomycosis in pregnancy is rare but has been linked to preterm birth. In one study, 10 out of 17 identified cases of actinomycosis in pregnancy were complicated by chorioamnionitis and preterm delivery [85]. Penicillin is usually the first-line treatment and is considered safe during pregnancy. Dental health should be monitored during pregnancy, as poor dental hygiene can be a risk factor for actinomycosis.
Immunocompromised hosts — Immunocompromised individuals may be at higher risk for opportunistic infections, including actinomycosis. Furthermore, infections may be more severe and prognosis may be worse. In a retrospective review of 33 French patients with actinomycosis during a 12 year period (1997 to 2009), 20 (61 percent) were immunocompromised, including solid and hematological malignancies, uncontrolled diabetes mellitus, bone marrow transplant recipients, immunosuppressive therapy, and human immunodeficiency virus (HIV) infection [86]. Mortality was higher in immunocompromised patients (7/20; 21 percent) compared to non-immunocompromised patients (0/13; 0 percent). It is unclear whether the excess mortality was directly related to underlying disease or the infection.
SUMMARY AND RECOMMENDATIONS
●Distinguishing characteristics – Actinomycosis has two unique characteristics that distinguish it from other infections:
•Tendency to spread without regard for anatomical barriers (including tissue planes or lymphatic drainage). (See 'Spread across tissue planes' above.)
•Formation of sulfur granules that can be seen macroscopically as well as on Gram stain or histology stains. (See 'Formation of sulfur granules' above.)
The presence of either of these findings should prompt immediate suspicion of actinomycosis. (See 'When to suspect actinomycosis' above.)
●Microbiology – Actinomycosis is caused by branching gram-positive bacteria belonging to the order Actinomycetales, family Actinomycetaceae, genus Actinomyces.
The bacteria are non-spore-forming, non-acid fast, strict or facultative anaerobes with a variable cellular morphology, ranging from diphtheroid to coccoid filaments (picture 2).
Actinomyces spp are part of the normal flora of the oral cavity, intestinal tract, and female genital tract and are often found as part of polymicrobial infections. (See 'Microbiology' above.)
●Clinical manifestations – Actinomycosis is distinguished by its propensity to form painless purulent abscesses and multiple draining sinus tracts that evolve with time into fistulae and lead to extensive tissue fibrosis. These characteristic lesions usually develop slowly, over weeks to months, with adherence to overlying skin that confers a bluish or reddish appearance. Over time, sinus tracts invariably form on the skin surface or mucosa, eventually erupting to express a thick yellow or serous exudate, which yields the characteristic sulfur granules (picture 1). (See 'Signs and symptoms' above and 'Formation of sulfur granules' above.)
●When to suspect actinomycosis – Actinomycosis should be suspected in any patient presenting with indolent, constitutional symptoms and with fistulas, sinus tracts, and/or masses that are spreading to adjacent structures without regard to tissue planes (image 1). If actinomycosis is suspected, antibiotics should be avoided, when possible, until a specimen is obtained to optimize detection. (See 'When to suspect actinomycosis' above.)
●Approach to diagnosis
•Obtaining specimens – To test for actinomycosis, we obtain blood cultures as well as any fluid or tissue from any present mass, fistula, or sinus tract and send to microbiology and pathology labs for testing. The most appropriate specimens for submission are pus, sulfur granules, tissue, or fluid. Swabs, sputum and stool samples should be avoided due to high likelihood of contamination from commensal flora. (See 'Obtain specimens for testing' above.)
•Sending specimens for testing – All collected specimen samples should be sent to:
-Microbiology laboratory: Gram stain, aerobic and anaerobic culture, and an acid-fast bacilli (AFB) stain
-Pathology laboratory: hematoxylin-eosin staining and Grocott-Gomori-methenamine staining
Due to the slow-growing nature of the organism, cultures should be held for at least 14 days. (See 'Sending specimens for testing' above.)
•Establishing the diagnosis – Definitive diagnosis requires isolation and identification of pathogen on either culture or histopathology of a usually sterile site (eg, lung tissue). Isolation of Actinomyces spp on a non-sterile site specimen (eg, sputum, stool) warrants further evaluation to determine whether the patient has actinomycosis. (See 'Establishing a diagnosis' above.)
ACKNOWLEDGEMENTS —
The UpToDate editorial staff acknowledges Norman Marcon, MD, FRCP(C), and Louis-Michel Wong Kee Song, MD, FRCP(C), who contributed to earlier versions of this topic review.
We are saddened by the death of Itzhak Brook, MMD, MScD, who passed away in January 2025. UpToDate acknowledges Dr. Brook's past work as an author for this topic.
