Actinomycosis

OVERVIEW: What every practitioner needs to know

Are you sure your patient has actinomycosis? What should you expect to find?

• Actinomycosis has clinical manifestations that depend on where the infection is present. The largest number of patients will have a slow or moderately slow progression process involving the face/neck. One of the hallmarks is a draining lesion that may have been preceded by a localized swelling. This can be painful but is usually well tolerated and subacute. Fever may be present and there may be other systemic symptoms such as weight loss.
• Physical findings correlate with the local aspects of the disease. The entity “lumpy jaw” reflects the area of swelling associated, usually, with an odontogenic focus of infection. The draining lesion may also be noted to have concretions called “sulfur granules” that can be expressed, or may spontaneously emerge. There may be an odor, but this is most likely present in mixed anaerobic infections and not associated with pure actinomycosis. Infections in other body sites may also be characterized by nodules and draining lesions. Lesions with Actinomyces usually have other bacteria present including some aerobes but largely anaerobes.

How did the patient develop actinomycosis? What was the primary source from which the infection spread?

• Actinomyces and related gram-positive bacteria are common and may form part of the normal oral mucosal flora. The disease results from the penetration of these bacteria into deeper tissues. Pelvic actinomycosis is strongly associated with intrauterine devices. Actinomyces can be present in the distal gut and the genitals.
• There is little characteristic epidemiology for actinomycosis in general. Pelvic disease is much more likely when an intrauterine device (IUD) is in place. Orofacial diseases may occur in the presence of underlying tooth pathology, trauma or surgery, but many cases occur in people with healthy dentition and no obvious trauma.

Which individuals are of greater risk of developing actinomycosis?

• This infection can impact people of any age or background. While there is a slight predilection for men when it comes to cervicofacial disease, pelvic disease is almost entirely found in women. It can be present in all parts of the world. The rarity of this illness means that most practitioners will see very few cases in a lifetime, and even a busy infectious diseases practice may see few.
• Local pathology seems to be permissive for actinomycosis although it is not universal. Dental caries and gingivitis may be found in patients with cervicofacial actinomycosis, but these are common conditions. The contribution of associated aspects of poor health such as diabetes, cancer, malnutrition, etc. have been suggested, but a causal association is not firmly established and even in patients with many comorbidities it is rare to develop actinomycosis.

Beware: there are other diseases that can mimic actinomycosis:

• Because of the subacute to chronic pace of actinomycosis, it is most likely to be confused with malignancy, benign tumor or granulomatous disease (e.g., mycobacterial or fungal).

What laboratory studies should you order and what should you expect to find?

Results consistent with the diagnosis

Routine laboratory tests such as blood counts, liver chemistries, etc., seldom help make the diagnosis because they tend to be normal or abnormal as the result of another medical disease.

Direct visualization of “sulfur granules” emanating from the site of the infection.

Results that confirm the diagnosis

Culture of an actinomycete from affected site is the gold standard of diagnosis. This is challenging for several reasons. Actinomyces spp. are microaerophilic and grow best when cultured anaerobically. This can be difficult for many clinical laboratories. Even anaerobic transport can be challenging to find in many office settings. Second, the growth of Actinomyces spp. can be inhibited by prior anti-bacterial treatments. This is often the case when clinicians evaluating the patient suspect “infection” and treat empirically. Third, Actinomyces are often present in mixed infections and may grow slower than the co-pathogens. Fourth, it can be challenging to confirm the presence of Actinomyces or provide species level identification even in labs that can grow the organism.

Finding characteristic organisms by pathology or by staining of “sulfur granules” may not give a species level diagnosis, but can be quick and easy as compared to culture. In practice, this is often how the infection is diagnosed. Actinomyces can be easily gram stained. Their characteristic appearance as thin, filamentous gram-positive rods can be an excellent clue in the right clinical setting.

Acid-fast staining of Actinomyces either from culture or from clinical specimens is negative. This helps to distinguish them from mycobacteria. Modified acid-fast staining (using a less potent acid to leach out the stain from the specimen) is also negative for Actinomyces and this helps distinguish them from Nocardia spp. which often stain positive with the modified acid-fast stain.

What imaging studies will be helpful in making or excluding the diagnosis of actinomycosis?

• For cervicofacial actinomycosis, the imaging studies usually begin with plain radiographs of the affected area. There is often minimal to no direct bone involvement, so cross sectional imaging studies such as computed tomography (CT) scans are usually needed to track the extent of the disease. Imaging is not essential to make the diagnosis, but following changes in images can corroborate clinical assessment.
• Limited CT scan ($$) will probably be done prior to having the diagnosis. Repeat scans are not necessary to monitor treatment, but they can be helpful if clinical improvement flags or new symptoms emerge.

What consult service or services would be helpful for making the diagnosis and assisting with treatment?

If you decide the patient has actinomycosis, what therapies should you initiate immediately?

The core treatment strategy is adequate antibiotics. Even if surgery has been performed, antibiotics are used to clean up residual bits of infection and prevent the need for more extensive further debridement. If surgery is being contemplated, a trial of antibiotics can reduce the extent of future surgery or completely treat the infection and preclude the need for surgery. Treatment courses have not been studied in a controlled fashion due to the rarity of the infection, but general principle involves long courses of treatment. The bulk of the treatment regimen can be given orally.

1. Penicillin: The usual regimen starts with high doses of parenteral penicillin (18-24 million units/d in divided doses) followed by oral amoxicillin. he duration of parenteral therapy is unknown, patients with significant suppuration will usually get 2-6 weeks of IV therapy with a total course of 6-12 months of oral medications. In very mild disease, the whole treatment course can be oral. Penicillin resistance has not been described.

2. Alternatives (e.g. for allergic patients) include erythromycin, tetracycline and clindamycin. Less compelling evidence (case reports) exist for broad spectrum beta-lactams such as ceftriaxone, piperacillin-tazobactam and carbapenems.

3. Drugs to be avoided include the anti-staphylococcal penicillins, oral first generation cephalosporins and metronidazole. Since aminoglycosides require aerobic bacterial metabolism to work and are toxic when given over long periods, this class should be completely avoided.

4. Little clinical evidence is available for some agents that have good in vitro activity and might be used as alternatives. This list includes linezolid, azithromycin, vancomycin and fluoroquinolones with strong gram-positive/anaerobic activity such as moxifloxacin.

If I am not sure what pathogen is causing the infection what anti-infective should I order?

Making a diagnosis of actinomycosis is very helpful since the duration of therapy for this disease is longer than most other bacterial infections. Empiric therapy is often given because delays in diagnosis are common. If penicillin cannot be used, the other first-line drugs such as tetracyclines and clindamycin are usually effective and might be used in other clinical scenarios of which actinomycosis could be part of the differential diagnosis. But it could be very tough to treat actinomycosis without at least considering the possibility because of the long course of treatment that is recommended. Treatments for actinomycosis will be inadequate for mycobacterial, fungal or nocardial disease. They might be useful for mixed anaerobic infections. It goes without saying that they have no role in the non-infectious causes of syndromes sometimes confused with actinomycosis.

What complications could arise as a consequence of actinomycosis?

What should you tell the family about the patient’s prognosis?

• Although the microbiologic challenge of actinomycosis is largely related to the difficulty of maintaining adherence to a long course of therapy, the problem tends to be the structural changes that persist even after cure. Regression of swelling can be incomplete and surgical co-management can be useful. Surgery can be delayed until the full effects of antibiotics can be assessed.

How do you contract actinomycosis and how frequent is this disease?

Because actinomycetes are present in the environment and in humans as saprophytes, there may not be a clear source of infection from the environment. Actinomycetes are hard to grow in the clinical laboratory and may be present more than is documented by laboratory tests. Similarly, they may be present as part of a mixed flora infection where treatment of the other organisms is also crucial.

No particular clues from epidemiology.

Disease is rare in all clinical settings.

Bacterial disease. Can occur in mixed infections with other bacteria. The importance of identifying associated organisms is unknown since treatment courses tend to be monitored by clinical outcome more than correlation with culture and susceptibility testing.

Not known to be transmitted zoologically.

What pathogens are responsible for this disease?

There are a number of species associated with clinical manifestations of actinomycosis. Initial culture is done in a way that permits anaerobes and microaerophilic slow growing organisms to thrive. The time to growth is often over a week and sometimes longer than two weeks. Many clinical laboratories do not routinely keep specimens that long. Laboratory confirmation of species is usually done by reference laboratories because it is a challenging process for most clinical labs. The results may not be available for weeks. The most common species is A. israelii. Other species of interest are A. naeslundii and A. meyeri. Because actinomycosis is polymicrobial, it can be helpful to identify concomitant organisms including Haemophilus (Actinobacillus) actinomycetemcomitans. These accompanying bacteria may be less susceptible to beta-lactams alone.

Other gram-positive rods have been associated with clinical actinomycosis, but they are even rarer than Actinomyces and their pathogenic potential is ambiguous: these include members of the Arachnia, Propionibacterium, and Eubacterium genera.

How do these pathogens cause actinomycosis?

The pathogenesis of the disease is unclear. Since Actinomyces are part of normal flora and almost never cause disease, it would be helpful to know if certain strains possess pathogenicity elements or if certain hosts are susceptible to infection. Local trauma seems to play a role in some cases. The clearest example is the rare but well documented association of pelvic actinomycosis with IUDs.

What other clinical manifestations may help me to diagnose and manage actinomycosis?

Actinomycosis presenting as a disease outside the oral/cervicofacial area or the cervix in the presence of an IUD can be challenging to diagnose clinically. Disease of the lungs can occur from aspiration of oral contents. It is usually not apparent unless the disease extends into nodes that are sampled surgically or via needle aspiration, or if the infection extends directly outside the lung and involves the chest wall. In this setting is can easily be confused with malignancy since few other pulmonary infections can cross the pleura and invade muscle and soft tissue.

A slow progression of symptoms is suggestive of actinomycosis. Response to antibiotic courses is variable, but relapse after short courses of anti-infectives could also trigger thoughts of this diagnosis. Swelling out of proportion to pain may be present. Lesions with spontaneous drainage (even without visible, gritty “sulfur granules”) are a good clue.

Feeling a firm mass that is not inflamed or tender could suggest actinomycosis. Expressing gritty concretions or seeing them on a bandage or gauze can be clinically helpful as well as providing a specimen for staining.

What other additional laboratory findings may be ordered?

Serologic tests for the agents of actinomycosis are appealing, but their utility is limited. False positive and false negative results are common. Polymerase chain reaction (PCR) tests for actinomycosis are not commercially available but might be helpful in the future. Since Actinomyces is part of the normal oral flora, specimen collection is important to avoid contamination with saliva. Finding Actinomyces nucleic acids in a draining lesion might become a very useful diagnostic test.

How can actinomycosis be prevented?

There is no known prevention for actinomycosis except for normal oral hygiene. There is no preventive measure for women with IUDs. There is no vaccine and there is no likelihood that one will be researched or developed.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

While there is general consensus that actinomycosis requires a long period of treatment, the evidence-base for optimal treatment is unsatisfying. This is a result of the rarity of the condition, the variety of clinical manifestations, the lack of validated in vitro susceptibility testing and the presence or absence of co-infecting agents. The suggestion that initial intravenous treatment is necessary has been challenged in several case series including one from Korea with 28 patients treated for thoracic actinomycosis. The duration of oral antibiotics ranged from 76-412 days, but the bulk of patients got less than 3 days of IV treatment and there were no relapses noted in the follow-up period. A review of the treatment of cervicofacial actinomycosis supported penicillin as the drug of choice with a treatment duration of 2-12 months. Some experts prefer amoxicillin clavulanate for better coverage of anaerobes other than Actinomyces.

Wong, VK, Turmezel, TD, Weston, VC.. “Actinomycosis”. BMJ. 2011 Oct 11. pp. 343.d6099(Excellent up-to-date review of actinomycosis with attention to microbiology, epidemiology, clinical features and treatment.)

Sung, HY, Lee, IS, Kim, Si. “Clinical features of abdominal actinomycosis: a 15-year experience of a single institute”. J Korean Med Sci. vol. 26. 2011 Jul. pp. 932-7. (This 15-year review of abdominal actinomycosis in a Korean hospital indicates that outcomes of treatment are good and recurrences are rare when a long course of therapy is prescribed.)

Akhaddar, A, Elouennass, M, Baallal, H, Boucetta, M.. “Focal intracranial infections due to Actinomyces species in immunocompetent patients: diagnostic and therapeutic challenges”. World Neurosurg. vol. 74. 2011 Aug-Sept. pp. 346-350. (This case series documents a good outcome for five cases of intracranial actinomycosis in France.)

Sullivan, DC, Chapman, SW.. “Bacteria that masquerade as fungi: actinomycosis/nocardia”. Proc Acad Thorac Soc. vol. 7. 2010 May. pp. 216-21. (This review paper contrasts actinomycosis with nocardiosis. The distinction is important since these two different organisms can look alike microscopically and therefore can lead to diagnostic confusion.)

Bartlett, AH, Rivera, AL, Krishnamurthy, R, Baker, CJ.. “Thoracic actinomycosis in children: case report and review of the literature”. Pediatr Infect Dis J. vol. 27. 2008 Feb. pp. 165-9. (This case report and review cover the manifestations of actinomycosis in children.)

Sudhakar, SS, Ross, JJ.. “Short-term treatment of actinomycosis: two cases and a review”. Clin Infect Dis. vol. 38. 2004 Feb 1. pp. 444-7.

Treatment summary

Valour, F, Senechal, A, Dupieux, C. “Actinomycosis: etiology, clinical features, diagnosis, treatment and management”. Infect Drug Resist.. vol. 7. 2014. pp. 183-197. (This paper lists the consensus management approaches to the major clinical manifestations of actinomycosis.)

Choi, J, Koh, W-J, Kim, TS. “Optimal duration of IV and oral antibiotics in the treatment of thoracic actinomycosis”. Chest. vol. 128. 2005. pp. 2211-17.

Oostman, O. Curr Infect Dis Rep. vol. 7. 2005. pp. 170

DRG CODES and expected length of stay

Length of hospital stay can vary from no hospital days to enough time for the initiation of antibiotics and possible surgery.

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