Johns Hopkins Antibiotic (ABX) Guide

Actinomyces

MICROBIOLOGY

  • Thin, branching (filamentous) Gram positive bacillus.
    • Microaerophilic, grow best anaerobically.
    • VERY fastidious.
  • Agents: A. israelii, A. gerencseriae, A. naeslundii, A. odontolyticus, A. viscosus, A. meyer and Propionibacterium propionicum.
  • Normal flora of mouth, gut, genital tract.
  • Diagnosis is often made by histopathology -- not by culture, even when suspected.

CLINICAL[Top]

  • Nearly always part of a mixed infection, especially with flora such as Actinobacillus actinomycetemcomitans, Eikenella corrodens, Bacteroides spp, S. aureus, Streptococcus spp.
  • Characteristic chronic lesion: dense fibrosis ("woody"), draining fistulae, "sulfur granules."
    • Infection may advance through tissue planes with no respect for anatomical boundaries.
  • Diagnosis: characteristic Gram stain (filamentous rods) in tissue or sulfur granule with radiating Gram positive bacilli seen on histopathology or by culture.
    • Recovery important only if from normally uncontaminated sources, e.g., cleanly obtained tissue, needle aspirates, OR examination of sulfur granules, etc.
  • Main differential is Nocardia [see table]. Looks similarly 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.
Comparison with Nocardia

Actinomyces

Nocardia

Agents:

Agents of actinomycosis

N. asteroides and other species

Gram stain:

Filamentous, GPB

Filamentous GPB

Modified AFB:

Negative

Positive (weakly)

Source:

Mouth flora

Soil

Host:

Previously healthy, poor dentition

Decreased cell mediated immunity

Clinical features:

Indurated, fistula

Indurated with sulfur granules

Course:

Indolent

Indolent

Rx:

Penicillin G, ampicillin/amoxicillin, antipseudomonal PCNs, most cephalosporins, macrolides, tetracycline, imipenem, clindamycin

TMP-SMX, imipenem, amikacin, linezolid

SITES OF INFECTION[Top]

  • Oral cervico-facial: characteristic "lumpy jaw," loss of temporomandibular angle of jaw by swelling.
    • Osteonecrosis of jaw: post chemotherapy, radiation therapy or post-bisphosphonate (controversial)
  • Pelvic infection: classically, IUD-associated.
  • Thoracic: pneumonia or mass lesion: may be confused with malignancy.
  • Intra-abdominal:abscess or mass lesion.
  • Musculoskeletal: lesions in either muscle, bone or (rarely) joint.
  • Cardiac: endocarditis (The "A" of HACEK, Actinobacillus actinomycetemcomitans [Aggregatibacter actinomycetemcomitans])
  • CNS: meningitis (rare), encephalitis (rare), brain abscess
  • Disseminated: rare

TREATMENT[Top]

Antibiotics

  • Note: clinical response is often slow, and very long courses are required to prevent relapse.

Miscellaneous

  • Surgery: usually reserved for suspected neoplasm, to establish diagnosis, lesion in vital area (epidural, CNS, etc) or unresponsiveness to abx.
  • Surgical procedures: debulking, excision of fistula tracts, abscess drainage.

Selected Drug Comments

Drug

Recommendation

Ceftriaxone

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.

Clindamycin

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.

Doxycycline

Good drug for actinomycosis. The agents are susceptible and clinical experience seems good. An advantage is the availability of oral & parenteral forms. Most will start therapy with high IV doses of penicillin or clindamycin, and use doxycycline for a prolonged oral maintenance phase.

Imipenem/cilastatin

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.

Metronidazole

This drug won’t work. Actinomyces are not susceptible in vitro. This means they are probably not true anaerobes.

Penicillin

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.

Ampicillin

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.

Amoxicillin

Preferred drug for oral treatment--either initially for mild-moderate infections, or maintenance therapy after initial parenteral course.

FOLLOW UP[Top]

  • Use of high dose abx and long duration of antibiotics justified by tradition and perceived need for penetration into dense fibrotic tissue.

OTHER INFORMATION[Top]

  • 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.

Basis for recommendation[Top]

  1. Author opinion;

    Comment: No professional society guideline statements exist for the treatment of actinomycoses. Long duration of antibiotic therapy guided by case series reports and expert opinion.

  2. Wong VK, Turmezei TD, Weston VC: Actinomycosis. BMJ 343:, 2011  [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[Top]

  1. Akhan SE et al: Pelvic actinomycosis mimicking ovarian malignancy: three cases. Eur J Gynaecol Oncol 29:294, 2008  [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

  2. Smith AJ et al: Antimicrobial susceptibility testing of Actinomyces species with 12 antimicrobial agents. J Antimicrob Chemother 56:407, 2005  [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

  3. Sarkonen N et al: Characterization of Actinomyces species isolated from failed dental implant fixtures. Anaerobe 11:231, 2005  [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.

  4. Valicenti JF et al: Detection and prevalence of IUD-associated Actinomyces colonization and related morbidity. A prospective study of 69,925 cervical smears. JAMA 247:1149, 1982  [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

  5. Yildiz O, Doganay M: Actinomycoses and Nocardia pulmonary infections. Curr Opin Pulm Med 12:228, 2006  [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.

  6. Hansen T et al: Actinomycosis of the jaws--histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis. Virchows Arch 451:1009, 2007  [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

  7. Acevedo F et al: Actinomycosis: a great pretender. Case reports of unusual presentations and a review of the literature. Int J Infect Dis 12:358, 2008  [PMID:18164641]

    Comment: Called "the great pretender" due to variable presentation -- most commonly -- cervicofacial followed by pelvic and thoracic infection. Three case reports here: inferior caval vein syndrome, acute cholecystites and acute cardiac tamponade.
    Rating: Important

  8. Yi F et al: Actinomycotic infection of the abdominal wall mimicking a malignant neoplasm. Surg Infect (Larchmt) 9:85, 2008  [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

  9. Christodoulou N, Papadakis I, Velegrakis M: Actinomycotic liver abscess. Case report and review of the literature. Chir Ital 56:141, 2004 Jan-Feb  [PMID:15038660]

    Comment: Case report of an actinomycotic liver abscess. It was 6.8 x 4.6cm on CT scan, it was drained and drainage showed "sulfur granules". A total of 57 have been reported.

  10. Kim TS et al: Thoracic actinomycosis: CT features with histopathologic correlation. AJR Am J Roentgenol 186:225, 2006  [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.

  11. Holmberg K: Diagnostic methods for human actinomycosis. Microbiol Sci 4:72, 1987  [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

  12. Han JY et al: An overview of thoracic actinomycosis: CT features. Insights Imaging 4:245, 2013  [PMID:23242581]

    Comment: CT anatomical features: parenchymal, bronchiectatic, endocbronchial and extrapulmonary.
    Rating: Important

  13. Holm P; Studies on etiology of human actinomycosis; Acta Pathol Microbio Scand; 1950; Vol. 27; pp. 736;

    Comment: A review of the companion organisms. Nearly all cases are mixed infections. Most common is Actinobacillus actinomycetemcomitans - an association so strong that the recovery of this organism permits the assumption of actinomycosis. Other companions - Bacteroides, Fusobacteria, Streptococci, Peptostreptococci, Eikenella, etc.

  14. Pulverer G, Schütt-Gerowitt H, Schaal KP: Human cervicofacial actinomycoses: microbiological data for 1997 cases. Clin Infect Dis 37:490, 2003  [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

  15. Kramer J; Instant Replay: The Green Bay Diary of Jerry Kramer; The World Publishing Co; 1968; pp. 48-50;

    Comment: This football great reported to Green Bay spring practice with abdominal pain and fever. He was discovered to have abdominal actinomycosis secondary to a splinter from chopping wood 20 years earlier - testimony to the indolent nature of this infection. (Unfortunately, he called it a fungus; fortunately, he recovered and made the famous block that gave Green Bay the Super Bowl championship).

  16. Maki K et al: Endobronchial actinomycosis associated with a foreign body--successful short-term treatment with antibiotics--. Intern Med 49:1293, 2010  [PMID:20606362]

    Comment: Case report of endobronchial actimnomyces associated with a fish bone swallowed 28 months prior to detection.

  17. Lancella A et al: Two unusual presentations of cervicofacial actinomycosis and review of the literature. Acta Otorhinolaryngol Ital 28:89, 2008  [PMID:18669075]

    Comment: Review of "the typical case" -- Patients presented with enigmatic cervicofacial mass, no fever, no trauma and no dental procedures or pathology. Diagnosis was based on histopathology.
    Rating: Important

  18. Cheon JE et al: Thoracic actinomycosis: CT findings. Radiology 209:229, 1998  [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.

  19. Berardi RS: Abdominal actinomycosis. Surg Gynecol Obstet 149:257, 1979  [PMID:380028]

    Comment: Review of abdominal actinomycosis - usually presents as a periappendiceal mass which accounts for two thirds of cases. Most cases present as slowly evolving inflammatory masses with microabscesses, abscesses or draining sinuses. The woody hard feature at surgery may suggest cancer. CT scans show multicystic contrast enhanced masses. CT guided bx may avert need for surgery.

  20. Smego RA: Actinomycosis of the central nervous system. Rev Infect Dis 9:855, 1987 Sep-Oct  [PMID:3317731]

    Comment: Review of CNS actinomycosis - usually presents as a brain abscess with headache and focal neurologic deficit +/- fever; CT scan shows ring-enhancing mass that may be mistaken for brain tumor or pyogenic brain abscess. There may also be chronic meningitis. CSF cultures rarely grow actinomyces even when present.

  21. Hall V: Actinomyces--gathering evidence of human colonization and infection. Anaerobe 14:1, 2008  [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

  22. Heffner JE: Pleuropulmonary manifestations of actinomycosis and nocardiosis. Semin Respir Infect 3:352, 1988  [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.

  23. Wohlgemuth SD, Gaddy MC: Surgical implications of actinomycosis. South Med J 79:1574, 1986  [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

  24. Song JU et al: Treatment of thoracic actinomycosis: A retrospective analysis of 40 patients. Ann Thorac Med 5:80, 2010  [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

  25. Sudhakar SS, Ross JJ: Short-term treatment of actinomycosis: two cases and a review. Clin Infect Dis 38:444, 2004  [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

  26. Lee IJ et al: Abdominopelvic actinomycosis involving the gastrointestinal tract: CT features. Radiology 220:76, 2001  [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.

  27. Mardis JS, Many WJ: Endocarditis due to Actinomyces viscosus. South Med J 94:240, 2001  [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.

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