Vol. 21, No. 1
THE JOHNS HOPKINS MICROBIOLOGY NEWSLETTER
Tuesday, January 15, 2002
 
 

The patient is a 13-year-old white male with a past medical history significant for a cytogenetic abnormality involving deletion of the short arm of chromosome 4, and submucosal cleft palate. Three to four days prior to his admission, he developed a rapidly growing anterior left chest wall mass, chest pain, dry cough, progressive shortness of breath and fever (100.2 F on the day of admission). The CAT scan of the chest revealed a triangular soft tissue density lateral to his left ventricle, eroding through the chest wall, with consolidation of the underlying lung, and a moderate sized left pleural effusion. His laboratory work up was notable for white blood cell count 32,400 / cu mm, hemoglobin 8 g/dl, and platelet count 494,000 / cumm. He was empirically started on clindamycin, and azithromycin for a suspected post-obstructive pneumonia. He underwent an incisional biopsy of the chest wall mass, which revealed an abscess formation, granulation tissue, histiocytic reaction, and colonies of filamentous organisms that were Gram and Gomori methenamine silver stain positive, but negative for acid-fast organisms (Kinyoun’s and Fite stains) (Figures 1and 2). Overall, the clinical and histological findings were most consistent with actinomycosis. His antimicrobial therapy was switched to penicillin G and he was discharged on oral amoxicillin (80 mg/kg/day) for a period of 4-6 months.

Organism:

The causative agents of actinomycosis in humans include Actinomyces israelii, which is the most common species in clinical infections, A. naeslundii, A. odontolyticus, A. viscous, A. meyeri, A. pyogenes, Propionibacterium propionicum, and Bifidobacterium dentium. A. israelii are non-spore forming Gram-positive, branching filamentous rods, with a diameter of 1 micron, and extreme variability in length.

Clinical manifestations:

Thoracic actinomycosis is usually due to aspiration pneumonia, and less likely secondary to direct extension from the head and neck or abdominal cavity. Typically, the symptoms of the thoracic disease include fever, weight loss, chest pain, and less commonly hemoptysis. There is no specific radiographic picture with usual findings of pleural thickening, effusion or empyema, and pulmonary parenchymal involvement. Classically, extension to the chest wall with the development of a soft tissue mass, and/or a draining sinus is characteristic. Other entities in the differential diagnosis of pulmonary actinomycosis include tuberculosis, nocardiosis, histoplasmosis, blastomycosis, cryptococcosis, mixed infection, bronchogenic carcinoma, lymphoma, mesothelioma, and pulmonary infarction. The most common location of infection is oral-cervical. Presence of sulfur granules in the tonsillar tissue, in the absence of pathologic tissue reaction, is consistent with colonization and not a disease process. Another common location of infection is pelvis, which is typically a result of an intrauterine contraceptive device use. Other documented actinomycosis sites include abdominal cavity, central nervous system, mediastinum, musculoskeleton, and disseminated disease.

Epidemiology:

Actinomyces spp. are endogenous flora of mucus membranes. A. israelii is always found in the oral cavity, and often is found in the genitourinary tract, gastrointestinal tract, and bronchi. A. israelii has never been isolated from nature and person-to person transmission has never been documented. Although infection may occur at any age, the peak incidence of actinomycosis is between 10 to 60 years of age, with a 3:1 male predominance. Poorer dental hygiene and increased oral trauma have been postulated for the higher infection rate in males. Although in Europe and the United States the estimated incidence of actinomycosis in the 1960’s and 1970’s was 0.3 to 1/100,000/year, these numbers are probably and underestimation due to unrecognized, empirically treated infections involving the oral-cervicofacial area.

Diagnosis:

Obtaining the appropriate specimen by fine needle aspiration or biopsy is usually necessary for establishing the diagnosis. While most species of Actinomyces are microaerophilic or facultative, optimal growth requires strict anaerobic processing.  A. israelii characteristically forms a "molar tooth" colony on agar and grows as clumps in broth. Traditional tests for identification of Actinomyces species include indole, catalase, urase, gelatin hydrolysis, and fermentation of cellobiose, trehalose, and arabinose. Immunofluoresence testing may be used for confirmation of suggestive organisms. Identification of sulfur granules or "grains" in pus or histologic sections of surgical specimen is very helpful in the diagnosis (Figure 1). On hematoxylin-eosin stains, the sulfur granules appear eosinophilic and are composed of organisms coated by a proteinaceous material (Splendore-Hoeppli phenomenon). On Gram and silver stains, they are composed of branching rods. Nocardia may show similar histologic pattern; however, Nocardia is acid fast positive by Fite stain whereas Actinomyces are acid fast negative.

Pathogenesis and pathology:

Disruption of the mucosal barrier is a critical step in the pathogenesis of actinomycosis. Oral and cervicofacial infections are commonly associated with trauma or dental procedures. Pelvic, pulmonary, and abdominal infections may occur due to IUD, aspiration, or gastrointestinal surgery, respectively. Presence of "companion microbes" may aid in inhibition of host defenses or reduction in oxygen tension. Although cases of actinomycosis have been documented in the setting of steroid use, acute leukemia during chemotherapy, solid organ transplantation, and HIV infection, it is not clear which aspect of the immune mechanism is responsible in preventing and or controlling this infection.

Treatment:

Administration of antibiotics at high doses and for a prolonged period is usually required for treating the infection. Typically, penicillin G is given for 2- 6 weeks, followed by 6-12 months of oral amoxicillin, ampicillin, or penicillin V. In the cases of allergy to penicillin, tetracycline, doxycycline, erythromycin, and clindamycin are appropriate alternatives. Although surgical removal combined with antimicrobial therapy has been advocated, several studies indicate that prolonged medical therapy may be a sufficient initial approach for curing the infection.

References:
1.    Rein, MF. Principles and Practice of Infectious Diseases, 5^th Edition. Edited by GL Mandell, JE Bennett, and R Dolan. Churchill Livingstone, Inc., Philadelphia, 2000.

2.    Koneman et. al. Color Atlas and Textbook of Diagnostic Microbiology, 5^th Edition, Lippincott-Raven, Philadelphia, 1997.

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