Brain Abscess Sustained by Actinomyces meyeri in an Immunocompetent Patient

Actinomycosis is a rare, chronic and slowly progressive granulomatous disease, caused by filamentous Gram positive anaerobic bacteria from Actinomycetaceae family (genus Actinomyces) belonging to endogenous flora of mucous membranes [1]. These bacteria normally colonize oral cavity, vagina and other mucous membranes but they become pathogenic and can initiate a prolonged chronic inflammatory process if the integrity of the mucosal barri er is compromised, with dissemination to any site of the organism [1].

Actinomycosis is a rare, chronic and slowly progressive granulomatous disease, caused by filamentous Gram positive anaerobic bacteria from Actinomycetaceae family (genus Actinomyces) belonging to endogenous flora of mucous membranes [1]. These bacteria normally colonize oral cavity, vagina and other mucous membranes but they become pathogenic and can initiate a prolonged chronic inflammatory process if the integrity of the mucosal barri er is compromised, with dissemination to any site of the organism [1].
Actinomycosis is classified into several clinical forms, according to anatomical site of infection: orocervicofacial, thoracic, abdominopelvic, central nervous system (CNS), musculoskeletal and disseminated forms. The clinical features are often misdiagnosed and anearly diagnosis needs a high level of clinical suspicion [2].
The involvement of CNS represents an uncommon condition (especially consequent to a haematogenous diffusion of microorganism), but it's undoubtedly the most critical site of infection. The disease usually is characterized by "mass effect" symptoms, such as headache, dizziness and focal neurological signs related to the site of involvement. Surgical approach is often necessary to improve medical therapy, especially for difficult localizations and large masses, with evidence of compression of nearest nervous structures.
In the last years, CNS localization by Actinomyces Spp. has been occasionally reported [3][4][5][6]: in particular abscesses by Actinomyces meyeri have been found in a small proportion of cases, especially in the context of disseminated diseases, with only secondary involvement of CNS [7].
We describe a young woman suffering from primary thalamic abscess due to A. meyeri, without any other systemic localization, successfully treated after prompt diagnosis and antibiotic therapy.

Discussion
A 41-years old woman was initially admitted to First Aid of our Hospital, because of fever (38°C), headache, vomit, confusion and dysarthria. Emerging blood test showed mild leukocytosis (white blood cells 11840/mmc, neutrophils 10510/mmc), reactive-C protein (RCP) 7.50 mg/dl, whereas a brain CT scan detected an expansive thalamic lesion with a wide central necrosis and perilesionaledema.
Her medical history was negative, apart from a dental fracture, treated with conservative approach six months before the onset of the clinical symptoms. Tuberculin sensitivity test, interferon-gamma releasing assay, HIV and Toxoplasma gondii serology were negative. Trans-thoracic echocardiography, chest X-ray, orthopantomogram

Abstract
Actinomycosis is a rare granulomatous disease, caused by filamentous Gram positive anaerobic bacteria, which may become pathogenic following disruption of anatomical barriers with invasion of host's deep tissues and dissemination of infection to any site of the organism. A. israelii is found in most clinical presentations.
We describe a case of a 41 years-old immunocompetent woman affected by thalamic abscess due to Actinomyces meyeri, presenting with fever, headache, vomit, confusion. A brain Computed Tomography (CT) and a Magnetic Resonance Imaging (MRI) revealed an expansive thalamic lesion with wide central necrosis and perilesionaledema. The patient was immediately addressed to a first evacuation of the mass, followed by a second drainage because of recurrence of the abscess. Microbiological and histological findings from intraoperatory specimens, resulted positive for A. meyeri. Ampicillin 20 g plus rifampicin 1200 mg/day was started, followed by ceftriaxon 4 g/day for 2 weeks and by amoxicillin 3 g/day. The treatment was discontinued after 9 months; brain MRIs performed at the end of therapy and after 3 and 6 months from the interruption of therapy revealed a gradual but complete resolution of cerebral abscess.
deceleration of electrical cortical activity. Antibiotic therapy was continued with only ampicillin 5 g every 6 hours in a day. Clinical conditions significantly improved with complete regression of fever and neurological symptoms. A further brain MRI did show significant reduction of abscess cavity and edema. The patient was therefore discharged with antibiotic treatment consisting of ceftriaxone, 4 g/day i.m. for 2 weeks, followed by amoxicillin 3 g/day, orally.
Admitted as outpatient to our Department after two weeks, the patient underwent brain MRIs at 3 rd and 6 th months of antibiotic treatment. These revealed a progressive resolution of cerebral abscess (Figure 1). Antibiotics were discontinued after 9 months, without any sign of recurrence of disease after 1 year of follow up.

Conclusion
Actynomicosis is an "endogenous infection". Among the more than 30 known species, A. israelii is the most common human pathogen. Less common species include A. naeslundii, A. odontolyticus, A. viscous, A. meyeri, A. turricensis and A. radingae.
The orocervical form includes about 50% of all reported cases [7]. It usually follows dental manipulation or trauma to the mouth. Other localizations consist of thoracic (15-20%) and abdomino-pelvic (20%) actinomycosis, whereas CNS is a rare site of disease and the infection typically arises from haematogenous spread or direct extension of orocervical infection. The disease usually occurs as brain abscess, meningitis/meningoencephalitis, actinomycoma, subdural empyema or epidural abscess [2].
A. meyeri can cause disseminated forms, by haematogenous spread and systemic involvement. In our case, CNS localization was primitive and no other site of infection was found. Moreover, A. meyeri was isolated from the brain. This was never described so far.
Reports of CNS actinomycosis by A. meyeri are extremely rare, especially in immunocompetent persons. One review described well documented cases of disseminated infection by A. meyeri, treated with drainage of infection focus and antibiotic therapy [8]. Other cases reported intracranial actinomycosis [3][4][5][6]9], but in none of them A. meyeri was recognized as the causative pathogen of primary brain abscess. Only one recent article [10] has reported a cervical actinomycosis with paravertebral abscess and spondylitis imputed to an infection by A. meyeri: in this case an avulsion of teeth 46 and 47, presumed to be the entry point of the infectious process.
Our patient instead was immunocompetent, no predisposing factors for this infection were found and all causes of immunosuppression were excluded. Accumulating evidence suggests in fact that actynomicosis may be associated with impairment of immune system (transplantations, HIV, alcoholism, denutrition etc.) [11,12].
Despite the availability of various therapeutic options, the choice therapy seems to consist of high doses of beta-lactams, to which we firstly added rifampicin, in order to amplify the bactericidal effect and diffusion in the CNS. Although variable, the duration of therapy should be a long-term therapy, up to 12 months.
In our case, the early drainage of the abscess has allowed a relative short-term intravenous therapy, followed by a maintenance oral therapy, with good tolerability.
Because of the absence of predisposing factors, the diagnosis was difficult as actinomycosis can mimic tuberculosis, nocardiosis, other bacterial or mycotic abscesses and cancer. In this case, definitive and abdomen ultrasonography were negative. A brain MRI confirmed the mass, with a compressing effect over cerebral 3 rd ventricle ( Figure  1). The patient was promptly addressed to Neurosurgery Department, in order to perform a diagnostic and therapeutic evacuation of the brain mass.
During surgical drainage, an intraoperatory specimen of the lesion was collected for microbiological tests and antibiotics consisting of ceftriaxone 4 g/day. i.v. associated to rifampicin 1200 mg/day i.v, were administered. Results from microbiology detected A. meyeri (sensitive to all antibiotics tested by our reference laboratory). These were later confirmed by cytological and histological analyses (Figure 2).
A second brain MRI, repeated to define the outcome of neurosurgical procedure, showed recurrence of the abscess. Because of worsening of patient's conditions, a second evacuation was recommended; ceftriaxone was discontinued and ampicillin i.v. (5 g every 6 hours/day) plus continuous infusion of vancomycin 2 g/day and rifampicin were given at the above dosage.
Three weeks after, the patient was addressed to Department of Infectious Diseases to continue antibiotic therapy. At the entry, the patient was febrile (37.5°C), clinical conditions were quite fair and physical examination showed mild left lower limb hyposthenia. Blood examinations were normal. An electroencephalogram showed diffuse  diagnosis was reached and later confirmed by microbiological and histological features.
In conclusion, actinomycotic focal cerebral infections may occur with greater frequency than previously recognized. Although primary infection is extremely rare and controversial, A. meyeri should be always suspected even in immune competent patients with brain mass and/or neurological signs without evident risk factors.