A case of otitis media complicated by intracranial infection with Actinomyces turicensis

Introduction: Actinomycosis is a granulomatous suppurative infection caused by filamentous Gram-positive anaerobic bacteria from the family Actinomycetaceae. To our knowledge, this is the first reported case of otogenic brain abscess associated with Actinomyces turicensis. Case presentation: We report the case of an immunocompetent 5-year-old boy with recurrent otitis media who re-presented to the emergency department with a 3-week history of otorrhoea, progressive anorexia, vomiting and lethargy. He was admitted with a working diagnosis of otitis media and dehydration, and was treated with intravenous fluids and oral co-trimoxazole. He subsequently developed abnormal posturing with a reduced Glasgow coma score and seizures. Urgent computed tomography revealed a cerebellar abscess with obstructive hydrocephalus for which he underwent urgent neurosurgical intervention. Tissue and aspirate cultures revealed a polymicrobial infection with A. turicensis. The patient has since undergone long-term antibiotic treatment and has made a good recovery. Conclusion: This case demonstrates the successful use of long-term antibiotic therapy and neurosurgical intervention to treat otogenic brain abscess associated with A. turicensis infection. To the best of our knowledge, this is the first such documented case. Our report also provides a timely reminder that, despite a reduced incidence in the developed world, intracranial complications of otitis media continue to occur and a high index of suspicion is required.


Introduction
Actinomycosis is a slowly progressive granulomatous disease caused by filamentous Gram-positive anaerobic bacteria from the family Actinomycetaceae. Commensals of the oropharynx, gastrointestinal tract and urogenital tract, Actinomyces spp. can become pathogenic. Actinomyces israelii is considered the most common human pathogen in this family and the orocervicofacial, thoracic and abdominopelvic sites are those most commonly affected (Wong et al., 2011). Intracranial infection with Actinomyces spp. is rare, and there are a limited number of cases reported in the literature. Diagnosis is difficult, and there remains no consensus about treatment of cerebral actinomycosis. This report discusses the presentation, diagnosis and management of a case of otitis media complicated by intracranial infection with the species Actinomyces turicensis, which, to the best of our knowledge, has not been documented previously.

Case report
A 5-year-old boy with a background of recurrent otitis media re-presented to the emergency department with a 3-week history of ongoing otorrhoea with progressive anorexia, vomiting and lethargy. He had been seen multiple times in the proceeding 3 weeks by both his GP and the emergency department and had initially been given a course of oral amoxicillin. Swabs from his otorrhoea had grown Proteus mirabilis and meticillin-resistant Staphylococcus aureus (MRSA), and he had also therefore been given a course of oral co-trimoxazole and regular gentamicin/ dexamethasone ear drops. There was no history to suggest that he was immunocompromised.
On examination, observations were stable and he was apyrexial with a temperature of 36.7 u C, although his parents reported fevers at home. He was alert and rousable but appeared in significant pain and was 5 % dehydrated. His right ear contained thick pale green exudate and, when microsuctioned, revealed an inflamed auditory canal. The tympanic membrane was intact but with fluid behind it. Overall appearances were felt to be consistent with otitis media. There was no cervical lymphadenopathy, and examination of the chest and abdomen was normal. Initial neurological examination revealed no focal neurological signs and no evidence of meningism. Pupils were equal and reactive.
The patient was diagnosed with ongoing otitis media and dehydration. Intravenous (i.v.) fluids were commenced and oral co-trimoxazole continued. Overnight, nursing staff noted an episode of decerebrate posturing and decreased responsiveness. Upon assessment by the on-call doctor, his Glascow coma score was 13 (E3, M6 and V4) and the posturing had ceased. Pupils were equal and reactive but with a bilateral fixed downward left lateral gaze. The patient underwent an urgent computed tomography (CT) scan of the head, the findings of which were consistent with a right cerebellar abscess secondary to complicated severe right middle ear infection (Figs 1 and 2). There was associated obstructive hydrocephalus.

Investigations
Initial bloods at presentation showed a neutrophilic lymphocytosis (white cell count 15.1610 9 l 21 , neutrophils 13.4610 9 l 21 ) with a mildly elevated C-reactive protein (23 mg l 21 ). Renal function was normal (urea 5.6 mmol l 21 , creatinine 29 mmol l 21 ). Blood cultures did not yield significant growth.
The urgent CT of the head revealed a cystic mass in the right cerebellar hemisphere, measuring 28640617 mm, with surrounding oedema and significant mass effect distorting the brainstem to the left and resulting in obstructive hydrocephalus. The right middle ear and mastoid air cells were completely ossified with adjacent bony irregularity and cortical destruction consistent with osteomyelitis complicating a severe middle ear infection (Figs 1 and 2).
Tissue from the right mastoid obtained from later operative intervention grew A. turicensis, Proteus mirabilis and Peptoniphilus harei with cerebellar aspirates positive for Bacteroides thetaiotaomicron and Anaerococcus hydrogenalis in addition. No MRSA was isolated from deep-tissue samples.
A presumptive identification of an Actinomyces sp. was made on the basis of typical Gram-stained findings of Grampositive branching filamentous rods. The classical sulfur granules were not seen in this case, but further presumptive evidence for actinomycoses was provided by matrix-assisted laser desorption/ionization mass spectrometry of the cultured organism, suggesting A. turicensis. This was confirmed by sequencing of the 16S rRNA gene by PCR.

Treatment
Immediately after obtaining the first series of non-contrast CT images, the patient had a generalized seizure that responded promptly to i.v. midazolam. Following this, he was maintaining his own airway but responding only to painful stimuli. He was transferred to the intensive care unit where he was intubated and ventilated. Sedation was maintained with propofol and midazolam infusions. He was loaded with i.v. phenytoin and a mannitol infusion was commenced. I.v. vancomycin and cefotaxime were given in addition to i.v. dexamethasone. Once stabilized, the patient was transferred to a tertiary centre for neurosurgical intervention.
At the tertiary centre, the patient underwent drainage of the cerebellar abscess with external ventricular drain (EVD) insertion and right mastoidectomy. It was felt that otitis media had caused cholesteatoma formation and subsequent mastoiditis, which in turn led to secondary intracranial pathology. A right lateral gaze palsy was noted post-operatively, which was likely to be iatrogenic. Antibiotics were changed to i.v. cefotaxime and metronidazole in view of the mastoid tissue and cerebellar aspirate culture results. Following removal of the EVD, the patient developed signs of raised intracranial pressure and subsequently underwent redrainage of the abscess with insertion of a second EVD, which was removed 12 days later. The patient was discharged home 5 weeks after presentation with a continuous ambulatory 24-h benzylpenicillin infusion, oral ciprofloxacin and metronidazole.

Outcome and follow-up
Repeat magnetic resonance imaging a month following discharge showed a significant improvement in the

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appearance of the posterior fossa with resolution of the mass effect but mild residual signal abnormality and enhancement in the region of the abscess. Revision right tympanomastoidectomy was performed uneventfully and included the removal of the remainder of the cholesteatoma. Antibiotic cover was switched to oral amoxicillin and ciprofloxacin ear drops after this procedure. It is anticipated that the patient will continue oral amoxicillin for 6 months.
In terms of acquired disability, the patient was noted to have a mildly ataxic gait with a lean to the right when walking. At his most recent follow-up, 3 months post-operative, this had almost completely resolved. His right lateral gaze palsy persists. There has been no gross acquired learning disability or deafness and the patient is now back at school.

Discussion
Actinomycosis is a granulomatous suppurative infection caused by filamentous Gram-positive anaerobic bacteria from the family Actinomycetaceae (Gazzano et al., 2010;Wong et al., 2011). These bacteria are commensals of the human oropharynx, gastrointestinal tract and urogenital tract but can become pathogenic when tissue integrity is breached and direct or haematogenous spread occurs (Akhaddar et al., 2010;Fabbri et al., 2014;Wong et al., 2011). Infection is frequently polymicrobial, and the most commonly affected sites are the cervicofacial region, abdomen and thorax (Wong et al., 2011;Gazzano et al., 2010). Cerebral infection, as in our patient, is rare, and indeed there are a limited number of cases of cerebral actinomycosis and fewer than 30 cases of tympanomastoid actinomycosis infection reported in the English language literature (Fabbri et al., 2014;Gazzano et al., 2010).
Of more than 30 Actinomyces species, A. israelii is the most common human pathogen (Fabbri et al., 2014;Wong et al., 2011). To the best of our knowledge, this is the first reported case of intracranial abscess associated with the species A. turicensis. The case is also remarkable in that actinomycosis infection is most common in the third decade of life and is particularly rare in children (Gazzano et al., 2010;Puzzilli et al., 1998). Olah et al. (2004) described a 10-year-old boy with a background of complex congenital heart disease who was diagnosed with cerebral abscess secondary to A. israelii. This patient also underwent neurosurgical intervention and was successfully treated with a 4-week course of ceftriaxone. In contrast to this, our patient was immunocompetent with no predisposing factors such as head trauma, dental procedures, diabetes or congenital heart disease.
The diagnosis of actinomycosis infection can be difficult (Akhaddar et al., 2010;Wong et al., 2011). Clinically, it may mimic tuberculosis, nocardiosis and malignancies (Fabbri et al., 2014;Wong et al., 2011). Blood tests may show a non-specific leucocytosis and raised C-reactive protein. CT and magnetic resonance imaging also tend to be non-specific in the early stages of infection; however, later they may demonstrate characteristic sinus tract formation and infiltration of surrounding tissue across tissue planes (Wong et al., 2011). The slow-growing nature of Actinomyces spp. means that growth in culture may take up to 3 weeks (Roth & Ram, 2010). Combined with its sensitivity to oxygen, this means that making an actinomycosis culture diagnosis can be challenging (Gazzano et al., 2010;Roth & Ram, 2010). Alternatively, a histological diagnosis may be sought through demonstration of Grampositive filamentous organisms and sulfur granules (Wong et al., 2011). Faster and more accurate identification of Actinomyces spp. is available through newer molecular genetic methods such as PCR and 16S rRNA gene sequencing (Wong et al., 2011).
Optimal treatment for actinomycosis infection remains unclear (Akhaddar et al., 2010;Fabbri et al., 2014;Roth & Ram, 2010). Frequently, an aggressive approach, as seen in our case, involving a combination of surgery and longterm antibiotic treatment is taken (Akhaddar et al., 2010;Gazzano et al., 2010;Roth & Ram, 2010;Wong et al., 2011). Following a review of five cases of intracranial actinomycosis infection, Akhaddar et al. (2010) proposed aspiration of all abscesses larger than 2 cm, and craniotomy for abscesses that enlarge over 2 weeks or do not shrink after 4 weeks of antibiotic therapy. With regard to antibiotic treatment, high-dose i.v. penicillin G is traditionally used for 2-6 weeks followed by oral penicillin V for 6-12 months (Wong et al., 2011). Actinomyces spp. have, however, been shown to be susceptible to a much wider range of antimicrobials including b-lactams, clarithromycin, erythromycin, doxycycline and clindamycin, although not all of these are thought to provide good central nervous system penetration (Smith et al., 2005). Modern approaches therefore now tend to individualize the type and length of antibiotic treatment based on the site and severity of infection as well as patient response (Wong et al., 2011). Metronidazole is not effective against pathogenic Actinomyces spp. (Smith et al., 2005); however, it was used with cefotaxime in our patient due to the polymicrobial nature of his infection. The use of ciprofloxacin was advocated by Akhaddar et al. (2010), who reported an excellent response in the four patients in their case series in whom it was used. Finally, Puzzilli et al. (1998) commented that treatment of intracranial actinomycosis in juvenile patients should not differ from that in other age groups. This report therefore also adds to the scant literature available that supports their conclusion.
In conclusion, this case demonstrates the successful use of tailored long-term antibiotic therapy, combined with neurosurgical intervention, to treat otogenic brain abscess associated with A. turicensis infection, which, to the best of our knowledge, has not been documented previously. The development and use of antibiotics mean that the incidence of intra-and extracranial complications of otitis media in the developed world is now low (Agrawal et al., 2005;Daniero et al., 2012;Smith & Danner, 2006). This case therefore also serves as a timely reminder that, despite this, complications do continue to occur and that a high index of clinical suspicion is required.