Endgames Case Report

An agitated man with earache

BMJ 2010; 341 doi: http://dx.doi.org/10.1136/bmj.c3824 (Published 15 September 2010) Cite this as: BMJ 2010;341:c3824
  1. Matthijs C Brouwer, neurologist,
  2. Diederik van de Beek, neurologist
  1. 1Department of Neurology, Centre of Infection and Immunity Amsterdam (CINIMA), Academic Medical Centre, University of Amsterdam, PO Box 22660, 1100DD Amsterdam, Netherlands
  1. Correspondence to: D van de Beek d.vandebeek{at}amc.uva.nl

    A 39 year old man presented to his general practitioner with a one day history of earache and discharge of bloody pus from his right ear. He reported having a cold during the week before the earache started. The doctor diagnosed him with acute otitis and prescribed amoxicillin with clavulanic acid. Overnight the patient developed headache, nausea, and vomiting and was referred to the emergency department of our hospital.

    In the emergency department he was systemically unwell with a blood pressure of 90/55 mm Hg, temperature of 39.5ºC, and pulse rate of 100 beats/min. He had an altered mental status with agitated behaviour and he did not obey commands. He opened his eyes in response to voices, localised painful stimuli, and uttered inappropriate words. Physical examination showed neck stiffness without other neurological deficits.

    Laboratory results on admission showed a white cell count of 20.1×109/l, platelets 194×109/l, C reactive protein 252 mg/l, and serum glucose of 6.9 mmol/l. His arterial blood gas on 5 l of oxygen via a nasal cannula showed pH 7.45, partial pressure of oxygen 8.6, partial pressure of carbon dioxide 4.5, base excess −0.6, and standard bicarbonate 22.8. A chest radiograph was normal. The patient’s medical history was unremarkable.

    Questions

    • 1 What is the most likely diagnosis?

    • 2 What investigations may aid in diagnosis?

    • 3 What are the common organisms and risk factors associated with this condition?

    • 4 How should it be treated?

    Answers

    1 What is the most likely diagnosis?

    Short answer

    The most likely diagnosis is bacterial meningitis.

    Long answer

    The classic triad of symptoms and signs of bacterial meningitis are fever, altered mental status, and neck stiffness, which were all present in our patient. This classic triad cannot be used to prove or exclude bacterial meningitis because it is absent in 56% of adults with the disease.1 Almost all patients (95%) present with at least two of four symptoms: headache, fever, neck stiffness, and altered mental status as defined by a score below 14 on the Glasgow coma scale.1 The sensitivity and specificity for most symptoms and signs in bacterial meningitis is unknown, except for Kernig’s sign, Brudzinski’s sign, and nuchal rigidity. These meningeal signs were found to be of limited diagnostic value in differentiating adults with and without bacterial meningitis in a prospective study (Kernig’s sign: sensitivity 5%, specificity 95%; Brudzinski’s sign: sensitivity 5%, specificity 95%; nuchal rigidity: sensitivity 30%, specificity 68%).2

    Several studies have shown high specificity and sensitivity of serum C reactive protein greater than 40 mg/l (sensitivity 93%, specificity 100%)3 and procalcitonin greater than 0.5 ng/ml (sensitivity 99%, specificity 93%)4 in patients with bacterial meningitis for differentiating between viral or aseptic and bacterial meningitis. Although raised concentrations of these markers are suggestive of bacterial infection, they do not establish the diagnosis of bacterial meningitis.

    2 What investigations may aid in diagnosis?

    Short answer

    To establish the diagnosis of bacterial meningitis a lumbar puncture should be performed. Cranial imaging before lumbar puncture is needed in selected cases to rule out brain shift but should not delay initiation of appropriate treatment.

    Long answer

    A lumbar puncture is mandatory whenever bacterial meningitis is suspected. The procedure can be harmful, however; patients with space occupying lesions, such as subdural empyema or a brain abscess, may present with symptoms that seem to be identical to those of bacterial meningitis, and in these patients lumbar puncture may be complicated by brain herniation. Computed tomography or magnetic resonance imaging of the brain can be used to detect risk factors for brain herniation. Imaging should not delay the start of treatment, however, because this is associated with a worse outcome.5 6 A prospective study of adults with suspected meningitis showed that clinical features can be used to identify patients who are unlikely to have abnormal findings on cranial computed tomography.7 Cranial imaging should precede lumbar puncture in patients who have new onset seizures, an immunocompromised state, signs that are suspicious for space occupying lesions, or moderate-severe impairment of consciousness.8 Other reasons not to perform (immediate) lumbar puncture are coagulopathy or local skin infection.8

    Characteristic cerebrospinal fluid (CSF) findings in bacterial meningitis are polymorphonuclear pleocytosis, hypoglycorrhachia, and raised protein. Gram staining of the CSF is a quick and well validated method of determining the causative micro-organism in bacterial meningitis. CSF culture is the gold standard for the diagnosis of bacterial meningitis and can detect the causative organism in 80-85% of cases.9 10 Blood cultures can help detect the causative organism and establish susceptibility patterns if CSF cultures are negative or unavailable. Blood cultures are positive in 75% of patients with pneumococcal meningitis.

    3 What are the common organisms and risk factors associated with this condition?

    Short answer

    The most common causative micro-organisms in bacterial meningitis are Streptococcus pneumoniae and Neisseria meningitidis. Predisposing conditions are otitis media, sinusitis, pneumonia, and immunocompromise.

    Long answer

    S pneumoniae (pneumococcus) and N meningitidis (meningococcus) cause about 80% of all cases of bacterial meningitis in adults.1 Predisposing conditions for pneumococcal meningitis are distant foci of infection, immunocompromise, and genetic risk factors.11 12 Contiguous or distant foci of infection, including pneumonia, otitis media, mastoiditis, sinusitis, and endocarditis are described in 50-60% of patients with pneumococcal meningitis.11 Because of the high prevalence of otitis media and mastoiditis in these patients, an otolaryngologist needs to be consulted to determine the need for emergency surgery.11 Meningococcal disease has been associated with smoking, living in the same household as a patient with bacterial meningitis, having contacts with meningococcal disease, and possessing genetic risk factors.12

    4 How should it be treated?

    Short answer

    Antimicrobial treatment for adults with bacterial meningitis of unknown cause consists of intravenous vancomycin and ceftriaxone. Adjunctive dexamethasone should be started with the first dose of antibiotics. Immediate empirical treatment is potentially life saving and must not be delayed by diagnostic procedures.

    Long answer

    Because of the increasing resistance of S pneumoniae to penicillin and third generation cephalosporins, the combination of vancomycin and a third generation cephalosporin is advised for adults with bacterial meningitis of unknown cause.8 13 Elderly and immunocompromised patients are at risk for less common causes of bacterial meningitis, such as Listeria monocytogenes, so should also be treated with amoxicillin. In areas with very low penicillin resistance rates, monotherapy with penicillin may be considered in immunocompetent patients up to 50 years old, but many experts recommend combination treatment for all patients until the results of in vitro susceptibility testing are known.8 13 The recommended duration of treatment is 10-14 days.13

    Adjunctive dexamethasone decreases hearing loss in survivors of bacterial meningitis,14 and studies in high income countries found that it also decreased mortality.15 However, the use of dexamethasone remains controverial because study results have been conflicting. Guidelines from the Infectious Diseases Society of America, European Federation of Neurological Sciences, and British Infection Society recommend adjunctive dexamethasone as standard treatment for patients with suspected or confirmed pneumococcal meningitis.

    Immediate emergency treatment is potentially life saving and must not be delayed by diagnostic procedures.

    Patient outcome

    The symptoms and signs of central nervous system infection, combined with raised serum inflammatory markers, were suggestive of bacterial meningitis. Mastoiditis with a secondary systemic infection and delirium was a possibility, but further investigations were needed to look for meningitis. Other diagnoses included in the differential were brain abscess and subdural empyema. Pneumococcal infection was suspected in our patient on the basis of the acute otitis media and mastoiditis.

    We performed cranial computed tomography on admission because the patient had moderate impairment of consciousness. We started empirical treatment with antimicrobials and adjunctive dexamethasone before the scan was performed. The scan showed right mastoid opacification and intracranial air, but no contraindications for lumbar puncture. It could be argued that a cranial computed tomography was not needed before the lumbar puncture because the patient localised painful stimuli symmetrically and he had no focal neurological abnormalities, making brain shift unlikely.

    CSF examination showed a white cell count of 1200/mm3, glucose 2.5 mmol/l, and protein 1.09 g/l; Gram positive diplococci were detected on a CSF Gram stain. On the basis of these results we concluded that the patient had pneumococcal meningitis. CSF culture confirmed the diagnosis and also showed that this pneumococcal strain was sensitive for penicillin. Blood cultures were negative. The consulted otolaryngologist concluded that mastoidectomy was not indicated. The patient made a full recovery.

    Notes

    Cite this as: BMJ 2010;341:c3824

    Footnotes

    • Competing interest statement: All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: (1) no support from any organisation for the submitted work; (2) no relationships with organisations that might have an interest in the submitted work in the previous three years; (3) no spouses, partners, or children with financial relationships that may be relevant to the submitted work; (4) and no non-financial interests that may be relevant to the submitted work.

    • Provenance and peer review: Not commissioned; externally peer reviewed.

    • Patient consent obtained.

    References

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