World Meningitis Day: empirical diagnosis and treatment

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Meningitis is an inflammation that occurs in the meninges and subarachnoid space that can also involve the cortex and brain parenchyma given the close anatomical relationship between the cerebrospinal fluid and the brain. Acute meningitis can be caused by a variety of etiologic agents, but meningitis of bacterial etiology is considered the most serious cause, and can be acquired by the community as well as in the hospital environment as a complication of invasive neurosurgical procedures. Today’s column will focus on community bacterial meningitis in honor of April 24, World Meningitis Day.

How does the epidemiology of community bacterial meningitis behave?

The most prevalent bacterial agents of bacterial meningitis are S. pneumoniaand is N. meningitis, the prevalence of which varies depending on age group and location. In Brazil, meningococcus is the main cause of bacterial meningitis, while pneumococcus is in second place in this ranking.

For meningococcal meningitis, the incidence has been reduced over the last few years, with a record of less than one case per 100,000 inhabitants, between 2014 and 2016. Approximately 30% of reported cases occur in children under five years of age. age. The lethality of the disease in Brazil has been around 20% in recent years. In the most severe form, meningococcemia, the lethality reaches almost 50%.

A relevant fact about pneumococcal meningitis is that, in Brazil, children up to 2 years of age are the most affected by this etiology.

The majority form of transmission of the agents occurs through the respiratory route, although there are also cases by the enteral route (as happens in cases of infection by listeriosis).

Bacterial meningitis is a medical emergency, whose early clinical recognition and prompt treatment is essential for a better clinical outcome.

Clinical manifestations vary according to age group…

  • In neonates: The clinical picture can be presented by symptoms/signs considered non-specific: irritability, hyporexia, hyper or hypotonia. Fever and epileptic seizures affect <40% and <35% of cases, respectively.
  • In adults: A prospective study carried out in the Netherlands with 1268 adults with community bacterial meningitis found a high prevalence of the following classic clinical commemoratives: 83% with headache, 75% with nuchal rigidity, 74% with fever above 38ºC and 71% with sensorineural lowering (defined as Glasgow below 14).

The presence of the classic triad (fever, nuchal rigidity, and sensory impairment) was reported in only 41% of patients!

The presence of signs of meningeal irritation may be present on physical examination, such as: (1) Nuchal stiffness, (2) Kernig’s sign (pain after knee extension maneuver that was at 90° with the hip flexed), and (3) Brudzinski’s sign (knee and hip flexion reaction after cervical flexion). However, the absence of these signs does not exclude the possibility of meningitis. A study carried out in the United States showed that signs of meningeal irritation have low sensitivity (between 5-30%) and high specificity (68-95%).

How to perform the diagnosis?

Spinal cord collection with cerebrospinal fluid (CSF) is essential to confirm or rule out a suspected meningitis. Through the characteristics present in the CSF, it is possible to induce and discriminate the responsible etiologies.

Changes in CSF results in cases of meningitis:

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Before an invasive test such as a lumbar puncture, the clinician should always consider whether this procedure is safe. History of central nervous system (CNS) lesions, presence of focal neurological deficits, immunosuppression status or significant sensorium lowering are warning signs that may indicate abnormalities in the brain parenchyma, and therefore, before lumbar puncture, they should be submitted to neuroimaging as skull tomography.

Exams performed using the LCR material:

  • Bacteria cultures: Considered the gold standard, it can be positive in 50-90% of patients depending on the pathogen – although this sensitivity may decrease if antibiotic therapy has already been started.
  • Direct bacterioscopy using the Gram technique: Although not very specific, it helps to detect bacterial morphology in 70-90% and 30-90% of cases of pneumococcal and meningococcal meningitis, respectively.
  • Latex agglutination test: It has a sensitivity with wide variability, it is also pathogen dependent. It has sensitivity between 59 to 100% and 22 to 93% for S. pneumoniae and N. meningitisrespectively.
  • Real time PCR: It has an increasing clinical application, being interesting mainly for the diagnosis of patients in which antibiotic therapy was started before lumbar puncture.

Read too: Strict control of systolic blood pressure can compromise cerebral blood flow?

empirical treatment

Mortality for acute bacterial meningitis is high, so treatment should be started in suspected cases even before the diagnosis has been confirmed. Blood cultures and serum laboratory tests should be performed immediately.

The choice of initial empiric antibiotic regimen should be based on age group, local epidemiological pattern of pneumococcal resistance, and the need to introduce amoxicillin or ampicillin to cover disease. L. monocytogenes.

The species of S. pneumoniae Penicillin resistance has increased around the world, altering the initial empirical therapy of bacterial meningitis in many regions, including Brazil. Importantly, for pneumococcal meningitis, penicillin resistance occurs when the minimum inhibitory concentration (MIC) is ≥ 0.2ɥg/ml.

There are cases, however, of pneumococcus with resistance also to third-generation cephalosporins – defined by MIC ≥ 0.2ɥg/ml. guidelines of Infectious Diseases Society of America (IDSA) and European Society of Clinical Microbiology and Infectious Diseases (ESCMID) recommend the use of third-generation cephalosporin and vancomycin as part of the initial empirical treatment for bacterial meningitis. However, in countries where the prevalence of cephalosporin-resistant pneumococcus is < 1%, the recommendation to use ceftriaxone alone is more appropriate.

In Brazil, the incidence of pneumococci isolated in CSF samples not susceptible to penicillin reached values ​​above 30%. These same studies demonstrate that, in our country, pneumococcal resistance to third-generation cephalosporins is still low.

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*Vancomycin should only be introduced in cases of suspected/confirmed cephalosporin-resistant pneumococcus.

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# van de Beek, Diederik, et al. “Community-acquired bacterial meningitis.” Nature reviews Disease primers 2.1 (2016): 1-20. # General Coordination for the Development of Epidemiology in Services. Health Surveillance Department. Ministry of Health. “Health Surveillance Guide.” (2017).

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