Important: Please note that bacterial meningitis is a medical emergency. If you suspect that you or someone else may be infected, please consult a physician immediately.
The three traditional symptoms of meningitis include fever, severe headache, and stiffness of the neck4,5,9,11. While these have been dubbed “the classic triad,” studies have suggested that in actuality, less than half of all meningitis patients simultaneously display these three symptoms at the time they are admitted to a clinic6.
Due to increased intracranial pressure resulting from the vigorous inflammatory immune response within the CSF, altered mental status is another extremely common symptom. Ranging from mild stupor to coma, the symptom is presented in more than 75% of all meningitis cases6,9,10. Subsequently, it is more common that patients upon admission will present at least two of the following four symptoms: fever, severe headache, stiffness of the neck, and altered mental status6.
Other suggestive, however less common, symptoms include the following: a patient’s inability to fully extend his or her legs (Kernig sign); a patient’s involuntary flexion of hip and knee muscles following flexion of the neck muscles (Brudzinsky sign); nausea; vomiting; photophobia; dilated, poorly reactive pupils; seizure; sixth nerve palsies; and Cushing reflex (hypertension, an abnormally slow or unsteady heart rhythm, and irregular respiration)4,5,6,10,11. Along with decreased consciousness, these symptoms are indicative of increasing cerebrospinal fluid (CSF) pressure, decreased blood flow to the brain, brain swelling, and neuron damage attributable to metalloproteases and oxygen and nitrogen radicals released by leukocytes that have crossed the blood-brain barrier4,5,11.
Skin rashes may also be present, particularly among those patients infected with N. meningitides. Skin lesions due to meningococcemia can be found on the trunk and lower extremities, in the mucous membranes and conjunctiva, and on the palms and soles3,4,11.
Infants
Among infants, as well as severely mentally altered patients, it is difficult to diagnose meningitis based on the above, generalized symptoms, for these patients are unable to verbalize sensations of neck stiffness or severe headache. Infants in particular will display only nonspecific signs of systemic infection, such as fever, irritability, drowsiness, vomiting, seizure, and bulging fontanel. Those infants most likely to be infected are premature, male, and less than one month old. Infants are also more at risk if their mothers suffered from third trimester complications or infections, such as urinary tract infections and puerperal fever4,11.
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Based on the aforementioned generalized symptoms, it virtually impossible to discern precisely which organism is to blame for the bacterial infection. Therefore, in nearly every case, diagnostic tests must be preformed in order to discover which organism is responsible so that appropriate and effective antibiotic treatment may be administered1,2,3,4,11.
In every case, a lumbar puncture (or spinal tap) is performed if meningitis is suspected. In more than 90% of patients, the CSF opening pressure will be over 180 mmH2O, and approximately 20% will have opening pressures of over 400 mmH2O, which is suggestive of brain swelling and a high risk of cerebral hernia4,11.
Following the lumbar puncture, samples of the CSF are cultured to determine the causative organism. Additionally, skin lesion biopsies and blood cultures should also be performed. However, it may take days to weeks to obtain the results from cultures and biopsies, thus they are not immediately useful in emergency situations1,2,3,4.
Alternatively, a set of tests may be performed to assist in more rapidly obtaining the correct diagnosis until the results of a bacterial culture are obtained. Polymorphonuclear (PMN) leukocytosis ( >100 leukocytes/μL of CSF), pleocytosis, decreased glucose concentration (<2.2 mmol/L of CSF), and increased protein concentration (>45 mg/dL of CSF) are each highly suggestive of bacterial meningitis. Gram stains, of CSF samples can easily identify strains of S. pneumoniae and H. influenzae, although N. meningities is relatively difficult to identify from such tests. Similarly, the limulus amebocyte lysate assay is useful for rapidly identifying the endotoxins of gram-negative bacteria that may be present in the CSF. The specificity of this test is relatively high at 100%, which renders it a useful alternative for making a rapid and accurate gram-negative diagnosis. Other highly sensitive and rapid tests include counterimmuno electrophoresis (CIE), RIA, and ELISA; however these tests are controversial due to their relatively high expense, and many do not believe them to be cost-effective because gram-stains alone appear to be sufficient in diagnosing most cases. The latex agglutination (LA) test has high specificity and is useful for rapid identification of S. pneumoniae, H. influenzae, N. meningitides, and several other causative bacteria; however, the sensitivity of this test ranges from 70 to 100%, and therefore this test may not be highly reliable in all cases. More recently, PCR tests are being developed to detect bacterial DNA, but the specificity and sensitivity of these tests are not very high at present, and so these test are not presently recommended4,11.
Prognostic Factors
Left untreated, meningitis is usually fatal. The mortality rate of pneumococcal meningitis is consistently higher than among meningitis patients infected with N. meningitides and H. influenzae. Population-specific mortality rates are highest among the elderly and infants, and at least half of all infants suffer serious neurological sequelae following infection. In general, a minority patients suffer long-term sequelae following recovery; however, approximately 25 percent of adult cases report long term sequelae including decreased intellectual function, memory impairment, seizures, hearing loss, dizziness, and gait disturbances4,11.
Other factors associated with increased mortality rate include the following: bacteremia; coma; seizures; alcoholism; diabetes mellitus; multiple myeloma; head trauma; low level of consciousness (a Glasgow coma scale of less than 10); signs of increased intracranial pressure; age (infancy or over 50 years); the need for mechanical ventilation; delay in the initiation of treatment (defined as ER admission to commencement of antibiotic therapy time of over 6 hours); decreased CSF glucose; and increased CSF protein concentration4,6,7,8,10,11.
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Antibiotic therapy should begin as soon as meningitis is suspected, and early treatment should not significantly impact the findings of a lumbar puncture if the procedure is performed within a few hours of the commencement of treatment 4,8,11.
The duration of antibiotic treatment lasts 10 to 14 days for most patients; however, persistent parameningeal infections will require therapy of longer duration. Additionally, should a patient suffer bacteriologic or symptomatic relapse—specifically fever, drowsiness, or hemiparesis—after the discontinuation of treatment, antibiotic therapy should begin again immediately4,11.
Because infections with S. pneumoniae, N. meningitides, and H. influenzae are the most common causes of bacterial meningitis globally, and because of the increasing prevalence of penicillin- and cephalosporin-resistant S. pneumoniae strains, initial empirical therapy should include a third-generation cephalosporin (such as ceftriaxone or cefotaxime) and vanocomycin. This drug combination has been found to be highly effective against most the most common strains of meningitis causing bacteria. However, once the bacteriologic agent and the susceptibility of the strain are known, the therapeutic regimen should be tailored accordingly1-4,11.
Antibiotic therapy
β-Lactam antibiotics
β-Lactam antibiotics, which include cephalosporins and penicillins, covalently bind to and inhibit the activity of penicillin binding proteins (PBP), which are enzymes needed for bacterial cell wall synthesis. The action of PBPs is primarily bactericidal, ultimately leading to cell lysis. Until recently, penicillin was reactive with nearly all strains of S. pneumoniae, N. meningitides, and H. influenzae, but, particularly in the case of S. pneumoniae, penicillin resistance, as well as first and second generation cephalosporin resistance, is increasingly prevalent1-4,11.
Penicillin
Penicillin and ampicillin have traditionally been the antibiotics of choice for treating H. influenzae infection; however, more recently clinicians have encountered β-lactamase producing strains, which are subsequently resistant to penicillins and most first and second generation cephalosporins. As such, alternative antibiotic regimens may be employed, including third generation cephalosporins, trimethoprim-sulfamethoxazole, tetracycline, chloramphenicol, and aminoglucosides1-4,11.
Third-generation cephalosporins
Third-generation cephalosporins, a more recently developed form of β-Lactam antibiotics, are presently effective against most strains of S. pneumoniae, N. meningitides, and H. influenzae, and these antibiotic agents readily cross the blood-brain barrier. If a patient has a history of life-threatening β-Lactam intolerance, imipenem may be substituted1-4,11
Vancomycin
Vancomycin has demonstrated effectiveness against all presently known gram-positive strains, including S. pneumoniae and N. meningitides, but this agent is less reliable for it is not capable of crossing the blood-brain barrier in every case4.
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