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Empiric treatment of Meningitis

Meningitis

Meningitis is an inflammation (swelling) of the protective membranes covering the brain and spinal cord. A bacterial or viral infection of the fluid surrounding the brain and spinal cord usually causes the swelling. However, injuries, cancer, certain drugs, and other types of infections also can cause meningitis. It is important to know the specific cause of meningitis because the treatment differs depending on the cause.

Empiric Treatment

The typical bacterial causes of acute meningitis vary with the age of the patient. In neonates, Streptococcus agalactiae and Escherichia coli predominate. Now that the Haemophilus influenzae type B vaccine is widely used, Streptococcus pneumonia and Neisseria meningitidis have become the most common bacteria isolated from small children.

N. meningitidis is the major cause of acute bacterial meningitis in older children and young adults, whereas S. pneumoniae is seen with greatest frequency in older adults. In a minority of the very young, of older individuals, and of those who are immunocompromised, Listeria monocytogenes will be identified as the cause of acute bacterial meningitis. Aerobic gram-negative bacilli are also a concern in older individuals.

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An understanding of the pathogenesis of acute bacterial meningitis aids one in choosing appropriate therapy. In this disease, bacteria multiply in the CSF, which often lacks antibodies and complement. Because of these deficiencies in the immune response, antibiotics that merely inhibit bacterial growth (i.e., those that are bacteriostatic) are not sufficient for cure. Rather, antibiotics must actually kill the bacteria (i.e., have bactericidal activity) to sterilize the CSF. In addition, the antibiotics must efficiently cross the blood–brain barrier to reach the CSF in concentrations sufficient for killing. As a result, many antibiotics are administered at higher doses to patients with meningitis relative to patients with other infections.

Finally, a significant portion of the tissue damage associated with bacterial meningitis is thought to result from the inflammation provoked by the large numbers of bacteria in the CSF and meninges; this inflammatory response may be enhanced by the rapid lysis of these bacteria when they are initially exposed to bactericidal antibiotics. For this reason, some experts recommend the concomitant administration of corticosteroids with antimicrobial agents in some situations.

In the absence of a diagnostic Gram stain of CSF, antimicrobial therapy for acute bacterial meningitis must be empiric. Third-generation cephalosporins (cefotaxime, ceftriaxone) are the backbone of most empiric antimicrobial regimens because they are bactericidal, penetrate relatively well into the CSF, and are effective against most strains of S. pneumoniae, N. meningitidis, and H. influenzae.

However, the percentage of S. pneumoniae strains resistant to cephalosporins is increasing in many parts of the world. Although cephalosporins achieve high levels in the lungs and are effective therapy for pneumonia caused by all but the most resistant strains, they fail to reach levels sufficient for killing of moderately resistant strains in the CSF. Thus, it is now recommended that vancomycin be used in conjunction with a cephalosporin as empiric therapy for acute bacterial meningitis.

Ampicillin should be added in infants younger than 3 months of age and in adults older than 50 years to provide coverage of L. monocytogenes and S. agalactiae. (Note that L. monocytogenes is one of the few gram-positive bacteria against which vancomycin is not effective—hence, the need for ampicillin.)

In compromised patients such as those who develop meningitis following neurosurgery or those who have CSF shunts or are receiving high doses of steroids, treatment should be broadened to cover staphylococci or antibiotic-resistant gram-negative bacilli.

In infants younger than 3 months of age, the Gram stain CSF findings are not often diagnostic, and these patients should all receive at least a third-generation cephalosporin plus vancomycin until culture results are available. However, in adults, the results of a Gram stain specimen of CSF should guide the initial choice of antibiotics for acute bacterial meningitis. Because of the requirement for bactericidal activity and efficient penetration into the CSF, only a subset of potentially useful antibiotics is suitable for treating meningitis. Gram-positive cocci in pairs in the CSF of an adult patient suggest S. pneumoniae, which should be treated with a third-generation cephalosporin (cefotaxime, ceftriaxone) plus vancomycin to ensure effective therapy against penicillin-resistant strains. In contrast, gram-positive cocci in a specimen from an infant younger than 3 months of age suggest S. agalactiae

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, for which ampicillin plus gentamicin should be given.

Gram-negative diplococci indicate N. meningitidis, which should be treated with penicillin G or ampicillin. Small pleomorphic gram-negative bacilli are consistent with H. influenzae, which is treated with a third-generation cephalosporin (cefotaxime, ceftriaxone). Larger gram-negative bacilli, especially in a neonate, suggest E. coli, which is treated with a third-generation cephalosporin (cefotaxime, ceftriaxone). Gram-positive bacilli suggest L. monocytogenes and require the use of penicillin G or ampicillin. Some experts would also add gentamicin for synergistic killing. In all cases, therapy should be adjusted accordingly once susceptibility results are available.

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