Staphylococcal Meningitis Treatment & Management

Bacterial meningitis is a medical emergency. Once purulent meningitis is confirmed by CSF analysis, initial treatment measures include administration of antibiotics with effective CNS penetration and maintenance of adequate blood pressure. Initial antibiotic selection should be based on Gram stain or rapid bacterial antigen tests. If the spinal tap is delayed or the organism cannot be rapidly identified, empiric selection of an antibiotic with effective CNS penetration should be based on age and underlying disease status, since delay in treatment is associated with adverse clinical outcome.

See Meningitis for complete information on the condition and general treatment strategies.

Standard empirical therapy varies according to age. In infants younger than age 4 weeks, such therapy employs ampicillin plus cefotaxime or an aminoglycoside.

Infants aged 4-12 weeks should be treated with ampicillin plus a third-generation cephalosporin.

In children aged 12 weeks to 18 years, a third-generation cephalosporin or ampicillin plus chloramphenicol is an appropriate combination.

Adults aged 18-50 years and individuals with basilar skull fracture should be treated with a third-generation cephalosporin, while individuals older than age 50 should be treated with ampicillin plus a third-generation cephalosporin.

Newer Antibiotics

The following newer antibiotics have helped broaden therapeutic options for staphylococcal meningitis.

• Daptomycin is a new lipopeptide antibiotic with an excellent bactericidal activity against gram-positive microorganisms, including methicillin-susceptible S aureus (MSSA) and methicillin-resistant staphylocci (MRSA). ^{[11, 12, 13]} Daptomycin has potent bactericidal activity against gram-positive bacteria that is concentration-dependent. When given at a dose of 6 mg/kg, its penetration into inflamed meninges was 5% (compared to 2% in noninflamed meninges) and was therefore significantly more effective than vancomycin in sterilizing CSF. ^[14]

• Linezolid, the first oxazolidinone, is an addition to the armamentarium for the treatment of staphylococcal meningitis. It exhibits a broad spectrum of of activity against gram-positive bacteria, including MRSA and coagulase-negative staphylococci (CoNS), glycopeptide-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. ^{[15, 16]}

As clinical experience increases with these newer antibiotics, they certainly have the potential to replace the older antibiotics.

Immunocompromised patients should receive the combination of vancomycin, ampicillin, and ceftazidime. Patients who have experienced head trauma, have a CSF shunt or who have undergone a neurosurgical procedure should be treated with vancomycin and ceftazidime.

Vancomycin should be added to empirical regimens when highly penicillin- or cephalosporin-resistant strains of Streptococcus pneumoniae are suspected. Ampicillin should be added to empirical treatment at any age if Listeria monocytogenes is a consideration.

If allergy to penicillins and cephalosporins precludes the use of these agents, chloramphenicol is a reasonable alternative.

Dose calculations are based not only on a patient’s age, as discussed above, but also on his/her renal and hepatic functions.

Once S aureus meningitis is confirmed and sensitivity determined, therapy may be altered or simplified by using vancomycin, oxacillin, or nafcillin alone. For methicillin-sensitive S aureus, nafcillin or oxacillin is standard therapy. If the infective organism is methicillin-resistant S aureus (MRSA) or S epidermidis, vancomycin is the drug of choice.

Most experts recommend addition of rifampin if the patient shows no clinical improvement 72 hours after initial treatment of S aureus meningitis. ^{[17, 18, 19]}

Most cases of bacterial meningitis are treated for a period of 10-14 days, except when a parameningeal focus of infection persists (as in most cases of staphylococcal meningitis). In such cases, treatment should be continued for a longer period. Effects of therapy should be tagged to clinical improvement.

Use of steroids in S aureus meningitis is controversial. While adjunctive dexamethasone is beneficial for H influenzae type B and pneumococcal meningitis, and although some authors favor its use in all types of bacterial meningitis, at present the routine use of dexamethasone is not recommended.

Shunt removal is often necessary to optimize therapy. If infection is suspected, CSF should be removed from the shunt and sent for studies. Treatment should be started if initial results point to meningeal inflammation and should be modified according to culture results. If infections are difficult to eradicate or if the shunt cannot be removed, direct instillation of the antimicrobial agent is warranted. Daily intraventricular vancomycin doses range from 4-10 mg. Gentamicin doses are 1-2 mg/day for children and 4-8 mg/day for adults. Combination with an IV agent is always required. Intraventricular teicoplanin also has been employed successfully. Since the entire shunt has a propensity to be contaminated once one section is infected, partial shunt revision is not recommended.

In cases of S aureus meningitis due to septicemia, once the source of infection is identified, surgical debridement or excision may be indicated.

Obstructive or normal pressure hydrocephalus may complicate the clinical picture, leading to further obtundation. When either of these is present, neurosurgical consultation for shunting should be considered.

Bed rest and general supportive measures are needed by the patient until the acute illness phase has passed; thereafter, physical activity may be increased gradually as tolerated.

Monitoring all aspects of recovery, including those related to cognitive sequelae, normal pressure hydrocephalus, and seizures, is important.

Seizures are more frequent after H influenzae meningitis than after S aureus meningitis. In fulminant meningitis, incidence of strokes is increased because of venulitis, which leads to microinfarcts.

The most effective way to protect patients against Staphylococcal meningitis is vaccination. However, due to S aureus' high adaptability, remarkable epidemiologic transition, its poorly understood pathomechanism and immunity against pathogens—critical requirements for induction of cellular immunity and effective vaccine development—it is challenging to develop a potent anti-S aureus vaccine that is both safe and efficacious. Protective immunity against S aureus is incompletely understood. ^[20] Animal models, especially murine models, despite multiple trials have not predicted vaccine success in humans. Further, S aureus is much more complex with multiple, extensive array of  virulence factors, including hemolysins, toxins, and superantigens that manifest as a very broad range of diseases in infected patients. These effectively neutralize the host's immune responses far more effectively than most bacterial pathogens making vaccine development very difficult. ^[21] Despite a few vaccine clinical trials that showed lack of efficacy, intensive research continues unabated in the attempt to find either an effective universal Staphylococcus aureus vaccine or a narrowly focused S aureus vaccine.