Meningitis Treatment & Management

Updated: Oct 12, 2017
  • Author: Rodrigo Hasbun, MD, MPH; Chief Editor: Michael Stuart Bronze, MD  more...
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Treatment

Approach Considerations

If the patient is in shock or hypotensive, crystalloid should be infused until euvolemia is achieved. If the patient’s mental status is altered, seizure precautions should be considered, seizures should be treated according to the usual protocol, and airway protection should be considered. If the patient is alert and in stable condition with normal vital signs, oxygen should be administered, intravenous (IV) access established, and rapid transport to the emergency department (ED) initiated. Institution of an ED triage protocol may help identify patients at risk.

In acute meningitis, regardless of presentation, a lumbar puncture (LP) and cerebrospinal fluid (CSF) examination are indicated to identify the causative organism and, in bacterial meningitis, the antibiotic sensitivities. Computed tomography (CT) of the head should be performed a before LP, if indicated. If no mass effect is present on head CT, LP is performed to obtain microbiology studies.

The performance of radiographic imaging should not delay the initiation of empiric antimicrobial therapy; such therapy should be initiated before head CT if indicated. It is vital to begin treatment as early as possible in the disease course; delay may contribute significantly to morbidity and mortality. In acutely ill patients, antibiotic therapy should be initiated promptly; in many of these cases, one should strongly consider giving adjunctive dexamethasone before the first antibiotic dose, or at least concomitantly with the dose. [17]

The patient’s condition and ED organization may warrant 8-12 hours of watchful waiting, followed by reexamination of the CSF (this should be done sooner if the patient’s condition deteriorates). If initial granulocytosis changes to mononuclear predominance, CSF glucose remains normal, and the patient continues to look well, the infection is most likely nonbacterial.

Treatment of complications

Systemic complications of acute bacterial meningitis must be treated, including the following:

Signs of hydrocephalus and increasing intracranial pressure (ICP) should be watched for. Fever and pain should be managed, straining and coughing controlled, seizures prevented, and systemic hypotension avoided. In otherwise stable patients, sufficient care includes elevating the head and monitoring neurologic status. When more aggressive maneuvers are indicated, some authorities favor early use of diuresis (ie, furosemide 20 mg IV or mannitol 1 g/kg IV), provided that circulatory volume is protected.

Hyperventilation in intubated patients, with an arterial carbon dioxide tension (PaCO2) of 25-30 mm Hg as the goal, may briefly lower ICP; hyperventilation to a PaCO2 lower than 25 mm Hg may decrease cerebral blood flow disproportionately and lead to CNS ischemia. Placement of an ICP monitor should be considered in comatose patients or those with signs of increased ICP. With elevated ICP, CSF should be removed until pressure decreases by 50%; ICP should then be maintained at less than 300 mm H2 O.

Because seizure activity increases ICP, seizures must be aggressively controlled if present. Control may be accomplished by giving lorazepam 0.1 mg/kg IV and IV load with phenytoin 15 mg/kg or phenobarbital 5-10 mg/kg.

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Treatment of Subacute Meningitis

In patients with subacute meningitis, CSF examination constitutes the critical step in documenting the presence or absence of a CNS infection and the type of infecting organism.

If the patient’s condition is serious and antibiotics have been given (potentially masking symptoms and hindering growth of organisms on culture), a bacterial infection is assumed to be present. Adequate antibiotic coverage is provided, and the patient is admitted. The LP is repeated if necessary to rule out partially treated bacterial meningitis.

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Treatment of Bacterial Meningitis

Bacterial meningitis (including meningococcal meningitis, Haemophilus influenzae meningitis, and staphylococcal meningitis) is a neurologic emergency that is associated with significant morbidity and mortality. Initiation of empiric antibacterial therapy is therefore essential for better outcome. [24, 25] (See tables 7 and 8 below.)

Table 7. Recommended Empiric Antibiotics for Suspected Bacterial Meningitis, According to Age or Predisposing Factors [25] (Open Table in a new window)

Age or Predisposing Feature

Antibiotics

Age 0-4 wk

Ampicillin plus either cefotaxime or an aminoglycoside

Age 1 mo-50 y

Vancomycin plus cefotaxime or ceftriaxone*

Age >50 y

Vancomycin plus ampicillin plus ceftriaxone or cefotaxime plus vancomycin*

Impaired cellular immunity

Vancomycin plus ampicillin plus either cefepime or meropenem

Recurrent meningitis

Vancomycin plus cefotaxime or ceftriaxone

Basilar skull fracture

Vancomycin plus cefotaxime or ceftriaxone

Head trauma, neurosurgery, or CSF shunt

Vancomycin plus ceftazidime, cefepime, or meropenem

CSF = cerebrospinal fluid.

*Add ampicillin if Listeria monocytogenes is a suspected pathogen.

Table 8. Specific Antibiotics and Duration of Therapy for Acute Bacterial Meningitis (Open Table in a new window)

Bacteria

Susceptibility

Antibiotic(s)

Duration (days)

Streptococcus pneumoniae

Penicillin MIC ≤0.06 μg/mL

Recommended: Penicillin G or ampicillin

Alternatives: Cefotaxime, ceftriaxone, chloramphenicol

10-14

Penicillin MIC ≥0.12 μg/mL

Cefotaxime or ceftriaxone MIC ≥0.12 μg/mL

Recommended: Cefotaxime or ceftriaxone

Alternatives: Cefepime, meropenem

Cefotaxime or ceftriaxone MIC ≥1.0 μg/mL

Recommended: Vancomycin plus cefotaxime or ceftriaxone

Alternatives: Vancomycin plus moxifloxacin

Haemophilus influenzae

Beta-lactamase−negative

Recommended: Ampicillin

Alternatives: Cefotaxime, ceftriaxone, cefepime, chloramphenicol, aztreonam, a fluoroquinolone

7

Beta-lactamase−positive

Recommended: Cefotaxime or ceftriaxone

Alternatives: Cefepime, chloramphenicol, aztreonam, a fluoroquinolone

Beta-lactamase−negative, ampicillin-resistant

Recommended: Meropenem

Alternatives: Cefepime, chloramphenicol, aztreonam, a fluoroquinolone

Neisseria meningitidis

Penicillin MIC < 0.1 μg/mL

Recommended: Penicillin G or ampicillin

Alternatives: Cefotaxime, ceftriaxone, chloramphenicol

7

Penicillin MIC ≥0.1 μg/mL

Recommended: Cefotaxime or ceftriaxone

Alternatives: Cefepime, chloramphenicol, a fluoroquinolone, meropenem

Listeria monocytogenes

...

Recommended: Ampicillin or penicillin G

Alternative: TMP-SMX

14-21

Streptococcus agalactiae

...

Recommended: Ampicillin or penicillin G

Alternatives: Cefotaxime, ceftriaxone, vancomycin

14-21

Enterobacteriaceae

...

Recommended: Cefotaxime or ceftriaxone

Alternatives: Aztreonam, a fluoroquinolone, TMP-SMX, meropenem, ampicillin

21

Pseudomonas aeruginosa

...

Recommended: Ceftazidime or cefepime

Alternatives: Aztreonam, meropenem, ciprofloxacin

21

Staphylococcus epidermidis

 

Recommended: Vancomycin

Alternative: Linezolid

Consider addition of rifampin

 

MIC= minimal inhibitory concentration; TMP-SMX = trimethoprim-sulfamethoxazole.

It is vital to institute empiric antimicrobial therapy (ie, antibacterial treatment or, in selected cases, antiviral or antifungal therapy) as soon as possible. The choice of agents is usually based on the known predisposing factors, initial CSF Gram stain results, or both. Once the pathogen has been identified and antimicrobial susceptibilities determined, the antibiotics may be modified for optimal targeted treatment.

Bacterial resistance, especially penicillin resistance among S pneumoniae strains, has been increasing worldwide. In March 2008, the US Food and Drug Administration (FDA) revised the susceptibility breakpoints for penicillin versus S pneumoniae. For nonmeningeal infections, the breakpoints are as follows:

  • < 2 µg/mL – Susceptible

  • 4 µg/mL – Intermediate

  • >8 µg/mL – Resistant

For meningitis, the breakpoints are as follows:

  • < 0.06 µg/mL – Susceptible

  • ≥0.12 µg/mL – Resistant

With the new meningitis criteria (≥0.12 μg/mL), the prevalence of resistance was 34.8% in 2008, whereas with the old criteria (≥2 μg/mL), it was 12.3% for CSF. [26] The geographic distribution of this resistance is variable, and it is important to know the regional patterns when deciding on local empiric antibiotic therapy (see Medication). A large observational study of 548 pneumococcal meningitis cases from Brazil showed that penicillin resistance was associated with higher mortality even after adjustment for age and severity of illness. [27]

Appropriate antibiotic treatment for the most common types of bacterial meningitis reduces the risk of death. Mortality is higher with pneumococcal meningitis. In a nationwide observational cohort study from The Netherlands, adjunctive use of dexamethasone decreased pneumococcal meningitis mortality from 30% to 20%. [28]

The chosen antibiotic should attain adequate levels in the CSF, and its ability to do so usually depends on its lipid solubility, molecular size, and protein-binding capacity, as well as on the patient’s degree of meningeal inflammation. The penicillins, certain cephalosporins (ie, third- and fourth-generation agents), the carbapenems, fluoroquinolones, and rifampin provide high CSF levels.

Monitoring for possible drug toxicity during treatment (eg, with blood counts and renal and liver function monitoring) is warranted. The antimicrobial dose must be adjusted on the basis of the patient’s renal and hepatic function. At times, obtaining serum drug concentrations may be necessary to ensure adequate levels and to avoid toxicity in drugs with a narrow therapeutic index (eg, vancomycin and aminoglycosides). The patient must also be monitored for complications from the disease (eg, hydrocephalus, seizures, or hearing defects).

Antibiotic therapy: neonates to age 1 month

In the first month of life, the most common microorganisms are group B or D streptococci, Enterobacteriaceae (eg, E coli), and L monocytogenes. Primary treatment consists of a combination of ampicillin and cefotaxime. The recommended dosage for cefotaxime is 50 mg/kg IV every 6 hours, up to 12 g/day. Ampicillin dosages are as follows:

  • Age 0-7 days – 50 mg/kg IV every 8 hours

  • Age 8-30 days – 50-100 mg/kg IV every 6 hours

Alternative treatment consists of ampicillin plus gentamicin. Gentamicin dosages are as follows:

  • Age 0-7 days – 2.5 mg/kg IV or intramuscularly (IM) every 12 hours

  • Age 8-30 days – 2.5 mg/kg IV or IM every 8 hours

Most authorities recommend adding acyclovir 10 mg/kg IV every 8 hours for herpes simplex encephalitis.

Antibiotic therapy: age 1-3 months

In infants 1-3 months of age, the first-line agent is cefotaxime (50 mg/kg IV every 6 hours, up to 12 g/day) or ceftriaxone (75 mg/kg initially, then 50 mg/kg every 12 hours, up to 4 g/day) plus ampicillin (50-100 mg/kg IV every 6 hours). An alternative agent is chloramphenicol (25 mg/kg orally or IV every 12 hours) plus gentamicin (2.5 mg/kg IV or IM every 8 hours).

If the local prevalence of drug-resistant S pneumoniae (DRSP) is higher than 2%, vancomycin (15 mg/kg IV every 8 hours) should be added. Treatment with dexamethasone (0.4 mg/kg IV every 12 hours for 2 days or 0.15 mg/kg IV every 6 hours for 4 days) should be strongly considered, starting 15-20 minutes before the first dose of antibiotics.

Antibiotic therapy: age 3 months to 7 years

In older infants or young children (age 3 months to 7 years), the most common microorganisms are S pneumoniae, N meningitidis, and H influenzae. Primary treatment is with either cefotaxime (50 mg/kg IV every 6 hours, up to 12 g/day) or ceftriaxone (75 mg/kg initially, then 50 mg/kg every 12 hours, up to 4 g/day).

If the prevalence of DRSP is greater than 2%, vancomycin (15 mg/kg IV every 8 hours) should be added. In countries with a low prevalence of DRSP, penicillin G (250,000 units/kg/day IM or IV in 3-4 divided doses) may be considered. Because of the increasing prevalence of DRSP, penicillin G is no longer recommended in the United States.

An alternative (which may also be chosen if the patient is severely allergic to penicillin) is chloramphenicol (25 mg/kg orally or IV every 12 hours) plus vancomycin (15 mg/kg IV every 8 hours). Treatment with dexamethasone (0.4 mg/kg IV every 12 hours for 2 days or 0.15 mg/kg IV every 6 hours for 4 days) should be strongly considered, starting 15-20 minutes before the first dose of antibiotics.

Antibiotic therapy: age 7-50 years

In an older child or an otherwise healthy adult (age 7-50 years), the most common microorganisms in bacterial meningitis are S pneumoniae, N meningitidis, and L monocytogenes. In areas where the prevalence of DRSP is greater than 2%, primary treatment consists of with either cefotaxime or ceftriaxone plus vancomycin. Pediatric dosing is as follows:

  • Cefotaxime – 50 mg/kg IV every 6 hours, up to 12 g/day

  • Ceftriaxone – 75 mg/kg initially, then 50 mg/kg every 12 hours, up to 4 g/day

  • Vancomycin – 15 mg/kg IV every 8 hours

Adult dosing is as follows:

  • Cefotaxime – 2 g IV every 4 hours

  • Ceftriaxone – 2 g IV every 12 hours

  • Vancomycin – 750-1000 mg IV every 12 hours or 10-15 mg/kg IV every 12 hours

Some experts add rifampin (pediatric dose, 20 mg/kg/day IV; adult dose, 600 mg/day orally). If Listeria is suspected, ampicillin (50 mg/kg IV every 6 hours) is added.

An alternative (which may also be chosen if the patient is severely penicillin-allergic) is chloramphenicol (12.5 mg/kg IV every 6 hours; not bactericidal) or clindamycin (pediatric dose, 40 mg/kg/day IV in 3-4 doses; adult dose, 900 mg IV every 8 hours; active in vitro but no clinical data) or meropenem (pediatric dose, 20-40 mg/kg IV every 8 hours; adult dose, 1 g IV every 8 hours; active in vitro but few clinical data). Imipenem is a proconvulsant and must be avoided.

In areas with a low prevalence of DRSP, cefotaxime or ceftriaxone plus ampicillin is recommended. Pediatric dosing is as follows:

  • Cefotaxime – 50 mg/kg IV every 6 hours, up to 12 g/day

  • Ceftriaxone – 75 mg/kg initially, then 50 mg/kg every 12 hours, up to 4 g/day

  • Ampicillin – 50 mg/kg IV every 6 hours

Adult dosing is as follows:

  • Cefotaxime – 2 g IV every 4 hours

  • Ceftriaxone – 2 g IV every 12 hours

  • Ampicillin – 50 mg/kg IV every 6 hours

An alternative (which may also be chosen if the patient is severely penicillin-allergic) is chloramphenicol (12.5 mg/kg IV every 6 hours) plus trimethoprim-sulfamethoxazole (TMP-SMX; TMP 5 mg/kg IV every 6 hours) or meropenem (pediatric dose, 20-40 mg/kg IV every 8 hours; adult dose, 1 g IV every 8 hours).

Data on the need for dexamethasone treatment in adults are limited, though there is support for its use in developed countries when S pneumoniae is the suspected organism. The first dose of dexamethasone (0.4 mg/kg every 12 hours IV for 2 days or 0.15 mg/kg every 6 hours for 4 days) should be administered 15-20 minutes before the first dose of antibiotics.

Antibiotic therapy: age ≥50 years

In adults older than 50 years or adults with disabling disease or alcoholism, the most common microorganisms are S pneumoniae, coliforms, H influenzae, Listeria species, P aeruginosa, and N meningitidis.

Primary treatment, if the prevalence of DRSP is greater than 2%, is with either cefotaxime (2 g IV every 4 hours) or ceftriaxone (2 g IV every 12 hours) plus vancomycin (750-1000 mg IV every 12 hours or 10-15 mg/kg IV every 12 hours). If the CSF Gram stain shows gram-negative bacilli, ceftazidime (2 g IV every 8 hours) is given. In areas of low DRSP prevalence, treatment consists of cefotaxime (2 g IV every 4 hours) or ceftriaxone (2 g IV every 12 hours) plus ampicillin (50 mg/kg IV every 6 hours). Other options are meropenem, TMP-SMX, and doxycycline.

The Infectious Diseases Society of America guidelines recommend adjunctive dexamethasone in patients with suspected or proven community-acquired bacterial meningitis, but only in high-income countries. [17] The first dose of dexamethasone (0.4 mg/kg IV every 12 hours for 2 days or 0.15 mg/kg every 6 hours for 4 days) is given 15-20 minutes before the first dose of antibiotics.

Dexamethasone should be continued if the culture grows either S pneumoniae or H influenzae. However, some experts advise that adjunctive treatment should be continued irrespective of the causative bacterium because of the low incidence of adverse events.

Antibiotic therapy: HIV-infected patients

In HIV-infected patients, if an ED workup does not identify a pathogen, serum and CSF samples should be drawn for cryptococcal antigen testing. Empiric treatment should proceed as in adults older than 50 years (pending results of all blood and CSF tests) to cover the bacterial pathogens, particularly S pneumoniae and L monocytogenes, for which this patient population is most at risk. (See Meningitis in HIV.)

Steroid therapy

The use of corticosteroids (typically, dexamethasone, 0.15 mg/kg every 6 hours for 2-4 days) as adjunctive treatment for bacterial meningitis improves outcome by attenuating the detrimental effects of host defenses (eg, inflammatory response to the bacterial products and the products of neutrophil activation). Controversy surrounds this practice, however, in that dexamethasone may interrupt the cytokine-mediated neurotoxic effects of bacteriolysis, which are at maximum in the first days of antibiotic use. [29]

Theoretically, the anti-inflammatory effects of steroids decrease blood-brain barrier permeability and impede penetration of antibiotics into CSF. Decreased CSF levels of vancomycin have been confirmed in steroid-treated animals but not in comparably treated humans. Many authorities believe that all other antibiotics achieve minimal inhibitory concentrations (MICs) in CSF regardless of steroid use, and even vancomycin may not be affected to a clinically significant extent.

Nevertheless, the use of steroids has been shown to improve the overall outcome of patients with certain types of bacterial meningitis, including H influenzae, tuberculous, and pneumococcal meningitis.

In a meta-analysis by Brouwer et al, corticosteroids significantly reduced hearing loss and neurologic sequelae but did not reduce overall mortality. However, there was a trend toward lower mortality in adults receiving corticosteroids, and subgroup analyses showed that corticosteroids reduced severe hearing loss in H influenzae meningitis and reduced mortality in S pneumoniae meningitis. However, the investigators found no beneficial effect for patients in low-income countries. [30]

On the other hand, a meta-analysis of individual patient data by van de Beek et al was unable to identify which patients were most likely to benefit from dexamethasone treatment; indeed, no significant reduction in death or neurologic disability was found in any subgroups, including those determined by specific causative organisms, predexamethasone antibiotic treatment, HIV status, or age. The researchers concluded that the benefits of adjunctive dexamethasone in bacterial meningitis remain unproven. [31]

In developing countries, the use of oral glycerol (rather than dexamethasone) has been studied as adjunctive therapy in the treatment of bacterial meningitis in children. In limited studies, it appears to reduce the incidence of neurologic sequelae while causing few side effects. [32]

Intrathecal antibiotics

Intrathecal administration of antibiotics can be considered in patients with nosocomial meningitis (eg, meningitis developing after neurosurgery or placement of an external ventricular catheter) that does not respond to IV antibiotics. Although the FDA has not approved any antibiotics for intraventricular use, vancomycin and gentamicin are often used in this setting. Other agents used intrathecally include amikacin, polymyxin B, and colistin. [33]

Intrathecal antibiotic dosages have been determined empirically and are adjusted on the basis of the CSF concentrations of the agent. Typical daily doses are as follows [33] :

  • Vancomycin: 5-20 mg

  • Gentamicin: 1-2 mg in infants and children, 4–8 mg in adults

  • Amikacin: 30 mg (range, 5-50 mg)

  • Polymyxin B: 2 mg in infants and children, 5 mg in adults

  • Colistin (usually formulated as colistimethate sodium): 10 mg once daily or 5 mg every 12 hours

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Treatment of Viral Meningitis

Most cases of viral meningitis are benign and self-limited. Often, patients need only supportive care and require no specific therapy. In certain instances, specific antiviral therapy may be indicated, if available. Instituting antiretroviral therapy may be necessary for patients with HIV meningitis that occurs during an acute seroconversion syndrome. In patients with immune deficiency (eg, agammaglobulinemia), immunoglobulin replacement has been used to treat chronic enteroviral infections.

Herpes simplex meningitis

The antiviral management of HSV meningitis is controversial. Acyclovir (10 mg/kg IV every 8 hours) has been administered for HSV-1 and HSV-2 meningitis. Some experts do not advocate antiviral therapy unless associated encephalitis is present, because the condition is usually benign and self-limited. This is exemplified by Mollaret syndrome, a recurrent but benign syndrome of lymphocytic pleocytosis that is now attributed to HSV.

Cytomegalovirus meningitis

Ganciclovir and foscarnet are used for cytomegalovirus (CMV) meningitis in immunocompromised hosts. Ganciclovir is given in an induction dosage of 5 mg/kg IV every 12 hours for 21 days and a maintenance dosage of 5 mg/kg every 24 hours. Oral valganciclovir (900 mg/day) can be used for maintenance if immunosuppression continues (as, for example, in AIDS patients or transplant recipients). Foscarnet is given in an induction dosage of 60 mg/kg IV every 8 hours for 21 days and a maintenance dosage of 90-120 mg/kg IV every 24 hours.

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Treatment of Fungal Meningitis

Causes of fungal meningitis include the following:

  • Cryptococcus

  • C immitis

  • H capsulatum

  • Candida species

  • S schenckii (rarely)

Immune compromise is a predisposing factor in many of these cases and is often a consideration in the selection of treatment regimens.

Cryptococcal meningitis

Cryptococcal meningitis is a major opportunistic infection in AIDS patients. For initial therapy in these cases, administer amphotericin B (0.7-1 mg/kg/day IV) for at least 2 weeks, with or without flucytosine (100 mg/kg orally), in 4 divided doses. Liposomal preparations of amphotericin B may be used in patients who either have or are predisposed to develop renal dysfunction (amphotericin B liposome 3-4 mg/kg/day or amphotericin B lipid complex 5 mg/kg/day).

Fluconazole is given for consolidation therapy (400 mg/day for 8 weeks); itraconazole is an alternative if fluconazole is not tolerated. For maintenance therapy, long-term administration of fluconazole (200 mg/day) is most effective in preventing relapse (superior to itraconazole and amphotericin B at 1 mg/kg weekly). The risk of relapse is high in patients with AIDS.

In many cases, cryptococcal meningitis is complicated by increased ICP. Measuring the opening pressure during the LP is strongly advised. Efforts should be made to reduce such pressure through repetition of LP or insertion of a lumbar drain or a shunt. Medical maneuvers, such as administration of mannitol, have also been used.

The role of newer triazoles, such as voriconazole and posaconazole, has not been investigated. Echinocandins do not have activity against cryptococcus.

In resource-limited areas, amphotericin B and fluconazole are the optimal agents for treatment of HIV-related acute cryptococcal meningitis. Hence, treatment would consist of amphotericin and flucytosine, and policy makers and national departments of health in such countries should consider adding drugs that are typically unavailable in such settings (eg, flucytosine) for HIV treatment programs. [34] (See Meningitis in HIV.)

Induction and consolidation therapy for cryptococcal meningitis in patients who do not have AIDS and are not transplant recipients involves giving amphotericin B (0.7-1 mg/kg/day) plus flucytosine (100 mg/kg/day) for at least 4 weeks. Treatment may be extended to 6 weeks in patients with neurologic complications. After this initial period, fluconazole (400 mg/day) is given for at least 8 weeks. LP is recommended after 2 weeks to document sterilization of the CSF. If the infection persists, longer induction therapy is recommended (6 weeks).

Solid-organ transplant recipients with cryptococcal meningitis should be treated with liposomal amphotericin B (3-4 mg/kg/day IV) or amphotericin B lipid complex (5 mg/kg/day IV) plus flucytosine (100 mg/kg/day in 4 divided doses) for at least 2 weeks of induction therapy. This is followed by consolidation treatment with fluconazole (400-800 mg/day orally for 8 weeks) and then maintenance treatment with fluconazole (200 mg/day orally for 6-12 months).

Coccidioides immitis

The preferred treatment for meningitis caused by C immitis is oral fluconazole (400 mg/day). Some physicians initiate therapy with a larger dose of fluconazole (as high as 1000 mg/day) or with a combination of fluconazole and intrathecal amphotericin B. Itraconazole (400-600 mg/day) has been reported to be comparably effective. Lifelong treatment is usually required. (See Coccidioidomycosis.)

Histoplasma capsulatum

The recommended treatment for H capsulatum meningitis is liposomal amphotericin B (5 mg/kg/day IV for a total of 175 mg/kg given over 4-6 weeks), followed by oral itraconazole (200-300 mg 2 or 3 times daily for at least 1 year or until the resolution of CSF abnormalities and Histoplasma antigen levels). Blood levels of itraconazole should be measured to ensure good absorption of the oral drug.

This infection is associated with a poor outcome. Approximately 20-40% of patients with meningitis succumb to the infection despite amphotericin B therapy, and 50% of responders relapse after treatment is discontinued.

Candida species

The preferred initial therapy for candidal meningitis is amphotericin B (0.7 mg/kg/day). Flucytosine (25 mg/kg every 6 hours) is usually added and adjusted to maintain serum levels of 40-60 µg/mL. Azoles may be used for follow-up therapy or suppressive treatment.

The risk of relapse is high, and the duration of treatment is arbitrary. Some recommend continuing treatment for a minimum of 4 weeks after the complete resolution of symptoms. The removal of prosthetic materials (eg, ventriculoperitoneal shunts) is a significant component of therapy in candidal meningitis associated with neurosurgical procedures.

Sporothrix schenckii

The lipid formulation of amphotericin B is the recommended initial treatment; after the patient responds, itraconazole (200 mg twice daily) is recommended as step-down therapy and should be given to complete a total of at least 12 months of therapy. [35] Using itraconazole to achieve lifelong suppression may be attempted after initial therapy with amphotericin B. Fluconazole is less active against Sporothrix than itraconazole is.

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Treatment of Tuberculous Meningitis

Treatment of tuberculous meningitis with a combination of first-line drugs is advocated. The selection depends on the resistance pattern in the community and the results of susceptibility testing (once available). Isoniazid and pyrazinamide attain good CSF levels (approximating blood levels). Rifampin penetrates the blood-brain barrier less efficiently but still attains adequate CSF levels. Ethambutol and streptomycin may also be part of combination therapy.

The dosages of drugs for tuberculous meningitis are similar to those used for pulmonary tuberculosis, as follows:

  • Isoniazid 300 mg/day

  • Rifampin 600 mg/day

  • Pyrazinamide 15-30 mg/kg/day

  • Ethambutol 15-25 mg/kg/day

  • Streptomycin 7.5 mg/kg every 12 hours

The recommended duration of treatment is 9-12 months. [36]

Corticosteroid therapy is indicated for patients with stage 2 or stage 3 disease (ie, those with evidence of neurologic deficits or deterioration in mental function). The rationale lies in the reduction of inflammatory effects associated with mycobacterial killing by the antimicrobial agents. The agent usually chosen is dexamethasone; the recommended dose is 60-80 mg/day, which may be tapered gradually during a span of 6 weeks.

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Treatment of Syphilitic Meningitis

The treatment of choice for neurosyphilis is aqueous crystalline penicillin G (2-4 million U/day IV every 4 hours for 10-14 days), often followed with IM penicillin G benzathine (2.4 million U). An alternative is procaine penicillin G (2.4 million U/day IM) plus probenecid (500 mg orally every 6 hours for 14 days), followed by IM benzathine penicillin G (2.4 million U). These regimens are also used for neurosyphilis in patients with HIV infection. Because penicillin G is the treatment of choice, penicillin-allergic patients should undergo penicillin desensitization.

After treatment, CSF examination is repeated regularly (eg, every 6 months) to document the success of therapy. Failure of the cell count to normalize or the serologic titers to fall may warrant retreatment.

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Treatment of Parasitic Meningitis

Primary amebic meningoencephalitis (PAM), caused by N fowleri, is usually fatal. The few survivors reported in the scientific literature benefited from early diagnosis and treatment with high-dose IV and intrathecal amphotericin B or miconazole and rifampin.

Treatment of helminthic eosinophilic meningitis (such as that caused by A cantonensis or G spinigerum) is largely supportive. It includes adequate analgesia, therapeutic CSF aspiration, and the use of anti-inflammatory agents, such as corticosteroids. Anthelmintic therapy may be contraindicated, because clinical deterioration and death may occur as a consequence of severe inflammatory reactions to the dying worms.

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Treatment of Lyme Meningitis

Ideally, neurologic complications of Lyme disease (other than Bell palsy) are treated with parenteral antibiotics. The drug of choice is ceftriaxone (2 g/day for 14-28 days). The alternative therapy is penicillin G (20 million U/day for 14-28 days). Doxycycline (100 mg orally or IV every 12 hours for 14-28 days) or chloramphenicol (1 g every 6 hours for 14-28 days) has also been used. Treatment for only 10 days has been associated with a high rate of residual symptoms.

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Prevention

Vaccination and chemoprophylaxis are 2 means of preventing meningitis.

H influenzae vaccine

Vaccination against H influenzae type B (Hib) is strongly recommended in susceptible individuals (though there is no standard recommendation for H influenzae vaccination in adults). Vaccination against S pneumoniae is also strongly encouraged for susceptible individuals, including people older than 65 years and individuals with chronic cardiopulmonary illnesses. It is not known whether the adult use of conjugate pneumococcal vaccine decreases the incidence of S pneumoniae meningitis.

N meningitidis serogroups A, C, Y, and W-135 vaccine

Vaccinations against encapsulated bacterial organisms (eg, S pneumoniae and N meningitidis) are encouraged for people with functional or structural asplenia. Vaccinations should always be administered expeditiously to individuals who undergo splenectomy.

Vaccination with quadrivalent meningococcal polysaccharide vaccine should be offered to all high-risk populations, including those who have underlying immune deficiencies, those who travel to hyperendemic areas and epidemic areas, and those who do laboratory work that involves routine exposure to N meningitidis. College students who live in dormitories or residence halls are at modest risk; they should be informed about the risk and offered vaccination.

One vaccine protects against 4 strains of N meningitidis. As of February 2008, the CDC Advisory Committee on Immunization Practices (ACIP) no longer recommends routine immunization of children with this vaccine, but the ACIP continues to recommend routine immunization of teenagers and all children or adults at increased risk. [37]

In 2010, the ACIP issued updated recommendations for the use of meningococcal conjugate vaccines. Two recommendations focus on the routine vaccination of adolescents and on a primary series of vaccinations of persons aged 2-55 years with certain risk factors for meningococcal infection. [38]

Regarding the routine use of vaccines in adolescents, the 2010 CDC-ACIP guidelines specifically recommend 1 dose of meningococcal conjugate vaccine, preferably starting at 11 or 12 years. A booster dose should be given at age 16 years. If the primary dose was at age 13-15 years, the booster can be given at age 16-18 years. No booster is needed if the primary dose was given at age 16 years or later. [38]

Regarding specific recommendations for individuals with certain risk factors for meningococcal infection, the ACIP stated that HIV-infected individuals aged 11-18 years should be given a primary series of 2 doses, 2 months apart. This should be followed by a booster dose administered at age 16 years (if the primary dose was at age 11 or 12) or at age 16-18 years (if the primary dose was at age 13-15 years). No booster is needed if the primary dose was given at age 16 years or later. [38]

Persons aged 2-55 years who have persistent complement component deficiency or asplenia (functional or anatomic) should be given a primary series of 2 doses, 2 months apart, followed by a booster dose every 5 years. If a 1-dose primary series was given, the booster dose should be given as soon as possible, then every 5 years thereafter. [38]

In persons aged 2-55 years with a protracted increased risk for exposure to meningitis, the 2010 ACIP guidelines recommend a 1-dose primary series. The booster dose should be given after 3 years for children aged 2-6 years and after 5 years for persons aged 7 years or older, if the person remains at increased risk. [38]

N meningitidis serogroup B vaccine

According to the CDC, in 2012, approximately 500 cases of meningococcal disease were reported; of those, 160 resulted from serogroup B.

In October 2014, the FDA approved the first meningococcal vaccine for serogroup B (Trumenba) under the breakthrough therapy designation and accelerated approval regulatory pathways. Recent outbreaks of serogroup B meningococcal disease on a few college campuses have heightened concerns for this potentially deadly disease.

Approval was based on 3 randomized trials conducted in the United States and Europe in about 2800 adolescents. Among participants who were given 3 doses of the vaccine, 82% developed antibodies against 4 different N meningitidis serogroup B strains representative of those that cause serogroup B meningococcal disease in the United States compared with less than 1% before vaccination. [39]

In January 2015, a second meningococcal serogroup B vaccine was approved (Bexsero). [40]

Pneumococcal vaccine

The ACIP recommends administration of 13-valent pneumococcal polysaccharide-protein conjugate vaccine as part of routine childhood immunization. [41] The ACIP recommends targeted use of the 23-valent pneumococcal polysaccharide vaccine (PPSV23, formerly PPV23) in children aged 2-18 years with underlying medical conditions that increase the risk of pneumococcal disease or complications. Vaccination against measles and mumps effectively eliminates aseptic meningitis syndrome caused by these pathogens. In September 2014, the CDC recommended that all adults aged 65 years or older receive both PCV13 (13-valent pneumococcal conjugate vaccine) and PPSV23 (23-valent pneumococcal polysaccharide vaccine) as part of routine vaccination. [42]

Chemoprophylaxis

After exposure to an index case involving H influenzae, N meningitidis, or S pneumoniae, temporary nasopharyngeal carriage of the organism is typical. An association between carriage and the risk of disease has been described, especially for N meningitidis and H influenzae. This is the basis for the recommendations on chemoprophylaxis. However, such prophylaxis does not treat incubating invasive disease; accordingly close monitoring of individuals at highest risk is crucial.

To eliminate nasopharyngeal carriage of Hib and to decrease invasion of colonized susceptible individuals, rifampin (20 mg/kg/day for 4 days) is given. The index patient may need chemoprophylaxis if the administered treatment does not eliminate carriage.

Prophylaxis is suggested for contacts of persons with meningococcal meningitis (eg, household contacts, daycare center members who eat and sleep in the same dwelling, close contacts in military barracks or boarding schools, and medical personnel performing mouth-to-mouth resuscitation). Rifampin (600 mg PO every 12 hours for 2 days) can rapidly eradicate the carrier stage, and the prophylaxis persists for as long as 10 weeks after treatment.

Alternative agents for adults include ceftriaxone (250 mg IM in a single dose); this agent is also the safest choice in pregnant patients. Ceftriaxone has been shown to eradicate the carrier state for 14 days. Ciprofloxacin (500-750 mg in a single dose) is also effective.

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Consultations

Consultation with an infectious diseases specialist is indicated. Consultation with a neurosurgeon is indicated in patients with any of the following:

  • Severe intracranial hypertension

  • Evidence of paranasal and mastoid infection that warrants surgical drainage

  • Skull fractures

  • Foreign body–associated infections (eg, ventriculoperitoneal shunts)

  • Associated abscess formation

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Long-Term Monitoring

Vigilant surveillance for the development of complications is required in patients with meningitis. Seizure precautions are indicated, especially for patients with impaired mental function. Proper isolation precautions are indicated in cases of invasive meningococcal disease.

Patients must be monitored for potential adverse effects of medications, such as hypersensitivity reactions, cytopenia, or liver dysfunction. Drug-level monitoring may be needed for some antibiotics (eg, vancomycin and the aminoglycosides).

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