Treatment of Bacterial Meningitis

Bacterial meningitis (including meningococcal meningitis, Haemophilus influenzaemeningitis,

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)

Recommended: Penicillin G or ampicillin

Penicillin MIC 0.06 g/mL

Penicillin MIC 0.12 g/mL

Streptococcus
pneumoniae

Cefotaxime or ceftriaxone MIC 0.12

g/mL

Alternatives: Cefotaxime, ceftriaxone, chloramphenicol

Recommended: Cefotaxime or ceftriaxone

Alternatives: Cefepime, meropenem

10-14

Recommended: Vancomycin plus cefotaxime or ceftriaxone

Haemophilus influenzae

Cefotaxime or ceftriaxone MIC 1.0

g/mL

Alternatives: Vancomycin plus moxifloxacin

Beta-lactamasenegative

Recommended: Ampicillin

Alternatives: Cefotaxime, ceftriaxone, cefepime, chloramphenicol,

aztreonam, a fluoroquinolone

Recommended: Cefotaxime or ceftriaxone

Beta-lactamasepositive

Alternatives: Cefepime, chloramphenicol, aztreonam, a fluoroquinolone

Recommended: Meropenem

Beta-lactamasenegative, ampicillinresistant

Alternatives: Cefepime, chloramphenicol, aztreonam, a fluoroquinolone

Recommended: Penicillin G or ampicillin

Penicillin MIC < 0.1 g/mL

Neisseria meningitidis

Alternatives: Cefotaxime, ceftriaxone, chloramphenicol

Recommended: Cefotaxime or ceftriaxone

Penicillin MIC 0.1 g/mL

Alternatives: Cefepime, chloramphenicol, a fluoroquinolone, meropenem

Recommended: Ampicillin or penicillin G

Listeria monocytogenes

...

Alternative: TMP-SMX

14-21

Recommended: Ampicillin or penicillin G

Streptococcus agalactiae

...

Alternatives: Cefotaxime, ceftriaxone, vancomycin

14-21

Recommended: Cefotaxime or ceftriaxone

Enterobacteriaceae

...

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

ampicillin

21

Pseudomonas
aeruginosa

...

Recommended: Ceftazidime or cefepime

21

Alternatives: Aztreonam, meropenem, ciprofloxacin

Recommended: Vancomycin

Alternative: Linezolid
Staphylococcus
epidermidis
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 pneumoniaestrains, 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 g/mL Susceptible

4 g/mL Intermediate
>8 g/mL Resistant
For meningitis, the breakpoints are as follows:

< 0.06 g/mL Susceptible

0.12 g/mL Resistant
With the new meningitis criteria (0.12 g/mL), the prevalence of resistance was 34.8% in 2008, whereas
with the old criteria (2 g/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 patients 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 patients 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 orH 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, 48 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