Empirical Antibiotic Therapy

In a patient with clinical signs and symptoms suggestive of acute bacterial meningitis, antibiotic therapy should begin immediately after drawing blood cultures for Gramís stain and bacterial culture.7  The choice of antibiotic therapy is influenced by the patientís age, predisposing factors, underlying diseases, and the most probable meningeal pathogen (Table 1).

In newborns, the most common causative organisms of bacterial meningitis are Streptococcus agalactiae (group B streptococcus), Escherichia coli, and Listeria monocytogenes.  Empiric therapy of bacterial meningitis is neonates, includes a combination of a third-generation cephalosporin and ampicillin.  Neisseria meningitidis and Streptococcus pneumoniae are the most common meningeal pathogens in infants and children with community-acquired bacterial meningitis in the United States.8  Worldwide, Hemophilus influenzae is a major cause of bacterial meningitis in infants and children, however, the incidence has declined in the United States and other industrialized countries due to the routine use of the Hemophilus influenzae type b (Hib) conjugate vaccine.9, 10  N. meningitidis and S. pneumoniae are also the most common causative organisms of community-acquired bacterial meningitis in immunocompetent adults, and these organisms are increasingly resistant to penicillin and the cephalosporins.  Empiric therapy of bacterial meningitis in children and adults should be based on the possibility that penicillin and cephalosporin-resistant pneumococci are the causative organisms of the meningitis, and include a third or fourth generation cephalosporin, either ceftriaxone (pediatric dose: 100 mg/kg/day in a 12 hour dosing interval; adult dose: 2 gm every 12 hours) or cefepime (pediatric dose: 150 mg/kg/day in an 8 hour dosing interval; adult dose: 2 gm every 12 hours) plus vancomycin (pediatric dose: 40-60 mg/kg/day in a 6 or 12 hour dosing interval; adult dose: 500-750 mg every 6 hours). Individuals who are 50 years of age or older, and those who are immunocompromised due to organ transplantation, cancer, immunosuppressive therapy, chronic disease (diabetes), pregnancy, alcoholism, or corticosteroid therapy are at risk for meningitis caused by Listeria monocytogenes.  Ampicillin (2-2.5 grams every 4 hours) is added to the empiric regimen for patients at risk for L. monocytogenes infection.  Gram-negative bacilli and staphylococci are the most common causative organisms of bacterial meningitis in the patient who has undergone a neurosurgical procedure, with the exception of insertion of a shunt. Coagulase-negative staphylococci and Staphylococcus aureus are the most common pathogens causing shunt infections. (See Table 1).  Empiric therapy of meningitis in the postneurosurgical patient should include a combination of vancomycin and either ceftazidime or meropenem.11

Specific Antibiotic Therapy

After the causative organism is identified, therapy should be modified based on antimicrobial sensitivity testing.  Duration of antibiotic therapy depends on the organism and the clinical response to treatment.  Uncomplicated N. meningitidis meningitis can be treated with intravenous antibiotics for 4 to 7 days.  However, meningitis due to S. pneumoniae, H. influenzae, and group B streptococci requires 10 to 14 days of intravenous antibiotics and L. monocytogenes meningitis requires 3 to 4 weeks of intravenous antibiotics.11

Patients with suspected N. meningitidis meningitis should be in respiratory isolation for 24 hours after initiation of intravenous antibiotics.  Any person that has had close contact with the patient from the onset of the disease should receive chemoprophylaxis (Table 2).11-14  Rifampin 10 mg/kg (up to a maximum of 600 mg) orally every 12 hours for two days has been the therapy of choice in the past.  However, the use of rifampin during pregnancy is contraindicated and there is evidence for resistance to rifampin in outbreaks of N. meningitidis meningitis.  Ceftriaxone as a single dose of 125 mg in children and 250 mg in adults is an appropriate alternative, but it must be given parenterally.  Ciprofloxacin 500 mg orally as a single dose is another alternative in adults, but is not approved for routine pediatric use.  Patients with meningitis due to pathogens other than N. meningitidis do not require isolation or prophylaxis for close contacts.

Adjunctive Therapy

Multiple studies have demonstrated reduced mortality and neurological sequelae in bacterial meningitis with the use of corticosteroids.  A recent Cochrane review showed the benefit of using dexamethasone in children and adults with acute bacterial meningitis regardless of the causative organism.15  Although some of the studies do not show statistically significant improvement of outcomes, the overall trend is in favor of using dexamethasone for acute bacterial community-acquired meningitis of any etiology.15  There are insufficient studies in patients with CSF shunts, patients who have had neurosurgical procedures, and patients with hospital-acquired meningitis to determine if corticosteroids are beneficial.16, 17

With regard to timing of corticosteroid use, the available studies show a clear benefit for initiating dexamethasone therapy just before or with the first dose of intravenous antibiotics.16  Although not directly studied, the benefit of dexamethasone therapy appears to decline with time from initial antimicrobial dosing.16  The dose of dexamethasone has differed among studies, but a dose of 0.4 to 0.6 mg/kg/day in children and 40 mg per day in adults divided every 6 hours has been demonstrated to be efficacious.15, 16  Most studies continued dexamethasone for 4 days of therapy.16  One study compared 2 days of dexamethasone to 4 days in children and found equal efficacy.  However, the physicians in this study were not blinded so the results should be interpreted with caution.  Current recommendations are to start dexamethasone in all patients with suspected community-acquired meningitis before or with the first dose of intravenous antibiotics.  Patients that have already received multiple doses of intravenous antibiotics and patients with hypersensitivity to steroids, CSF shunt, recent neurosurgical procedure, or hospital-acquired meningitis should not receive steroids routinely.16  The recommended dose of dexamethasone is 0.1 to 0.15 mg/kg every 6 hours in children and 10 mg every 6 hours in adults and this should be continued for 4 days in cases of confirmed bacterial meningitis regardless of the causative microorganism.

Table 1.  Empirical therapy for bacterial meningitis

Population/etiology

Microorganism(s)

Treatment

Newborns

Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes

Cefotaxime plus ampicillin

Infants and children

Neisseria meningitidis, Streptococcus pneumoniae, Hemophilus influenzae*

Ceftriaxone or cefotaxime plus vancomycin plus dexamethasone

Healthy, immunocompetent adults (younger than age 50): community acquired

S. pneumoniae, N. meningitides

Ceftriaxone, cefotaxime or cefepime plus vancomycin plus dexamethasone

Neurosurgical patient, or hospital-acquired

Gram-negative bacilli, including Pseudomonas aeruginosa, staphylococci

Ceftazidime or meropenem plus vancomycin

Shunt infection

Coagulase negative staphylococci, Staphylococcus aureus

Vancomycin

Adult older than 50 years of age, immunocompromised (see text)

L. monocytogenes, gram-negative bacilli, including P. aeruginosa, Streptococcus pneumoniae

Cetazidime or meropenem plus ampicillin plus vancomycin plus dexamethasone

*Incidence has declined since the introduction of H. influenzae type b vaccine.


 

Table 2. Dosing of antimicrobial agents for prophylaxis of bacterial meningitis

Age

Antimicrobial agent

Dosing

Infants < 1 month

Rifampin

5 mg/kg every 12 hours PO for 2 days

Infants ≥ 1 month

Rifampin

10 mg/kg every 12 hours PO for 2 days

Children

Ceftriaxone or

125 mg once IM or IV

 

Rifampin

10 mg/kg every 12 hours PO for 2 days

Adults

Ceftriaxone or

250 mg once IM or IV

 

Ciprofloxacin or

500 mg once PO

 

Rifampin

600 mg every 12 hours PO for 2 days