eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease

Meningitis, Bacterial: Treatment & Medication

Author: Martha L Miller, MD, Associate Professor of Pediatrics, Division of Infectious Diseases, University of New Mexico School of Medicine
Coauthor(s): Aditya H Gaur, MD, Assistant Member, Department of Infectious Diseases, St Jude Children's Research Hospital; Ashir Kumar, MBBS, MD, FAAP, Professor, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University; Consulting Staff, Department of Pediatrics, EW Sparrow Hospital
Contributor Information and Disclosures

Updated: Jan 4, 2008

Treatment

Medical Care

• Neonatal
  • Initiate treatment as soon as meningitis is suspected. Ideally, blood and CSF cultures should be obtained before antibiotics are administered. If a newborn is on a ventilator and clinical judgment dictates that a spinal tap may be hazardous, it can be deferred until the infant is stable. A spinal tap performed a few days following initial treatment still reveals cellular and chemical abnormalities but culture results may be negative.
  • Establish intravenous access, and meticulously monitor fluid administration. Neonates with meningitis are prone to develop hyponatremia due to SIADH. These electrolyte changes also contribute to the development of seizures, especially during the first 72 hours of disease.
  • Increased intracranial pressure secondary to cerebral edema is rarely a management problem in infants. Monitor blood gas levels closely to ensure adequate oxygenation and metabolic stability.
  • MRI with gadoteridol, ultrasonography, or CT scanning with contrast is needed to delineate intracranial pathology. A recent Pediatric Academic Societies meeting in May 2005 resulted in the recommendation that MRIs with contrast should be performed for neonates with uncomplicated meningitis 7-10 days after treatment initiation to ensure that no complicating pathology is present. All newborns recovering from meningitis should have auditory evoked potential studies to screen for hearing impairment.
• Infants and children: Management of acute bacterial meningitis involves both appropriate antimicrobial therapy and supportive measures. All patients should have an audiologic evaluation upon completion of therapy.
• Fluid and electrolyte management
  • Closely monitor patients by checking vital signs and neurologic status and by ensuring an accurate record of intake and output.
  • By prescribing the correct type and volume of fluid, the risk of development of brain edema can be minimized. The child should receive fluids sufficient to maintain systolic blood pressure at around 80 mm Hg, urinary output of 500 mL/m²/d, and adequate tissue perfusion. While care to avoid SIADH is important, underhydrating the patient and risk of decreased cerebral perfusion are equally concerning as well.
  • Dopamine and other inotropic agents may be necessary to maintain blood pressure and adequate circulation.

Medication

Antimicrobial therapy for neonates

Antibiotics should be administered as soon as venous access is established. Traditionally, initial antimicrobial treatment consists of ampicillin and an aminoglycoside combination (ampicillin and cefotaxime also appropriate). If S pneumoniae is suspected, vancomycin should be added. Initial empiric therapy for late-onset disease in preterm infants should include an antistaphylococcal agent and ceftazidime, amikacin, or meropenem. See Tables 1-2.

Ampicillin provides good coverage for gram-positive cocci, including group B streptococci, enterococci, L monocytogenes, some strains of E coli, and H influenzae type b. Ampicillin also achieves adequate levels in CSF.

Aminoglycosides (eg, gentamicin, tobramycin, amikacin) have good activity against most gram-negative bacilli, including P aeruginosa and S marcescens. However, aminoglycosides achieve only marginal levels in both CSF and ventricular fluid, even when the meninges are inflamed.

Several third-generation cephalosporins achieve good CSF levels and have emerged as effective agents against gram-negative infections. There has been considerable experience with cefotaxime and ceftriaxone. Ceftriaxone competes with bilirubin for binding of albumin, and therapeutic levels of ceftriaxone decrease the reserve albumin concentration in newborn serum by 39%; thus, ceftriaxone may increase the risk of bilirubin encephalopathy, especially in high-risk newborns. Ceftriaxone also causes sludging of bile. None of the cephalosporins have any activity against L monocytogenes and enterococci and, therefore, should not be used as a single agent for initial treatment. A combination of ampicillin and a third-generation cephalosporin is required.

If the offending pathogen is proven to be an ampicillin-susceptible bacterium with a low minimum inhibitory concentration (MIC) for ampicillin, then ampicillin may be continued alone. Cefotaxime and ceftriaxone also provide good activity against most penicillin-resistant S pneumoniae. Both vancomycin and cefotaxime should be administered in patients with S pneumoniae meningitis before antibiotic susceptibility results are available.

Among the aminoglycosides, gentamicin and tobramycin have been used extensively in combination with ampicillin. Despite concerns about the adequacy of their CSF levels, these agents have proven effective when combined with a beta-lactam antibiotic for the treatment of meningitis caused by organisms such as group B streptococci and susceptible enterococci. Routine intrathecal administration of aminoglycosides offers no additional benefit in this capacity.

Infections involving S aureus, anaerobes, or P aeruginosa may require other antimicrobials, such as oxacillin, methicillin, vancomycin, or a combination of ceftazidime with aminoglycoside. CSF penetration and safety of antimicrobial agents should determine usage.

Etiologic agent and clinical course dictate duration of treatment; however, a 10- to 21-day treatment is usually adequate for group B streptococcal infection. It may take longer to sterilize the CSF with gram-negative bacillary meningitis, and 3-4 weeks of treatment is usually necessary.

Indications for repeat lumbar puncture include lack of clinical improvement or meningitis caused by resistant S pneumoniae strains or by gram-negative enteric bacilli. In neonates with gram-negative bacillary meningitis,examination of CSF during treatment is necessary to verify that cultures are sterile. Reexamination of CSF for chemistries and culture should be performed 48-72 hours after treatment initiation; further specimens are obtained based upon demonstrating lack of sterilization or lack of apparent clinical response. 

Table 3). Initial antibiotic selection should provide coverage for all 3 common pathogens: S pneumoniae, N meningitidis, and H influenzae.

As per the 2004 Infectious Diseases Society of America (IDSA) practice guidelines for bacterial meningitis, the combination of vancomycin and either ceftriaxone or cefotaxime is recommended for those with suspected bacterial meningitis, with targeted therapy based upon susceptibilities of isolated pathogens. This combination provides adequate coverage for most penicillin-resistant pneumococci and beta-lactamase resistant H influenzae type b. Of note, ceftazidime has poor activity against pneumococci and should not be substituted for cefotaxime or ceftriaxone.

Because vancomycin poorly penetrates the CNS, a higher dose of 60 mg/kg/d is recommended when vancomycin is used to treat CNS infections. Cefotaxime or ceftriaxone is adequate if pneumococci are susceptible to cefotaxime. However, if S pneumoniae isolates have a higher MIC for cefotaxime and fall in the intermediate resistance group, there have been concerns regarding prompt sterilization of the CSF, and a high dose of cefotaxime (300 mg/kg/d) with vancomycin (60 mg/kg/d) may be preferred. In the rare event that a pneumococcal isolate has high resistance to cefotaxime or ceftriaxone, vancomycin alone may not be adequate for prompt sterilization of the CSF, and rifampin should be added to the regimen to provide 4- to 8-fold CSF cidal activity against the pathogen.

Carbapenem treatment is another valid option for cephalosporin-resistant carbapenem-susceptible isolates. Meropenem is preferred over imipenem because of the risk of seizures with the latter antibiotic. The role of other new classes of antibiotics, such as the oxazolidinones (linezolid), remains an area of investigation. Fluoroquinolones may be an option for patients who either cannot use other antibacterials or have failed previous therapy, but they should be used with caution as resistance may develop during treatment.

Administer all antibiotics intravenously to achieve adequate serum and CSF levels. An intraosseous route is acceptable if venous access is not an option. In patients with a history of significant hypersensitivity to beta-lactam antimicrobial agents (penicillins and cephalosporins) the choice of alternative agent varies with the etiology of meningitis. Vancomycin and rifampin should be considered for S pneumoniae. Chloramphenicol can also be used if minimum bactericidal concentration is <4 µg/mL. Chloramphenicol is recommended for patients with meningococcal meningitis who have significant hypersensitivity to beta-lactam antimicrobial agents.

Examination of the CSF at the end of treatment has not proven helpful in predicting relapses or recrudescence of meningitis. H influenzae type b isolates can persist in the nasopharyngeal secretions, even after a successful treatment of meningitis. For this reason, the patient must be given rifampin 20 mg/kg once daily for 4 days if high-risk children are at home or at a childcare center (unless the medication was ceftriaxone). N meningitidis and S pneumoniae usually are eradicated from the nasopharynx after successful treatment of meningitis.

Phlebitis at the intravenous site and antibiotic fever are the most common of several causes of secondary fever in patients with meningitis. Thoroughly evaluate any patient with fever. 

Table 3. Dose Guidelines of Intravenous Antimicrobials in Infants and Children With Bacterial Meningitis

Open table in new window

*Minimal experience in pediatrics and not licensed for treatment of meningitis.

†Caution in use for treatment of meningitis because of possible seizures.

Duration of antimicrobial therapy

The IDSA 2004 guidelines for management of bacterial meningitis provide the following information on length of therapy with antibiotics with the caveat that "the guidelines are not standardized and that duration of therapy may need to be individualized on the basis of the patient's clinical response:"

• N meningitidis - 7 days
• H influenzae - 7 days
• S pneumoniae - 10-14 days
• S agalactiae - 14-21 days
• Aerobic gram-negative bacilli - 21 days or 2 weeks beyond first sterile culture (whichever is longer)
• L monocytogenes ->21 days

Dexamethasone administration

Experimental studies have revealed a correlation between outcome and the severity of the inflammatory process in the subarachnoid space.¹ Animal models of bacterial meningitis have shown decreased inflammation, reduction in cerebral edema and intracranial pressure, and lessening brain damage with use of dexamethasone.

Better understanding of the mechanisms of inflammation in meningitis led to controlled double-blind clinical trials. In these trials, the beneficial effects of adjunctive dexamethasone were demonstrated in infants and children with H influenzae type b meningitis. Follow-up examination demonstrated a significant decrease in the incidence of neurologic and audiologic sequelae, with evidence of clinical benefit being greatest for overall hearing impairment. As a result, the IDSA guidelines recommend the use of adjunctive dexamethasone in cases of H influenzae type b meningitis to be initiated 10-20 minutes prior to or at least concomitant with the first antimicrobial dose at 0.15 mg/kg q6h for 2-4 days.

A prospective double-blind placebo-controlled multicenter trial in adults with bacterial meningitis showed benefits (lower percentage of unfavorable outcomes including death) in the subgroup of patients with pneumococcal meningitis but not others. Although, data from pediatric patients so far does not demonstrate a clear clinical benefit with dexamethasone use in patients with S pneumoniae meningitis, a recent Cochrane review recommended consideration of the use of corticosteroids in children (non-neonates) with bacterial meningitis in high-income countries. However, given the lack of clear benefit favoring dexamethasone use in this setting and the concerns about decreased antibiotic penetration in the CSF with its use, decision to use this agent is considered on a case-by-case basis after weighing the potential risks and benefits. Likewise, data are insufficient to recommend adjunctive steroids in neonates with bacterial meningitis.

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