meningitis%20-%20acute,%20bacterial%20(pediatric)
MENINGITIS - ACUTE, BACTERIAL (PEDIATRIC)
Acute meningitis is the bacterial infection of the subarachnoid space and cerebrospinal fluid that may cause local and systemic inflammatory response.
Common symptoms in newborns are lethargy, fever, seizures, irritability and bulging fontanelle. While in children the common symptoms are fever, nuchal rigidity (incidence increases with age) and altered consciousness.
Meningeal signs are stiff neck, Kernig's or Brudzinski's signs) are not reliably present in infants <6 months of age.
It may also observe the presence of persistent vomiting, changes in behavior or other psychological/neurologic signs.

Principles of Therapy

General Principles of Antibiotic Therapy

  • Optimal antibiotic treatment entails that the drug have a bactericidal effect in the cerebrospinal fluid (CSF)
  • Initial antibiotic therapy must be started promptly, as soon as venous access is established

Pharmacotherapy

Empiric Therapy for Patients [w/ increased intracranial pressure (ICP) prior to lumbar puncture (LP) or w/ a nondiagnostic cerebrospinal fluid (CSF) Gram Stain]

  • If LP is delayed or no etiologic agent can be identified, empiric therapy should be instituted & should be directed to the most likely pathogens on the basis of the patient’s age & underlying health status
  • Below is a list of the likely pathogens of acute bacterial meningitis in different groups of patients, depending on age/predisposing factors:
Predisposing Factor of Patient Likely Pathogens
Age <1 month Streptococcus agalactiae, E coli, L monocytogenes or Klebsiella sp
Age 1-23 months N meningitidis, S pneumoniae, H influenzae, S agalactiae or E coli
Age 2-12 years
S pneumoniae or N meningitidis
Impaired cellular immunity
L monocytogenes or Gram negative bacilli
Penetrating head trauma,neurosurgery, CSF shunt
S aureus, coagulase negative staphylococci (especially S epidermidis), aerobic Gram-negative bacilli including P  aeruginosa; also Propionibacterium acnes in CSF shunt patients

Empiric Antibiotic Therapy for Patients w/ a Non-diagnostic CSF Gram Stain
Predisposing factor of patient Recommended antibiotics
Age <1 month Ampicillin or Benzylpenicillin +
(Cefotaxime or aminoglycoside)
Age 1- 23 months
Vancomycin/Teicoplanin +
(Cefotaxime or Ceftriaxone)* or
Vancomycin/Teicoplanin +
Ampicillin + Chloramphenicol
Age 2 years & older
Vancomycin/Teicoplanin +
(Cefotaxime or Ceftriaxone)*
Impaired cellular immunity  Ampicillin + Ceftazidime +
Vancomycin/Teicoplanin
Penetrating head trauma,neurosurgery, or CSF shunt  Vancomycin/Teicoplanin +
(Ceftazidime, Ceftriaxone or
Meropenem 
Basilar skull fracture
Vancomycin/Teicoplanin +
(Cefotaxime or Ceftriaxone) 
Modify treatment regimen for optimal therapy once culture & susceptibility results are received
*May consider adding Rifampicin if Dexamethasone is also given.
** Ceftriaxone is contraindicated in premature infants, infants w/ jaundice, hypoalbuminemia or acidosis.

Positive Cerebrospinal Fluid Gram Stain
Antibiotic Therapy for Patients w/ a Presumptive Diagnosis by CSF Gram Stain
Presumptive pathogen based on Gram stain  Recommended antibiotics
Escherichia coli
Cefotaxime or Ceftriaxone +
Aminoglycoside 
Haemophilus influenzae
Ceftriaxone or Penicillin or Cefotaxime 
Listeria monocytogenes  Ampicillin or Cefotaxime or
Ceftriaxone + Gentamicin 
Neisseria meningitidis  Cefotaxime or Ceftriaxone 
Streptococcus pneumoniae  Vancomycin + (Cefotaxime or
Ceftriaxone)* 
Modify treatment regimen for optimal therapy once culture & susceptibility results are received   
*Consider adding Rifampicin if Dexamethasone is also given.

Considerations for Patients Diagnostic Gram Stain Results

  • A presumptive diagnosis may be made based on the results of the CSF Gram stain
  • Modify treatment regimen for optimal therapy once culture & susceptibility results are available

Antibiotic Therapy
Aminoglycosides

  • Traditional 1st-line treatment in combination w/ Ampicillin for neonates
  • Good activity against Gram negative bacilli
  • Minimal penetration in the cerebrospinal fluid (CSF) & ventricular fluids, even w/ meningeal inflammation
  • Combination w/ beta-lactam antibiotics have been proven effective for common pathogens: group B Streptococci & susceptible Enterococci

Cephalosporins

  • Broad-spectrum cephalosporins used in meningitis include 3rd generation cephalosporins (eg Cefotaxime, Ceftriaxone) & 4th generation cephalosporins (eg Cefepime)
  • Cefotaxime or Ceftriaxone
    • Drug of choice for empirical therapy of H influenzae type b meningitis
    • Very active against aerobic Gram negative bacilli & Penicillin-resistant strains
  • Cefepime
    • Has in vitro activity similar to that of Cefotaxime & Ceftriaxone against H influenzae, N meningitidis, & S pneumoniae & greater In vitro activity against Enterobacter sp & P aeruginosa
  • Ceftazidime
    • Usually reserved for P aeruginosa (combine w/ aminoglycoside)

Chloramphenicol

  • H influenzae, S pneumoniae & N meningitidis are highly susceptible
  • May be given to meninggococcal meningitis patients w/ significant hypersensitivity to beta-lactam antimicrobial agents

Co-trimoxazole (Sulfamethoxazole (SMZ) & Trimethoprim (TM))

  • Alternative for patient w/ L monocytogenes meningitis & Penicillin allergy

Penicillins

  • Ampicillin
    • Ampicillin combined w/ an aminoglycoside is the standard therapy for beta-lactamase-negative H Influenzae
    • May also be used w/ Gentamicin in susceptible strains of Enterococci
  • Penicillin G
    • The drug of choice for susceptible isolates of S pneumoniae
    • May also be used in combination w/ an aminoglycoside for L monocytogenes & S agalactiae
  • Nafcillin & Oxacillin
    • Standard therapy for Methicillin-susceptible S aureus

Carbapenem

  • Meropenem has a broad range of In vitro activity & less seizure proclivity than Imipenem
  • W/ similar clinical & microbiologic outcomes as 3rd generation cephalosporins
  • Useful in patients w/ Gram negative isolates resistant to standard therapy
  • May be used in combination w/ another agent for Gram negative bacilli that produce extended spectrum beta-lactamases

Quinolones

  • Indicated only for patients who have not responded to or cannot receive standard antimicrobial therapy
  • Indicated for multidrug-resistant Gram negative bacilli

Rifampicin

  • May be used in combination w/ a 3rd generation cephalosporin (w/ or w/o Vancomycin) as resistance rapidly develops if given as single agent
  • Given w/ Vancomycin for patients w/ CSF shunt infections caused by Staphylococci, especially in cases in which the shunt cannot be removed

Teicoplanin

  • Structurally similar to Vancomycin
  • May be used as an alternative to Vancomycin in treatment of aerobic & anaerobic bacterial infection for both immunocompetent & immunodeficient patients
  • Easy to administer, well-tolerated & has low toxicity potential

Vancomycin

  • Used in combination w/ a 3rd generation Cephalosporin, & maintained at serum concentrations of approximately 15-20 mcg/mL
  • Concomitant administration of Dexamethasone results in decreased brain inflammation & poor entry of Vancomycin into the CSF
  • Consider intrathecal administration in patients not responding to IV administration

Duration of Antibiotic Therapy

  • Duration of therapy has been based more on tradition than on scientific evidence
    • 7 days for H influenzae
    • 7 days for N meningitidis
    • 10-14 days for S pneumoniae
    • 14-21 days for Group B streptococci (eg S agalactiae)
    • 21 days for aerobic Gram negative bacilli (in the neonate, duration is 2 weeks beyond 1st sterile CSF culture or for 3 weeks, whichever is longer)
    • ≥21 days for L monocytogenes
  • Treatment must always be individualized on the basis of clinical & microbiologic response
  • Intravenous (IV) administration of antibiotic is recommended for the duration of treatment to ensure adequate CSF concentrations of specific antimicrobial agents are achieved

Pathogen-Specific Therapy

  • If culture results are positive, tailor treatment regimen based on the results
  • If test is available, perform minimum inhibitory concentration (MIC) determination for Streptococcus pneumoniae
  • Alternative regimens may be used in case of allergy to the recommended drug
Organisms Recommended Antibiotics   Alternative Antibiotics
S pneumoniae
Penicillin MIC >2 mcg/mL
Vancomycin + (Cefotaxime or Ceftriaxone)*
 
S pneumoniae
Penicillin MIC 0.1-1 mcg/mL 
Cefotaxime or Ceftriaxone
Cefepime or Meropenem
S pneumoniae
Penicillin MIC <0.1 mcg/mL 
Ampicillin or Penicillin G  Cefotaxime, Ceftriaxone or Chloramphenicol
N meningitidis
Penicillin MIC 0.1-1 mcg/mL 
Cefotaxime or Ceftriaxone  Chloramphenicol, Meropenem 
N meningitidis
Penicillin MIC <0.1 mcg/mL
Ampicillin or Penicillin G
Cefotaxime, Ceftriaxone or Chloramphenicol
E coli or other Enterobacteriaceae‡
Cephalosporin (3rd generation)
Ampicillin, Aztreonam, Meropenem or quinolone 
Streptococcus agalactiae
Ampicillin or Penicillin G
(consider adding aminoglycoside) 
Cefotaxime or Ceftriaxone
L monocytogenes
Ampicillin or Penicillin G
(consider adding aminoglycoside) 
Meropenem 
Pseudomonas aeruginosa‡  Cefepime or Ceftazidime
(consider adding aminoglycoside) 
Aztreonam, Ciprofloxacin or Meropenem
(consider adding aminoglycoside) 
H influenzae beta-lactamase negative
Ampicillin  Cefepime, Cefotaxime, Ceftriaxone, Chloramphenicol or quinolone
H influenzae beta-lactamase positive
Cephalosporin (3rd generation)
Cefepime, Chloramphenicol 
Staphylococcus aureus Methicillin-sensitive
Nafcillin or Oxacillin  Vancomycin or Meropenem 
S aureus Methicillin-resistant  Vancomycin† or Teicoplanin  Linezolid 

Adjunctive Therapy

  • Includes anti-inflammatory therapy, agents to reduce the intracranial pressure (ICP) & anticonvulsants

Anti-inflammatory Therapy

Dexamethasone

  • Action: Significantly reduces release of proinflammatory cytokines from macrophages & astrocytes, which were stimulated by endotoxin from infecting bacteria
  • Should be started by IV route 10-20 minutes before or at the same time as the 1st dose of antibiotic
    • Dexamethasone should not be given to infants or children who have already received antibiotics
  • Recommended in children >3 months old w/ bacterial meningitis especially if H influenzae is suspected
  • Dosage: 0.15 mg/kg/dose IV every 6 hours x 2-4 days

Agents to Decrease Intracranial Pressure (ICP)

Mannitol

  • Action: Produces an osmolar gradient between the brain & plasma causing a shift of fluid from the central nervous system (CNS) to the plasma, resulting in excretion during an osmotic diuresis
  • Dosage: 0.5-1.0 g/kg/dose IV

Furosemide

  • Action: Reduces brain swelling by venodilation & diuresis w/o causing an increase in intracranial blood volume
  • Dosage: 1.0 mg/kg/dose IV

Anticonvulsants

  • Administer if patient has seizures
  • Diazepam or Lorazepam may be given for immediate treatment of seizures at the following dosages:
    • Diazepam (0.1-0.2 mg/kg/dose IV)
    • Lorazepam (0.5-1.0 g/kg/dose IV)
  • Phenytoin may be given to reduce likelihood of recurrence at 15-20 mg/kg loading dose, then maintained at 5 mg/kg/24 hours
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