Meningitis%20-%20acute,%20bacterial%20(pediatric) Treatment

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

Empiric Therapy for Patients (With Increased Intracranial Pressure [ICP] Prior to Lumbar Puncture [LP] or with a Nondiagnostic Cerebrospinal Fluid [CSF] Gram Stain)

• If LP is delayed or no etiologic agent can be identified, empiric therapy should be instituted and should be directed to the most likely pathogens on the basis of the patient’s age and 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:

Considerations for Patients Diagnostic Gram Stain Results

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

Antibiotic Therapy
Aminoglycosides

• Eg Amikacin, Gentamicin 
• Traditional 1st-line treatment in combination with Ampicillin for neonates
• Good activity against Gram-negative bacilli
• Minimal penetration in the CSF and ventricular fluids, even with meningeal inflammation
• Combination with beta-lactam antibiotics have been proven effective for common pathogens: Group B Streptococci and susceptible Enterococci

Aztreonam

• May be used for meningitis due to aerobic Gram-negative bacilli
• Treatment option for patients with contraindications to beta-lactam antimicrobial agents or Meropenem

Cephalosporins

• Broad-spectrum cephalosporins used in meningitis include 3rd generation cephalosporins (eg Cefotaxime, Ceftriaxone) and 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 and Penicillin-resistant strains
  • Combination with Penicillin, Amoxicillin or Ampicillin recommended for neonates <1 month old, or with Vancomycin or Rifampicin for children aged >1 month to 18 years with reduced S pneumoniae antimicrobial sensitivity
• Cefepime
  • Has in vitro activity similar to that of Cefotaxime and Ceftriaxone against H influenzae, N meningitidis, and S pneumoniae and greater in vitro activity against Enterobacter sp and P aeruginosa
• Ceftazidime
  • Usually reserved for P aeruginosa (combine with aminoglycoside)

Chloramphenicol

• H influenzae, S pneumoniae and N meningitidis are highly susceptible
• May be given to meninggococcal meningitis patients with significant hypersensitivity to β-lactam antimicrobial agents

Co-trimoxazole (Sulfamethoxazole [SMZ] and Trimethoprim [TM])

• Alternative for patient with L monocytogenes meningitis and Penicillin allergy

Penicillins

• Ampicillin
  
  • Ampicillin combined with an aminoglycoside is the standard therapy for beta-lactamase-negative H Influenzae
  • May also be used with Gentamicin in susceptible strains of Enterococci

• Penicillin G
  • The drug of choice for susceptible isolates of S pneumoniae and N meningitidis
    
  • May also be used in combination with an aminoglycoside for L monocytogenes and S agalactiae

• Nafcillin and Oxacillin
  
  • Standard therapy for Methicillin-susceptible S aureus meningitis

Meropenem

• Meropenem has good in vitro activity against L monocytogenes
• Has less seizure proclivity than Imipenem
• With similar clinical and microbiologic outcomes as 3rd-generation cephalosporins
• Useful in patients with Gram negative isolates resistant to standard therapy
• May be used in combination with 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 with a 3rd-generation cephalosporin (with or without Vancomycin) as resistance rapidly develops if given as single agent
• Given with Vancomycin for patients with 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 and anaerobic bacterial infection for both immunocompetent and immunodeficient patients
• Easy to administer, well-tolerated and has low toxicity potential

Vancomycin

• Used in combination with a 3rd generation Cephalosporin, and maintained at serum concentrations of approximately 15-20 mcg/mL
• Combination with 3rd generation cephalosporin is an alternative option for immunocompromised patients
• Concomitant administration of Dexamethasone results in decreased brain inflammation and poor entry of Vancomycin into the CSF
• Consider intrathecal administration in patients not responding to IV administration

Patient Monitoring During Antibiotic Therapy

• Repeat CSF exam is suggested for patients with no clinical improvement after 24-36 hours of therapy initiation or 2-3 days after initiation of treatment for patients with Gram negative bacillary meningitis

Duration of Antibiotic Therapy

• Duration of therapy has been based more on tradition than on scientific evidence
  
  • 7-10 days for H influenzae
  • 5-7 days for N meningitidis
  • 10-14 days for S pneumoniae
  • 14-21 days for Group B streptococci (eg S agalactiae)
  • At least 14 days for S aureus 
  • 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)
  • 14-21 days for L monocytogenes
• Treatment must always be individualized on the basis of clinical and 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

ADJUNCTIVE THERAPY

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

Anti-inflammatory Therapy

Dexamethasone

• Action: Significantly reduces release of proinflammatory cytokines from macrophages and 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 with bacterial meningitis especially if H influenzae is suspected
• Dosage: 0.15 mg/kg/dose IV 6 hourly x 2-4 days

Agents to Decrease Intracranial Pressure (ICP)

Mannitol

• Action: Produces an osmolar gradient between the brain and 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 and diuresis without 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 (0.1 mg/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