Pediatric Bacterial Meningitis in the Philippines

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Pediatric Bacterial Meningitis in the Philippines

• Cecilia C. Maramba-Untalan, MD

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Bacterial Meningitis in the Philippines

• One of the top leading causes of mortality in
  children 0-4 yrs old
• Pathogens and susceptibility patterns are
  different from those identified in other
  countries
• Management recommendations must be appropriate
  for the Philippine setting
• Task Force on Meningitis convened in order to
  address this problem

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Signs and Symptoms of Meningitis

• are variable and depend on the age of the
  patient, and the duration of illness before
  treatment
• neonates and young infants may have minimal signs
  and symptoms
• signs of symptoms of neonatal sepsis are
  indistinguishable from neonatal meningitis
• all neonates being evaluated for sepsis should be
  evaluated for meningitis

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Signs and Symptoms of Bacterial Meningitis
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Laboratory Diagnosis of Bacterial Meningitis

• Lumbar puncture is essential
• Cornerstone in the diagnosis
• should be performed in all cases whenever the
  diagnosis of meningitis is known or suspected on
  the basis of clinical signs
• Contraindications to doing a lumbar tap
• 1. presence of significant cardio-pulmonary
  compromise and shock
• 2. signs of increased ICP
• 3. suspected case of space occupying lesion
• 4. infection in the area that the spinal needle
  will traverse to obtain CSF
• 5. hematologic problems

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CSF Findings in Bacterial Meningitis

• CSF pressure - usually elevated
• CSF cells count and chemistry
• leukocytosis- gt1000/cu mm
• PMN - 90
• Glucose- lt40 mg/dl
• CSF blood to glucose ratio lt0.40
• Protein 50-500 mg/dl
• c. stained smears of CSF
• gram stain - () for bacteria
• AFB smear - (-)
• India ink - (-)
• d. CSF culture
• a negative culture does rule out
  meningitis

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Other CSF Tests Useful in Diagnosis Bacterial
Meningitis

• Antigen detection tests - Coagglutination -
• -
  Latex agglutination
• - antigens of H. influenzae B, S.
  pneumoniae, Group B. streptococcus, E. coli and
  Neisseria meningitidis
• Antigen detection tests should never be
  substituted for culture and gram stain
• if only a small amount of CSF is obtained, do
  gram stain and culture

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Other Useful Laboratory Tests

• Culture of other normally sterile fluids aside
  from CSF
• Blood culture- should be obtained in every
  patient suspected of having bacterial meningitis
• Middle ear fluid- in patients with otitis media
• do not do cultures from throat, nasopharynx and
  urine

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Neuroimaging and Bacterial Meningitis

• Cranial Ultrasound
• - when lumbar puncture is contraindicated and
  when the anterior fontanel is open
• - most useful in diagnosing complications of
  meningitis
• - normal ultrasound does not rule out the
  presence of meningitis
• Study by Lee, et al
• 224 cases of bacterial meningitis
• 202 had abnormal cranial ultrasound findings
• highly echogenic sulci- 75
• thick, highly echogenic convexity
  leptomeninges - 47
• hydrocephalus - 44
• effusion or empyema - 33
• malacic changes - 9

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Neuroimaging and Bacterial Meningitis

• Computed tomography and Magnetic resonance
  Imaging
• - in early stages of meningitis may be normal
  or nonspecific
• Study by Cabral, et al - out of 41 children
  with bacterial meningitis, only 14 had abnormal
  CT scan
• For MRI
• -meningeal enhancement demonstrated is
  nonspecific and is also seen in tumors,
  intracranial hemorrhage, trauma and after
  radiation therapy
• indicated only for cases of suspected
  intracranial complications of bacterial
  meningitis and are not routinely required

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Empiric Therapy for Bacterial Meningitis

• Bacterial meningitis is a medical emergency,
  delay in treatment may lead to increased sequelae
  or death
• Drug of choice must be bactericidal for pathogen
  involved
• Must achieve adequate levels in the CSF
• Initial regimen should cover most likely
  pathogens for specific age groups, and reach
  bactericidal levels in the CSF
• Knowledge of local susceptibility patterns is
  essential

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Philippine Data

• Meningitis is the 8th leading cause of death in
  0-4 yrs old
• (Arciaga)
• most common cause is H. influenzae and S.
  pneumoniae
• lt1 yr old - Gram negative bacilli
• Group B streptococcus is an infrequent cause of
  meningitis and Listeria monocytogenes has not
  been isolated in CSF cultures
• For a developing country with limited resources,
  the most cost-effective drug must be used.

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• No significant resistance of H. influenzae to
  cotrimoxazole, ampicillin and chloramphenicol
• The three drugs are still recommended for use for
  H. influenzae

Carlos C, et al. (Philippine) Antimicrobial
Resistance Surveillance Program, January-December,
2000
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• Higher resistance to penicillin than 1999
• Only 13(18) of 72 resistance isolates were sent
  for confirmation of which only 4(6) were truly
  penicillin resistant by MIC
• True extent of penicillin resistant S. pneumoniae
  still unknown

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Pseudomonas aeruginosa- resistance was generally
higher than 1999. Many Enterobacteriacae show
high resistance rates. Aminoglycosides have high
resistance rates. Physicians should base their
treatment recommendations for gram negative
bacilli on their regions prevailing resistance
patterns.
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Empiric Therapy for Bacterial Meningitis
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Empiric Therapy for Bacterial Meningitis
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Specific Antimicrobial Therapy for Bacterial
Meningitis
Tunkel AR, Scheld WM, Amer Family Physician 1997,
56(5)1355-62
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Duration of Therapy of Bacterial Meningitis
Pathogen
Suggested duration
of therapy (days) H. influenzae
7-10 S. pneumoniae
10-14 N. meningitidis
7 Grp. B. streptococci
14-21 G(-) bacilli
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Quagliarello, et al, NEJM 1997, 336(10)708-716
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Rational for Use of Dexamethasone

• The bacteria that have invaded the CSF
  proliferate, undergo degradation, and release
  toxins and techoic acids. The inflammatory
  response is activated and principal mediators are
  IL-1ß, TNF, PAF, PMNs and macrophages.
• promote leukocyte-cerebral capillary endothelial
  cell interaction, platelet-mediated thrombosis,
  and cytotoxic, interstitial and vasogenic edema
• dexamethasone inhibits the synthesis of
  interleukin 1 and TNF

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• Meta-analysis of 11 trials
• (mostly in developed countries)
• dexamethasone given prior to antibiotics reduces
  the incidence of hearing loss for Hib meningitis,
  but did not decrease mortality
• McIntyre et al. JAMA. 1997 278925-931

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Dexamethasone studies from developing countries

• Islamabad (placebo controlled double-blind,
  2mos-12 yrs on Ampicillin and Chloramphenicol)-
  dexamethasone group had increased risk of
  sequelae and worsened mortality
• Pakistan- (double-blind placebo controlled
  trial in 89 children)

may be due to late presentation of patients use
of antibiotics prior to hospital presentation
CSF results wherein no bacteria was isolated 1997
WHO Workshop on the Treatment of Bacterial
Meningitis in Developing Countries
Dexamethasone as routine adjuvant therapy was
NOT recommended

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• THE ROUTINE USE OF DEXAMETHASONE IN CHILDREN WITH
  BACTERIAL MENINGITIS IN THE PHILIPPINE SETTING IS
  NOT RECOMMENDED
• Task force Meningitis, PSMID

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Use of Dexamethasone may be used

• a. in cases where the causative organism can be
  reliably diagnosed, particularly those with H.
  influenzae meningitis
• b. in patients with markedly increased
  intracranial pressure
• - dose of 0.15 mg/kg/dose IV q 6 hrs for 2 days
• - 1st dose of dexamethasone should be given prior
  to or with the 1st dose of antibiotics
• - give with an H2 antagonist

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Supportive management

• IV Fluids and hydration
• maintain normal blood pressure, watch out for
  SIADH
• Control of increased intracranial pressure
• Nutritional support
• Prevention- chemoprophylaxis, immunizations,
  infection control

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Conclusions

• Must come up with own guidelines because
  conditions in other countries are different and
  specific recommendations may be inappropriate for
  other settings
• Local data is essential to provide a rational
  approach to the management of bacterial
  meningitis in children

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TASK FORCE ON MENINGITIS

• SUBGROUP ON DIAGNOSIS
• Lulu C. Bravo, MD
• Aida Salonga, MD
• Rose Capeding, MD
• Ma. Liza Gonzales, MD
• Rosalinda Soriano, MD
• Enrique Carandang, MD
• Michelle Medalla, MD
• Mabel San Juan

• SUBGROUP ON THERAPY
• Salvacion R. Gatchalian, MD (Chairman of Task
  Force)
• Malen Ortiz, MD
• Rosemarie Arciaga, MD
• Estrella Paje-Villar, MD
• Celia Carlos, MD
• Elaine Galicia, MD
• Cecilia Maramba-Untalan, MD
• Grace Martinez, MD
• Ms. Jenny Panisales

• SUBGROUP ON PREVENTION
• Josefina Carlos, MD
• Prof. Grace Agustin
• Prof. Victoria Vidal
• Cleotilde How, MD
• Mary Anne Banez, MD
• Ms. Racquel Ardiente
• Lorna Abad, MD

convened by Philippine Society of Microbiology
and Infectious Diseases