Pediatric Bacterial Pediatric Bacterial Meningitis in the PhilippinesMeningitis in the Philippines
Cecilia C. Maramba-Cecilia C. Maramba-Untalan, MDUntalan, MD
Bacterial Meningitis in the Philippines
One of the top leading causes of mortality in children 0-4 yrs oldPathogens and susceptibility patterns are different from those identified in other countriesManagement recommendations must be appropriate for the Philippine settingTask Force on Meningitis convened in order to address this problem
Signs and Symptoms of Signs and Symptoms of MeningitisMeningitis
are variable and depend on the age of the patient, and the duration of illness before treatmentneonates and young infants may have minimal signs and symptomssigns of symptoms of neonatal sepsis are indistinguishable from neonatal meningitisall neonates being evaluated for sepsis should be evaluated for meningitis
Signs and Symptoms of Bacterial Signs and Symptoms of Bacterial MeningitisMeningitis
Signs and Signs and symptomssymptoms
NeonatesNeonates Older infants and childrenOlder infants and children
NonspecificNonspecific Fever or hypothermia, abnormally sleepy or lethargic, disinterest in feeding, poor feeding, cyanosis, grunting, apneic episodes, vomiting
Fever, anorexia, confusion, irritability, photophobia, nausea, vomiting, headache, seizure
Meningeal Meningeal inflammationinflammation
Neck rigidity, Neck rigidity, Kernig and Brudzinski sign
Increased Increased intracranial intracranial pressurepressure
Bulging fontanel, diastasis of sutures, convulsions, opisthotonus
Headache, bulging fontanel, diastasis of sutures in infants, papilledema, mental confusion, altered state of consciousness
Focal Focal neurologic neurologic signssigns
Hemiparesis, ptosis, facial nerve palsy
Hemi paresis, ptosis, deafness, facial nerve palsy, optic neuritis
Lumbar puncture is essentialCornerstone in the diagnosisshould 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 tap1. presence of significant cardio-pulmonary compromise and
shock2. signs of increased ICP3. suspected case of space occupying lesion4. infection in the area that the spinal needle will traverse to obtain
CSF5. hematologic problems
Laboratory Diagnosis of Bacterial MeningitisLaboratory Diagnosis of Bacterial Meningitis
CSF Findings in Bacterial Meningitis
a. CSF pressure - usually elevatedb. CSF cells count and chemistry leukocytosis- >1000/cu mm % PMN - 90% Glucose- <40 mg/dl CSF blood to glucose ratio <0.40 Protein 50-500 mg/dlc. stained smears of CSF gram stain - (+) for bacteria AFB smear - (-) India ink - (-) d. CSF culture *a negative culture does rule out meningitis
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 meningitidisAntigen detection tests should never be substituted for culture and gram stainif only a small amount of CSF is obtained, do gram stain and culture
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
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 meningitisStudy by Lee, et al*
224 cases of bacterial meningitis202 had abnormal cranial ultrasound findingshighly echogenic sulci- 75%
thick, highly echogenic convexity leptomeninges - 47% hydrocephalus - 44% effusion or empyema - 33% malacic changes - 9%
Neuroimaging and Bacterial Neuroimaging and Bacterial MeningitisMeningitis
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 indicated only for cases of suspected intracranial complications of bacterial meningitis and are complications of bacterial meningitis and are not not routinely requiredroutinely required
Empiric Therapy for Bacterial Empiric Therapy for Bacterial MeningitisMeningitis
Bacterial meningitis is a medical emergency, delay in treatment may lead to increased sequelae or deathDrug of choice must be bactericidal for pathogen involvedMust achieve adequate levels in the CSFInitial regimen should cover most likely pathogens for specific age groups, and reach bactericidal levels in the CSFKnowledge of local susceptibility patterns is essential
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
<1 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.
Carlos C, et al. (Philippine) Antimicrobial Resistance Surveillance Program,January-December, 2000
34
11
0
2
4
6
8
10
12%
resi
stan
ce
AMP CHL SXT
Percent resistance of Hemophilus influenzae, 2000
No significant resistance of H. influenzae to cotrimoxazole, ampicillin and chloramphenicol
The three drugs are still recommended for use for H. influenzae
Higher resistance to penicillin than 1999Only 13(18%) of 72 resistance isolates were sent for confirmation of which only 4(6%) were truly penicillin resistant by MICTrue extent of penicillin resistant S. pneumoniae still unknown
7
18.4
11.8
0
2
4
6
8
10
12
14
16
18
20
% r
esis
tan
ce
CHL PEN SXT
Percent resistance of Streptococcus pneumoniae 2000
3.7
76.3
33.6
5.8
19.1
56.2
1.90
10
20
30
40
50
60
70
80
% r
esis
tanc
e
AMIK AMP AMS CRO GEN SXT FEP
Percent resistance of Escherichia coli , 2000
8.9
40
13.6
23.9
0.72.6
0
5
10
15
20
25
30
35
40
% r
esis
tan
ce
AMK AMS CRO GEN IMP FEP
Percent resistance of Klebsiella spp, 2000
13.9
33.9
17.6
32.5
14.0
7.4
0
5
10
15
20
25
30
35
% r
esis
tanc
e
AMK CIP CAZ GEN IMP FEP
Percent resistance of Pseudomonas aeruginosa , 2000
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 region’s prevailing resistance patterns.
Empiric Therapy for Bacterial MeningitisEmpiric Therapy for Bacterial Meningitis
Patient group
Likely etiology Antimicrobial choice
Primary Alternative
0-2 mos E. coliGram (-) bacilliS. pneumoniae
Ampicillin or Penicillin + Aminoglycoside
Ampicillin + Cefotaxime or Ceftriaxone
2mos – 5 yrs H. influenzaeS. pneumoniaeN. meningitidis
Ampicillin or Chloramphenicol
Cefotaxime or Ceftriaxone
>5 yrs S. pneumoniaeN. meningitidis
Penicillin G Chloramphenicol
Empiric Therapy for Bacterial MeningitisEmpiric Therapy for Bacterial Meningitis
Patient group Likely etiology Antimicrobial choice
Primary Alternative
Immunodeficient G(-) organismsS. aureusS. pneumoniae
Ampicillin + Ceftazidime +Aminoglycoside
TMP/SMX + Ceftazidime +Aminoglycoside
Neurosurgical problems & open head trauma
S. pneumoniaeS. aureusColiformsP. aeruginosa
Oxacillin + Ceftazidime or TMP/SMX
Ceftazidime + Vancomycin
Closed head trauma
S. pneumoniae Penicillin G Chloramphenicol or Ceftriaxone or Cefotaxime
Shunt meningitis and meningocoeles
S. epidermidisS. aureusColiforms
Oxacillin + Cefotaxime or Ceftriaxone
Vancomycin + Ceftriaxone or Cefotaxime
Bacteria Standard therapy Alternative therapiesH. Influenzae ß lactamase negative ß lactamase positive
AmpicillinChloramphenicol
Chloramphenicol, 3rd gen Ceph1
Neissersia meningitidis Penicillin MIC <0.1 µg/ml
Penicillin MIC >0.1 µg/mlPenicillinChloramphenicol
Ampicillin3rd gen Ceph
Streptococcus pneumoniae Penicillin MIC <0.1 µg/ml Penicillin MIC 0.1- 1.0 µg/ml Penicillin MIC >2.0 µg/ml
Penicillin3rd gen cephVancomycin + 3rd gen ceph
Ampicillin, ChloramphenicolMeropenem, VancomycinMeropenem
Enterobacteriaceae 3rd gen ceph Cefepime, Meropenem, Cotrimoxazole
Pseudomonas aeruginosa Ceftazidime + aminoglycoside
Cefepime, Meropenem + aminoglycoside
Staphylococcus aureus Methicillin sensitive Methicillin resistant
Oxacillin or nafcillinVancomycin
Vancomycin
Specific Antimicrobial Therapy for Bacterial Meningitis*
Tunkel AR, Scheld WM, Amer Family Physician 1997, 56(5):1355-62
Duration of Therapy of Bacterial Meningitis*
Pathogen Suggested duration of therapy (days)
H. influenzae 7-10S. pneumoniae 10-14N. meningitidis 7Grp. B. streptococci 14-21
G(-) bacilli 21
*Quagliarello, et al, NEJM 1997, 336(10):708-716
• Rational for Use of Rational for Use of DexamethasoneDexamethasone
The bacteria that have invaded the CSF The bacteria that have invaded the CSF proliferate, undergo degradation, and release proliferate, undergo degradation, and release toxins and techoic acids. The inflammatory toxins and techoic acids. The inflammatory response is activated and principal mediators are response is activated and principal mediators are IL-1ß, TNF, PAF, PMN’s and macrophages.IL-1ß, TNF, PAF, PMN’s and macrophages. promote leukocyte-cerebral capillary endothelial promote leukocyte-cerebral capillary endothelial cell interaction, platelet-mediated thrombosis, cell interaction, platelet-mediated thrombosis, and cytotoxic, interstitial and vasogenic edemaand cytotoxic, interstitial and vasogenic edema dexamethasone inhibits the synthesis of dexamethasone inhibits the synthesis of interleukin 1 and TNFinterleukin 1 and TNF
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; 278:925-931
Dexamethasone studies from developing Dexamethasone studies from developing countriescountries
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)
DexamethasoneDexamethasone PlaceboPlacebo
Mortality 25% 12%
Neurologic sequelae 26.5% 24%
Hearing impairment 24% 30%
may be due to late presentation of patients; use of antibiotics prior to hospital presentation; CSF results wherein no bacteria was isolated1997 WHO Workshop on the Treatment of Bacterial Meningitis in 1997 WHO Workshop on the Treatment of Bacterial Meningitis in Developing Countries: Dexamethasone as routine adjuvant therapy Developing Countries: Dexamethasone as routine adjuvant therapy was NOT recommendedwas NOT recommended
THE ROUTINE USE OF THE ROUTINE USE OF DEXAMETHASONE IN DEXAMETHASONE IN CHILDREN WITH BACTERIAL CHILDREN WITH BACTERIAL MENINGITIS IN THE MENINGITIS IN THE PHILIPPINE SETTING IS NOT PHILIPPINE SETTING IS NOT RECOMMENDED*RECOMMENDED*
*Task force Meningitis, PSMID*Task force Meningitis, PSMID
Use of Dexamethasone may be Use of Dexamethasone may be used: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
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
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
TASK FORCE ON MENINGITIS*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 ofMicrobiology and Infectious Diseases