Transcript Neonatal Meningitis: Current Treatment Options Ma. Teresa C. Ambat, MD Neonatology-TTUHSC 7/10/2008 Introduction • Bacterial menigitis: 0.4 neonates / 1000 LB • Consequence of hematogenous disssemination.

Neonatal Meningitis:
Current Treatment Options
Ma. Teresa C. Ambat, MD
Neonatology-TTUHSC
7/10/2008
Introduction
• Bacterial menigitis: 0.4 neonates / 1000 LB
• Consequence of hematogenous disssemination of
bacteria during sepsis episode
– Occurs in 10-20% of infants with bacteremia
• Extension from infected skin
• VPS or reservoirs may be the primary site of
infection
Introduction
• All organisms that cause neonatal infection or
sepsis can result in CNS disease  severe
consequences to the developing brain
• Early diagnosis and therapy is mandatory 
improve short and long term outcomes
Do infants with meninigitis have
positive blood cultures?
• Infants with meningitis with sterile blood
cultures
– 40% of >34 wks GA
– 50% of VLBW
– Perform LP if sepsis/meningitis is suspected
• Meningitis in infants admitted to the NICU with
respiratory distress is very uncommon
– LP is not mandatory in these infants
– LP should be done if blood culture +
What is the treatment of meningitis
in neonates?
• Gram negative
– 3rd generation (cefotaxime) or 4th generation (cefepime)
cephalosporin or
– Carbapenem (meropenem)
– + aminoglycoside until sterilization of CSF (concentration low
in CSF)
– Most are resistant to ampicillin, may be used in susceptible
organism
– Continued treatment based on in vitro susecpetibility
• B lactamase producing (Enterobacter, Serratia, P.
aeruginosa, Citrobacter, indole + Proteus)
• ESBL (Enterobacteriaceae – Klebsiella, E Coli)
– Carbapenem (meropenem or imepenem) + aminoglycoside
Treatment
• GBS
– Ampicillin or Pen G
– + gentamicin for synergy (discontinued after CSF
sterilization by rpt LP 24/48 hrs after treatment or after
1 week)
• Preterm in the NICU
– S aureus, CONS, enterococci, multipy-resistant
pathogens
– Emperic treatment: Ampicillin, nafcillin or vancomycin
+ aminoglycoside, cefotaxime or meropenem –
depending on predominant pathogens in the NICU
Treatment
• Fungal infection
– Candida spp
– Amphotericin B: treatment of choice, used
successfully as monotherapy
– Amphotericin B lipid formulation: if renal toxicity
– Fluconazole: excellent CNS penetration, + ampho B
if persistent fungemia or poor clinical response
– Newer azoles – Voriconazole: limited experience
– Echinocandins – Caspofungin, micafungin: poor CNS
penetration
What is the duration of treatment
for meningitis in neonates?
• Dependent on causative organism, sites of infection, clinical
severity, and course
– Uncomplicated bacteremia: 7 days
– Sepsis/pneumonia: 7-10 days
– Meningitis: 14-21 days, dependent on causative agent
• Gram negative bacilli
– Minimum 21 days or 2 weeks after the first sterile CSF
culture whichever is longer
– Repeat LP after 21 days, before discontinuation of tx:
determine adequacy of therapy
– Abnormal CSF findings (glucose <25, protein >300 or
>50%PMNs) – warrant continued therapy
Duration of treatment
• GBS meningitis
– Minimum of 14 days
– End of therapy LP – dependent on clinical
course (seizures, hypotension, prolonged + CSF
cultures, abnormal neuroimaging)
• Other organisms: optimal duration not known
– S aureus: at least 3 weeks
– Carebral abscess: prolonged tx of 4-6 wks
Red Book Recommendation: GBS meningitis
• Ampicillin + aminoglycoside – initial treatment
• Pen G alone – GBS indentified with clinical and
microbiologic responses documented
• GBS meningitis
– Penicillin G < 7 days: 250-400K u/k/day q8
>7 days: 450-500K u.k.day q4-6
– Ampicillin
<7 days: 200-300 mg/k/day q8
>7 days: 300mg/k/day q4-6
Red Book Recommendation: GBS meningitis
• Duration of treatment
– Uncomplicated meningitis: 14 days
– Complicated course: longer, ventriculitis - 4 wks
• 2nd LP 24 to 48 hrs after initiation of therapy assists in
management and prognosis
• Additional LP + diagnostic imaging – if response is in
doubt and neurologic abnormalities persist
Should other therapies be
considered?
• Gram negative bacilli meningitis
– Associated with persistently + CSF cultures, median
duration of 3 days
– Duration of positivity correlates with long term
prognosis and impacts duration of therapy
– For Gram-negative bacilli: daily or every other day
LP to determine occurrence and timing of CSF
sterilization
Should other therapies be
considered?
• Intraventricular therapy
– Generally not recommended
– An option in those with ventricular drain in place and
persistently + CSF cultures
– Parenteral vs parenteral + intrathecal (gentamicin 1
mg/day x 3 days): No difference in case fatality or
neurologic sequelae
– Intraventricular gentamicin 2.5mg: Higher mortality
(43% vs 13%)
– Greater inflammatory injury as a result of this tx
Should other adjunctive therapies be
provided to an infant with meningitis?
• Dexamethesone
– No studies available in neonates, use not
recommended
• Prophylactic fluconazol
– Should be considered in preterm infants (<1000g)
who require prolonged broad-spectrum antimicrobial
therapy
– Shown to decrease incidence of candidiasis
What if the infant’s CSF is abnormal
but routine bacterial cultures of CSF
and blood are sterile?
• Most frequent reason: previous antimicrobial
therapy
• IVH can result in inflammatory changes in the
absence of an infectious process
• When sepsis/meningitis suspected
– Repeat LP should be performed
– Pathogens producing aseptic meningitis should be
ruled out
– CSF should be sent for anaerobic, mycoplasma,
fungal and viral cultures, herpes/enteroviruses PCR
When should neuroimaging be considered and
what type of examination is recommended?
• Cranial US
– Safe, convenient, available at the bedside
– Ventricular size, development of hydrocephalus
– Periventricular white matter (increased PV
echogenicity  PVL in ischemia)
– Not identify infarct, abscess, subdural empyema
• CT
– Abscess, subdural collections, hydrocephalus
When should neuroimaging be considered and
what type of examination is recommended?
• MRI
– Indication: abnormal US, seizures, persistent + CSF
cultures, due to organisms (Citrobacter, fungi)
– Experts recommend brain MRI be performed on every
case of neonatal meningitis
• Hearing evaluation for all infants with meningitis
What is the outcome of meninigitis
in neonates?
• PT, BW <1000g
– Low (<70) mental and psychomotor indexes, CP, vision
impairment and HC (<10%)
• Gram negative enteric menigitis
– 20-30% mortality
– 30-50% neurologic sequelae (hydrocephalus, seizure disorder,
developmental delay, CP, hearing loss)
• GBS meningitis
– 25% mortality
– 25-30% major neurologic sequelae (spastic quadriplegia,
profound MR, hemiparesis, deafness, cortical blindness)
– 15-20% mild-moderate sequelae
– 50-60% normal
– Seizures during acute illness associated with poor prognosis
References
• Kaufman D, Zanelli S, Sanchez P. Neonatal meningitis:
current treatment options. Neurology: Neonatology
questions and controversies 210-230, 2008.
• Red Book 2006.