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Neonatal Meningitis: Current Treatment Options

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

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Neonatal Meningitis: Current Treatment Options

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  1. Neonatal Meningitis: Current Treatment Options Ma. Teresa C. Ambat, MD Neonatology-TTUHSC 7/10/2008

  2. 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

  3. 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

  4. 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 +

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. References • Kaufman D, Zanelli S, Sanchez P. Neonatal meningitis: current treatment options. Neurology: Neonatology questions and controversies 210-230, 2008. • Red Book 2006.

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