Neonatal Meningitis Medication
- Author: David C Dredge, MD; Chief Editor: Amy Kao, MD more...
Aggressive antimicrobial intervention is lifesaving in neonates with suspected meningitis. Because distinguishing viral from bacterial meningitis is difficult early in the clinical course, a combination of agents is often necessary, providing coverage for both types of infection.
In most institutions, acyclovir is the preferred antiviral therapy, but the best antibacterial therapy remains subject to debate. The combination of ampicillin and gentamicin is a common regimen. Many centers use cefotaxime in addition to or instead of gentamicin, particularly when gram-negative infections are suspected. Selection of antibiotics should be based on likely pathogens, local patterns of antibacterial drug sensitivities, and hospital policies.
In addition to the medications listed below, pleconaril is an experimental agent that interferes with attachment, entry, and uncoating of enteroviruses. It was shown to be well tolerated by neonates in a single, small, double-blinded study. Data supporting the efficacy of pleconaril are limited, although a larger clinical trial is currently under way. At present, this drug is available only for compassionate use or in clinical trials.
Antiviral agents inhibit viral replication and activity.
Acyclovir is the preferred treatment for herpes simplex virus (HSV) meningitis. Intravenous (IV) therapy is treatment of choice for neonatal HSV infection, regardless of clinical presentation. Acyclovir is activated by herpes-specific thymidine kinase; it prevents viral replication by inhibiting viral DNA polymerase. Because it is excreted primarily by the kidneys, dosing must be modified in patients with renal impairment.
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Either gram-positive or gram-negative organisms may cause bacterial sepsis and meningitis. Combination therapy is necessary.
Ampicillin has bactericidal activity against susceptible organisms. The combination of ampicillin with an aminoglycoside is the initial treatment of choice for neonates with presumptive group B streptococcal (GBS) meningitis and for most other suspected bacterial infections of the central nervous system (CNS).
Penicillin G interferes with synthesis of cell-wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms. It can be given alone to treat GBS meningitis when susceptibility of CSF isolates to the drug has been demonstrated.
Cefotaxime is a third-generation cephalosporin with a gram-negative spectrum of activity; it has lower efficacy against gram-positive organisms. It arrests bacterial cell-wall synthesis, which, in turn, inhibits bacterial growth.
Whereas ampicillin plus an aminoglycoside remains the initial treatment of choice for bacterial meningitis, some investigators recommend ampicillin plus a cephalosporin (eg, cefotaxime) as initial treatment. The rapid emergence of cephalosporin-resistant strains limits the use of the latter combination, unless gram-negative bacterial meningitis strongly suspected. Treatment typically lasts 21 days, with most authorities recommending 14-21 days from the first negative CSF culture.
Gentamicin is the prototypical aminoglycoside for combining with ampicillin to treat neonatal meningitis, but organism sensitivities and hospital protocols vary widely. Evolving bacterial resistance may necessitate the use of higher doses.
Anticonvulsants prevent seizure recurrence and terminate clinical and electrical seizure activity.
Phenobarbital increases the activity of gamma-aminobutyric acid, an inhibitory neurotransmitter in the central nervous system. This medication is typically used as the first-line agent in the treatment of neonatal seizures. An IV dose may require approximately 15 minutes to attain peak levels in the brain. Typically, a loading dose of 20 mg/kg IV is given initially, with additional bolus doses of 5-10 mg/kg if seizure activity persists, to a maximum total dose of 40 mg/kg.
Fosphenytoin is the diphosphate ester salt of phenytoin and acts as a water-soluble prodrug of that agent. After administration, plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin. Phenytoin, in turn, stabilizes neuronal membranes and decreases seizure activity.
To eliminate the need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses, express the dose in terms of phenytoin sodium equivalents (PE). Although fosphenytoin can be administered either IV or IM, IV administration is preferable and should be used in emergency situations.
Fosphenytoin is typically considered the second choice of anticonvulsants in neonates if phenobarbital does not control seizures.
Lorazepam is a benzodiazepine anticonvulsant that is used in cases that are refractory to phenobarbital and phenytoin. By increasing the action of gamma-aminobutyric acid (GABA) the major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the CNS, including the limbic system and the reticular formation.
Volpe JJ. Bacterial and fungal intracranial infections. Neurology of the Newborn. 5th. Philadelphia, Pa: Saunders Elsevier; 2008. 916-56.
Volpe JJ. Viral, protozoal, and related intracranial infections. Neurology of the Newborn. 5th. Philadelphia, Pa: Saunders Elsevier; 2008. 851-915.
Krebs VLJ, Costa GAM. Clinical outcome of neonatal bacterial meningitis according to birth weight. Arq. December 2007. 65:1149-1153. [Medline].
Davies PA, Rudd PT. Incidence; The Developing Brain. Neonatal Meningitis. Cambridge, England: Cambridge University Press; 1994. Ch 1.
Klinger G, Chin CN, Beyene J, et al. Predicting the outcome of neonatal bacterial meningitis. Pediatrics. 2000 Sep. 106(3):477-82. [Medline].
Heath PT, Nik Yusoff NK, Baker CJ. Neonatal meningitis. Arch Dis Child Fetal Neonatal Ed. 2003 May. 88(3):F173-8. [Medline].
Tiskumara R, Fakharee SH, Liu C-Q, Nuntnarumit P, Lui K-M, Hammoud M, et al. Neonatal infections in Asia. Arch Dis Child Fetal Neonatal Ed. March 2009. 94:F144-8. [Medline].
Zaidi AK, Thaver D, Ali SA, Khan TA. Pathogens associated with sepsis in newborns and young infants in developing countries. Pediatr Infect Dis J. 2009 Jan. 28(1 Suppl):S10-8. [Medline].
Puopolo KM, Madoff LC, Eichenwald EC. Early-onset group B streptococcal disease in the era of maternal screening. Pediatrics. 2005 May. 115(5):1240-6. [Medline].
CDC. Trends in perinatal group B streptococcal disease - United States 2000-2006. Morb Mortal Wkly Rep. February 2009. 58:109-112. [Medline].
CDC. Enterovirus surveillance--United States, 2002-2004. MMWR Morb Mortal Wkly Rep. 2006 Feb 17. 55(6):153-6. [Medline].
Tebruegge M, Curtis N. Enterovirus infections in neonates. Semin Fetal Neonatal Med. March 2009. 1-6. [Medline].
Levorson RE, Jantausch BA, Wiedermann BL, Spiegel HM, Campos JM. Human parechovirus-3 infection: emerging pathogen in neonatal sepsis. Pediatr Infect Dis J. 2009 Jun. 28(6):545-7. [Medline].
Selvarangan R, Nzabi M, Selvaraju SB, Ketter P, Carpenter C, Harrison CJ. Human parechovirus 3 causing sepsis-like illness in children from midwestern United States. Pediatr Infect Dis J. 2011 Mar. 30(3):238-42. [Medline].
Hunter JH, Petrosyan M, Ford HR, Prasadarao NV. Enterobacter sakazakii: An emerging pathogen in infants and neonates. Surg Infect (Larchmt). October 2008. 9:533-539.
Kimberlin D. Herpes simplex virus, meningitis, and encephalitis in neonates. Herpes. 2004. 11 Supp 2:65A-76A. [Medline].
Thaver D, Zaidi AK. Burden of neonatal infections in developing countries: a review of evidence from community-based studies. Pediatr Infect Dis J. 2009 Jan. 28(1 Suppl):S3-9. [Medline].
de Louvois J, Halket S, Harvey D. Effect of meningitis in infancy on school-leaving examination results. Arch Dis Child. 2007 Nov. 92(11):959-62. [Medline].
Chang CJ, Chang HW, Chang WN, Huang LT, Huang SC, CHang YC. Seizures complicating infantile and childhood bacterial meningitis. Pediatr Neurol. September 2004. 32:165-171. [Medline].
Stevens JP, Eames M, Kent A, et al. Long term outcome of neonatal meningitis. Arch Dis Child Fetal Neonatal Ed. 2003. 88:F179-184. [Medline].
Bedford H, de Louvois J, Halket S, et al. Meningitis in infancy in England and Wales: follow up at age 5 years. BMJ. 2001 Sep 8. 323(7312):533-6. [Medline].
Pong A, Bradley JS. Bacterial meningitis and the newborn infant. Infect Dis Clin North Am. 1999 Sep. 13(3):711-33, viii. [Medline].
Unhanand M, Mustafa MM, McCracken Gh, Nelson JD. Gram-negative enteric bacillary meningitis: a twenty-one year experience. J Pediatr. January 1993. 122:15-21. [Medline].
Miyairi I, Causey KT, DeVincenzo JP, Buckingham SC. Group B streptococcal ventriculitis: a report of three cases and literature review. Pediatr Neurol. May 2006. 34:395-399. [Medline].
Ment LR, Ehrenkranz RA, Duncan CC. Bacterial meningitis as an etiology of perinatal cerebral infarction. Pediatr Neurol. September/October 1986. 2:276-279. [Medline].
Fitzgerald KC, Golomb MR. Neonatal arterial ischemic stroke and sinovenous thrombosis associated with meningitis. J Child Neurol. July 2007. 22:818-822. [Medline].
Bao X, Wong V. Brainstem auditory-evoked potential evaluation in children with meningitis. Pediatr Neurol. 1998 Aug. 19(2):109-12. [Medline].
Committee on Medical Liability, American Academy of Pediatrics. Berger JE ed, Deitschel CH Jr ed. Medical Liability for Pediatricians. 6th ed. 2004. 163, 169.
Malbon K, Mohan R, Nicholl R. Should a neonate with possible late onset infection always have a lumbar puncture?. Arch Dis Child. 2006 Jan. 91(1):75-6. [Medline].
Garges HP, Moody MA, Cotten CM, et al. Neonatal meningitis: what is the correlation among cerebrospinal fluid cultures, blood cultures, and cerebrospinal fluid parameters?. Pediatrics. 2006 Apr. 117(4):1094-100. [Medline].
Shah DK, Daley AJ, Hunt RW, Volpe JJ, Inder TE. Cerebral white matter injury in the newborn following Escherichia coli meningitis. Eur J Paediatr Neurol. 2005. 9:13-17. [Medline].
Malik GK, Trivedi R, Gupta A, Singh R, Prasad KN, Gupta RK. Quantitative DTI assessment of periventricular white matter changes in neonatal meningitis. Brain Dev. May 2008. 30:334-341. [Medline].
Klinger G, Chin CN, Otsubo H, et al. Prognostic value of EEG in neonatal bacterial meningitis. Pediatr Neurol. 2001 Jan. 24(1):28-31. [Medline].
Poblano A, Gutierrez R. Correlation between the neonatal EEG and the neurological examination in the first year of life in infants with bacterial meningitis. Arq Neuropsiquiatr. September 2007. 65:576-580. [Medline].
Stoll BJ, Hansen N, Fanaroff AA, et al. To tap or not to tap: high likelihood of meningitis without infection in very low birthweight infants. Pediatrics. 2004. 113:1181-6. [Medline].
Alarcon A, Pena P, Salas S, Sancha M, Omenaca F. Neonatal early onset Escherichia coli sepsis: trends in incidence and antimicrobial resistence in the era of intrapartum antimicrobial prophylaxis. Pediatr Infect Dis J. April 2004. 23:295-299. [Medline].
Pickering LD, ed. Red Book: 2006 Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, Ill: American Academy of Pediatrics; 2006.
Thaver D, Ali SA, Zaidi AK. Antimicrobial resistance among neonatal pathogens in developing countries. Pediatr Infect Dis J. 2009 Jan. 28(1 Suppl):S19-21. [Medline].
Chaudhuri A. Adjunctive dexamethasone treatment in acute bacterial meningitis. Lancet Neurol. 2004 Jan. 3(1):54-62. [Medline].
Wellman MB, Sommer DD, McKenna J. Sensorineural hearing loss in postmeningitic children. Otol Neurotol. 2003 Nov. 24(6):907-12. [Medline].