Neonatal meningitis

Suzanne Liu MD

Infectious Disorders

Updated 02.24.2024
Released 09.21.1993
Expires For CME 02.24.2027

Neonatal meningitis

Author: Suzanne Liu MD

See Contributor Disclosures

Editor: John E Greenlee MD

Neonatal meningitis

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Introduction

Overview

Neonatal meningitis represents an important clinical challenge for both the child neurologist and the pediatrician. The clinical presentation of meningitis in newborn infants is frequently nonspecific, and spinal fluid abnormalities may be difficult to differentiate from values typically seen in newborn infants. For this reason, meningitis should be suspected in a newborn who develops poor feeding, irritability, fever, or hypothermia; this is frequently, but not invariably, accompanied by a CSF white blood cell count greater than 30 cells/mm3 and a CSF:serum glucose ratio less than 0.5. Seizures may also suggest the presence of meningitis, although clinical seizures in the newborn may be more subtle or atypical than those seen in older children or adults. Empiric antimicrobial therapy includes a combination of ampicillin and a third- or fourth-generation cephalosporin (usually cefotaxime or ceftazidime) (64). Although adjunctive dexamethasone therapy is recommended in children and adults, there is insufficient evidence to date to recommend dexamethasone therapy for neonatal meningitis.

Key points

	• Neonatal meningitis includes infections occurring within the immediate postpartum period and also infections occurring during the first few weeks of life. The condition is usually divided into cases occurring within 72 hours of delivery (early onset) and cases occurring after 72 hours postpartum (late onset) up until 28 days of age.
	• The major causes of neonatal meningitis are Streptococcus agalactiae (Group B streptococci, GBS) and Gram-negative organisms, in particular Escherichia coli.
	• The diagnosis of neonatal meningitis is often difficult. Typical signs of meningeal inflammation are frequently absent, and neonates may present with nonspecific irritability. The neonate may be febrile, euthermic, or hypothermic and may be tachypneic, have apneic spells, or be excessively somnolent. Seizures may occur, but may not resemble seizures seen in older children or adults.
	• CSF findings in neonatal meningitis may not easily be distinguished from CSF values typically seen in neonates. However, meningitis should be strongly suspected if CSF white blood cell count is greater than 30 cells/mm3 and the CSF:serum glucose ratio is less than 0.5.
	• Empiric treatment of neonatal meningitis involves use of a third- or fourth-generation cephalosporin to cover S agalactiae and Gram-negative organisms, plus ampicillin to cover Listeria monocytogenes.
	• Aminoglycosides such as gentamicin do not reliably reach therapeutic concentrations in CSF, and intrathecal administration of these agents has not been effective. Intraventricular administration has been found to increase mortality and is contraindicated.
	• Intrapartum administration of antibiotics to mothers infected with S agalactiae has proven crucial to preventing meningitis in the newborn infant.

Historical note and terminology

Although the first description of bacterial meningitis was recorded by Gaspard Vieusseux in 1806 (66), meningitis as a condition of neonates was not reported until 1873, and Flensborg, in one of the first reviews of the condition, was able to identify only 131 cases from the world’s literature (17; 70). That neonatal meningitis was an important condition in the newborn period did not become well-recognized until the 1950s (70). The first manuscript devoted to the neuropathology of neonatal bacterial meningitis in neonates was published in 1966 (05).

Current understanding of neonatal meningitis has been achieved through work in three major areas. The first of these has been an understanding of the disease itself: the realization that neonatal meningitis is not rare, that its etiologic organisms and pathogenesis differ from those associated with childhood and adult meningitis, and that its presentation does not usually resemble that seen in older individuals. The second area has been progress in the treatment of neonatal meningitis. Early clinical trials demonstrated that systemic ampicillin and an aminoglycoside still resulted in 50% mortality and long-term morbidity, that addition of intrathecal gentamicin did not improve outcome, and that use of intraventricular gentamicin resulted in increased mortality (42). Predictably effective antibiotic treatment of neonatal Gram-negative meningitis was achieved only following the advent of the third-generation cephalosporins. The third theme, of great importance over the last two decades, has been the realization that the incidence of S agalactiae meningitis can be reduced by peripartum treatment of mothers testing positive for the organism. Despite these advances, however, neonatal meningitis remains a dangerous condition: although mortality has declined to roughly 10%, an adverse outcome will still be found in 20% to 70% of patients (03; 04; 36; 47).

Clinical manifestations

Presentation and course

The signs of meningitis in the neonate are nonspecific (53; 04; 36). The infant may become irritable or lethargic and often develops poor feeding. Vomiting or diarrhea may occur. The patient may be afebrile, but may also develop either fever or hypothermia, may become tachypneic – at times with outright respiratory distress – or may have apneic spells (53; 04; 36). Seizures may occur, but these may be subtle or fragmentary. Multifocal clonic movements, brief tonic spasms, and fragmentary stereotypic movements such as buccolingual movements, limb stiffening, and “bicycling movement” may all represent neonatal seizures. Apnea may represent an epileptic phenomenon, and neonates may also have electrographic seizure activity on electroencephalography without recognizable clinical signs. Older literature emphasized the importance of a high-pitched “meningeal” cry, but this is often absent. The presence of a bulging fontanel is a late sign, indicating significantly increased intracranial pressure (27). Nuchal rigidity is rarely present in the newborn with meningitis (67; 53; 04). The neonate’s level of consciousness may deteriorate from lethargy to obtundation to stupor and coma. Deterioration in the level of consciousness is a sign of raised intracranial pressure.

Prognosis and complications

Focal neurologic deficits may develop as a result of arterial cerebrovascular disease, intracranial hemorrhage, or developing brain abscess. Generalized seizure activity and status epilepticus may be due to fever, hyponatremia, anoxia from decreased cerebral perfusion, or toxicity from antimicrobial agents. The presence of focal clonic seizures or seizures with a consistent focal onset suggests localized cerebral injury. Involvement of cranial nerves by the exudate may result in cranial nerve palsies, in particular, involving the second, third, sixth, seventh, or eighth cranial nerves. Hearing loss due to the meningitis may be due to direct involvement of cranial nerve VIII or to purulent labyrinthitis. In contrast to adult meningitis, where concomitant brain abscess is rare, brain abscess may occasionally occur in neonatal meningitis; this association is particularly strong, with infections caused by Citrobacter sp (40).

Clinical vignette

A 10-day-old neonate was brought to the emergency department for a seizure. The parents complained that the baby had been irritable and not eating for 24 hours. On examination, the neonate was febrile and lethargic. Examination of the cerebrospinal fluid revealed 50 white blood cells/mm3, 80% polymorphonuclear leukocytes, a protein concentration of 190 mg/dL, and a CSF:serum glucose ratio of 0.4. Empiric antimicrobial therapy was initiated with ampicillin and cefotaxime. Cerebrospinal fluid Gram stain demonstrated a Gram-negative bacillus, and Escherichia coli grew in culture. Antimicrobial sensitivity tests demonstrated the organism was resistant to ampicillin, but susceptible to the cephalosporins. CSF culture was negative on repeat lumbar puncture performed 24 hours after the initiation of antimicrobial therapy.

Biological basis

Etiology and pathogenesis

Etiological agents. The most common organisms associated with neonatal meningitis in the developed world are Streptococcus agalactiae (group B streptococci), followed in order of frequency by E coli, other Gram negatives, and L monocytogenes (53; 44; 59; 52; 29; 04; 19; 48; 36; 08). In a Canadian study of E Coli and S agalactiae each accounted for one third of cases of bacterial meningitis in early onset meningitis. In numerous studies S agalactiae is the most common pathogen, including 59% of cases of neonatal meningitis overall from France and 52% of cases from United Kingdom (19; 37; 47). Other bacteria identified include E coli (28%), other Gram-negative organisms (4%), N meningitides (3%), and L monocytogenes (1.5%) (19). In term infants, S agalactiae accounted for 77% of cases and E coli for 28%, and in late-onset meningitis for 50% versus 33%. In contrast, E coli was more commonly isolated in preterm infants (45% vs. 33% for S agalactiae) and accounted for 54% of cases in very preterm infants (58; 19). However, in a study of 6956 very low birth weight infants with late-onset sepsis, where the likelihood of nosocomial infection is much higher, the major organism was coagulase-negative Staphylococcus species (48% of cases) followed by coagulase-positive Staphylococcus aureus (8% of cases) and E coli (5% of cases) (11). Less common causes include Neisseria meningitidis, Klebsiella species, Streptococcus pneumoniae, Cronobacter sp, Mycoplasma hominis, or Candida species (53; 44; 59; 52; 29; 12; 25; 04; 19; 56; 30; 49; 02; 47). Burkholderia pseudomallei, the agent of melioidosis, remain a cause of neonatal meningitis in some underdeveloped countries (61). In recent years, the agent Elizabethkingia meningoseptica (previously Chrysobacterium meningosepticum) and Elizabethkingia anopheles group have been associated with neonatal meningitis in multiple locations worldwide (32; 31). Laboratory differentiation of these two species is difficult, and it is thought that some cases previously thought to be caused by E meningoseptica are actually caused by E anopheles (31).

Meningitis due to S agalactiae occurs at two points in time: within the first 48 hours of the postnatal period, or at seven days to six weeks of age (52; 48). Cases occurring in the immediate postnatal period represent acquisition of the agent from the mother at the time of birth, and meningitis often occurs as part of a systemic infection; cases in older infants more frequently occur as an isolated meningitis. S agalactiae cases of late onset disease have been noted to be increasing in France since 2013 (51). In the United States, late onset disease rates are higher than early onset disease (0.23 per 1000 live births vs. 0.31 per 1000 live births) (46).

The incidence of neonatal meningitis associated with these and other organisms in the developing world may vary significantly according to geographic location, with higher incidence and higher mortality in developing nations (18; 36).

Pathogenesis. In cases of early-onset meningitis, the neonate becomes infected from the mother’s genitourinary tract; late-onset meningitis may be of nosocomial origin (36). Abnormalities of pregnancy and delivery, including prematurity, premature rupture of membranes, traumatic delivery, and caesarian section, are known risk factors (70). Meningitis in the newborn is usually associated with sepsis. Cases of S agalactiae sepsis and meningitis may occasionally be due to mastitis and infected breast milk (68). Cronobacter species may exist as contaminants of infant formula and have been associated with sepsis, enterocolitis, and meningitis, predominantly in infants under four weeks of age (30; 69). Despite extensive research dating back over 50 years, the precise sequence of events involved in meningeal invasion in neonatal meningitis is not fully understood. Studies by Kim indicate that entry of E coli across the blood-brain barrier requires a high level of bacteremia, followed by entry of the organism into brain microvascular endothelial cells and movement across these cells into the subarachnoid space (33). Meningeal infection in neonatal meningitis is frequently accompanied by ventriculitis.

Multiplication of bacteria within the subarachnoid space and ventricles initiates a cascade of events in which multiplication and lysis of bacteria are followed by the release of bacterial cell wall components. These, in turn, induce meningeal inflammation by stimulating the production of inflammatory cytokines and chemokines, in particular, tumor necrosis factor alpha (TNF-alpha) within the CSF space. TNF-alpha and IL-1 act synergistically to alter the permeability of the blood-brain barrier. The alteration in blood-brain barrier permeability during bacterial meningitis results in vasogenic cerebral edema and allows leakage of serum proteins and other molecules into the CSF. In a landmark clinical study, intraventricular administration of gentamicin in Gram-negative meningitis was found to greatly amplify this process, with increased inflammation and consequent increase in mortality (43; 45; 42).

Meningeal inflammation results in the formation of a purulent exudate in the subarachnoid space. The purulent exudate obstructs the flow of CSF through the ventricular system and diminishes the resorptive capacity of the arachnoid granulations in the dural sinuses. This leads to obstructive and communicating hydrocephalus and interstitial edema. Involvement of cranial nerves by the exudate may cause cranial nerve palsies, in particular, involving cranial nerve VIII. The inflammatory process may also affect arteries. The resulting arteritis may cause focal or multifocal ischemia and stroke, with significant increase in mortality and long-term morbidity. Two major patterns of stroke have been reported in neonatal meningitis: occlusion of deep perforating arteries causing infarcts in basal ganglia, thalamus, and periventricular white matter; and superficial patchy infarcts involving the cortical surface (28). Cerebral ischemia resulting from alterations in cerebral blood flow causes cytotoxic edema. The combination of interstitial, vasogenic, and cytotoxic edema leads to raised intracranial pressure and coma. In addition, bacteria and the inflammatory cytokines induce the production of excitatory amino acids, reactive oxygen and nitrogen species (free oxygen radicals, nitric oxide, and peroxynitrite), and other mediators that induce massive apoptosis of brain cells. The inflammatory mediators, IL-1, TNF, and IL-6, stimulate oligodendrocyte cell death and white matter injury resulting in periventricular leukomalacia (01). Hearing loss due to purulent labyrinthitis is common in children surviving acute infection.

Diagnostic workup

The diagnosis of bacterial meningitis is based on examination of the cerebrospinal fluid. Normal opening pressure in the neonate is 50 mm H2O or less. The normal CSF white blood cell count in the full-term neonate is 0 to 30 cells/mm3, of which 60% may be polymorphonuclear leukocytes. The normal CSF protein concentration is less than or equal to 150 mg/dL (34; 53). The normal CSF:serum glucose ratio is 0.81 (16; 23). It can be difficult to differentiate infected from uninfected CSF in the neonate. A CSF white blood cell count that is higher than 30 cells/mm3 and a CSF:serum glucose ratio lower than 0.5 strongly suggests bacterial meningitis. Microorganisms can be detected on Gram stain of CSF in 80% of cases of meningitis due to group B streptococcus or E coli, but the Gram stain is often negative in neonates with L monocytogenes meningitis due to the relatively low numbers of bacteria in the CSF (53). Cerebrospinal fluid cultures are usually positive. The latex particle agglutination assays that detect antigens of group B streptococcus and the E coli K1 antigen in CSF are no longer recommended as part of the routine diagnostic CSF studies for neonatal meningitis because a negative bacterial antigen test does not rule out infection. However, the latex particle agglutination assay may be helpful in the neonate who has been pretreated with antimicrobial therapy and whose Gram stain and CSF culture are negative.

Multiplex polymerase chain reaction (PCR) panels have been developed to provide a diagnosis within hours. An analysis of such a panel (BioFire Diagnostics LLC, Salt Lake City, UT, U.S.) shows a 90% sensitivity for detection of all pathogens (viral, bacterial, and yeast), and a 97% specificity (60). Included pathogens on these panels are frequently E coli, H influenzae, L monocytogenes, N meningitidis, S pneumoniae, and S agalactiae. However, there are no good data available showing that rapid diagnostic tests alter management or outcomes of patients with suspected bacterial meningitis.

Blood cultures are usually positive, and the peripheral white blood cell count is increased. The serum sodium concentration may be low. Acute phase reactants, such as the C-reactive protein and erythrocyte sedimentation rate, are usually abnormal. Serum procalcitonin levels of 0.5 ng/mL or greater are predictive of bacterial infection (13). The serum procalcitonin level is minimal in viral infections (21).

Positive cultures on repeat lumbar puncture have been reported in 22% of infants with neonatal meningitis, in particular, during the first week of treatment (22; 36). Detection of organisms on repeat lumbar puncture is associated with higher mortality.

Management

Antibiotic treatment. In most neonates, initial empirical antimicrobial therapy is based on the possibility that the meningitis is due to either group B streptococcus, ampicillin-resistant Gram-negative bacilli, or Listeria monocytogenes. Treatment over the years has included a combination of ampicillin and an aminoglycoside or, because gentamicin may not reach therapeutic levels in CSF, ampicillin and a third- or fourth-generation cephalosporin (ie, cefotaxime). Many centers will use all three agents (ampicillin, gentamicin, and cefotaxime) until antibiotic susceptibilities become available (15). This is due in part to likelihood of systemic sepsis as well as meningitis and also to the emergence of cephalosporin-resistant Gram-negative organisms such as Enterobacter, Klebsiella, and Serratia species (07). In some very low birth weight infants, particularly those older than one week of age, consideration should include coverage of coagulase-negative staphylococcus or other staphylococcal organisms. In this instance, vancomycin should replace ampicillin. Treatment regimens for cefotaxime and ampicillin are shown in Table 1 (62; 36).

Table 1. Treatment Regimens

Antibiotic	Infants 0 to 7 days	Infants 8 to 28 days
Cefotaxime	100 to 150 mg/kg per day given every 8 to 12 hours	150 to 200 mg/kg per day given every 6 to 8 hours
Ampicillin	150 mg/kg per day given every 8 hours	200 mg/kg per day given every 6 to 8 hours
Gentamicin	5 mg/kg per day given every 12 hours	7.5 mg/kg per day given every 8 hours
Vancomycin	20 to 30 mg/kg given every 8 to 12 hours	30 to 45 mg/kg given every 6 to 8 hours

The fourth-generation cephalosporin, cefepime (50 mg/kg every 12 hours), can be used instead of cefotaxime (14). As noted above, standard guidelines recommend a combination of ampicillin and gentamicin as one regimen of empiric therapy of neonatal meningitis or a combination of ampicillin plus cefotaxime (62; 64). It has been suggested that therapeutically adequate serum levels of gentamicin with peak levels below toxic range can be achieved in premature infants by administering gentamicin at doses of 3 mg/kg in infants under 35 weeks of gestation and 4 mg/kg in infants 36 weeks of gestation (24). Data concerning the effectiveness of this regimen in neonatal meningitis are limited. Aminoglycosides have nephrotoxicity and can cause hearing loss and vestibular dysfunction. Thus, aminoglycosides should be discontinued as soon as possible if antibiotic susceptibilities permit it. Intraventricular administration of gentamicin should not be used (42; 55). Occasional strains of Gram-negative enteric bacilli are resistant to the aminoglycosides (53).

Once the antibiotic sensitivities of an organism are known, antimicrobial therapy can be modified accordingly. Uncomplicated meningitis due to group B streptococci is treated for 14 days, whereas that due to Gram-negative bacilli is treated for a minimum of 21 days after sterilization of CSF cultures (53). Meningitis due to L monocytogenes requires treatment for at least 21 days. The neonate with Gram-negative meningitis should undergo repeat lumbar puncture to document sterilization of the CSF after 24 to 48 hours of treatment (62).

Organisms of the Elizabethkingia group (E meningosepticum and E anopheles) have proven resistant to many antibiotics (32). Suggested empiric agents, guided by in vitro susceptibility data, have included vancomycin, rifampicin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and minocycline (32).

Use of dexamethasone. Although dexamethasone has been recommended in the treatment of children and adults with bacterial meningitis, there have been insufficient randomized controlled trials of meningitis in newborns to assess the drug’s efficacy in this population (65). However, in a randomized controlled trial from India involving 80 patients with neonatal meningitis randomized to receive either dexamethasone or placebo, use of dexamethasone significantly reduced mortality, CSF cell counts, and CSF concentrations of IL-1β and tumor necrosis factor α (TNF-alpha) (41). These results, although promising, have not yet been confirmed by other investigators.

Subdural effusions in neonatal meningitis. A sterile subdural effusion may develop in the course of bacterial meningitis in the newborn, but is much less common in neonates than in older infants or children. In neonates, the effusion is not usually associated with clinical symptomatology or neurologic sequelae. When necessary, these may be treated with subdural taps, but this is rarely needed. In one case, an effusion not responsive to serial subdural punctures was reported to respond to acetazolamide (06).

Outcomes

Infection during the perinatal and neonatal periods remains a dangerous condition and an important contributor to an adverse neurodevelopmental outcome (01; 19; 10; 36). Current mortality in Western countries is 13% to 16% overall, but approaches 25% in small-for-gestational-age or premature infants, regardless of the causative organism (19). Mortality in developing nations is significantly higher. Approximately 50% of neonates with bacterial meningitis have neurologic sequelae, including cerebral palsy, epilepsy, cognitive impairment, neuromotor problems, and hearing loss (39; 35). Bacterial meningitis may be complicated by hydrocephalus, cytotoxic and hypoxic-ischemic injury, and ischemic and/or hemorrhagic stroke. Infants may be left with motor deficits, cognitive disorders, seizures, visual impairment, and long-term cognitive impairment. Stroke in the presence of neonatal meningitis is a highly adverse prognostic indicator: in one series, the presence of stroke was associated with a rate of death or serious neurologic outcome approaching 75% (28). In a study of patients with meningitis ages one month to 18 years, absence of CSF pleocytosis and elevated protein were associated with worse prognosis, as was meningitis associated with S pneumoniae (38).

References

01: Adams-Chapman I, Stoll BJ. Neonatal infection and long-term neurodevelopmental outcome in the preterm infant. Curr Opin Infect Dis 2006;19(3):290-7. PMID 16645492
02: Arfi A, Cohen R, Varon E, Béchet S, Bonacorsi S, Levy C. Case-control study shows that neonatal pneumococcal meningitis cannot be distinguished from group B Streptococcus cases. Acta Paediatr 2017;106(12):1915-8. PMID 28508419
03: Bedford H, de Louvois J, Halket S, Peckham C, Hurley R, Harvey D. Meningitis in infancy in England and Wales: follow up at age 5 years. BMJ 2001;323(7312):533-6. PMID 11546697
04: Berardi A, Lugli L, Rossi C, et al. Neonatal bacterial meningitis. Minerva Pediatr 2010;62(3 Suppl 1):51-4. PMID 21089719
05: Berman PH, Banker BQ. Neonatal meningitis. Pediatrics 1966;38:6-24. PMID 5936882
06: Bhat YR, Prakashini K, Sen S. Subdural effusion complicating neonatal meningitis: successful treatment with acetazolamide. Indian J Pediatr 2009;76(1):103-5. PMID 19391014
07: Boyer-Mariotte S, Duboc P, Bonacorsi S, Lemeland JF, Bingen E, Pinquier D. CTX-M-15-producing Escherichia coli in fatal neonatal meningitis: failure of empirical chemotherapy. J Antimicrob Chemother 2008;62(6):1472-4. PMID 18772159
08: Bundy LM, Noor A. Neonatal meningitis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2022.
09: Byington CL, Rittichier KK, Bassett KE, et al. Serious bacterial infections in febrile infants younger than 90 days of age: the importance of ampicillin-resistant pathogens. Pediatrics 2003;111:964-8. PMID 12728072
10: Chu SM, Hsu JF, Lee CW, et al. Neurological complications after neonatal bacteremia: the clinical characteristics, risk factors, and outcomes. PLoS One 2014;9(11):e105294. PMID 25364821
11: Cohen-Wolkowiez M, Moran C, Benjamin DK, et al. Early and late onset sepsis in late preterm infants. Pediatr Infect Dis J 2009;28(12):1052-6. PMID 19953725
12: Cohen-Wolkowiez M, Smith PB, Mangum B, et al. Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures. J Perinatol 2007;27(2):97-100. PMID 17080094
13: Dubos F, Moulin F, Gajdos V, et al. Serum procalcitonin and other biologic markers to distinguish between bacterial and aseptic meningitis. J Pediatr 2006;149:72-6. PMID 16860131
14: Ellis JM, Rivera L, Reyes G, et al. Cefepime cerebrospinal fluid concentrations in neonatal bacterial meningitis. Ann Pharmacother 2007;41(5):900-1. PMID 17426074
15: Fernando AM, Heath PT, Menson EN. Antimicrobial policies in the neonatal units of the United Kingdom and Republic of Ireland. J Antimicrob Chemother 2008;61(3):743-5. PMID 18238883
16: Fishman RA. Composition of the cerebrospinal fluid. In: Fishman RA, editor. Cerebrospinal fluid in diseases of the nervous system. Philadelphia: W.B. Saunders, 1992;253-343.
17: Flensborg EW. Akute Meningitis bei Neugeborenen. Acta Paediatrica 1943;30:305-23.
18: Furyk JS, Swann O, Molyneux E. Systematic review: neonatal meningitis in the developing world. Trop Med Int Health 2011;16(6):672-9. PMID 21395927
19: Gaschignard J, Levy C, Romain O, et al. Neonatal bacterial meningitis: 444 cases in 7 years. Pediatr Infect Dis J 2011;30(3):212-7. PMID 21416693
20: GBD 2016 Meningitis Collaborators. Global, regional, and national burden of meningitis, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2018;17(12):1061-82. PMID 30507391
21: Gendrel D, Raymond J, Assicot M, et al. Measurement of procalcitonin levels in children with bacterial or viral meningitis. Clin Infect Dis 1997;24:1240-2. PMID 9195090
22: Greenberg RG, Benjamin DK Jr, Cohen-Wolkowiez M, et al. Repeat lumbar punctures in infants with meningitis in the neonatal intensive care unit. J Perinatol 2011;31(6):425-9. PMID 21164430
23: Greenlee JE, Carroll K. Cerebrospinal fluid in central nervous system infections. Chapter 2. In: Scheld WM, Whitley RJ, Marra CM, editors. Infections of the central nervous system. 3rd edition. Philadelphia: Lippincott Williams & Wilkins, 2004:5-30.
24: Hansen A, Forbes P, Arnold A, O’Rourke E. Once-daily gentamicin dosing for the preterm and term newborn: proposal for a simple regimen that achieves target levels. J Perinatol 2003;23(8):635-9. PMID 14647159
25: Hata A, Honda Y, Asada K, Sasaki Y, Kenri T, Hata D. Mycoplasma hominis meningitis in a neonate: case report and review. J Infect 2008;57(4):338-43. PMID 18790539
26: Heath PT, Jardine LA. Neonatal infections: group B streptococcus. BMJ Clin Evid 2010;2010. pii: 0323. PMID 21418675
27: Heath PT, Okike IO, Oeser C. Neonatal meningitis: can we do better? Adv Exp Med Biol 2011;719:11-24. PMID 22125031
28: Hernandez MI, Sandoval CC, Tapia JL, et al. Stroke patterns in neonatal group B streptococcal meningitis. Pediatr Neurol 2011;44(4):282-8. PMID 21397170
29: Holt DE, Halket S, de Louvois, J, Harvey D. Neonatal meningitis in England and Wales: 10 years on. Arch Dis Child Fetal Neonatal Ed 2001;84(2):F85-9. PMID 11207221
30: Hunter CJ, Bean JF. Cronobacter: an emerging opportunistic pathogen associated with neonatal meningitis, sepsis and necrotizing enterocolitis. J Perinatol 2013;33(8):581-5. PMID 23538645
31: Janda JM, Lopez DL. Mini review: new pathogen profiles: Elizabethkingia anophelis. Diagn Microbiol Infect Dis 2017;88(2):201-5. PMID 28342565
32: Jean SS, Lee WS, Chen FL, Ou TY, Hsueh PR. Elizabethkingia meningoseptica: an important emerging pathogen causing healthcare-associated infections. J Hosp Infect 2014;86(2):244-9. PMID 24680187
33: Kim KS. Current concepts on the pathogenesis of Escherichia coli meningitis: implications for therapy and prevention. Curr Opin Infect Dis 2012;25(3):273-8. PMID 22395761
34: Klein JO, Feigin RD, McCracken GH. Report of the task force on diagnosis and management of meningitis. Pediatrics 1986;78:959-82. PMID 3763317
35: Kloek AT, Brouwer MC, Schmand B, Tanck MWT, van de Beek D. Long-term neurologic and cognitive outcome and quality of life in adults after pneumococcal meningitis. Clin Microbiol Infect 2020;26(10):1361-7. PMID 32006689
36: Ku LC, Boggess KA, Cohen-Wolkowiez M. Bacterial meningitis in infants. Clin Perinatol 2015;42(1):29-45.** PMID 25677995
37: Lin MC, Chi H, Chiu NC, Huang FY, Ho CS. Factors for poor prognosis of neonatal bacterial meningitis in a medical center in Northern Taiwan. J Microbiol Immunol Infect 2012;45(6):442-7. PMID 22571998
38: Lin WL, Chi H, Huang FY, Huang DT, Chiu NC. Analysis of clinical outcomes in pediatric bacterial meningitis focusing on patients without cerebrospinal fluid pleocytosis. J Microbiol Immunol Infect 2016;49(5):723-8. PMID 25442861
39: Lucas MJ, Brouwer MC, van de Beek D. Neurological sequelae of bacterial meningitis. J Infect 2016;73(1):18-27. PMID 27105658
40: Martinez-Lage JF, Martínez-Lage Azorín L, Almagro M, Bastida ME, Reyes S, Tellez C. Citrobacter koseri meningitis: a neurosurgical condition. Eur J Paediatr Neurol 2010;14(4):360-3. PMID 19717321
41: Mathur NB, Garg A, Mishra TK. Role of dexamethasone in neonatal meningitis: a randomized controlled trial. Indian J Pediatr 2013;80(2):102-7. PMID 23054852
42: McCracken GH Jr. A historical perspective on pharmacological studies of gentamicin for therapy of neonatal meningitis. J Pediatr Pharmacol Ther 2006;11(1):4-9. PMID 23118642
43: McCracken GH Jr, Mustafa MM, Ramilo O, Olsen KD, Risser RC. Cerebrospinal fluid interleukin 1-beta and tumor necrosis factor concentrations and outcome from neonatal gram-negative enteric bacillary meningitis. Pediatr Infect Dis J 1989;8(3):155-9. PMID 2652086
44: Moreno MT, Vargas S, Poveola R, Saez-Llorens X. Neonatal sepsis and meningitis in a developing Latin American country. Pediatr Infect Dis J 1994;13:516-20. PMID 8078740
45: Mustafa MM, Mertsola J, Ramilo O, Saez-Llorens X, Risser RC, McCracken GH Jr. Increased endotoxin and interleukin-1 beta concentrations in cerebrospinal fluid of infants with coliform meningitis and ventriculitis associated with intraventricular gentamicin therapy. J Infect Dis 1989;160(5):891-5. PMID 2809260
46: Nanduri SA, Petit S, Smelser C, et al. Epidemiology of invasive early-onset and late-onset group B streptococcal disease in the United States, 2006 to 2015: Multistate laboratory and population-based surveillance. JAMA Pediatr 2019;173(3):224-33. PMID 27105658
47: Ouchenir L, Renaud C, Khan S, et al. The epidemiology, management, and outcomes if bacterial meningitis in infants. Pediatrics 2017;140(1):e20170476. PMID 28600447
48: Oh W. Early onset neonatal group B streptococcal sepsis. Am J Perinatol 2013;30(2):143-7. PMID 23322392
49: Okike IO, Johnson AP, Henderson KL, et al. Incidence, etiology, and outcome of bacterial meningitis in infants aged <90 days in the United kingdom and Republic of Ireland: prospective, enhanced, national population-based surveillance. Clin Infect Dis 2014;59(10):e150-7. PMID 24997051
50: Perlman JM, Rollins N, Sanchez PJ. Late-onset meningitis in sick, very-low-birth-weight infants. Am J Dis Child 1992;146:1297-301. PMID 1415065
51: Plainvert C, Hays C, Touak G, et al. Multidrug-resistant hypervirulent group B streptococcus in neonatal invasive infections, France, 2007-2019. Emerg Infect Dis 2020;26(11):2721-24. PMID 33079049
52: Pong A, Bradley JS. Bacterial meningitis and the newborn infant. Infect Dis Clin North Am 1999;13(3):711-33. PMID 10470563
53: Saez-Llorens X, McCracken GH. Bacterial meningitis in neonates and children. Infect Dis Clin North Am 1990;4:623-44. PMID 2277192
54: Schrag S, Gorwitz R, Fultz-Butts K, Schuchat A. Prevention of perinatal group B streptococcal disease revised guidelines from the CDC. MMWR 2002;51(RR-11):1-22. PMID 12211284
55: Shah SS, Ohlsson A, Shah VS. Intraventricular antibiotics for meningitis in neonates. Cochrane Database Syst Rev 2012;7:CD004496. PMID 22786491
56: Shane AL, Hansen NI, Stoll BJ, et al. Methicillin-resistant and susceptible Staphylococcus aureus bacteremia and meningitis in preterm infants. Pediatrics 2012;129(4):e914-22. PMID 22412036
57: Stoll BJ, Hansen N, Fanaroff AA, et al. To tap or not to tap: high likelihood of meningitis without sepsis among very low birth weight infants. Pediatrics 2004;113:1181-6. PMID 15121927
58: Stoll BJ, Hansen NI, Higgins RD, et al. Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003. Pediatr Infect Dis J 2005;24(7):635-9. PMID 15999007
59: Synnott MB, Morse DL, Hall SM. Neonatal meningitis in England and Wales: a review of routine national data. Arch Dis Child 1994;71:F75-80. PMID 7979482
60: Tansarli GS, Chapin KC. Diagnostic test accuracy of the BioFire® FilmArray® meningitis/encephalitis panel: a systematic review and meta-analysis. Clin Microbiol Infect 2020;26(3):281-90. PMID 31760115
61: Thatrimontrichai A, Maneenil G. Neonatal melioidosis: systematic review of the literature. Pediatr Infect Dis J 2012;31(11):1195-7. PMID 22739573
62: Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39:1267-84. PMID 15494903
63: van de Beek D, Brouwer MC, Koedel U, Wall EC. Community-acquired bacterial meningitis. Lancet 2021;398(10306):1171-83. PMID 34303412
64: van de Beek D, Cabellos C, Dzupova O, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clin Microbiol Infect 2016;22 Suppl 3:S37-62. PMID 27062097
65: van de Beek D, de Gans J, McIntyre P, Prasad K. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev 2007;(1):CD004405. PMID 17253505
66: Vieusseux G. Memoire sur la maladie qui a regne a Geneve au printemps de 1805. J Med Chi Pharm 1806;11:163-82.
67: Volpe JJ. Bacterial and fungal intracranial infections. In: Volpe JJ, editor. Neurology of the Newborn. 2nd ed. Philadelphia: WB Saunders, 1987:596-635.
68: Wang LY, Chen CT, Liu WH, Wang YH. Recurrent neonatal group B streptococcal disease associated with infected breast milk. Clin Pediatr (Phila) 2007;46(6):547-9. PMID 17579109
69: Yan Q, Fanning S. Strategies for the identification and tracking of cronobacter species: an opportunistic pathogen of concern to neonatal health. Front Pediatr 2015;3:38. PMID 26000266
70: Ziai M, Haggerty RJ. Neonatal meningitis. New Engl J Med 1958;259(7):314-20. PMID 13566471

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Suzanne Liu MD

Dr. Liu of the University of Utah School of Medicine has no relevant financial relationships to disclose.
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Editor

John E Greenlee MD

Dr. Greenlee of the University of Utah School of Medicine has no relevant financial relationships to disclose.
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Former Authors

Betsy EP Ostrander MD
Alan R Seay MD (original author), Karen L Roos MD, John E Greenlee MD, and Francis M Filloux MD

Patient Profile

Age range of presentation: 0-01 month
Sex preponderance: male=female
Heredity: none
Population groups selectively affected: Children of mothers receiving inadequate prenatal care, especially premature infants or those with low birth weight, and cases in which there is premature rupture of membranes
Occupation groups selectively affected: none selectively affected

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Neonatal meningitis

Associated Disorders

Bacterial central nervous system infection
Bacterial colonization
Bacterial meningitis
Cerebral infarction
E coli
- Group B streptococci
- Hydrocephalus
- Increased intracranial pressure
- Language disorders
- Listeria monocytogenes
- Meningitis
- Meningoencephalitis
- Motor deficits
- Neisseria meningitidis
- Neonatal seizures
- Neonatal sepsis
- Staphylococcus aureus
- Streptococcus agalactiae
- Visual impairments

Differential Diagnosis

sepsis without meningitis
viral meningoencephalitis
brain abscess
congenital malformations of the nervous system
head trauma
- brain trauma
- neonatal malaria
- hypoxic-ischemic encephalopathy
- subependymal-intraventricular hemorrhage

Also Relevant

CNS listeriosis
Gram-negative bacillary meningitis
Meningococcal meningitis
Recurrent meningitis
Viral meningitis

Neonatal meningitis

Neonatal meningitis

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Table 1. Treatment Regimens

Outcomes

Special considerations

Pregnancy

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

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Prion diseases

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Neonatal meningitis

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Table 1. Treatment Regimens

Outcomes

Special considerations

Pregnancy

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Prion diseases

Rabies

Malaria

Neuropathies associated with cytomegalovirus infection

Genital herpes: neurologic complications

Neurocysticercosis

Trichinosis

Zika virus: neurologic complications

This is an article preview.
Start a Free Account
to access the full version.