ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد ایتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Bacterial meningitis in the neonate: Treatment and outcome

Bacterial meningitis in the neonate: Treatment and outcome
Authors:
Morven S Edwards, MD
Carol J Baker, MD
Section Editors:
Sheldon L Kaplan, MD
Joseph A Garcia-Prats, MD
Deputy Editor:
Carrie Armsby, MD, MPH
Literature review current through: Apr 2022. | This topic last updated: Mar 15, 2021.

INTRODUCTION — Bacterial meningitis is more common in the first month than at any other time of life [1]. Despite advances in neonatal intensive care, meningitis in the neonate remains a devastating disease.

The treatment and outcome of bacterial meningitis in the neonate (age <1 month) will be discussed here. The clinical features, diagnosis, and complications of bacterial meningitis are discussed separately, as is bacterial meningitis in older children:

(See "Bacterial meningitis in the neonate: Clinical features and diagnosis".)

(See "Bacterial meningitis in the neonate: Neurologic complications".)

(See "Bacterial meningitis in children older than one month: Clinical features and diagnosis".)

(See "Bacterial meningitis in children older than one month: Treatment and prognosis".)

SUPPORTIVE CARE — Initial care for all neonates with meningitis should be provided in an intensive care unit setting. Supportive care measures are a crucial part of the management of neonates with bacterial meningitis [2]. These may include:

Management of cardiovascular instability or shock (algorithm 1) (see "Neonatal shock: Management")

Provision of oxygen and additional respiratory support as needed (see "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn" and "Overview of mechanical ventilation in neonates")

Careful fluid therapy, avoiding both hypo- and hypervolemia (see "Fluid and electrolyte therapy in newborns")

Prevention and management of hypoglycemia (see "Management and outcome of neonatal hypoglycemia")

Control of seizures (see "Treatment of neonatal seizures")

Nutritional support (see "Approach to enteral nutrition in the premature infant" and "Parenteral nutrition in infants and children")

ANTIMICROBIAL THERAPY — For neonates whose clinical and initial cerebrospinal fluid (CSF) findings are suggestive of bacterial meningitis (eg, CSF pleocytosis, increased CSF protein and/or decreased CSF glucose, organism present on Gram stain), broad-spectrum antimicrobial therapy should be initiated as soon as possible. An appropriate regimen includes agents that have adequate CSF penetration at appropriate doses to achieve adequate levels in the CSF [3].

When the results of the CSF and blood cultures, including antimicrobial susceptibilities, are available, antimicrobial therapy is tailored to the specific pathogen. (See 'Definitive therapy' below.)

Empiric therapy — The initial choice of antimicrobials for suspected bacterial meningitis in the neonate is based on the timing of onset (ie, early versus late onset), likely pathogens (table 1), and local susceptibility patterns within the nursery or neonatal intensive care unit and within the community. (See "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on 'Etiology'.)

In some cases of clinically suspected neonatal meningitis (eg, CSF pleocytosis and negative Gram stain), empiric therapy for herpes simplex virus is also appropriate, as discussed separately. (See "Neonatal herpes simplex virus infection: Management and prevention", section on 'Acyclovir therapy'.)

Early-onset and community-acquired late-onset meningitis — For most neonates, the initial empiric therapy for suspected bacterial meningitis is ampicillin plus an aminoglycoside (usually gentamicin) plus an expanded-spectrum cephalosporin (eg, cefotaxime [where available], ceftazidime, or cefepime). This regimen is appropriate for neonates with early-onset meningitis (typically defined as within the first week after birth for term and near-term neonates and within the first 72 hours for preterm neonates) and for neonates admitted from the community with late-onset meningitis (typically defined as ≥7 days after birth for term and near-term neonates and >72 hours after birth for preterm neonates). Alternatives to cefotaxime are discussed below. (See 'If cefotaxime is unavailable' below.)

Adding an expanded-spectrum cephalosporin to the regimen of ampicillin and gentamicin broadens empiric coverage for gram-negative organisms and provides optimal activity in the CSF against pneumococci. High rates of ampicillin resistance among Escherichia coli isolates and a link between maternal intrapartum ampicillin prophylaxis and E. coli resistance have been reported in very low birth weight infants (birth weight <1500 g) [2,4]. However, this not the case in near-term or term infants, in whom group B streptococcus (GBS) remains the most likely early-onset pathogen [2,4]. Ampicillin resistance is a concern in community-acquired late-onset infections in term and preterm neonates. In one survey of febrile infants <90 days old presenting to an emergency department, nearly 80 percent of infants with meningitis had ampicillin-resistant pathogens [5]. The authors of the study conclude that the initial regimen should contain ampicillin and gentamicin plus an expanded-spectrum cephalosporin because of the risk of GBS and Listeria monocytogenes infection in this age group, as well as for treatment of ampicillin-resistant gram-negative enteric organisms. We agree with this practice.

Antibiotic coverage generally should not be narrowed based on the Gram stain results, because they are subject to observer misinterpretation. Empiric broad-spectrum therapy should be continued pending confirmation of the organism and susceptibility results [6]. (See 'Definitive therapy' below.)

In the neonatal intensive care unit setting, ongoing use of an expanded-spectrum cephalosporin should be restricted to neonates with suspected bacterial meningitis based on clinical findings and CSF parameters. When use of cefotaxime (and, by analogy, another third- or fourth-generation cephalosporin) is routine (eg, when it is used more broadly for all neonates treated for "rule out sepsis"), rapid emergence of cefotaxime-resistant strains (especially Enterobacter cloacae, Klebsiella pneumoniae, and Serratia species) can occur [7].

If meningitis resulting from a multidrug-resistant (MDR) gram-negative organism is strongly suspected (eg, when the CSF Gram stain reveals gram-negative bacilli and positive screen for extended-spectrum beta-lactamase), the empiric regimen should substitute meropenem for the cephalosporin.

The choice of empiric antibiotic therapy for suspected sepsis more broadly in preterm and term neonates is discussed separately. (See "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Empiric antibiotic therapy' and "Management and outcome of sepsis in term and late preterm infants", section on 'Initial empiric therapy'.)

Late-onset meningitis in neonates hospitalized since birth — The empiric regimen for treatment of late-onset (typically defined as ≥7 days after birth for term and near-term neonates and >72 hours after birth for preterm neonates) suspected meningitis in neonates who remain hospitalized since birth consists of vancomycin plus an aminoglycoside plus an expanded-generation cephalosporin (eg, cefotaxime [where available], ceftazidime, or cefepime). Ampicillin should be added to the vancomycin-aminoglycoside regimen if GBS, L. monocytogenes, or enterococci are suspected (eg, on the basis of the Gram stain) because vancomycin concentrations in the CSF are not bactericidal for these organisms. If MDR gram-negative rods are a concern (based on the susceptibility patterns in the particular intensive care unit), meropenem should be substituted for the expanded-spectrum cephalosporin.

If cefotaxime is unavailable — If cefotaxime is unavailable, alternative expanded-spectrum cephalosporin agents include ceftazidime and cefepime [8,9]. Ceftriaxone generally should not be used in neonates, because it can displace bilirubin from albumin binding sites, which might contribute to kernicterus and may precipitate if used with intravenous calcium, leading to severe reactions [10,11]. Meropenem is another alternative, particularly if there is concern for infection due to an MDR gram-negative organism. The determination of whether to provide empiric therapy for MDR organisms is based upon susceptibility patterns of gram-negative organisms at the particular neonatal intensive care unit. MDR gram-negatives remain uncommon in neonatal intensive care units in the United States, but Enterobacteriaceae infections resistant to extended-spectrum beta-lactams are an emerging problem in older infants and children [12].

Definitive therapy — Once the causative agent and the in vitro antimicrobial susceptibility results are known, empiric antimicrobial therapy should be altered accordingly. Guidance for treating the most common causes of neonatal meningitis are provided below.

Group B streptococcus — GBS is uniformly susceptible to penicillin and ampicillin. Penicillin G monotherapy is the appropriate definitive therapy once the neonate is improving clinically and repeat lumbar puncture (LP) documents CSF sterilization (see 'Repeat lumbar puncture' below). Duration of treatment is 14 to 21 days (see 'Duration' below). Treatment of neonatal GBS infections, including GBS meningitis, is summarized in the table and discussed in detail separately (table 2). (See "Group B streptococcal infection in neonates and young infants", section on 'Definitive therapy'.)

Escherichia coli and other gram-negative organisms — Ampicillin is the agent of choice for neonatal meningitis resulting from ampicillin-susceptible strains of E. coli.

Ampicillin-resistant E. coli and other gram-negative organisms usually are initially treated with a combination of an extended-spectrum cephalosporin (eg, cefotaxime if available) plus an aminoglycoside, usually gentamicin; the aminoglycoside is discontinued once sterility of the CSF is documented. Appropriate monotherapy is continued to complete a minimum of 21 days.

The prevalence of antimicrobial resistance among K. pneumoniae has increased markedly since the 1990s [13]. The hospital microbiology laboratory should provide assistance for appropriate testing of gram-negative organisms for MDR patterns.

Infections caused by MDR enteric organisms are generally treated with meropenem. Meropenem should be administered for the entire course of therapy for neonates with meningitis that is caused by MDR gram-negative organisms, although there are limited data documenting the optimal dose and tolerance of meropenem in neonates.

Other pathogens

Coagulase-negative staphylococciVancomycin is the antimicrobial of choice for proven meningitis caused by coagulase-negative staphylococci. These organisms rarely invade the meninges except as a complication of bacteremia accompanying intraventricular hemorrhage in very low birth weight infants (birth weight <1500 g) or as a result of surgical manipulations or placement of a ventriculoperitoneal shunt. Such infections invariably are of late onset.

Sterilization of the CSF usually is achieved promptly after initiation of vancomycin, unless shunt material has not been removed. If the CSF is persistently positive, consideration should be given to adding rifampin (5 mg/kg every 12 hours) to vancomycin for synergy. However, it is uncertain whether combination therapy truly improves clearance of the infection. (See "Infections of cerebrospinal fluid shunts and other devices", section on 'Staphylococci'.)

Listeria – The combination of ampicillin and gentamicin is more effective than ampicillin alone in vitro and in animal models of infection, and it is appropriate for initial therapy (table 3). When the CSF has been sterilized and the infant has improved clinically, a 14- to 21-day course of treatment can be completed with ampicillin monotherapy. (See "Treatment and prevention of Listeria monocytogenes infection", section on 'Antibiotic therapy'.)

Staphylococcus aureus – The standard therapy for methicillin-susceptible S. aureus (MSSA) meningitis is nafcillin or oxacillin [6,14]. Treatment duration is typically 14 days. The preferred therapy for methicillin-resistant S. aureus (MRSA) meningitis is vancomycin [6,14,15]. Treatment duration is at least 14 days. Some experts suggest adding rifampin to vancomycin for treatment of MRSA infection, but there are no clinical studies to suggest efficacy. Treatment of MSSA and MRSA infections is discussed in greater detail separately. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Definitive antimicrobial therapy'.)

Duration — The duration of antibiotic therapy depends upon the results of CSF and blood cultures, the clinical course, and whether the neonate was pretreated with antibiotics prior to the LP.

Positive CSF culture – The suggested duration of antibiotic therapy for different causative organisms is as follows:

GBS or other gram-positive organisms (eg, L. monocytogenes or Enterococcus) – A 14-day course is sufficient for neonates with an uncomplicated course [16].

E. coli or other gram-negative enteric pathogens – A 21-day course is the minimum [17].

A longer course of therapy is required for neonates with meningitis whose course is complicated. Prolonged treatment, sometimes for as long as eight weeks, may be required for neonates with ventriculitis, abscesses, or multiple areas of infarction or hemorrhage with resulting encephalomalacia. (see "Bacterial meningitis in the neonate: Neurologic complications")

Negative CSF culture with positive blood culture and CSF pleocytosis – For neonates with CSF pleocytosis and bacteremia but a negative CSF culture (obtained before antibiotic therapy), we usually continue meningeal doses of antimicrobial therapy for 10 days for gram-positive bacteremia (eg, GBS) and 14 days for gram-negative bacteremia.

Negative CSF and blood cultures – For neonates in whom cultures were obtained before antibiotic therapy and both blood and CSF cultures are negative after 48 hours, we suggest discontinuing antibiotic therapy.

Pretreated or LP delayed – Some neonates may be exposed to antibiotics prior to undergoing LP (eg, because the LP is delayed due to clinical instability, because the mother received intrapartum antibiotic prophylaxis, or because the infant was receiving antibiotics for another reason [eg, prophylaxis for vesicoureteral reflux]). This can result in negative CSF culture. However, in most cases, other CSF parameters, (eg, cell count and protein concentration) will permit accurate diagnosis so long as the LP is not traumatic. (See "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on 'Interpretation of cerebrospinal fluid'.)

Our approach to managing pretreated neonates is as follows:

For neonates in whom the LP was delayed because of clinical instability, meningeal doses of antimicrobial therapy should be continued until the LP can be safely performed.

The total duration of therapy in pretreated neonates depends upon the CSF evaluation and blood culture result:

-Neonates with CSF pleocytosis and positive blood culture are treated for 10 days for gram-positive infection (eg, GBS) and 14 days for gram-negative infection.

-For neonates with normal CSF profile and negative blood and CSF cultures, we usually discontinue antibiotic therapy when cultures are sterile after 48 hours.

-For neonates who have a CSF pleocytosis and negative blood and CSF cultures, we individualize the duration of meningitic doses of antimicrobial therapy based on clinical parameters, including whether there is a noninfectious explanation for the pleocytosis (eg, intraventricular hemorrhage). (See "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on 'Differential diagnosis'.)

ADJUNCTIVE THERAPY — Adjunctive immunomodulatory therapy is not a routine part of management of neonatal meningitis. Though there is evidence from experimental models that immune modulation may positively impact the outcome of neonatal meningitis, the modalities that have undergone clinical investigation thus far have either been shown to be ineffective or they have not been adequately studied.

In particular, we suggest not using glucocorticoid therapy to reduce the risk of neurologic sequelae in neonatal meningitis. There are limited data on the use of glucocorticoids in this setting. In a clinical trial involving 52 neonates randomly assigned to dexamethasone plus antibiotic therapy or antibiotic therapy alone, rates of mortality, neurologic disability, and hearing loss at two years were similar in both groups [18]. In an observational study of 263 infants <90 days old with bacterial meningitis, glucocorticoid therapy was not associated with lower mortality; however, only 8 percent of patients in this cohort received glucocorticoids [19]. The role of dexamethasone therapy in older infants and children with bacterial meningitis is controversial and is discussed separately. (See "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications".)

Adjunctive therapies for neonatal sepsis, which is a prelude to neonatal meningitis, are discussed separately. (See "Management and outcome of sepsis in term and late preterm infants", section on 'Adjunctive therapies'.)

MONITORING RESPONSE TO THERAPY

Ongoing evaluation — The response to therapy and the potential development of complications are monitored with:

Serial neurologic examinations.

Assessment of the overall clinical status (eg, vital sign trends, temperature stability, need for hemodynamic or respiratory support).

Repeat blood cultures – In bacteremic neonates, a repeat blood culture should be performed to document sterility of the blood stream. The follow-up blood culture is usually obtained at the time when the initial blood culture is reported as positive.

Repeat examination of the cerebrospinal fluid (CSF). (See 'Repeat lumbar puncture' below.)

Neuroimaging (See 'Neuroimaging' below.)

Most neonates with uncomplicated bacterial meningitis have clinical improvement within 24 to 48 hours of receiving appropriate antibiotic therapy. Clinical deterioration or failure to improve in this timeframe may suggest development of a complication (eg, obstructive ventriculitis, subdural effusion, brain abscess, intraventricular hemorrhage) or inadequate antimicrobial therapy. (See "Bacterial meningitis in the neonate: Neurologic complications".)

Repeat lumbar puncture — Most neonates with meningitis should have a repeat lumbar puncture (LP) performed 24 to 48 hours after initiation of antimicrobial therapy to document CSF sterilization [6,20]. Repeat LP is suggested for neonates with meningitis caused by group B streptococcus (GBS), E. coli, other gram-negatives, and Listeria and for neonates with a complicated course. This encompasses the majority of patients with neonatal meningitis.

Reevaluation of the CSF 24 to 48 hours after initiation of antimicrobial therapy is important for several reasons [20,21]:

In severe cases, gram-negative organisms may persist for several days. Delayed sterilization of the CSF is associated with an increased risk of developing neurologic sequelae (see 'Outcome' below). This clinical scenario is uncommon with the routine use of an extended-spectrum cephalosporin as initial empiric therapy. By contrast, gram-positive bacteria usually clear from the CSF rapidly (within 24 hours) after initiation of appropriate antimicrobial therapy unless there is high bacterial burden in the CSF [22].

The persistent identification of organisms on a Gram stain may be an early indication of inadequacy of antimicrobial therapy (eg, the organism is not susceptible to the concentration of antibiotic that is attained in the CSF).

Persistence of viable organisms more than 48 hours after initiation of antimicrobial therapy is an indication for diagnostic neuroimaging because it can indicate a purulent focus (eg, obstructive ventriculitis) that can require additional intervention or increased duration of antimicrobial therapy. (See 'Neuroimaging' below and "Bacterial meningitis in the neonate: Neurologic complications".)

Sterilization of the CSF is a criterion for discontinuing combination therapy for some pathogens (eg, GBS, Listeria). (See 'Definitive therapy' above and "Group B streptococcal infection in neonates and young infants", section on 'Definitive therapy'.)

In uncomplicated neonatal meningitis, the CSF culture obtained 24 to 48 hours after initiation of therapy should generally be sterile. A positive culture obtained 24 to 48 hours after initiation of therapy raises a concern for obstructive ventriculitis or intraventricular hemorrhage. The additional evaluation and management of such infants should be individualized and undertaken in consultation with specialists in pediatric infectious diseases and pediatric neurosurgery. (See "Bacterial meningitis in the neonate: Neurologic complications", section on 'Ventriculitis'.)

Neuroimaging — We perform magnetic resonance imaging (MRI) 48 to 72 hours before the anticipated end of therapy in all neonates with confirmed bacterial meningitis, even those with an apparently uncomplicated course. Neuroimaging may be warranted earlier in the course for neonates with signs suggesting neurologic complications. Neurologic complications should be considered if the neonate fails to improve clinically after 24 to 48 hours of appropriate antibiotic therapy. (See "Bacterial meningitis in the neonate: Neurologic complications".)

MRI is preferred over contrast-enhanced computed tomography (CT) because MRI provides better detail, optimizes assessment of injury to white matter, and avoids radiation exposure [23]. If there are focal findings that require extension of the course of antimicrobial therapy, treatment can be continued without interruption.

Cranial sonography – Early in the course of infection, cranial sonography is the most useful and practical neuroimaging technique. It is most helpful for assessing ventricular size and the presence of intraventricular hemorrhage. Cranial sonography also can demonstrate ventriculitis, echogenic sulci, abnormal parenchymal echogenicities, and extracerebral fluid collections [24,25]. In addition, because sonography can be performed at the bedside, it can be useful in defining the progression of complications in infants with prolonged seizure activity or focal neurologic deficits. (See "Bacterial meningitis in the neonate: Neurologic complications".)

MRI or CT – Similar to ultrasonography, early in the treatment course, MRI and CT with contrast enhancement can demonstrate the degree of cerebral edema, obstruction to CSF flow, infarction, abscess, and subdural fluid collections [26]. Later in the treatment course, contrast-enhanced MRI or CT is useful in detecting cerebral abscesses, persistent cerebritis, areas of infarct or encephalomalacia, and degree of cerebral cortical and white matter atrophy. These findings may influence duration of antimicrobial therapy and/or the need for early intervention services. (See "Bacterial meningitis in the neonate: Neurologic complications".)

Contrast-enhanced neuroimaging (MRI or CT) is integral to the care of all neonates with meningitis caused by organisms that have a propensity for formation of intracranial abscesses. These include Citrobacter koseri, Serratia marcescens, Proteus mirabilis, and Enterobacter sakazakii (now known as Cronobacter) [27-33]. (See "Bacterial meningitis in the neonate: Neurologic complications", section on 'Brain abscess'.)

FOLLOW-UP — Long-term follow-up for survivors of neonatal meningitis includes monitoring of hearing, vision, and developmental status. Hearing should be evaluated by auditory brainstem response within four to six weeks of completion of therapy [34]. (See "Hearing loss in children: Screening and evaluation".)

Survivors of neonatal meningitis are at risk for developmental delay and may be eligible to receive early intervention services in the United States (eligibility criteria vary by state). Appropriate referrals should be made as indicated. Developmental surveillance should continue throughout childhood. (See "Developmental-behavioral surveillance and screening in primary care", section on 'Approach to surveillance'.)

OUTCOME — Neonatal meningitis is a devastating disease. Advances in infant intensive care have reduced mortality, but morbidity remains high.

Mortality and disability – In the contemporary era, mortality from neonatal meningitis is approximately 10 percent [1,19,35-39]. However, survivors remain at high risk for neurologic sequelae and lifelong impairments, as illustrated below [36,38,39]. Approximately 15 to 20 percent of survivors have moderate to severe disability, and approximately 30 to 35 percent have mild disability. (See "Bacterial meningitis in the neonate: Neurologic complications".)

In a review of 101 term and late preterm neonates (ie, gestational ≥35 weeks) diagnosed with bacterial meningitis between 1979 and 1998, mortality declined from 17 percent in the early era (1979 to 1988) to 9 percent in the later era (1989 to 1998) [40]. Among survivors, 19 percent had moderate or severe disability at one year of age (defined as severe cerebral palsy, moderate to severe developmental delay, blindness, and/or deafness).

Prognostic factors – Factors predictive of death or serious adverse sequelae from bacterial meningitis include [37,38,40-48]:

Low birth weight (<2500 g) or preterm birth (<37 weeks gestation)

History of clinical signs for >24 hours before hospitalization

Leukopenia (white blood cell <5000/microL) and neutropenia at presentation

Very high cerebrospinal fluid (CSF) protein (>3 g/dL) and/or very low CSF glucose (<10 percent of blood glucose value)

Seizures occurring more than 72 hours after hospitalization

Focal neurologic deficits noted during the acute illness

Requirement for mechanical ventilation or inotropes

Delayed sterilization of the CSF

Neuroimaging findings of meningeal inflammation are generally not predictive of neurologic outcome, but the presence and size of parenchymal lesions (eg, thrombi, encephalomalacia) do have prognostic significance. In particular, abscess formation is associated with neurologic sequelae [25].

Outcomes in preterm neonates – The outcome is generally worse in preterm low birth weight infants compared with term infants. In one study of 113 infants with bacterial meningitis, long-term motor disability (spasticity or paresis) was noted in 27 percent of preterm infants compared with 10 percent of term infants [38].

Similarly, outcomes for preterm neonates with bacterial meningitis are generally worse compared with preterm neonates without meningitis. In one study of very low birth weight infants (birth weight <1500 g), after controlling for birth weight, intraventricular hemorrhage, chronic lung disease, and social risk factors, survivors of meningitis had a twofold higher risk of major neurologic disability (eg, cerebral palsy or abnormal tone, hydrocephalus, blindness, deafness, and severe developmental delay) at 20 months of age [49]. In a large cohort study of extremely low birth weight (birth weight <1000 g) infants, those with neonatal meningitis were more likely than uninfected infants to have cerebral palsy, neurodevelopmental impairment, and low mental developmental index scores [50]. Long-term neurologic outcome in preterm infants is discussed in greater detail separately. (See "Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention", section on 'Predicting outcome'.)

Outcomes by causative organism – Outcomes vary according to the causative organism:

Group B streptococcus (GBS) – Reported mortality rates of neonatal GBS meningitis range from 6 to 11 percent [43,51,52]. Long-term neurologic sequelae occur in approximately 20 to 40 percent of survivors.

In a study of 90 neonates diagnosed with GBS meningitis from 1998 through 2006, 5 percent of patients died acutely and an additional 5 percent died by three years of age [52]. Among the survivors, 56 percent had age-appropriate development, 25 percent had mild-to-moderate impairment, and 19 percent had severe impairment.

Outcomes of GBS infection in neonates are discussed in greater detail separately. (See "Group B streptococcal infection in neonates and young infants", section on 'Outcome'.)

E. coli – In a report of 325 young infants (71 percent were neonates, 35 percent were preterm) diagnosed with E. coli meningitis from 2001 to 2013, the overall mortality rate was 9 percent [37]. Mortality was approximately threefold higher in preterm infants compared with term infants (17 versus 5 percent, respectively). Short-term morbidities included seizures (13 percent), empyema (6 percent), intraventricular hemorrhage or hydrocephalus (5 percent), and cerebral venous thrombosis or stroke (3 percent). Long-term morbidities were not described. Preterm birth and severe hypoglycorrhachia (ie, CSF glucose <10 percent of blood glucose level) were the strongest predictors of death.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sepsis in neonates" and "Society guideline links: Bacterial meningitis in infants and children".)

SUMMARY AND RECOMMENDATIONS

Supportive care – Neonates with bacterial meningitis should receive initial care in an intensive care unit. Supportive care may include (see 'Supportive care' above):

Management of cardiovascular instability or shock (see "Neonatal shock: Etiology, clinical manifestations, and evaluation")

Appropriate respiratory support as needed (see "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn" and "Overview of mechanical ventilation in neonates")

Careful fluid therapy, avoiding both hypo- and hypervolemia (see "Fluid and electrolyte therapy in newborns")

Prevention and management of hypoglycemia (see "Management and outcome of neonatal hypoglycemia")

Control of seizures (see "Treatment of neonatal seizures")

Nutritional support (see "Approach to enteral nutrition in the premature infant" and "Parenteral nutrition in infants and children")

Empiric antimicrobial therapy – For neonates whose clinical and initial cerebrospinal fluid (CSF) findings suggest bacterial meningitis (eg, CSF pleocytosis, increased CSF protein and/or decreased CSF glucose, or organism present on Gram stain), broad-spectrum antimicrobial therapy should be initiated as soon as possible. The choice of the initial empiric regimen is based on the likely pathogens (table 1) and local susceptibility patterns (see 'Empiric therapy' above):

For most neonates, we suggest an empiric regimen that includes ampicillin plus an aminoglycoside (usually gentamicin) plus an expanded-spectrum cephalosporin (eg, cefotaxime [if available], ceftazidime, or cefepime) rather than other regimens (Grade 2C). This regimen is appropriate for neonates with early-onset meningitis (defined as within the first week after birth for term and near-term neonates and within the first 72 hours for preterm neonates) and for infants admitted from the community with late-onset meningitis (defined as ≥7 days after birth for term and near-term neonates and >72 hours after birth for preterm neonates). (See 'Early-onset and community-acquired late-onset meningitis' above.)

For infants with late-onset meningitis who continue to be hospitalized from birth, we suggest a regimen that includes vancomycin plus an aminoglycoside (usually gentamicin) plus an expanded-spectrum cephalosporin (eg, cefotaxime [if available], ceftazidime, or cefepime) (Grade 2C). If group B streptococcus (GBS), Listeria monocytogenes, or enterococci are suspected (eg, on the basis of the Gram stain), ampicillin should be added to the regimen. If multidrug-resistant (MDR) gram-negative rods are a concern (based on the susceptibility patterns in the particular intensive care unit), meropenem should be substituted for the expanded-spectrum cephalosporin. (See 'Late-onset meningitis in neonates hospitalized since birth' above.)

In some cases of clinically suspected neonatal meningitis (eg, CSF pleocytosis and negative Gram stain), empiric therapy for herpes simplex virus is also appropriate, as discussed separately. (See "Neonatal herpes simplex virus infection: Management and prevention", section on 'Acyclovir therapy'.)

Definitive antibiotic therapy – Once the causative agent and its in vitro antimicrobial susceptibility pattern are known, empiric antimicrobial therapy should be altered accordingly (see 'Definitive therapy' above):

GBS – GBS is uniformly susceptible to penicillin and ampicillin. Penicillin G monotherapy is the appropriate definitive therapy once clinical and microbiologic responses have been documented. Duration of treatment is 14 to 21 days. Treatment of neonatal GBS infections, including GBS meningitis, is summarized in the table and discussed in detail separately (table 2). (See "Group B streptococcal infection in neonates and young infants", section on 'Definitive therapy'.)

Escherichia coli and other gram-negatives – Treatment depends on the susceptibility pattern. Ampicillin is used for ampicillin-susceptible strains of E. coli. Ampicillin-resistant organisms usually are initially treated with a combination of an extended-spectrum cephalosporin plus an aminoglycoside (eg, gentamicin); the aminoglycoside is discontinued once sterility of the CSF is documented. Infections caused by MDR enteric organisms are treated with meropenem. Treatment duration is for a minimum of 21 days. (See 'Escherichia coli and other gram-negative organisms' above and 'Duration' above.)

Antibiotic regimens for other causes of neonatal meningitis are summarized above. (See 'Other pathogens' above.)

Monitoring – The response to therapy and the potential development of complications are monitored clinically, through serial neurologic examinations, repeat lumbar puncture (LP), and neuroimaging (see 'Monitoring response to therapy' above):

Neurologic complications should be considered in the neonate with meningitis who fails to improve clinically after 24 to 48 hours of appropriate antibiotic therapy. (See "Bacterial meningitis in the neonate: Neurologic complications".)

Most neonates should undergo repeat LP 24 to 48 hours after initiation of antibiotic therapy to document sterilization of the CSF. (See 'Repeat lumbar puncture' above.)

We perform magnetic resonance imaging (MRI) 48 to 72 hours before the anticipated discontinuation of antimicrobial therapy in all neonates with bacterial meningitis, even in those with an apparently uncomplicated course. Neuroimaging may be warranted earlier in the course for neonates with signs suggesting neurologic complications. (See 'Neuroimaging' above.)

Outcome – In the modern era, the mortality of neonatal bacterial meningitis is approximately 10 percent. Approximately 15 to 20 percent of survivors have moderate to severe disability, and approximately 30 to 35 percent have mild disability. (See 'Outcome' above.)

Follow-up – Long-term follow-up for survivors of neonatal meningitis includes monitoring of hearing, visual acuity, and developmental milestones. (See 'Follow-up' above.)

  1. Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998-2007. N Engl J Med 2011; 364:2016.
  2. Nizet V, Klein JO. Bacterial sepsis and meningitis. In: Infectious Diseases of the Fetus and Newborn Infant, 8th ed, Wilson CS, Nizet V, Maldonado YA, Remington JS, Klein JO (Eds), Elsevier Saunders, Philadelphia 2016. p.217.
  3. Sarff LD, Platt LH, McCracken GH Jr. Cerebrospinal fluid evaluation in neonates: comparison of high-risk infants with and without meningitis. J Pediatr 1976; 88:473.
  4. Alarcon A, Peña P, Salas S, et al. Neonatal early onset Escherichia coli sepsis: trends in incidence and antimicrobial resistance in the era of intrapartum antimicrobial prophylaxis. Pediatr Infect Dis J 2004; 23:295.
  5. 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.
  6. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004; 39:1267.
  7. Bryan CS, John JF Jr, Pai MS, Austin TL. Gentamicin vs cefotaxime for therapy of neonatal sepsis. Relationship to drug resistance. Am J Dis Child 1985; 139:1086.
  8. Puopolo KM, Lynfield R, Cummings JJ, et al. Management of Infants at Risk for Group B Streptococcal Disease. Pediatrics 2019; 144.
  9. Alternatives to consider during cefotaxime shortage. AAP News. Available at: http://www.aappublications.org/content/early/2015/02/25/aapnews.20150225-1 (Accessed on May 22, 2017).
  10. Donnelly PC, Sutich RM, Easton R, et al. Ceftriaxone-Associated Biliary and Cardiopulmonary Adverse Events in Neonates: A Systematic Review of the Literature. Paediatr Drugs 2017; 19:21.
  11. Bradley JS, Wassel RT, Lee L, Nambiar S. Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics 2009; 123:e609.
  12. Logan LK, Braykov NP, Weinstein RA, et al. Extended-Spectrum β-Lactamase-Producing and Third-Generation Cephalosporin-Resistant Enterobacteriaceae in Children: Trends in the United States, 1999-2011. J Pediatric Infect Dis Soc 2014; 3:320.
  13. Lautenbach E, Patel JB, Bilker WB, et al. Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes. Clin Infect Dis 2001; 32:1162.
  14. Aguilar J, Urday-Cornejo V, Donabedian S, et al. Staphylococcus aureus meningitis: case series and literature review. Medicine (Baltimore) 2010; 89:117.
  15. Liu C, Bayer A, Cosgrove SE, et al. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52:e18.
  16. American Academy of Pediatrics. Group B streptococcal infections. In: Red Book: 2018 Report of the Committee on Infectious Diseases, 31st ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Itasca, IL 2018. p.762.
  17. American Academy of Pediatrics. Serious bacterial infections caused by Enterobacteriaceae (with emphasis on septicemia and meniningitis in neonates). In: Red Book: 2018 Report of the Committee on Infectious Disease, 31st Ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Itasca, IL 2018. p.328.
  18. Daoud AS, Batieha A, Al-Sheyyab M, et al. Lack of effectiveness of dexamethasone in neonatal bacterial meningitis. Eur J Pediatr 1999; 158:230.
  19. Okike IO, Ladhani SN, Johnson AP, et al. Clinical Characteristics and Risk Factors for Poor Outcome in Infants Less Than 90 Days of Age With Bacterial Meningitis in the United Kingdom and Ireland. Pediatr Infect Dis J 2018; 37:837.
  20. Heath PT, Nik Yusoff NK, Baker CJ. Neonatal meningitis. Arch Dis Child Fetal Neonatal Ed 2003; 88:F173.
  21. Pong A, Bradley JS. Bacterial meningitis and the newborn infant. Infect Dis Clin North Am 1999; 13:711.
  22. McCracken GH Jr. The rate of bacteriologic response to antimicrobial therapy in neonatal meningitis. Am J Dis Child 1972; 123:547.
  23. Shah DK, Daley AJ, Hunt RW, et al. Cerebral white matter injury in the newborn following Escherichia coli meningitis. Eur J Paediatr Neurol 2005; 9:13.
  24. Raju VS, Rao MN, Rao VS. Cranial sonography in pyogenic meningitis in neonates and infants. J Trop Pediatr 1995; 41:68.
  25. Yikilmaz A, Taylor GA. Sonographic findings in bacterial meningitis in neonates and young infants. Pediatr Radiol 2008; 38:129.
  26. Volpe JJ. Bacterial and fungal intracranial infections. In: Neurology of the newborn, 4th ed, WB Saunders Company, Philadelphia 2001. p.774.
  27. Campbell JR, Diacovo T, Baker CJ. Serratia marcescens meningitis in neonates. Pediatr Infect Dis J 1992; 11:881.
  28. Kline MW, Kaplan SL. Citrobacter diversus and neonatal brain abscess. Pediatr Neurol 1987; 3:178.
  29. Graham DR, Band JD. Citrobacter diversus brain abscess and meningitis in neonates. JAMA 1981; 245:1923.
  30. Willis J, Robinson JE. Enterobacter sakazakii meningitis in neonates. Pediatr Infect Dis J 1988; 7:196.
  31. Renier D, Flandin C, Hirsch E, Hirsch JF. Brain abscesses in neonates. A study of 30 cases. J Neurosurg 1988; 69:877.
  32. Iversen C, Lehner A, Mullane N, et al. Identification of "Cronobacter" spp. (Enterobacter sakazakii). J Clin Microbiol 2007; 45:3814.
  33. Phan H, Lehman D. Cerebral abscess complicating Proteus mirabilis meningitis in a newborn infant. J Child Neurol 2012; 27:405.
  34. Harrison GJ. Approach to infections in the fetus and newborn. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th, Cherry JD, Harrison GJ, Kaplan SL, et al (Eds), Elsevier Saunders, Philadelphia 2014. p.877.
  35. Harvey D, Holt DE, Bedford H. Bacterial meningitis in the newborn: a prospective study of mortality and morbidity. Semin Perinatol 1999; 23:218.
  36. de Louvois J, Halket S, Harvey D. Neonatal meningitis in England and Wales: sequelae at 5 years of age. Eur J Pediatr 2005; 164:730.
  37. Basmaci R, Bonacorsi S, Bidet P, et al. Escherichia Coli Meningitis Features in 325 Children From 2001 to 2013 in France. Clin Infect Dis 2015; 61:779.
  38. Ouchenir L, Renaud C, Khan S, et al. The Epidemiology, Management, and Outcomes of Bacterial Meningitis in Infants. Pediatrics 2017; 140.
  39. 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:F85.
  40. Klinger G, Chin CN, Beyene J, Perlman M. Predicting the outcome of neonatal bacterial meningitis. Pediatrics 2000; 106:477.
  41. Unhanand M, Mustafa MM, McCracken GH Jr, Nelson JD. Gram-negative enteric bacillary meningitis: a twenty-one-year experience. J Pediatr 1993; 122:15.
  42. Anderson SG, Gilbert GL. Neonatal gram negative meningitis: a 10-year review, with reference to outcome and relapse of infection. J Paediatr Child Health 1990; 26:212.
  43. Levent F, Baker CJ, Rench MA, Edwards MS. Early outcomes of group B streptococcal meningitis in the 21st century. Pediatr Infect Dis J 2010; 29:1009.
  44. Edwards MS, Rench MA, Haffar AA, et al. Long-term sequelae of group B streptococcal meningitis in infants. J Pediatr 1985; 106:717.
  45. May M, Daley AJ, Donath S, et al. Early onset neonatal meningitis in Australia and New Zealand, 1992-2002. Arch Dis Child Fetal Neonatal Ed 2005; 90:F324.
  46. Franco SM, Cornelius VE, Andrews BF. Long-term outcome of neonatal meningitis. Am J Dis Child 1992; 146:567.
  47. 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; 31:425.
  48. ter Horst HJ, van Olffen M, Remmelts HJ, et al. The prognostic value of amplitude integrated EEG in neonatal sepsis and/or meningitis. Acta Paediatr 2010; 99:194.
  49. Doctor BA, Newman N, Minich NM, et al. Clinical outcomes of neonatal meningitis in very-low birth-weight infants. Clin Pediatr (Phila) 2001; 40:473.
  50. Stoll BJ, Hansen NI, Adams-Chapman I, et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA 2004; 292:2357.
  51. Phares CR, Lynfield R, Farley MM, et al. Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005. JAMA 2008; 299:2056.
  52. Libster R, Edwards KM, Levent F, et al. Long-term outcomes of group B streptococcal meningitis. Pediatrics 2012; 130:e8.
Topic 6016 Version 40.0

References