Bacterial meningitis in children older than one month: Clinical features and diagnosis

INTRODUCTION — Children with suspected bacterial meningitis require urgent evaluation and management, including prompt administration of appropriate antimicrobial therapy (table 1). The mortality rate of untreated bacterial meningitis approaches 100 percent. Even with optimal therapy, morbidity and mortality may occur. Neurologic sequelae are common among survivors.

The clinical features, evaluation, and diagnosis of bacterial meningitis in infants and children older than one month will be reviewed here. Other aspects of bacterial meningitis in pediatric patients are discussed separately:

●Treatment and prognosis (see "Bacterial meningitis in children older than one month: Treatment and prognosis")

●Bacterial meningitis in neonates (see "Bacterial meningitis in the neonate: Clinical features and diagnosis" and "Bacterial meningitis in the neonate: Treatment and outcome" and "Bacterial meningitis in the neonate: Neurologic complications")

●Neurologic complications (see "Bacterial meningitis in children: Neurologic complications" and "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications")

●Pathophysiology (see "Pathogenesis and pathophysiology of bacterial meningitis")

EPIDEMIOLOGY

Incidence — In a population-based surveillance study from the United States (2006 to 2007), the annual incidence of bacterial meningitis in children varied with age as follows [1]:

●<2 months – 81 per 100,000 population

●2 months to 2 years – 7 per 100,000 population

●2 through 10 years – 0.6 per 100,000 population

●11 through 17 years – 0.4 per 100,000 population

Causative organisms — The relative frequency of different causative pathogens varies by age and by geographic region. In addition, certain pathogens may be more likely depending upon the route of acquisition and underlying host factors (table 2). (See 'Predisposing factors' below.)

●Age – The most frequent pathogens vary according to age as follows [1-6]:

•Infants <3 months old – Group B streptococcus (GBS) and Escherichia coli are the most common pathogens in neonates and young infants. Other enteric gram-negative bacilli, Streptococcus pneumoniae, and Neisseria meningitidis are less common in this age group. Other uncommon pathogens include Enterococcus, Staphylococcus aureus, Listeria monocytogenes, group A streptococcus, and Haemophilus influenzae. (See "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on 'Etiology'.)

•Older infants and children – S. pneumoniae and N. meningitidis are the most common pathogens in this age group, together accounting for approximately 60 to 70 percent of cases [1,2,4,7]. As discussed below, the relative frequencies of these two pathogens vary somewhat in different geographic regions. Less common pathogens in this age group include group A streptococcus and GBS, H. influenzae, and other gram-negative organisms.

•Adolescents – N. meningitidis is the most common pathogen in adolescents, accounting for more than one-half of all cases [1,2,4,7].

●Geographic region – The most frequent pathogens vary somewhat from region to region [8]:

•North America – In North America, S. pneumoniae is the most frequent pathogen, accounting for 35 to 60 percent of cases, followed by N. meningitidis (15 to 25 percent), H. influenzae (15 to 20 percent, predominantly non-type B in the post-Hib vaccine era), GBS (10 to 15 percent), E. coli (7 percent), and L. monocytogenes (2 to 3 percent) [1,2,7,9-11].

•Europe – In the United Kingdom and Europe, N. meningitidis is more common than in North America, accounting for approximately 30 to 50 percent of cases, followed by S. pneumoniae, (20 to 40 percent), GBS (10 to 15 percent), and H. influenzae (5 to 15 percent) [4,8,12,13].

•Sub-Saharan Africa – In the meningitis belt in sub-Saharan Africa (figure 1), N. meningitidis accounts for approximately 50 to 60 percent of cases [14]; however, S. pneumoniae and H. influenzae are also important causes in this region [14,15]. In a systematic review and meta-analysis of the global burden of bacterial meningitis, S. pneumoniae accounted for 41 percent of cases among children in the entire African region; H. influenzae accounted for 13 percent and N. meningitidis 7.5 percent [8].

Impact of vaccination — After the introduction of the Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines to the infant immunization schedule (which occurred in the United States in 1990 and 2000, respectively), the incidence of bacterial meningitis declined in all age groups except infants <2 months old [1,3,4]. The median age shifted from <5 years to approximately 30 to 40 years, though the incidence remains highest among infants <2 months old [1,4,16].

●S. pneumoniae – The incidence of pneumococcal meningitis in children in the United States declined by 50 to 60 percent after widespread pneumococcal vaccination [1,2,17-20]. However, S. pneumoniae remains among the most common causes of bacterial meningitis in children [20].

After the heptavalent pneumococcal conjugate vaccine (PCV7) was added to the universal infant immunization schedule in the United States and other developed countries, rates of pneumococcal meningitis declined significantly, particularly in children <2 years old [1,18,21]. However, PCV7 covered only a small fraction of the >100 pneumococcal serotypes. Thus, while the incidence of PCV7 serotypes declined by >90 percent, there was an increase in disease caused by non-PCV7 serotypes [1,22,23].

Expanded pneumococcal conjugate vaccines were subsequently introduced (PCV10, PCV13, PCV15, PCV20) (table 3), which further reduced disease caused by vaccine serotypes by >90 percent, though rates of disease have still been sustained by serotype replacement [23].

●Hib – Before widespread vaccination for Hib in the United States, Hib was the major cause of bacterial meningitis in children [24]. In developing countries that do not routinely immunize against Hib, Hib continues to be a frequent cause of meningitis [25]. (See "Prevention of Haemophilus influenzae type b infection".)

Mechanisms of infection — There are three major mechanisms for developing meningitis (see "Pathogenesis and pathophysiology of bacterial meningitis"):

●Colonization of the nasopharynx, with subsequent bloodstream invasion followed by central nervous system (CNS) invasion

●Direct entry of organisms into the CNS from one of these sources:

•Contiguous infection (eg, sinusitis, mastoiditis) (see "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis", section on 'Complications' and "Acute mastoiditis in children: Clinical features and diagnosis", section on 'Complications')

•Trauma, neurosurgery, cerebrospinal fluid (CSF) leak, and congenital defects (dermal sinus, Mondini dysplasia) (see "Skull fractures in children: Clinical manifestations, diagnosis, and management", section on 'Complications')

•Medical devices (eg, CSF shunts, cochlear implants) (see "Infections of cerebrospinal fluid shunts" and "Cochlear implant infections")

●Invasion of the CNS following bacteremia from another localized source (eg, infective endocarditis) and/or bacteremia from immune defects (eg, innate immune dysfunction) (see "Infective endocarditis in children")

Predisposing factors — Risk factors for bacterial meningitis include:

●Congenital or acquired immunodeficiency (eg, asplenia, complement deficiency, hypogammaglobulinemia, HIV infection, glucocorticoid use, diabetes mellitus, other innate immune defects) (table 4).

●Anatomic defects of the spinal cord (eg, dermal sinus (picture 1)), brain, or inner ear (see "Cutaneous developmental anomalies in the newborn and infant", section on 'Cranial dermoid cysts and dermal sinus tracts').

●Acquired cranial defects due to basilar skull fracture or surgery (see "Skull fractures in children: Clinical manifestations, diagnosis, and management", section on 'Basilar skull fractures').

●Presence of a medical device (eg, CSF shunt, cochlear implant) (see "Infections of cerebrospinal fluid shunts" and "Cochlear implant infections").

●Parameningeal infections (eg, sinusitis, mastoiditis) (see "Acute bacterial rhinosinusitis in children: Clinical features and diagnosis", section on 'Complications' and "Acute mastoiditis in children: Clinical features and diagnosis", section on 'Complications').

●Recent infection (especially respiratory and ear infections) (see "Acute otitis media in children: Clinical manifestations and diagnosis", section on 'Complications of AOM').

●Recent exposure to someone with meningitis.

●Recent travel to an area with endemic meningococcal disease, such as sub-Saharan Africa (figure 1).

CLINICAL FEATURES

Course — Acute bacterial meningitis has two patterns of presentation [26,27]:

●Gradually progressive course – Most children with meningitis have a preceding febrile illness and then develop signs and symptoms of meningeal inflammation progressively over one to several days.

●Fulminant course – Patients with acute and fulminant meningitis present with manifestations of sepsis and meningitis that develop rapidly over several hours. The fulminant presentation is often complicated by severe brain edema.

Presentation — Most children with bacterial meningitis present with fever and symptoms and signs of meningeal inflammation (eg, nuchal rigidity, irritability, confusion or altered mental status, headache, photophobia, nausea, vomiting), often preceded by symptoms of upper respiratory tract infection [27]. The classic triad of fever, neck stiffness, and abnormal mental status occurs in a minority of affected children [19,27,28].

The clinical presentation is variable and nonspecific; no single sign is pathognomonic [28]. The symptoms and signs depend, to some extent, upon the duration of illness, host response to infection, and age of the child [26,29].

●Infants – In infants, manifestations may include [28,29]:

•Fever or hypothermia

•Lethargy

•Poor feeding

•Irritability

•Bulging fontanel

•Vomiting

•Diarrhea

•Respiratory distress

•Jaundice

•Seizures

●Children and adolescents – In children and adolescents, clinical manifestations may include [27,29]:

•Fever

•Headache

•Neck stiffness

•Photophobia

•Nausea/vomiting

•Confusion

•Lethargy

•Irritability

Advanced illness is characterized by lethargy, dehydration, or signs of septic shock. (See "Septic shock in children in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)".)

Clinical findings

●General appearance – Children with bacterial meningitis generally appear uncomfortable. In one study of 103 children with bacterial meningitis, three-quarters of the children were toxic-appearing at the time of admission [29].

Vital sign abnormalities (eg, tachycardia, tachypnea) are often present, particularly in young children. Patients with acute and fulminant presentation may present with hypotension and shock.

●Meningeal signs – Meningeal signs (nuchal rigidity, headache, photophobia, irritability) are present at the time of admission in the majority of patients.

Nuchal rigidity is manifest by the inability to place the chin on the chest, limitation of passive neck flexion, and Kernig and Brudzinski signs.

•Kernig sign – Kernig sign is present if the patient, in the supine position with the hip and knee flexed at 90°, cannot extend the knee more than 135° and/or there is flexion of the opposite knee (movie 1A).

•Brudzinski sign – Brudzinski sign is present if the patient, while in the supine position, flexes the lower extremities during attempted passive flexion of the neck (movie 1B).

Signs of meningeal irritation are present at the time of presentation in approximately 60 to 80 percent of affected children and can be elicited at some point during the hospital course in >90 percent of affected children [26,30-32]. Nuchal rigidity may not be elicited in comatose patients or those with focal or diffuse neurologic deficits [27]. In addition, nuchal rigidity may occur late in the course, particularly in young children.

While nuchal rigidity is highly suggestive of meningitis, it can occur in many other conditions, as summarized in the table (table 5) and discussed separately. (See 'Differential diagnosis' below and "Approach to neck stiffness in children".)

●Neurologic findings – Neurologic abnormalities may include depressed or altered mental status (eg, irritability, lethargy, confusion, somnolence), seizures, signs of elevated intracranial pressure (ICP), and other focal neurologic findings.

•Abnormal mental status – Most affected patients have an abnormal mental status at the time of presentation, which can range from irritability or confusion, to lethargy, to coma.

In a review of 235 children with bacterial meningitis, approximately three-quarters were irritable or lethargic, 7 percent were somnolent, and 15 percent were semicomatose or comatose at the time of admission [27]. In another study of 103 pediatric patients with bacterial meningitis, 28 percent had a Glasgow Coma Scale score (table 6) ≤10 at the time of admission [29].

The level of consciousness at the time of admission has prognostic significance [33]; patients who are obtunded, semicomatose, or comatose at the time of admission are more likely to have an adverse outcome [34]. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Prognostic factors'.)

•Seizures – Approximately 20 to 30 percent of patients with meningitis experience seizures prior to presentation or within the first 48 hours of admission [27,35,36]. Seizures are typically generalized. Focal seizures can occur later in the course, which may indicate cerebral injury [20,35,37]. (See "Bacterial meningitis in children: Neurologic complications", section on 'Seizures'.)

•Increased ICP – In infants, signs of increased ICP may include bulging fontanel or diastasis of the cranial sutures. In older children, signs of increased ICP may include headache, vomiting, and altered mental status [28]. The constellation of systemic hypertension, bradycardia, and respiratory depression (Cushing triad) is a late sign of increased ICP. Papilledema on funduscopic examination is suggestive of increased ICP at any age, but it is an uncommon finding in acute bacterial meningitis. The finding of papilledema should prompt evaluation for venous sinus occlusion, subdural empyema, or brain abscess. (See 'Neuroimaging' below and "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis".)

Other signs of increased ICP that may occur in bacterial meningitis include palsies of the third (figure 2), fourth (picture 2), and sixth (most common) cranial nerves. (See "Third cranial nerve (oculomotor nerve) palsy in children" and "Fourth cranial nerve (trochlear nerve) palsy" and "Sixth cranial nerve (abducens nerve) palsy", section on 'Clinical manifestations'.)

•Focal neurologic findings – Focal neurologic findings may include motor abnormalities (eg, hemiparesis, quadriparesis), asymmetric or absent tendon reflexes, or cranial nerve palsies (eg, abnormal pupillary light response, visual field defects, eye deviation or abnormal extraocular movements, facial asymmetry). (See "Detailed neurologic assessment of infants and children".)

In one review of 235 children with bacterial meningitis, 10 percent had focal neurologic findings at the time of admission [38]. The presence of focal neurologic signs at the time of admission was associated with increased risk of persistent neurologic abnormalities and cognitive impairment one year after discharge.

Focal neurologic findings also may occur as a late complication of meningitis. (See "Bacterial meningitis in children: Neurologic complications", section on 'Motor deficits'.)

●Cutaneous findings – Petechiae (picture 3) and purpura (picture 4) may occur with any of the bacterial pathogens but are most commonly seen in N. meningitidis. The lesions are usually more pronounced on the extremities and can be preceded by an erythematous maculopapular eruption. (See "Clinical manifestations of meningococcal infection", section on 'Rash'.)

●Other signs of focal infection – Another focus of infection (eg, otitis media, pneumonia, mastoiditis) may be present. (See "Acute otitis media in children: Clinical manifestations and diagnosis" and "Acute mastoiditis in children: Clinical features and diagnosis" and "Community-acquired pneumonia in children: Clinical features and diagnosis".)

●Systemic findings – Children with bacterial meningitis frequently present with systemic manifestations, which can range from fever and chills to septic shock, disseminated intravascular coagulation, acute respiratory distress syndrome, pericardial effusion, and septic or reactive arthritis. Most of these systemic complications are consequences of the bacteremia that frequently accompanies meningitis.

Arthritis is most common with meningococcal disease but may occur with other infections [27]. Early in the course of meningitis, arthritis may be related to direct invasion of the joint, whereas arthritis that develops late in the course is considered an immune complex-mediated event. (See "Clinical manifestations of meningococcal infection", section on 'Arthritis'.)

Pericardial effusions also may develop in patients with disseminated illness. They usually resolve during the course of antibiotic therapy [27]. In some cases, pericardial effusions are the cause of persistent fever and pericardiocentesis or an open drainage procedure may be required. (See "Clinical manifestations of meningococcal infection", section on 'Arthritis' and "Clinical manifestations of meningococcal infection", section on 'Pericarditis'.)

EVALUATION

Pace of evaluation — Suspected bacterial meningitis is a medical emergency, and immediate diagnostic steps must be taken to establish the specific cause (table 1). Ideally, a careful history, physical examination, blood tests, and lumbar puncture (LP) should be performed before the initiation of therapy for meningitis.

However, in fulminant cases with hypotension and end-organ failure, rapid intervention is particularly necessary; administration of antibiotics may precede complete history, examination, and LP. In such cases, blood culture should be obtained before administration of antibiotics and LP performed as soon as is feasible. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)

History and physical examination

●History – Important aspects of the history in the child with suspected bacterial meningitis include:

•History of present illness, including the course of illness (see 'Course' above), preceding illness, symptoms consistent with meningeal inflammation, and history of seizures. (See 'Clinical findings' above and 'Presentation' above.)

•Presence of predisposing factors, such as immunodeficiency, anatomic defects, prior neurosurgery, medical devices (eg, cerebrospinal fluid [CSF] shunt, cochlear implant) (table 4), travel to an area with endemic meningococcal disease (figure 1), or exposure to someone with bacterial meningitis. (See 'Predisposing factors' above.)

•Immunization history (particularly the H. influenzae type b [Hib] conjugate vaccine, pneumococcal conjugate or polysaccharide vaccine, and meningococcal conjugate or polysaccharide vaccine); receipt of a full series of any of these vaccines does not alter the need for CSF examination or initial empiric antibiotic therapy but, depending upon age, may affect the need for chemoprophylaxis or evaluation of the immune system. (See 'Assessment of immune function' below.)

•History of drug allergies, particularly anaphylactic reactions to antibiotics, which, if present, may affect the choice of antimicrobial therapy. (See "Penicillin allergy: Immediate reactions" and "Immediate cephalosporin hypersensitivity: Allergy evaluation, skin testing, and cross-reactivity with other beta-lactam antibiotics" and "Vancomycin hypersensitivity".)

•Recent use of antibiotics, which may affect the yield of blood and/or CSF culture. (See 'Interpretation' below.)

●Examination – Important aspects of the examination of a child with suspected bacterial meningitis include vital signs, general appearance, presence of meningeal signs, neurologic examination, and cutaneous examination.

•The vital signs are an important part of the assessment of volume status and detection of shock and/or elevated intracranial pressure (ICP). The constellation of systemic hypertension, bradycardia, and respiratory depression (Cushing triad) is a late sign of increased ICP. (See "Elevated intracranial pressure (ICP) in children: Clinical manifestations and diagnosis".)

•Elicitation of meningeal signs (movie 1A-B) and important aspects of the neurologic and cutaneous examinations are discussed above. (See 'Clinical features' above.)

•Patients with acute bacterial meningitis may also have clinical manifestations of another focal source of infection (eg, facial cellulitis, sinusitis, otitis media, arthritis, pneumonia).

Laboratory evaluation

Blood tests — Initial blood tests should include (table 1):

●Blood culture – Blood cultures are positive in approximately 60 to 85 percent of patients with bacterial meningitis [20,39,40].

●Complete blood count with differential.

●Inflammatory markers (eg, C-reactive protein, procalcitonin) – When used in isolation, C-reactive protein and procalcitonin are not sufficiently specific to accurately discriminate between viral and bacterial meningitis [41-46]. However, these tests can be helpful when used in conjunction with other variables (eg, as part of a clinical prediction rule as discussed separately). (See "Viral meningitis in children: Management, prognosis, and prevention", section on 'Assessing risk of bacterial meningitis'.)

●Serum electrolytes, glucose, blood urea nitrogen, and creatinine – These are helpful in assessing volume status and planning fluid administration. Serum glucose level is necessary for determining the CSF-to-blood glucose ratio.

●Coagulation studies (prothrombin time [PT], international normalized ratio [INR], activated partial thromboplastin time [aPTT]), particularly in patients with petechiae or purpuric lesions.

●Lactate level if there is concern for septic shock. (See "Septic shock in children in resource-abundant settings: Rapid recognition and initial resuscitation (first hour)", section on 'Obtain laboratory studies'.)

Lumbar puncture

Indications and contraindications — An LP should be performed in all children with suspected meningitis, unless specific contraindications to LP are present [27]. The threshold for CSF examination should be fairly low in patients with underlying conditions that may predispose them to bacterial meningitis. (See 'Predisposing factors' above.)

LP also should be considered in children with bacteremia and persistent fevers, even if meningeal signs are absent, since bacteremia can progress to meningitis [47].

Indications for performing neuroimaging prior to LP are listed below (see 'Neuroimaging' below). Additional contraindications to LP include cardiopulmonary compromise and skin infection over the LP site. (See "Lumbar puncture in children", section on 'Contraindications'.)

It is essential that antimicrobial therapy not be delayed if there is a contraindication to or inability to perform an LP or if the LP is delayed by the need for neuroimaging. In any of these situations, blood cultures should be obtained and empiric antibiotics administered as soon as is possible (before the imaging study in children who require imaging) (table 1). (See 'Initiation of empiric therapy' below and 'Neuroimaging' below.)

Tests to perform — CSF should be sent for:

●Cell count and differential

●Glucose and protein concentration

●Gram stain and culture

Additional testing for unusual pathogens may be warranted in special circumstances (eg, in immunocompromised hosts) [48]. It is helpful to reserve a tube of CSF for further testing, which may be necessary if the patient fails to improve as expected.

Interpretation — Characteristic CSF findings in bacterial meningitis include (table 7 and table 8):

●CSF pleocytosis with a predominance of neutrophils

●Elevated CSF protein

●Decreased CSF glucose

●Positive Gram stain

The following sections provide additional details on CSF cell count, CSF chemistries, interpretation of CSF studies in patients with traumatic LPs and those pretreated with antibiotics, and the approach to differentiating between bacterial and aseptic meningitis:

●Cell count – A CSF white blood cell (WBC) count >9 WBCs/microL is considered abnormal for infants <3 months of age, and CSF WBC >6/microL is abnormal in children ≥3 months old [27,49,50]. The CSF WBC count in acute bacterial meningitis is typically >1000 WBC/microL, with a predominance of neutrophils (table 7) [27]. However, early in the course (after bacterial invasion but before the inflammatory response), few or no WBCs may be present [51]. In addition, it is important to recognize that CSF pleocytosis may be lacking in children with innate immune defects who have meningitis. Neither the presence nor quantity of bands (immature neutrophils) in the CSF helps to distinguish bacterial from viral meningitis [52]. (See "Viral meningitis in children: Clinical features and diagnosis", section on 'Cerebrospinal fluid studies'.)

●Glucose and protein – The CSF glucose level in bacterial meningitis is typically low, usually <60 percent of the blood glucose level [53]. In more than one-half of cases, CSF glucose is <40 mg/dL (table 7) [27]. The CSF protein in acute bacterial meningitis typically ranges from 100 to 500 mg/dL (table 7) [27].

●Traumatic LP – When the LP is traumatic, small amounts of blood enter into the CSF, which can impact the CSF cell count and protein measurements:

•"Corrected" WBC count – Various formulas have been used to account for blood in the interpretation of the CSF cell count. These methods can help provide a rough estimate of the CSF WBC count when the LP is traumatic, but they cannot be used to exclude meningitis with complete confidence [54,55]. In most cases when the LP is traumatic, it is appropriate to treat presumptively for meningitis pending results of CSF culture. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)

Our approach to estimating the "corrected" CSF WBC, which we apply only if the CSF is not grossly bloody, is to subtract 1 WBC for every 1000 red blood cells (RBCs)/microL. Others subtract 1 WBC for every 500 RBCs/microL

•"Corrected" CSF protein – The CSF protein concentration may be increased in children with traumatic LP because of the increased protein concentration in plasma and the release of proteins from lysed RBCs [56]. A "corrected" CSF protein concentration can be estimated by subtracting 1 mg/dL for every 1000 RBCs/microL [56].

●Pretreated patients – Prior administration of antimicrobial agents, particularly oral antibiotics, generally has minimal effect on CSF cytology [57-61]. However, pretreatment with antibiotics may alter CSF chemistry results. In a study examining CSF chemistry results in 85 children with bacterial meningitis who received antibiotics ≥12 hours before LP compared with 146 children who had not received antibiotics, pretreated children had higher CSF glucose concentration (median 48 versus 29 mg/dL [2.66 versus 1.6 mmol/L], respectively) and lower CSF protein concentration (median 121 versus 178 mg/dL [1.21 versus 1.78 g/L], respectively) [61].

The impact of pretreatment on CSF culture results is discussed below. (See 'Cerebrospinal fluid culture' below.)

●Distinguishing between bacterial and aseptic meningitis – The clinical and laboratory findings of bacterial meningitis overlap with those of aseptic or viral meningitis (table 7 and table 8). In patients with CSF pleocytosis, clinical prediction rules can be used in conjunction with clinical judgment to identify patients with a very low risk of bacterial meningitis. The approach is summarized in the algorithm and discussed in greater detail separately (algorithm 1). (See "Viral meningitis in children: Management, prognosis, and prevention", section on 'Assessing risk of bacterial meningitis'.)

Initiation of empiric therapy — Once the results of the LP are available, empiric antibiotics should be initiated immediately if the findings suggest bacterial meningitis. If there is a high level of concern based upon clinical findings, empiric antibiotics should be administered immediately after the LP is performed without waiting for results. Empiric treatment is summarized in the table and discussed in greater detail separately (table 1). (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)

Microbiologic tests

Cerebrospinal fluid Gram stain — The presence of an organism on CSF Gram stain can suggest the bacterial etiology one day or more before culture results are available. The absence of organisms on Gram stain does not exclude the diagnosis [62]. The likelihood of detecting bacteria on Gram stain depends upon the number of organisms present and is enhanced by cytocentrifugation [63].

The likelihood of detecting bacteria also depends on the pathogen. CSF Gram stain is positive in approximately 80 to 90 percent of children with pneumococcal meningitis [35] and 70 to 80 percent of children with meningococcal meningitis [64]. In contrast, the Gram stain is positive in only one-half of patients with gram-negative bacillary meningitis and one-third of patients with Listeria meningitis [65,66].

Characteristic morphologic features of the common pathogens for bacterial meningitis in children are as follows:

●Gram-positive diplococci suggest S. pneumoniae (picture 5)

●Gram-negative diplococci suggest N. meningitidis (picture 6)

●Small pleomorphic gram-negative coccobacilli suggest Hib (picture 7)

●Gram-positive cocci or coccobacilli suggest group B streptococcus (GBS) (picture 8)

●Gram-positive rods and coccobacilli suggest L. monocytogenes (picture 9)

Gram stain results are subject to observer misinterpretation, and, therefore, broad-spectrum antimicrobial therapy should be continued until CSF culture results are available [67]. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.)

Cerebrospinal fluid culture — CSF cultures should be performed in all cases of suspected bacterial meningitis, regardless of the CSF cell count. Early in the disease process, the CSF culture may be positive in the absence of pleocytosis [51,68].

Isolation of a bacterial pathogen from the CSF culture confirms the diagnosis of bacterial meningitis. However, CSF culture may be negative in children pretreated with antibiotics prior to LP [51,69,70]. This is particularly true of meningococcal meningitis, in which the CSF is rapidly sterilized following administration of parenteral antibiotics [69,70]. CSF cultures can also be negative if bacteria are sequestered in pockets adjacent to, but not directly communicating with, the CSF (eg, epidural or subdural abscess).

In one review of 128 children with bacterial meningitis, CSF cultures were positive in 97 percent of patients who hadn't received any antibiotics, 67 percent of those pretreated with oral antibiotics, and 56 percent of those pretreated with parenteral antibiotics [69]. The likelihood of isolating an organism in CSF culture in pretreated patients depends in part upon the causative pathogen and the time interval between administering antibiotics and performing the LP. The study described above demonstrated this by reviewing CSF culture results of 55 children with bacterial meningitis who underwent serial LPs before and after administration of parenteral antibiotics [69] Among the nine children with meningococcal meningitis, all had sterile CSF cultures within two hours of receiving antibiotics (three were sterile within one hour). Sterilization of the CSF was slower with pneumococcal meningitis. The first negative culture was obtained four hours after administration of antibiotics, and five of seven were negative by 10 hours.

Other cultures — Culture of other sites should be obtained as indicated:

●Blood culture should be obtain in all patients, as discussed above. (See 'Blood tests' above.)

●Urine culture – Urine cultures should be obtained in infants (<12 months of age) who present with fever and nonspecific symptoms and signs of meningitis since a urinary tract infection may be the primary source of the meningitis pathogen in such patients [71]. However, a CSF pleocytosis can be seen in infants with urinary tract infection and sterile CSF cultures [71-74]. In such cases, the CSF pleocytosis may be related to a viral meningitis or an innate response to bacteria or bacterial products [75-77].

Urine cultures also should be obtained in children with anomalies of the urinary tract and in immunocompromised patients.

If possible, urine for culture should be obtained before antimicrobial therapy is administered. However, therapy should not be withheld if an adequate specimen cannot be promptly obtained.

●Skin biopsy – Gram stain and culture of purpuric lesions may have some use in the diagnosis of suspected meningococcal disease [78]. (See "Diagnosis of meningococcal infection", section on 'Skin biopsy'.)

●Middle ear fluid – In patients with concomitant otitis media or mastoiditis, a tympanocentesis can be performed to obtain middle ear fluid for Gram stain and culture, which may be helpful, particularly if CSF culture is negative. (See "Acute mastoiditis in children: Treatment and prevention", section on 'Drainage'.)

●No role for throat or nasopharyngeal cultures – Cultures of the nose and throat are not helpful in identifying the etiology of bacterial meningitis.

Molecular methods — Molecular methods (ie, polymerase chain reaction [PCR] and other nucleic acid amplification test [NAATs]) are increasingly used to assist in the diagnosis of central nervous system (CNS) infections. (See "Molecular diagnosis of central nervous system infections".)

●Multiplex (panel-based) testing – Multiplex or panel-based NAATs are now available that test for multiple bacterial and viral pathogens simultaneously in a single CSF sample (eg, FilmArray meningitis/encephalitis panel [BioFire]) [79-82]. These tests are highly sensitive and specific, though false-positive and false-negative results can occur [83]. If a multiplex panel is performed, it should be used in conjunction with standard microbiologic tests (eg, cultures of CSF and blood). Multiplex panels do not detect all causes of CNS infection nor do they provide any information on antimicrobial susceptibility.

●Meningococcal PCR – PCR of CSF and blood can be helpful for documenting meningococcal disease in the patient with negative cultures [84]. (See "Diagnosis of meningococcal infection", section on 'Polymerase chain reaction'.)

●Loop-mediated isothermal amplification (LAMP) – LAMP is another promising nucleic acid amplification method for rapid detection of meningococcus in respiratory and blood samples of infected children, but it is not yet commercially available [85].

Bacterial antigen tests — CSF latex agglutination tests add little to conventional testing with Gram stain and culture [86,87]. These tests are rarely used in the current era, given the availability of molecular tests, which are more sensitive and specific. However, in settings where molecular testing is not available, latex agglutination tests may play a role, particularly in children with negative bacterial cultures.

Assessment of immune function — The possibility of an immune deficiency or anatomic predisposition should be considered in the following settings:

●Hib meningitis or pneumococcal meningitis – For children who develop Hib meningitis or pneumococcal meningitis with a serotype contained in the pneumococcal vaccine despite having received at least three doses of the respective conjugate vaccines, it is reasonable to screen for underlying immune deficiency. This is particularly warranted if there are additional concerning features in the history or physical examination (eg, recurrent infections, poor growth). The initial evaluation may include measuring quantitative immunoglobulins, antibody titers to vaccine antigens, and complement activity. In addition, examining the peripheral blood smear may be helpful because the presence of Howell-Jolly bodies (picture 10) may indicate splenic hypofunction. The approach to evaluating immune function in children is discussed in greater detail separately. (See "Approach to the child with recurrent infections" and "Primary humoral immunodeficiencies: An overview" and "Assessing antibody function as part of an immunologic evaluation".)

●Unusual pathogens – If an unusual organism, such as S. aureus or another organism that commonly colonizes the skin, is isolated, a direct connection to the skin via a sinus tract should be sought [88].

Neuroimaging — In select children, it is appropriate to delay the LP while performing neuroimaging (typically with computed tomography) to exclude an intracranial process that would contraindicate an LP.

Indications for neuroimaging before LP in children with suspected bacterial meningitis include (table 1) [67]:

●Coma

●Papilledema

●Focal neurologic deficit

●CSF shunt in place

●History of hydrocephalus

●Recent CNS trauma or neurosurgery

In children who require neuroimaging before LP, blood cultures should be obtained and empiric antibiotics administered before imaging (table 1) [67]. LP should be performed as soon as possible after neuroimaging, provided that neuroimaging has not revealed any contraindications.

In patients with confirmed bacterial meningitis, herniation following LP is uncommon in the absence of focal neurologic findings or coma [89].

DIAGNOSIS — Acute bacterial meningitis should be suspected in children who present with fever and signs of meningeal inflammation. (See 'Presentation' above.)

The diagnosis of bacterial meningitis is confirmed by any of the following:

●Isolation of a bacterial pathogen from the cerebrospinal fluid (CSF) culture (see 'Cerebrospinal fluid culture' above)

●Isolation of bacteria from blood cultures in a patient with CSF pleocytosis (see 'Blood tests' above)

●Detection of a bacterial pathogen in the CSF by molecular methods (see 'Molecular methods' above)

The CSF culture may be negative in children who received antibiotic therapy before CSF examination. In such children, increased CSF cell count with a predominance of neutrophils, elevated CSF protein concentration, and/or decreased CSF glucose concentration usually are sufficient to establish the diagnosis of bacterial meningitis [57-60]; blood cultures and/or molecular tests may help to identify the specific pathogen [82]. (See 'Interpretation' above and 'Molecular methods' above.)

A negative culture of the CSF does not preclude the development of meningitis hours or days after lumbar puncture (LP); if clinical signs strongly suggest meningitis, repeat LP may be warranted. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Repeat lumbar puncture'.)

DIFFERENTIAL DIAGNOSIS

Fever, neck stiffness, and abnormal mental status — The characteristic presentation of meningitis is a triad of fever, neck stiffness, and abnormal mental status (eg, lethargy, confusion, irritability). Many other conditions can present with similar manifestations. The cerebrospinal fluid (CSF) examination and bacterial cultures differentiate bacterial meningitis from other causes:

●Febrile illness – Children with other infectious conditions can present with a constellation of symptoms that mimic meningitis. In a review of 650 children (ages 0 to 12 years) who underwent lumbar puncture (LP) for evaluation of possible meningitis, CSF findings were normal in 57 percent of patients [32]. Indications for LP included fever; headache; vomiting; nuchal rigidity; first episode of convulsion with fever; and encephalopathic, toxic, or septic appearance. Common conditions among children with normal CSF findings included:

•Pneumonia

•Otitis media

•Pharyngitis/tonsillitis

•Upper respiratory infection with cervical adenopathy

•Viral infection/herpangina (predominantly in children <5 years)

•Gastroenteritis

●Nuchal rigidity – While nuchal rigidity is highly suggestive of meningitis, it can occur in other conditions, such as retropharyngeal abscess, cervical spine injury or infection, and many others, as summarized in the table (table 5). The approach to evaluating neck stiffness in children is discussed separately. (See "Approach to neck stiffness in children".)

●Depressed mental status – Important causes of altered depressed mental status in children include head trauma, seizure, and ingestions (table 9). (See "Evaluation of stupor and coma in children" and "Approach to the child with occult toxic exposure".)

Cerebrospinal fluid pleocytosis — The clinical and laboratory findings of bacterial meningitis overlap with those of aseptic or viral meningitis (table 7 and table 8). In patients with CSF pleocytosis, clinical prediction rules can be used in conjunction with clinical judgment to identify patients with a very low risk of bacterial meningitis. The approach is summarized in the algorithm and discussed in greater detail separately (algorithm 1). (See "Viral meningitis in children: Management, prognosis, and prevention", section on 'Assessing risk of bacterial meningitis'.)

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: Bacterial meningitis in infants and children".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword[s] of interest.)

●Basics topics (see "Patient education: Meningitis in children (The Basics)" and "Patient education: Bacterial meningitis (The Basics)")

●Beyond the Basics topic (see "Patient education: Meningitis in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Etiology and risk factors – Streptococcus pneumoniae and Neisseria meningitidis are the most common causes of bacterial meningitis in infants and children older than one month of age. Risk factors for bacterial meningitis include (see 'Epidemiology' above):

•Anatomic defects of the spinal cord, brain, or inner ear

•Acquired cranial defects due to basilar skull fracture or surgery

•Medical devices (eg, cerebrospinal fluid [CSF] shunt, cochlear implant)

•Congenital or acquired immunodeficiency (table 4)

•Parameningeal infections (eg, sinusitis, mastoiditis)

•Recent infection (especially respiratory and ear infections)

•Recent exposure to someone with meningitis

•Recent travel to an area with endemic meningococcal disease (eg, sub-Saharan Africa (figure 1))

●Clinical presentation – Most patients with bacterial meningitis present with fever and symptoms and signs of meningeal inflammation, such as nuchal rigidity (movie 1A-B), headache, photophobia, and irritability. Petechiae (picture 3) and purpura (picture 4) may be present, particularly in patients with N. meningitidis infection. However, the clinical manifestations of bacterial meningitis are variable and nonspecific; no single sign is pathognomonic. (See 'Clinical features' above.)

●Evaluation – Suspected bacterial meningitis is a medical emergency, and immediate diagnostic steps must be taken to establish the specific cause (table 1). Ideally, a careful history, physical examination, blood tests, and lumbar puncture (LP) should be performed before the initiation of therapy for meningitis. The laboratory evaluation of children with suspected meningitis includes (see 'Evaluation' above):

•Blood tests (see 'Blood tests' above):

-Aerobic blood culture

-Complete blood count with differential

-Inflammatory markers (eg, C-reactive protein, procalcitonin)

-Serum electrolytes, glucose, blood urea nitrogen, and creatinine

-Coagulation studies (prothrombin time [PT], international normalized ratio [INR], activated partial thromboplastin time [aPTT])

-Lactate level if there is concern for septic shock

•CSF studies (see 'Lumbar puncture' above):

-Cell count and differential

-Glucose and protein concentration

-Gram stain and culture

If there is a contraindication to or inability to perform the LP or if the LP is delayed by the need for neuroimaging, blood cultures should be obtained and empiric antibiotics administered as soon as possible (table 1). (See 'Neuroimaging' above and 'Initiation of empiric therapy' above.)

●Interpretation – Laboratory findings characteristic of bacterial meningitis include CSF pleocytosis with a predominance of neutrophils, elevated CSF protein, decreased CSF glucose, and presence of an organism on CSF Gram stain (table 7 and table 8). (See 'Interpretation' above.)

●Diagnosis – The diagnosis of bacterial meningitis is confirmed by any of the following (see 'Diagnosis' above):

•Isolation of a bacterial pathogen from the CSF culture (see 'Cerebrospinal fluid culture' above)

•Isolation of bacteria from blood cultures in a patient with CSF pleocytosis (see 'Blood tests' above)

•Detection of a bacterial pathogen in the CSF by molecular methods (see 'Molecular methods' above)

●Differential diagnosis – Conditions that can present with symptoms similar to those of bacterial meningitis include other febrile illnesses (eg, pneumonia, otitis media), other conditions associated with neck stiffness (table 5), and other causes of altered or depressed mental status (table 9). The CSF examination and bacterial cultures differentiate bacterial meningitis from other causes. (See 'Differential diagnosis' above.)

The clinical and laboratory findings of bacterial meningitis overlap with those of aseptic or viral meningitis (table 7 and table 8). In patients with CSF pleocytosis, clinical prediction rules can be used in conjunction with clinical judgment to identify patients with a very low risk of bacterial meningitis. The approach is summarized in the algorithm and discussed in greater detail separately (algorithm 1). (See "Viral meningitis in children: Management, prognosis, and prevention", section on 'Assessing risk of bacterial meningitis'.)