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

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Official reprint from UpToDate www.uptodate.com 2014 UpToDate

Bacterial meningitis in children older than one month: Clinical features and diagnosis Author Sheldon L Kaplan, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Mar 2014. | This topic last updated: Mar 5, 2014. INTRODUCTION Meningitis is an inflammatory disease of the leptomeninges, the tissues surrounding the brain and spinal cord. The meninges consist of three parts: the pia, arachnoid, and dura mater. Meningitis reflects inflammation of the arachnoid mater and the cerebrospinal fluid (CSF) in both the subarachnoid space and in the cerebral ventricles. Suspected bacterial meningitis is a medical emergency, and immediate diagnostic steps must be taken to establish the specific cause so that appropriate antimicrobial therapy can be initiated. 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 and laboratory features of bacterial meningitis in infants and children older than one month will be reviewed here. The epidemiology, pathogenesis, treatment, prognosis, and prevention of acute meningitis and the clinical features, diagnosis, treatment, and prognosis of bacterial meningitis in neonates (<1 month of age) and adults are discussed separately. (See "Pathogenesis and pathophysiology of bacterial meningitis" and "Bacterial meningitis in children older than one month: Treatment and prognosis" and "Bacterial meningitis in the neonate: Clinical features and diagnosis" and "Bacterial meningitis in the neonate: Treatment and outcome" and "Epidemiology of bacterial meningitis in adults" and "Clinical features and diagnosis of acute bacterial meningitis in adults" and "Initial therapy and prognosis of bacterial meningitis in adults" and "Treatment of bacterial meningitis caused by specific pathogens in adults".) EPIDEMIOLOGY After the introduction of the Haemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines to the infant immunization schedule (in 1990 and 2000, respectively) the incidence of bacterial meningitis declined in all age groups except children younger than two months [1]. The median age shifted from <5 years to 42 years [1,2]. The peak incidence continues to occur in children younger than two months. In population-based surveillance (2006 to 2007), the incidence of bacterial meningitis in United States children varied with age [1]: ! <2 months 80.69 per 100,000 population ! 2 through 23 months 6.91 per 100,000 population ! 2 through 10 years 0.56 per 100,000 population ! 11 through 17 years 0.43 per 100,000 population Causative organisms The organisms responsible for acute bacterial meningitis depend in part upon the route of acquisition and underlying host factors (table 1 and table 2). The relative frequency of pathogens causing bacterial meningitis in children changed after the introduction of the Hib and pneumococcal conjugate vaccines to the routine childhood immunization schedule (figure 1) [3]. In a retrospective review of 231 cases of bacterial meningitis in children (1 month through 18 years of age) who presented to 20 pediatric emergency departments in the United States between 2001 and 2004, the most frequent pathogens varied according to age, as follows: ! "1 month and <3 months Group B streptococcus (39 percent), gram-negative bacilli (32 percent), Streptococcus pneumoniae (14 percent), Neisseria meningitidis (12 percent) ! "3 months and <3 years S. pneumoniae (45 percent), N. meningitidis (34 percent), group B streptococcus (11 percent), gram-negative bacilli (9 percent) ! "3 years and <10 years S. pneumoniae (47 percent), N. meningitidis (32 percent) ! "10 years and <19 years N. meningitidis (55 percent) Similar findings were noted in 587 cases of bacterial meningitis in children (0 to 18 years) identified through the Emerging Infections Program Network between 1998 and 2007 [1]. Before widespread vaccination for Hib in the United States, Hib was the major cause of bacterial meningitis in children [4]. Although the incidence of pneumococcal meningitis in children in the United States declined by 55 to 60 percent after widespread vaccination for S. pneumoniae, S. pneumoniae remains the most frequent cause of bacterial meningitis in children [1,3,5-7]. Even with prompt and appropriate therapy, pneumococcal meningitis is an important cause of childhood morbidity and mortality [3]. (See "Pneumococcal meningitis in children", section on 'Outcome'.) Predisposing factors In addition to specific factors that may predispose certain hosts to bacterial meningitis with a particular organism (table 2), the following factors also may increase the risk of bacterial meningitis [8]: ! Recent exposure to someone with meningococcal or Hib meningitis ! Recent infection (especially respiratory or otic infection) ! Recent travel to areas with endemic meningococcal disease, such as sub-Saharan Africa ! Penetrating head trauma ! Cerebrospinal fluid (CSF) otorrhea (including congenital defects, such as Mondini dysplasia) or CSF rhinorrhea ! Cochlear implant devices, particularly those with a positioner (see "Cochlear implant infections", section on 'Risk of meningitis') ! Anatomic defects (eg, dermal sinus (picture 1) or urinary tract anomaly) or recent neurosurgical procedure (eg, ventricular shunt placement) may predispose to meningitis with Staphylococcus aureus, coagulase-negative staphylococcus, and enteric gram-negative organisms, such as Escherichia coli and Klebsiella species [9]. (See "Epidemiology and clinical features of gram-negative bacillary meningitis".) Section Editors Morven S Edwards, MD Douglas R Nordli, Jr, MD Deputy Editor Mary M Torchia, MD

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

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CLINICAL FEATURES Course Acute bacterial meningitis has two patterns of presentation [10,11]. In the first, meningitis develops progressively over one or several days and may be preceded by a febrile illness. In the second, the course is acute and fulminant, with manifestations of sepsis and meningitis developing rapidly over several hours [10]. The rapidly progressive form is frequently associated with severe brain edema. Presentation Most patients with bacterial meningitis present with fever and symptoms and signs of meningeal inflammation (nausea, vomiting, irritability, anorexia, headache, confusion, back pain, and nuchal rigidity) [12-14]. These findings are often preceded by symptoms of upper respiratory infection [15]. However, the clinical manifestations of bacterial meningitis are variable and nonspecific; no single sign is pathognomonic [10,13]. Previous receipt of oral antibiotics does not affect the clinical presentation of acute bacterial meningitis. The symptoms and signs depend, to some extent, upon the duration of illness, the host response to infection, and the age of the patient [10]. The triad of fever, neck stiffness, and mental status changes is present in only 44 percent of adults with bacterial meningitis [7], and in even fewer children. In older children, clinical manifestations may include fever, headache, photophobia, nausea, vomiting, confusion, lethargy, and/or irritability [10,14]. In infants, manifestations may include fever, hypothermia, lethargy, respiratory distress, jaundice, poor feeding, vomiting, diarrhea, seizures, restlessness, irritability, and/or bulging fontanel [10,13,16]. Meningeal signs Although meningeal signs are present at the time of admission in the majority of patients, they are not invariably present. In one review of 1064 cases of acute bacterial meningitis in children older than one month, 16 (1.5 percent) had no meningeal signs during their entire period of hospitalization [17]. Nuchal rigidity may not be elicited in comatose patients or those with focal or diffuse neurologic deficits [14]. In addition, nuchal rigidity may occur late in the course, particularly in young children. 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 in 60 to 80 percent of children with bacterial meningitis at the time of presentation and in approximately 25 percent of children with normal cerebrospinal fluid (CSF) findings [11,15,18]. Other causes of nuchal rigidity are discussed below. (See 'Differential diagnosis' below.) Neurologic findings ! Altered consciousness In one review of 235 children with bacterial meningitis, approximately 78 percent were irritable or lethargic, 7 percent were somnolent, and 15 percent semicomatose or comatose at the time of admission [14]. Among patients with pneumococcal meningitis, 29 percent were semicomatose or comatose at the time of admission. The level of consciousness at the time of admission has prognostic significance [19]; patients who are obtunded, semicomatose, or comatose at the time of admission are significantly more likely to have an adverse outcome than those who are lethargic or somnolent [20]. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Prognostic factors'.) ! Increased ICP Increased intracranial pressure may be manifest by complaints of headache in older children and bulging fontanel or diastasis of the cranial sutures in infants [13,14]. Bulging fontanel is neither sensitive nor specific for bacterial meningitis. In one review, bulging fontanel was present in 20 percent of infants with meningitis, but also in 13 percent of infants with normal CSF and viral infections other than meningitis [18]. (See "Elevated intracranial pressure (ICP) in children".) Other signs of increased intracranial pressure that may occur in bacterial meningitis include palsies of the third, fourth, and sixth cranial nerves. (See "Third cranial nerve (oculomotor nerve) palsy in children" and "Fourth cranial nerve (trochlear nerve) palsy in children" and "Sixth cranial nerve (abducens nerve) palsy in children", section on 'Clinical manifestations'.) Papilledema, which takes several days to become apparent, is an uncommon finding in acute bacterial meningitis. The finding of papilledema should prompt evaluation for venous sinus occlusion, subdural empyema, or brain abscess [10]. (See 'Imaging' below.) ! Seizures Seizures, typically generalized, occur before admission to the hospital or within the first 48 hours of admission in 20 to 30 percent of patients with meningitis [14,21]. Seizures later in the course are more often focal and may indicate cerebral injury [10,21,22]. (See "Bacterial meningitis in children: Neurologic complications", section on 'Seizures'.) A simple seizure is rarely the sole manifestation of bacterial meningitis [23]. In one series of 410 consecutive cases of documented bacterial meningitis in children 2 months to 15 years of age, 27 percent had seizures at or before the time of presentation [23]. All of the children with bacterial meningitis who presented with seizures had other signs or symptoms of meningitis (altered consciousness, nuchal rigidity, petechial rash). Altered consciousness and nuchal rigidity may be difficult to assess during the post-ictal period, particularly in infants younger than one year. ! Focal findings In one review of 235 children with bacterial meningitis, focal neurologic findings (hemiparesis, quadriparesis, facial palsy, visual field defects) were present at the time of admission in 16 percent of patients overall and in 34 percent of those with pneumococcal meningitis [14]. The presence of focal neurologic signs at the time of admission correlated with persistent abnormal neurologic examination one year after discharge and with cognitive impairment. Focal neurologic findings also may occur late in the course of meningitis [10]. (See "Bacterial meningitis in children: Neurologic complications", section on 'Focal deficits'.) Cutaneous findings Petechiae and purpura may occur with any of the bacterial pathogens but are most commonly seen in N. meningitidis [10]. 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'.) Complications Complications that may occur during therapy for bacterial meningitis include seizures, increased ICP, cerebral edema, ischemia, infected subdural effusion, and disseminated illness (septic arthritis, pericarditis, etc). Neurologic complications are discussed separately. (See "Bacterial meningitis in children: Neurologic complications".) Arthritis is most common with meningococcal disease but may occur with other infections [14]. 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 [14]. In some cases, pericardial effusions

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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 Overview Suspected bacterial meningitis is a medical emergency, and immediate diagnostic steps must be taken to establish the specific cause (algorithm 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 'Immediate management'.) History Important aspects of the history in the child with suspected bacterial meningitis include: ! The course of illness. (See 'Course' above.) ! The presence of symptoms consistent with meningeal inflammation. (See 'Meningeal signs' above.) ! The presence of seizures, an important prognostic finding. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Prognosis'.) ! The presence of predisposing factors In addition to predisposing conditions delineated in the tables (table 1 and table 2), recent respiratory or ear infection, penetrating head trauma or craniotomy, travel to an area with endemic meningococcal disease, exposure to someone with bacterial meningitis, cochlear implantation device, or anatomic defects (eg, dermal sinus or urinary tract anomaly). (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 cerebrospinal fluid (CSF) examination or initial empiric therapy, but depending upon age, may affect the need for chemoprophylaxis or evaluation of the immune system. (See "Prevention of Haemophilus influenzae infection", section on 'Antibiotic prophylaxis of close contacts' and "Treatment and prevention of meningococcal infection" and "IgG subclass deficiency".) ! History of drug allergies, particularly anaphylactic reactions to antibiotics, which, if present, may affect the choice of antimicrobial therapy. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Chemoprophylaxis'.) ! Recent use of antibiotics, which may affect the yield of blood and/or CSF culture. (See 'Interpretation of CSF in pretreated patients' 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 provide clues to volume status, presence of shock, and the presence of increased intracranial pressure. The constellation of systemic hypertension (calculator 1 and calculator 2), bradycardia, and respiratory depression (Cushing triad) is a late sign of increased intracranial pressure. (See "Elevated intracranial pressure (ICP) in children".) ! Head circumference should be measured at the time of admission in children younger than 18 months of age [24]. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Monitoring'.) ! Elicitation of meningeal signs 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 other bacterial infections (eg, facial cellulitis, sinusitis, otitis media, arthritis, pneumonia). LABORATORY EVALUATION Blood tests Initial blood tests should include a complete blood count with differential and platelet count and two aerobic blood cultures of appropriate volume. Serum electrolytes and glucose, blood urea nitrogen, and creatinine concentrations are helpful in determining the cerebrospinal fluid- (CSF) to-blood glucose ratio, and in planning fluid administration. Evaluation of clotting function is especially indicated if petechiae or purpuric lesions are noted. (See 'Glucose and protein' below and "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Pretreatment evaluation'.) Blood cultures are positive in at least one-half of patients with bacterial meningitis [25]. In one prospective study, blood was obtained for culture from every patient with bacterial meningitis, 44 percent of whom had received antimicrobial therapy before evaluation [26]. Blood cultures were positive in 80 percent of children with H. influenzae type b (Hib) meningitis, 52 percent of children with pneumococcal meningitis, and 33 percent of children with meningococcal meningitis. Among children who were not pretreated with antibiotics, blood cultures were positive in approximately 90 percent of children with Hib and meningococcal meningitis and 80 percent of children with pneumococcal meningitis. CSF examination Analysis of the CSF is critical to the diagnosis of meningitis and the differentiation of bacterial from other etiologies (table 3). A lumbar puncture (LP) should be performed on any child in whom, after careful history and physical examination, the diagnosis of meningitis is suspected, unless specific contraindications to LP are present [14]. The threshold for CSF examination should be lower in high-risk patients (table 2). (See 'Predisposing factors' above.) LP also should be performed in children with bacteremia and meningeal signs or persistent fever (even if they have no meningeal signs), since bacteremia can progress to meningitis within hours [12,27]. In addition, repeat LP may be warranted in a child whose initial CSF culture was negative but in whom clinical signs of meningitis persist [10]. Contraindications to LP include cardiopulmonary compromise, signs of increased intracranial pressure, papilledema, altered respiratory effort, focal neurologic signs, and skin infection over the site for LP. (See "Lumbar puncture: Indications, contraindications, technique, and complications in children", section on 'Contraindications' and 'Predisposing factors' above.) 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 cranial imaging. 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) (algorithm 1). (See 'Initiation of empiric therapy' below and 'Imaging' below.) Examination of the CSF should include cell count and differential, glucose and protein concentration, Gram stain, and culture. Cytocentrifugation of CSF enhances the likelihood that laboratory personnel will detect bacteria on Gram-stained specimens. CSF cultures should be performed in all cases of suspected bacterial meningitis, regardless of the cell count. Early in the disease process, the CSF culture may be positive in the absence of pleocytosis [12,28]. Interpretation of CSF Certain laboratory findings are characteristic of bacterial meningitis and are present in most cases (table 3). These include CSF pleocytosis with a

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predominance of neutrophils, elevated CSF protein, decreased CSF glucose, the presence of an organism on CSF Gram stain, and isolation of a pathogenic organism from the CSF and blood culture. However, because CSF and blood cultures may be obtained at different points in time during the evolution of the disease process, varying combinations of positive or negative cultures of blood and CSF and the presence or absence of pleocytosis are possible [10]. Early in the course (after bacterial invasion but before the inflammatory response), the CSF culture may be positive in the absence of pleocytosis [12,28]. In some cases, pleocytosis is present and culture of the blood reveals a pathogen, but culture of the CSF does not. A negative culture of the CSF does not preclude the development of meningitis hours or days after LP; if clinical signs suggest meningitis, repeat LP may be warranted [10,12]. Cell count The CSF white blood cell (WBC) count in acute bacterial meningitis is typically >1000 WBC/microL, with a predominance of neutrophils (table 3) [14]. However, early in the course, few or no WBCs may be present. A CSF WBC count >6/microL is considered abnormal in children older than three months of age [14], and >9 WBCs/microL is considered abnormal for infants 29 to 90 days [29,30]. A traumatic LP can cause small amounts of bleeding into the CSF that can interfere with interpretation of the CSF cell count. Certain formulas can be used to aid in the interpretation of the cell count when the LP is traumatic. When the CSF is not grossly bloody, we subtract 1 WBC for every 1000 RBCs/microL. However, none of the formulas to "correct" the CSF WBC can be used with total confidence to exclude meningitis when the LP is traumatic [31,32]. Children in whom the LP is traumatic should be treated presumptively for meningitis pending results of CSF culture. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.) The presence of a single neutrophil in the CSF is considered abnormal [10,12]. However, this finding is not pathognomonic for bacterial meningitis; patients with aseptic meningitis can have 30 to 90 percent neutrophils on their initial CSF examination [10]. (See "Viral meningitis: Clinical features and diagnosis in children", section on 'CSF studies'.) Similarly, neither the presence nor quantity of bands (immature neutrophils) in the CSF helps to distinguish bacterial from viral meningitis [33]. Glucose and protein The CSF glucose in acute bacterial meningitis is <40 mg/dL in more than one-half of cases (table 3) [14]. In addition, the ratio of the CSF to blood glucose concentration is usually depressed (<0.6 ) [34]. The CSF protein in acute bacterial meningitis typically ranges from 100 to 500 mg/dL (table 3) [14]. 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 red blood cells (RBC) [35]. In children with traumatic LP the CSF protein concentration may be corrected by subtracting 1 mg/dL for every 1000 RBCs/microL [10,35]. 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 [36]. The probability of visualizing bacteria depends upon the number of organisms present [37] and is increased by cytocentrifugation. Broad-spectrum antimicrobial therapy should be continued until CSF culture results are available, because Gram stain results are subject to observer misinterpretation [38]. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.) An organism is visualized on CSF Gram stain in approximately 90 percent of children with pneumococcal meningitis [21] and 80 percent of children with meningococcal meningitis [39]. 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 [40,41]. Characteristic morphologic features of the common pathogens for bacterial meningitis in children are as follows: ! Gram-positive diplococci suggest S. pneumoniae (picture 2) ! Gram-negative diplococci suggest N. meningitidis (picture 3) ! Small pleomorphic gram-negative coccobacilli suggest Hib (picture 4) ! Gram-positive cocci or coccobacilli suggest group B streptococcus (picture 5) ! Gram-positive rods and coccobacilli suggest L. monocytogenes (picture 6) Culture Isolation of a bacterial pathogen from the CSF culture confirms the diagnosis of bacterial meningitis. However, a negative culture of the CSF at a particular point in time does not preclude the development of meningitis hours or days later [12,28]. In one review of 128 children with bacterial meningitis, CSF cultures were positive in 97 percent of patients who received neither oral nor parenteral antibiotics, 67 percent of patients who received oral antibiotics, and 56 percent of patients who received parenteral antibiotics before CSF cultures were obtained [42]. Rapid diagnostic tests Bacterial antigen tests should be reserved for cases in which the initial CSF Gram stain is negative and CSF culture is negative at 48 hours of incubation [43]. Polymerase chain reaction (PCR) of CSF and blood is most helpful for documenting meningococcal disease in the patient with negative cultures [44]. Interpretation of CSF in pretreated patients Prior administration of antimicrobial agents, particularly oral antibiotics, tends to have minimal effects on CSF cytology [25,45-48]. However, CSF chemistry results in pretreated patients must be interpreted with caution. In a retrospective review of 231 children with bacterial meningitis in the post-Hib and pneumococcal conjugate vaccine era, 85 children received antibiotics before LP [48]. Receipt of antibiotics for "12 hours before LP was associated with increased median CSF glucose concentration (48 versus 29 mg/dL [2.66 versus 1.6 mmol/L]) and decreased median CSF protein concentration (121 versus 178 mg/dL [1.21 versus 1.78 g/L]) [48]. Although the use of antimicrobial therapy before LP affects the CSF culture and perhaps the Gram stain [25,42,47], conventional teaching has been that a pathogen still can be identified in the CSF in the majority of patients up to several hours after the administration of antibiotics [25]. However, a review of 128 children with bacterial meningitis specifically addressed this question and found that the time interval between antibiotic administration and negative CSF cultures may be shorter than appreciated for children who receive parenteral antibiotics [42]: ! Among children with meningococcal meningitis who were treated with a parenteral dose of an extended-spectrum cephalosporin, three of nine LPs were sterile within one hour (occurring as early as 15 minutes), and all were sterile by two hours. ! 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. Additional cultures Culture of other sites should be obtained as indicated [10]. ! Gram stain and culture of petechial or purpuric lesions may identify the causative agent [10]. ! Urine cultures should be obtained in infants (<12 months of age) who present with fever and nonspecific symptoms and signs of meningitis, since urinary tract infection may be the primary source of the meningitis pathogen in such patients [10,49]. However, it is common to note a CSF pleocytosis in infants with urinary tract infection and sterile

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CSF cultures [49-53]. In such cases, the CSF pleocytosis may be related to a viral meningitis [54] or an innate response to bacteria or bacterial products [55,56]. (See "Evaluation and management of fever in the neonate and young infant (less than three months of age)" and "Fever without a source in children 3 to 36 months of age".) Urine cultures also should be obtained in children with anomalies of the urinary tract and in immunocompromised patients. (See 'Predisposing factors' above.) 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 [10]. ! In patients with concomitant otitis media, Gram-stained smear of middle ear fluid (obtained by needle aspiration) may permit immediate identification of the likely pathogen and may be helpful if the Gram-stained smear of the CSF is equivocal [10]. ! Cultures of the nose and throat are not helpful in identifying the etiology of bacterial meningitis [10]. Other tests Other tests for the diagnosis of bacterial meningitis have limited availability and/or undetermined utility for early diagnosis, as illustrated below. ! Despite its increasingly broad use, serum C-reactive protein is not a reliable indicator of severe infection [57]. ! In retrospective cohorts, elevated serum procalcitonin (>0.5 ng/mL) appears to be helpful in distinguishing bacterial from viral meningitis, but additional data are necessary before procalcitonin can be included in clinical decision rules [58]. ! The presence of tumor necrosis factor may distinguish bacterial from viral meningitis [59], but this assay is not generally available. ! The presence of IL-1 or IL-10 also may correlate with meningitis, but whether these indicators are sensitive and specific enough to accelerate the diagnosis remains to be determined [60]. The possibility of an immune deficiency should be considered in 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. In such children, we suggest that quantitative immunoglobulins and complement activity be obtained and that the peripheral blood smear be examined for Howell-Jolly bodies (picture 7). The presence of Howell-Jolly bodies most frequently indicates either absence of the spleen (eg, surgical removal) or splenic hypofunction. 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 [61]. An overview of primary immunodeficiencies and an approach to the diagnosis of splenic dysfunction are found elsewhere. (See "Primary humoral immune deficiencies: An overview" and "Approach to the adult patient with splenomegaly and other splenic disorders", section on 'Hyposplenism and asplenia'.) IMAGING It is not uncommon for lumbar puncture (LP) to be delayed while a computed tomographic (CT) scan is performed to exclude an intracranial process that would contraindicate an LP. Although concerns exist about herniation following LP in children, a review of the literature found that herniation was unlikely in children with bacterial meningitis unless they had focal neurologic findings or coma; furthermore, a normal CT does not absolutely exclude subsequent herniation [62,63]. Indications for imaging before LP in children with suspected bacterial meningitis include (algorithm 1) [38]: ! Coma ! The presence of a cerebrospinal fluid (CSF) shunt ! History of hydrocephalus ! Recent history of CNS trauma or neurosurgery ! Papilledema ! Focal neurologic deficit (with the exception of palsy of cranial nerve VI [abducens nerve] or VII [facial nerve]) In children who require neuroimaging before LP, blood cultures should be obtained and empiric antibiotics administered before imaging (algorithm 1) [38]. LP should be performed as soon as possible after neuroimaging provided that neuroimaging has not revealed any contraindications. DIAGNOSIS Acute bacterial meningitis should be suspected in children who present with fever and signs of meningeal inflammation. In infants, the clinical manifestations may include fever, hypothermia, lethargy, respiratory distress, jaundice, poor feeding, vomiting, diarrhea, seizures, restlessness, irritability, and/or bulging fontanel [10,16]. In older children, clinical manifestations may include fever, headache, photophobia, nausea, vomiting, confusion, lethargy, and/or irritability [10,14]. Previous receipt of oral antibiotics does not affect the clinical presentation of acute bacterial meningitis. (See 'Presentation' above.) Isolation of a bacterial pathogen from the cerebrospinal fluid (CSF) (by culture or other diagnostic techniques) confirms the diagnosis of bacterial meningitis. Isolation of bacteria from blood cultures in a patient with CSF pleocytosis also confirms the diagnosis, even if the CSF culture remains negative. Supportive findings include CSF pleocytosis with a predominance of neutrophils, decreased CSF glucose concentration (or ratio of CSF to blood glucose), elevated CSF protein, and isolation of the same pathogen from blood culture (table 3). However, because CSF and blood cultures may be obtained at different points in time during the evolution of the disease process, varying combinations of positive or negative cultures of blood and CSF and the presence or absence of pleocytosis are possible [10,12]. (See 'Laboratory evaluation' 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 [25,45-47]; blood cultures and/or rapid diagnostic tests may help to identify the pathogenic organism. (See 'Interpretation of CSF in pretreated patients' above.) DIFFERENTIAL DIAGNOSIS The clinical and laboratory findings of bacterial meningitis overlap with those of meningitis caused by viruses, mycobacteria, fungi, or protozoa (table 3). Other processes that can mimic bacterial meningitis include central nervous system (CNS) abscess, bacterial endocarditis with embolism, subdural empyema, and brain tumor [14,18]. Differentiation of these disorders from bacterial meningitis requires careful examination of cerebrospinal fluid (CSF) and neuroimaging. CSF pleocytosis The Bacterial Meningitis Score (BMS) is a clinical prediction rule for children with CSF pleocytosis (CSF white blood cell [WBC] count "10 cells/microL) that classifies children who have not been pretreated with antibiotics at very low risk of bacterial meningitis if they lack all of the following [64]: ! Positive CSF Gram stain ! CSF absolute neutrophil count (ANC) "1000 cells/microL ! CSF protein of "80 mg/dL ! Peripheral blood ANC of "10,000 cells/microL

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! History of seizure before or at the time of presentation In a meta-analysis of data from eight validation studies (one of which was prospective) including 5312 patients, bacterial meningitis was diagnosed in 23 percent [65]. The BMS missed nine patients with bacterial meningitis: three were younger than two months, three had petechiae or purpura, and three were older than two months and did not have petechiae or purpura; the six patients who were older than two months all had N. meningitidis. In pooled analysis, the sensitivity and specificity of the BMS for bacterial meningitis were 99.3 percent (95% CI 98.7-99.7 percent) and 62.1 percent (60.5 to 63.7 percent), respectively. These findings suggest that the BMS may be used in conjunction with clinical judgment to identify children with CSF pleocytosis who are at very low risk of bacterial meningitis and to assist clinical decision making. To avoid misclassification, the BMS should not be used in children who are younger than two months, immunocompromised, ill-appearing, have been pretreated with antibiotics, have petechiae or purpura on examination, have a ventriculoperitoneal shunt, or have recently had neurosurgery [64,65]. Normal CSF findings In a review of 650 children (0 to 12 years) who underwent lumbar puncture (LP) for evaluation of possible meningitis, CSF findings were normal in 57 percent of patients [18]. Indications for LP included fever; headache; vomiting; nuchal rigidity; first episode of convulsion with fever; and encephalopathic, toxic, or septic appearance. The incidence of normal CSF varied according to age, occurring in 83 percent of infants 0 to 8 weeks, 65 percent of children 8 weeks to 24 months, 53 percent of children 2 to 5 years, and 37 percent of children 5 to 12 years. Common conditions among children with normal CSF findings included: ! Right-sided pneumonia ! Otitis media (most presented with fever and irritability) ! Pharyngitis/tonsillitis ! Upper respiratory infection with cervical adenopathy ! Viral infection/ herpangina (predominantly in children <5 years) ! Gastroenteritis Additional causes of nuchal rigidity that should be considered in children evaluated for meningitis who have normal CSF findings include retropharyngeal abscess, cervical spine arthritis or osteomyelitis, spinal injury, and oculogyric crisis, esophageal foreign body, idiosyncratic reaction to phenothiazine, and various toxins (tetanus, black widow spider bites, scorpion stings) [66,67]. (See appropriate topic reviews). Additional causes of CNS symptoms in infants include anaphylaxis, seizure, head trauma, and stroke. (See appropriate topic reviews). INITIATION OF EMPIRIC THERAPY Empiric therapy for bacterial meningitis should be initiated immediately after the results of lumbar puncture (LP) are received or immediately after the LP is performed. It is essential that antimicrobial therapy not be delayed if there is a contraindication to or inability to perform an LP. If LP is delayed by the need for cranial imaging, blood cultures should be obtained and empiric antibiotic therapy administered before the imaging study (algorithm 1). (See 'Imaging' above.) Empiric treatment consists of bactericidal agent(s) that achieve significant levels in the cerebrospinal fluid (CSF), usually a third-generation cephalosporin and vancomycin. More specific treatment can be instituted when the etiologic agent is identified. (See "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.) Children in whom bacterial meningitis is suspected, or in whom bacterial meningitis cannot be excluded, based upon initial CSF findings should be admitted to the hospital. 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 5th to 6th 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 10th to 12th 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 e-mail 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 information: Meningitis in children (The Basics)" and "Patient information: Bacterial meningitis (The Basics)") ! Beyond the Basics topic (see "Patient information: Meningitis in children (Beyond the Basics)") SUMMARY AND RECOMMENDATIONS ! Streptococcus pneumoniae and Neisseria meningitidis are the most common causes of bacterial meningitis in infants and children older than one month of age. (See 'Causative organisms' above.) ! Certain host factors may predispose to bacterial meningitis with a particular organism (table 2). Additional risk factors for bacterial meningitis include exposure to someone with meningococcal or Haemophilus influenzae type b (Hib) meningitis, cochlear implantation device, recent neurosurgical procedure, or anatomic defect (dermal sinus or urinary tract anomaly). (See 'Predisposing factors' above.) ! Most patients with bacterial meningitis present with fever and symptoms and signs of meningeal inflammation (movie 1A-B). However, the clinical manifestations of bacterial meningitis are variable and nonspecific; no single sign is pathognomonic. (See 'Clinical features' above.) ! Suspected bacterial meningitis is a medical emergency, and immediate diagnostic steps must be taken to establish the specific cause (algorithm 1). (See 'Evaluation' above.) ! The laboratory evaluation of children with suspected meningitis should include a complete blood count with differential and platelet count, two aerobic blood cultures, and serum electrolytes, glucose, blood urea nitrogen, and creatinine. Evaluation of clotting function is especially indicated if petechiae or purpuric lesions are noted. (See 'Blood tests' above.) ! A lumbar puncture should be performed on any child in whom, after careful history and physical examination, the diagnosis of meningitis is suspected unless specific contraindications to lumbar puncture are present. Examination of the cerebrospinal fluid (CSF) should include cell count and differential, glucose and protein concentration, Gram stain, and culture. (See 'CSF examination' above.) ! If there is a contraindication to or inability to perform a lumbar puncture or if the lumbar puncture is delayed by the need for cranial imaging, blood cultures should be obtained and empiric antibiotics administered as soon as possible. (See 'CSF examination' above.)

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! Laboratory findings characteristic of bacterial meningitis include CSF pleocytosis with a predominance of neutrophils, elevated CSF protein, decreased CSF glucose, the presence of an organism on CSF Gram stain, and isolation of a pathogenic organism from the CSF and/or blood culture (table 3). (See 'Interpretation of CSF' above.) ! Isolation of a bacterial pathogen from the CSF (by culture or other diagnostic techniques) confirms the diagnosis of bacterial meningitis. (See 'Diagnosis' above.) ! In children who were treated with antibiotics before CSF was obtained, increased CSF cell count, elevated CSF protein concentration, and/or decreased CSF glucose concentration usually are sufficient to establish the diagnosis of meningitis; blood cultures and/or rapid diagnostic tests may help to identify the pathogenic organism. (See 'Interpretation of CSF in pretreated patients' above.) ! Empiric therapy for bacterial meningitis (a third-generation cephalosporin and vancomycin) should be initiated immediately after the results of lumbar puncture are received or immediately after the lumbar puncture is performed if the clinical suspicion for bacterial meningitis is high. (See 'Initiation of empiric therapy' above and "Bacterial meningitis in children older than one month: Treatment and prognosis", section on 'Empiric therapy'.) Use of UpToDate is subject to the Subscription and License Agreement. REFERENCES 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. Schuchat A, Robinson K, Wenger JD, et al. Bacterial meningitis in the United States in 1995. Active Surveillance Team. N Engl J Med 1997; 337:970. 3. Nigrovic LE, Kuppermann N, Malley R, Bacterial Meningitis Study Group of the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. Children with bacterial meningitis presenting to the emergency department during the pneumococcal conjugate vaccine era. Acad Emerg Med 2008; 15:522. 4. Wenger JD, Hightower AW, Facklam RR, et al. Bacterial meningitis in the United States, 1986: report of a multistate surveillance study. The Bacterial Meningitis Study Group. J Infect Dis 1990; 162:1316. 5. Kaplan SL, Mason EO Jr, Wald ER, et al. Decrease of invasive pneumococcal infections in children among 8 children's hospitals in the United States after the introduction of the 7-valent pneumococcal conjugate vaccine. Pediatrics 2004; 113:443. 6. Whitney CG, Farley MM, Hadler J, et al. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N Engl J Med 2003; 348:1737. 7. van de Beek D, de Gans J, Spanjaard L, et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med 2004; 351:1849. 8. Chvez-Bueno S, McCracken GH Jr. Bacterial meningitis in children. Pediatr Clin North Am 2005; 52:795. 9. Unhanand M, Mustafa MM, McCracken GH Jr, Nelson JD. Gram-negative enteric bacillary meningitis: a twenty-one-year experience. J Pediatr 1993; 122:15. 10. Feigin RD, McCracken GH Jr, Klein JO. Diagnosis and management of meningitis. Pediatr Infect Dis J 1992; 11:785. 11. Kilpi T, Anttila M, Kallio MJ, Peltola H. Severity of childhood bacterial meningitis and duration of illness before diagnosis. Lancet 1991; 338:406. 12. Klein JO, Feigin RD, McCracken GH Jr. Report of the Task Force on Diagnosis and Management of Meningitis. Pediatrics 1986; 78:959. 13. Curtis S, Stobart K, Vandermeer B, et al. Clinical features suggestive of meningitis in children: a systematic review of prospective data. Pediatrics 2010; 126:952. 14. Kim KS. Bacterial meningitis beyond the neonatal period. In: Feigin and Cherrys Textbook of Pediatric Infectious Diseases, 7th, Cherry JD, Harrision GJ, Kaplan SL, et al. (Eds), Elsevier Saunders, Philadelphia 2014. p.425. 15. Kaplan SL. Clinical presentations, diagnosis, and prognostic factors of bacterial meningitis. Infect Dis Clin North Am 1999; 13:579. 16. SWARTZ MN, DODGE PR. BACTERIAL MENINGITIS--A REVIEW OF SELECTED ASPECTS. 1. GENERAL CLINICAL FEATURES, SPECIAL PROBLEMS AND UNUSUAL MENINGEAL REACTIONS MIMICKING BACTERIAL MENINGITIS. N Engl J Med 1965; 272:725. 17. Geiseler PJ, Nelson KE. Bacterial meningitis without clinical signs of meningeal irritation. South Med J 1982; 75:448. 18. Levy M, Wong E, Fried D. Diseases that mimic meningitis. Analysis of 650 lumbar punctures. Clin Pediatr (Phila) 1990; 29:254. 19. Roine I, Peltola H, Fernndez J, et al. Influence of admission findings on death and neurological outcome from childhood bacterial meningitis. Clin Infect Dis 2008; 46:1248. 20. Kaplan SL, Feigin RD. Clinical presentations, prognostic factors and diagnosis of bacterial meningitis. In: Bacterial Meningtitis, Sande M, Smith AL, Root RK (Eds), Churchill Livingstone, New York 1985. p.83. 21. Arditi M, Mason EO Jr, Bradley JS, et al. Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use. Pediatrics 1998; 102:1087. 22. Pomeroy SL, Holmes SJ, Dodge PR, Feigin RD. Seizures and other neurologic sequelae of bacterial meningitis in children. N Engl J Med 1990; 323:1651. 23. Green SM, Rothrock SG, Clem KJ, et al. Can seizures be the sole manifestation of meningitis in febrile children? Pediatrics 1993; 92:527. 24. Feigin RD. Bacterial meningitis beyond the newborn period. In: Oski's Pediatrics: Principles and Practice, 4th ed, McMillan JA, Feigin RD, DeAngelis C, Jones MD (Eds), Lippincott Williams & Wilkins, Philadelphia 2006. p.942. 25. Talan DA, Hoffman JR, Yoshikawa TT, Overturf GD. Role of empiric parenteral antibiotics prior to lumbar puncture in suspected bacterial meningitis: state of the art. Rev Infect Dis 1988; 10:365. 26. Feigin RD, Dodge PR. Personal experience: Unpublished data for prospective studies of bacterial meningitis, 1974-1979. 27. Teele DW, Dashefsky B, Rakusan T, Klein JO. Meningitis after lumbar puncture in children with bacteremia. N Engl J Med 1981; 305:1079. 28. Onorato IM, Wormser GP, Nicholas P. 'Normal' CSF in bacterial meningitis. JAMA 1980; 244:1469. 29. Kestenbaum LA, Ebberson J, Zorc JJ, et al. Defining cerebrospinal fluid white blood cell count reference values in neonates and young infants. Pediatrics 2010; 125:257. 30. Byington CL, Kendrick J, Sheng X. Normative cerebrospinal fluid profiles in febrile infants. J Pediatr 2011; 158:130. 31. Bonadio WA, Smith DS, Goddard S, et al. Distinguishing cerebrospinal fluid abnormalities in children with bacterial meningitis and traumatic lumbar puncture. J Infect Dis 1990; 162:251. 32. Naqvi SH, Dunkle LM, Naseer S, Barth C. Significance of neutrophils in cerebrospinal fluid samples processed by cytocentrifugation. Clin Pediatr (Phila) 1983; 22:608. 33. Kanegaye JT, Nigrovic LE, Malley R, et al. Diagnostic value of immature neutrophils (bands) in the cerebrospinal fluid of children with cerebrospinal fluid pleocytosis. Pediatrics 2009; 123:e967. 34. Nigrovic LE, Kimia AA, Shah SS, Neuman MI. Relationship between cerebrospinal fluid glucose and serum glucose. N Engl J Med 2012; 366:576. 35. Nigrovic LE, Shah SS, Neuman MI. Correction of cerebrospinal fluid protein for the presence of red blood cells in children with a traumatic lumbar puncture. J Pediatr 2011; 159:158. 36. Neuman MI, Tolford S, Harper MB. Test characteristics and interpretation of cerebrospinal fluid gram stain in children. Pediatr Infect Dis J 2008; 27:309. 37. La Scolea LJ Jr, Dryja D. Quantitation of bacteria in cerebrospinal fluid and blood of children with meningitis and its diagnostic significance. J Clin Microbiol 1984; 19:187.
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38. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004; 39:1267. 39. Andersen J, Backer V, Voldsgaard P, et al. Acute meningococcal meningitis: analysis of features of the disease according to the age of 255 patients. Copenhagen Meningitis Study Group. J Infect 1997; 34:227. 40. Gray LD, Fedorko DP. Laboratory diagnosis of bacterial meningitis. Clin Microbiol Rev 1992; 5:130. 41. Mylonakis E, Hohmann EL, Calderwood SB. Central nervous system infection with Listeria monocytogenes. 33 years' experience at a general hospital and review of 776 episodes from the literature. Medicine (Baltimore) 1998; 77:313. 42. Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics 2001; 108:1169. 43. Maxson S, Lewno MJ, Schutze GE. Clinical usefulness of cerebrospinal fluid bacterial antigen studies. J Pediatr 1994; 125:235. 44. Kotilainen P, Jalava J, Meurman O, et al. Diagnosis of meningococcal meningitis by broad-range bacterial PCR with cerebrospinal fluid. J Clin Microbiol 1998; 36:2205. 45. Blazer S, Berant M, Alon U. Bacterial meningitis. Effect of antibiotic treatment on cerebrospinal fluid. Am J Clin Pathol 1983; 80:386. 46. Kaplan SL, Smith EO, Wills C, Feigin RD. Association between preadmission oral antibiotic therapy and cerebrospinal fluid findings and sequelae caused by Haemophilus influenzae type b meningitis. Pediatr Infect Dis 1986; 5:626. 47. Geiseler PJ, Nelson KE, Levin S, et al. Community-acquired purulent meningitis: a review of 1,316 cases during the antibiotic era, 1954-1976. Rev Infect Dis 1980; 2:725. 48. Nigrovic LE, Malley R, Macias CG, et al. Effect of antibiotic pretreatment on cerebrospinal fluid profiles of children with bacterial meningitis. Pediatrics 2008; 122:726. 49. Doby EH, Stockmann C, Korgenski EK, et al. Cerebrospinal fluid pleocytosis in febrile infants 1-90 days with urinary tract infection. Pediatr Infect Dis J 2013; 32:1024. 50. Bergstrm T, Larson H, Lincoln K, Winberg J. Studies of urinary tract infections in infancy and childhood. XII. Eighty consecutive patients with neonatal infection. J Pediatr 1972; 80:858. 51. Syrogiannopoulos GA, Grivea IN, Anastassiou ED, et al. Sterile cerebrospinal fluid pleocytosis in young infants with urinary tract infection. Pediatr Infect Dis J 2001; 20:927. 52. Finkelstein Y, Mosseri R, Garty BZ. Concomitant aseptic meningitis and bacterial urinary tract infection in young febrile infants. Pediatr Infect Dis J 2001; 20:630. 53. Schnadower D, Kuppermann N, Macias CG, et al. Sterile cerebrospinal fluid pleocytosis in young febrile infants with urinary tract infections. Arch Pediatr Adolesc Med 2011; 165:635. 54. Adler-Shohet FC, Cheung MM, Hill M, Lieberman JM. Aseptic meningitis in infants younger than six months of age hospitalized with urinary tract infections. Pediatr Infect Dis J 2003; 22:1039. 55. Kim KS. Pathogenesis of bacterial meningitis: from bacteraemia to neuronal injury. Nat Rev Neurosci 2003; 4:376. 56. Eliopoulou M, Georgakopoulos C, Beratis N. beta-Glucuronidase activity in cerebrospinal fluid pleocytosis due to urinary tract infection. Acta Paediatr 2007; 96:1053. 57. Singer JI, Buchino JJ, Chabali R. Selected laboratory in pediatric emergency care. Emerg Med Clin North Am 1986; 4:377. 58. Dubos F, Korczowski B, Aygun DA, et al. Serum procalcitonin level and other biological markers to distinguish between bacterial and aseptic meningitis in children: a European multicenter case cohort study. Arch Pediatr Adolesc Med 2008; 162:1157. 59. Leist TP, Frei K, Kam-Hansen S, et al. Tumor necrosis factor alpha in cerebrospinal fluid during bacterial, but not viral, meningitis. Evaluation in murine model infections and in patients. J Exp Med 1988; 167:1743. 60. van Furth AM, Roord JJ, van Furth R. Roles of proinflammatory and anti-inflammatory cytokines in pathophysiology of bacterial meningitis and effect of adjunctive therapy. Infect Immun 1996; 64:4883. 61. Givner LB, Kaplan SL. Meningitis due to Staphylococcus aureus in children. Clin Infect Dis 1993; 16:766. 62. Rennick G, Shann F, de Campo J. Cerebral herniation during bacterial meningitis in children. BMJ 1993; 306:953. 63. Shetty AK, Desselle BC, Craver RD, Steele RW. Fatal cerebral herniation after lumbar puncture in a patient with a normal computed tomography scan. Pediatrics 1999; 103:1284. 64. Nigrovic LE, Kuppermann N, Macias CG, et al. Clinical prediction rule for identifying children with cerebrospinal fluid pleocytosis at very low risk of bacterial meningitis. JAMA 2007; 297:52. 65. Nigrovic LE, Malley R, Kuppermann N. Meta-analysis of bacterial meningitis score validation studies. Arch Dis Child 2012; 97:799. 66. Silverman R, Kwiatkowski T, Bernstein S, et al. Safety of lumbar puncture in patients with hemophilia. Ann Emerg Med 1993; 22:1739. 67. Stein MT, Trauner D. The child with a stiff neck. Clin Pediatr (Phila) 1982; 21:559. Topic 5968 Version 20.0

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GRAPHICS Characteristic features of common causes of bacterial meningitis

Organism
Neisseria meningitidis Streptococcus pneumoniae Listeria monocytogenes Coagulasenegative staphylococci Staphylococcus aureus Gram-negative bacilli Haemophilus influenzae Bacteremia, foreign body, skin Various Nasopharynx, contiguous spread from local infection All ages Elderly adults and neonates Adults; infants and children if not vaccinated Endocarditis, surgery and foreign body, especially ventricular drains; cellulitis, decubitus ulcer Advanced medical illness, neurosurgery, ventricular drains, disseminated strongyloidiasis Diminished humoral immunity

Site of entry
Nasopharynx Nasopharynx, direct extension across skull fracture, or from contiguous or distant foci of infection Gastrointestinal tract, placenta

Age range
All ages All ages

Predisposing conditions
Usually none, rarely complement deficiency All conditions that predispose to pneumococcal bacteremia, fracture of cribriform plate, cochlear implants, CSF otorrhea from basilar skull fracture, defects of the ear ossicle (Mondini defect) Defects in cell-mediated immunity (eg, glucocorticoids, transplantation [especially renal transplantation]), pregnancy, liver disease, alcoholism, malignancy Surgery and foreign body, especially ventricular drains

Elderly adults and neonates All ages

Foreign body

Graphic 73706 Version 7.0

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Host immune defects predisposing to meningitis

Host problem
Absence of opsonizing antibody

Organism favored
Streptococcus pneumoniae Haemophilus influenzae

Frequency of defect actually leading to infection

Common in all age groups Common in very young children Rare Very rare Very rare Rare Rare About 5 percent eventually get cryptococcal meningitis Common presenting illness Rare Rare Very rare

Asplenia: surgical or functional

S. pneumoniae Neisseria meningitidis

Complement deficiency Glucocorticoid excess

N. meningitidis Listeria monocytogenes Cryptococcus neoformans

HIV infection

C. neoformans S. pneumoniae L. monocytogenes

Bacteremia/endocarditis Basilar skull fracture Graphic 72293 Version 7.0

Staphylococcus aureus; various gram-negative rods S. pneumoniae; other upper respiratory tract flora

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Etiology of bacterial meningitis in 231 children from 20 pediatric emergency departments, United States 2001-2004

%: percent. * Citrobacter diversus, Enterobacter cloacae, Klebsiella spp, Pasteurella multocida, Pseudomonas aeruginosa, Salmonella spp. Listeria monocytogenes (2 percent); group A streptococcus (2 percent), Moraxella catarrhalis (0.4 percent). Data from: Nigrovic LE, Kuppermann N, Malley R. Children with bacterial meningitis presenting to the emergency department during the pneumococcal conjugate vaccine era. Acad Emerg Med 2008; 15:522. Graphic 60662 Version 4.0

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Dermal sinus

Dermal sinus lesions may predispose to meningitis with Staphylococcus aureus, Coagulase-negative staphylococci, and enteric Gram-negative organisms, such as Escherichia coli and Klebsiella species.
Courtesy of Sheldon L Kaplan, MD. Graphic 79563 Version 2.0

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Management algorithm for infants (!1 month) and children with suspected bacterial meningitis

STAT: intervention should be performed emergently; CBC: complete blood count; PT: prothrombin time; PTT: partial thromboplastin time; BUN: blood urea nitrogen; CSF: cerebrospinal fluid. ! * Antimicrobial therapy should not be delayed if lumbar puncture cannot be performed or is unsuccessful. Decisions regarding the administration of dexamethasone should be individualized depending on careful analysis of the risks and benefits as discussed in the text. (See "Treatment and prognosis of acute bacterial meningitis in children"). ! ! Empiric antibiotic therapy and dexamethasone (if warranted) should be administered immediately after cerebrospinal fluid is obtained; if dexamethasone is to be administered, it should be given before, or immediately after, the first dose of antimicrobial therapy. Adapted from: 1. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004; 39:1267 2. Fleisher GR. Infectious disease emergencies. In: Textbook of Pediatric Emergency Medicine, 5th ed, Fleisher GR, Ludwig S, Henretig FM (Eds), Lippincott Williams & Wilkins, Philadelphia 2006. p.792. Graphic 74865 Version 6.0

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Cerebrospinal fluid analysis in central nervous system infection

Glucose (mg/dL)
<10* More common Bacterial meningitis 10 to 45 Bacterial meningitis

Protein (mg/dL)
>250 " Bacterial meningitis 50 to 250 # Viral meningitis Nervous system Lyme disease (neuroborreliosis) Neurosyphilis

Total white blood cell count (cells/microL)

>1000 Bacterial meningitis 100 to 1000 Bacterial or viral meningitis TB meningitis 5 to 100 Early bacterial meningitis Viral meningitis Neurosyphilis TB meningitis Some cases of mumps and LCMV Encephalitis Encephalitis

Less common

TB meningitis Fungal meningitis

Neurosyphilis Some viral infections (such as mumps and LCMV)

TB meningitis

LCMV: lymphocytic choriomeningitis virus; TB: tuberculosis. * <0.6 mmol/L. 0.6 to 2.5 mmol/L. ! >2.5 g/L. " 0.5 to 2.5 g/L. Graphic 76324 Version 6.0

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Streptococcus pneumoniae in cerebrospinal fluid

S. pneumoniae under high-power magnification (1000x) in CSF.

Courtesy of Harriet Provine. Graphic 72926 Version 3.0

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Neisseria meningitidis in cerebrospinal fluid

Gram stain of cerebrospinal fluid (x1000) shows inflammatory cells and kidney-shaped, gram-negative diplococci (arrows). Neisseria meningitidis grew from this specimen.
Courtesy of Harriet Provine. Graphic 61788 Version 3.0

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Haemophilus influenzae in cerebrospinal fluid

Gram stain of cerebrospinal fluid (x1000) shows inflammatory cells and small, pleomorphic, gram-negative coccobacilli. Haemophilus influenzae grew from this specimen.
Courtesy of Harriet Provine. Graphic 81383 Version 4.0

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Group B streptococcus in cerebrospinal fluid

Gram stain of cerebrospinal fluid (x1000) shows inflammatory cells and gram-positive coccobacilli. Streptococcus agalactiae (group B streptococcus) grew from this specimen.
Courtesy of Harriet Provine. Graphic 72503 Version 3.0

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Listeria monocytogenes in cerebrospinal fluid

Gram stain of cerebrospinal fluid (x1000) shows inflammatory cells and small, gram-positive rods and coccobacilli. Culture of this specimen revealed moderate-sized, beta-hemolytic colonies composed of small, motile gram-positive rods, confirmed to be Listeria monocytogenes.
Courtesy of Harriet Provine. Graphic 79633 Version 3.0

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Howell-Jolly bodies following splenectomy

This peripheral blood smear shows two red blood cells (RBC) that contain Howell-Jolly bodies (black arrows). Howell-Jolly bodies are remnants of RBC nuclei that are normally removed by the spleen. Thus, they are seen in patients who have undergone splenectomy (as in this case) or who have functional asplenia (eg, from sickle cell disease). Target cells (blue arrows) are another consequence of splenectomy.
Courtesy of Carola von Kapff, SH (ASCP). Graphic 60588 Version 5.0

Normal peripheral blood smear

High power view of a normal peripheral blood smear. Several platelets (black arrows) and a normal lymphocyte (blue arrow) can also be seen. The red cells are of relatively uniform size and shape. The diameter of the normal red cell should approximate that of the nucleus of the small lymphocyte; central pallor (red arrow) should equal one-third of its diameter.
Courtesy of Carola von Kapff, SH (ASCP). Graphic 59683 Version 2.0

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