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 treatment and prognosis 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:
●Clinical features, evaluation, and diagnosis (see "Bacterial meningitis in children older than one month: Clinical features and diagnosis")
●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")
PRETREATMENT EVALUATION — If possible, the pretreatment evaluation of children with suspected bacterial meningitis should include (table 1):
●Complete history and physical examination
●Blood tests (eg, complete blood count with differential, serum chemistries, coagulation studies, and inflammatory markers)
●Blood cultures
●Cerebrospinal fluid (CSF) studies (cell count and differential, glucose, protein)
●CSF Gram stain and culture
In cases in which the performance of a lumbar puncture (LP) is delayed by rapidly deteriorating clinical status or the need for neuroimaging, blood culture should be obtained before the administration of antibiotic therapy (table 1).
The pretreatment evaluation of infants and children with suspected bacterial meningitis is discussed in greater detail separately. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Evaluation'.)
GENERAL MANAGEMENT
Setting of care — Children who are suspected of having bacterial meningitis based upon the results of the initial evaluation (including history, physical examination, laboratory tests, and cerebrospinal fluid [CSF] examination) should be admitted to the hospital for ongoing management. The level of inpatient care (ward versus pediatric intensive care unit) is determined by the severity of illness. Admission to a pediatric intensive care unit is appropriate for children with hemodynamic instability (ie, septic shock), significant respiratory compromise, prolonged or recurrent seizures, severely depressed mental status, rapidly deteriorating clinical status, or other potentially life-threatening complications.
Supportive measures — General supportive measures include:
●Appropriate respiratory support for patients with hypoxia or labored breathing (see "Initial assessment and stabilization of children with respiratory or circulatory compromise")
●Establishing venous access (see "Vascular (venous) access for pediatric resuscitation and other pediatric emergencies")
●Appropriate hemodynamic support for children presenting with signs of shock (see "Septic shock in children: Rapid recognition and initial resuscitation (first hour)")
●Treatment of metabolic disturbances such as hypoglycemia, electrolyte abnormalities, and acidosis if present (see "Approach to hypoglycemia in infants and children", section on 'Treatment' and "Approach to the child with metabolic acidosis", section on 'Treatment')
●Treatment of seizures if present (see "Seizures and epilepsy in children: Initial treatment and monitoring")
Fluid management — Careful management of fluid and electrolyte balance is an important aspect of supportive therapy. Both over- and underhydration are associated with adverse outcomes [1]. Hypotonic fluids (eg, one-half or one-quarter normal saline) should be avoided because they deliver too much free water, which contributes to hyponatremia and can exacerbate cerebral edema.
The approach to initial fluid management depends on hemodynamic stability, volume status, and whether there is evidence of syndrome of inappropriate secretion of antidiuretic hormone (SIADH; eg, serum sodium <130 mEq/L):
●Shock – Children who are in shock should receive volume resuscitation with isotonic fluid to maintain blood pressure and cerebral perfusion. The management of septic shock in children is discussed separately. (See "Septic shock in children: Rapid recognition and initial resuscitation (first hour)".)
●Hypovolemia without shock – Children who are volume depleted, but not in shock, should receive volume repletion with isotonic fluids with careful and frequent attention to fluid status. Daily weight, urine output, and serum electrolytes should be monitored. (See "Treatment of hypovolemia (dehydration) in children".)
●SIADH – For children without signs of shock or hypovolemia who have evidence of SIADH (eg, serum sodium <130 mEq/L), we suggest moderate fluid restriction (ie, two-thirds to three-quarters of maintenance). Daily weight, urine output, serum electrolytes, and, if indicated, serum and urine osmolalities should be carefully monitored. Fluid administration can be liberalized gradually once serum sodium is >135 mEq/L. Most children can receive maintenance fluid intake within 24 to 48 hours of hospitalization. SIADH is common in children with bacterial meningitis. In one study, 10 percent of children with pneumococcal meningitis had initial serum sodium values <130 mEq/L [2]. (See "Treatment of hyponatremia: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and reset osmostat", section on 'Fluid restriction'.)
●Normovolemia without SIADH – Children without signs of shock, hypovolemia, or SIADH (eg, those with normal perfusion, normal serum sodium [≥135 mEq/L], and without signs of volume overload) can receive isotonic fluids at a maintenance rate (calculator 1 and calculator 2). However, fluid status and serum electrolytes should be reassessed regularly since SIADH can develop subsequent to the initial presentation. (See "Maintenance intravenous fluid therapy in children".)
Dexamethasone — The role of dexamethasone therapy to prevent hearing loss and other neurologic complications of bacterial meningitis in children is uncertain. This issue is discussed separately. (See "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications", section on 'Dexamethasone'.)
Monitoring — Children who are being treated for bacterial meningitis should be monitored carefully for complications (eg, seizures, signs of elevated intracranial pressure, development of infected subdural effusions), particularly during the first two to three days of treatment when complications are most likely to occur [3].
●Heart rate, blood pressure, and respiratory rate should be monitored regularly with a frequency appropriate to the care setting
●A complete neurologic examination should be performed daily; rapid assessment of neurologic function should be performed several times per day for the first several days of treatment
Infection control — All patients admitted to the hospital with meningitis should be placed on standard precautions [4-6]. (See "Infection prevention: Precautions for preventing transmission of infection", section on 'Standard precautions'.)
In addition, droplet precautions are recommended for patients with suspected Neisseria meningitidis and Haemophilus influenzae type b (Hib) meningitis until they have received 24 hours of effective therapy [4,5]. Patients should be in private rooms, and hospital personnel should wear a face mask when they are within 3 feet (1 meter) of the patient.
ANTIBIOTIC THERAPY
Avoidance of delay — Antibiotic therapy should be initiated immediately after lumbar puncture (LP) is performed if the clinical suspicion for meningitis is high (table 1). Delay in the administration of appropriate antibiotics can have a deleterious effect on outcome for patients who are deteriorating rapidly.
If neuroimaging is to be performed before LP, antibiotic therapy should be initiated immediately after blood culture is obtained, before neuroimaging is performed. Although the administration of antimicrobial therapy before LP may affect the yield of cerebrospinal fluid (CSF) Gram stain and culture, pathogens other than meningococcus usually can be identified in the CSF up to several hours after the administration of antibiotics. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Cerebrospinal fluid culture'.)
Treatment principles — There are two general principles of antibiotic therapy for bacterial meningitis:
●Bactericidal effect – Since the CSF is a site of impaired humoral immunity, a fundamental principle of therapy of bacterial meningitis is that antibiotics must achieve a bactericidal effect within CSF to result in optimal microbiologic cure [7,8]. This principle is supported by clinical observations of poor outcomes in patients receiving bacteriostatic therapy (eg, clindamycin, tetracycline) [9].
●Drug entry into CSF – Treatment of bacterial meningitis requires adequate concentration of antibiotics in the CSF. Most drugs reach concentrations in the CSF that are only 10 to 20 percent of peak concentrations in the serum. This is because the blood-brain barrier blocks macromolecule entry into the CSF, with small, lipophilic molecules penetrating most easily.
Inflammation increases the permeability of the blood-brain barrier, which can increase the peak concentration of drugs in the CSF. This was illustrated in one study that sequentially monitored CSF and serum penicillin levels in children with bacterial meningitis. The mean CSF:serum ratio two hours after administration of the same intravenous (IV) dose of penicillin was 42 percent on the first day of therapy but fell to less than 10 percent on the 10th day when the inflammatory changes had subsided [10]. (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states", section on 'Blood-brain barrier'.)
Because of the general limitation in antibiotic penetration into the CSF, all patients should be treated with parenteral antibiotics. Oral antibiotics are not appropriate for treatment of bacterial meningitis, since the dose and tissue levels tend to be considerably lower than with parenteral agents.
Empiric therapy — The organism causing bacterial meningitis seldom is known at the outset of therapy. As a result, the initial empiric treatment plan is based upon the most likely pathogens and local susceptibility patterns.
●Empiric regimen – The empiric regimen should include coverage for meningococcus and penicillin-resistant pneumococcus, the two most common causes of bacterial meningitis in infants and children. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Epidemiology'.)
For most patients, we suggest the following regimen [5,6]:
•Vancomycin 60 mg/kg/day IV (maximum dose 4 g/day) in four divided doses, plus
•Ceftriaxone 100 mg/kg/day IV (maximum dose 4 g/day) in two divided doses, or cefotaxime (where available) 300 mg/kg/day IV (maximum dose 12 g/day) in three or four divided doses
We suggest twice-daily ceftriaxone dosing rather than once daily to avoid the possibility of inadequate treatment in the event of dosing errors, delayed doses, or missed doses [3].
For children in whom cephalosporins or vancomycin are contraindicated (eg, severe allergy), consultation with a pediatric infectious diseases specialist is advised.
Additional coverage may be warranted in the following circumstances (table 2):
•Immune deficiency, neurosurgery, or medical device – Children with immune deficiency, recent neurosurgery, penetrating head trauma, or anatomic defects may require additional empiric coverage, as summarized in the table (table 2).
•Adjunctive dexamethasone – Some experts suggest the addition of rifampin to the empiric regimen if dexamethasone is administered [11]. (See "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications", section on 'Antibiotic regimen'.)
•Unusual pathogen on Gram stain – The CSF Gram stain may provide important clues for the need to broaden empiric therapy to cover for less common or unusual organisms. However, empiric antibiotics should not be narrowed based upon CSF Gram stain results, because Gram stain results are subject to observer misinterpretation [11]; broad-spectrum antimicrobial therapy should be continued until CSF culture results are available.
●Duration of empiric therapy – The duration of empiric therapy depends upon the culture results, CSF parameters, and clinical concern for bacterial meningitis:
•Positive culture – Once culture results are available, treatment should be modified based on the specific pathogen isolated in CSF and/or blood culture. (See 'Specific therapy' below.)
•Negative culture with normal CSF profile – For children who have a normal CSF profile and negative blood and CSF cultures, we usually discontinue antimicrobial therapy if cultures remain sterile after 48 to 72 hours of incubation.
•Negative culture with CSF pleocytosis – For children with CSF pleocytosis whose blood and CSF cultures remain negative after 48 to 72 hours, the decision to continue or discontinue empiric antibiotic therapy is individualized based upon the clinical status of the child and level of clinical concern for bacterial meningitis. Consultation with a pediatric infectious diseases specialist is advised if the clinician is uncertain how to manage such children. Important considerations include:
-CSF cultures may be negative in children who received antibiotic therapy before CSF examination (see "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Cerebrospinal fluid culture')
-Negative CSF culture does not preclude the development of meningitis hours or days after the LP; if clinical signs suggest meningitis, repeat LP may be warranted
-Molecular tests can help to identify the specific pathogen in some cases (see "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Molecular methods')
-Nonbacterial causes of CSF pleocytosis should also be considered (see "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Differential diagnosis' and "Viral meningitis in children: Clinical features and diagnosis", section on 'Distinguishing viral from bacterial meningitis')
Specific therapy — Once the causative agent and its in vitro antimicrobial susceptibility pattern are known, empiric antimicrobial therapy can be altered accordingly.
Streptococcus pneumoniae — The therapeutic options for pneumococcal meningitis are summarized in the table (table 3) and discussed in the following sections [6]. The increasing prevalence of antibiotic-resistant S. pneumoniae has important implications for the treatment of pneumococcal meningitis, as discussed below. (See "Resistance of Streptococcus pneumoniae to beta-lactam antibiotics" and "Microbiology and pathogenesis of Streptococcus pneumoniae".)
●Penicillin-susceptible isolates – In children with penicillin-susceptible isolates (minimum inhibitory concentration [MIC] ≤0.06 mcg/mL), treatment consists of [6]:
•Penicillin G 300,000 units/kg/day intravenously (IV) in four to six divided doses, or
•High-dose ceftriaxone or cefotaxime (ie, same dose as for empiric therapy)
●Penicillin-nonsusceptible, cephalosporin-susceptible isolates – In children with isolates that are penicillin-nonsusceptible (intermediate or resistant; MIC >0.06 mcg/mL) but susceptible to ceftriaxone and cefotaxime (MIC ≤0.5 mcg/mL), treatment consists of high-dose ceftriaxone or cefotaxime [6]. Ceftriaxone and cefotaxime can attain levels of only 3 to 8 mcg/mL in the CSF and achieve reliable bactericidal activity only if the MIC is ≤0.5 mcg/mL [12].
●Cephalosporin-nonsusceptible isolates – In children with isolates nonsusceptible to ceftriaxone and cefotaxime (intermediate [MIC = 1 mcg/mL] or resistant [MIC ≥2 mcg/mL]), treatment consists of:
•Vancomycin 60 mg/kg/day IV (maximum dose 4 g/day) in four divided doses, plus
•High-dose ceftriaxone or cefotaxime
•Rifampin (20 mg/kg/day IV in two divided doses) may be added in selected circumstances (as described below)
Treatment with extended-spectrum cephalosporins alone is generally not sufficient for isolates with intermediate susceptibility to ceftriaxone or cefotaxime (MIC = 1 mcg/mL) [6]. In the context of central nervous system infections, isolates with MICs ≥2 mcg/mL are considered resistant (table 4).
Rifampin may be added to the regimen (if the isolate is susceptible) in the following settings [6]:
•If the isolate has a high MIC for cephalosporins (≥4 mcg/mL)
•If the patient appears to be failing vancomycin
•If repeat cerebrospinal fluid culture is not sterile (see 'Repeat lumbar puncture' below)
•If the patient was treated with dexamethasone
●Other antimicrobials – Other antibiotics that are rarely used in the treatment of resistant pneumococcal meningitis include meropenem and respiratory fluoroquinolones (eg, moxifloxacin, levofloxacin, gemifloxacin) [13].
Meropenem is effective in vitro but should not be used for monotherapy [13].
Fluoroquinolones are not routinely recommended for use in children due to the potential risk of musculoskeletal toxicity. However, for serious infections such as meningitis, it is reasonable to use a systemic fluoroquinolone when no safe or effective alternative exists. (See "Fluoroquinolones", section on 'Children'.)
Chloramphenicol also has been used for patients with an allergy to penicillin and cephalosporin. Unfortunately, many penicillin-resistant strains are somewhat resistant to chloramphenicol killing (despite in vitro tests that show inhibition) and treatment failures of meningitis caused by penicillin-resistant S. pneumoniae have occurred when chloramphenicol was used [14].
Neisseria meningitidis — The preferred agents for meningococcal meningitis are third-generation cephalosporins (eg, ceftriaxone 100 mg/kg/day IV in two divided doses [maximum 4 g/day] or cefotaxime [where available] 225 to 300 mg/kg/day IV [maximum dose 12 g/day] in three or four divided doses). High-dose penicillin G (300,000 units/kg/day in four divided doses) is an alternative low-cost option. However, the susceptibility of the isolate to penicillin should be documented before switching to penicillin since beta-lactamase-producing N. meningitidis isolates have been reported [15,16]. The usual duration of antibiotic therapy is five to seven days, depending on the severity of initial illness and response to treatment. Patients treated with penicillin should receive antimicrobial therapy to eradicate nasopharyngeal carriage. Treatment of meningococcal meningitis is discussed in greater detail separately. (See "Treatment and prevention of meningococcal infection", section on 'Antibiotic therapy'.)
Haemophilus influenzae — Meningitis due to H. influenzae is usually treated with a third-generation cephalosporin such as ceftriaxone (100 mg/kg/day IV in two divided doses [maximum dose 4 g/day]) or cefotaxime (where available; 200 mg/kg/day IV in three or four divided doses [maximum dose 12 g/day]). Treatment duration is 7 to 10 days. Ampicillin is appropriate only if the infecting pathogen has been shown to be beta-lactamase negative. Treatment of H. influenzae meningitis and postexposure chemoprophylaxis are discussed in greater detail separately. (See "Epidemiology, clinical manifestations, diagnosis, and treatment of Haemophilus influenzae", section on 'Directed treatment' and "Prevention of Haemophilus influenzae type b infection", section on 'Postexposure chemoprophylaxis'.)
Listeria monocytogenes — The preferred regimen for treatment of meningitis due to L. monocytogenes in infants and children consists of ampicillin (300 mg/kg/day IV in four divided doses [maximum dose 12 g/day]) plus gentamicin (7.5 mg/kg/day IV in three divided doses) (table 5). The usual treatment duration is 21 to 28 days (gentamicin may not need to be continued for the entire duration). (See "Treatment and prevention of Listeria monocytogenes infection", section on 'Preferred regimen'.)
Group B streptococcus (GBS) — The preferred agents for treatment of GBS (Streptococcus agalactiae) meningitis are penicillin G (450,000 to 500,000 units/kg/day IV in four divided doses) or ampicillin (300 mg/kg/day IV in three divided doses). The usual treatment duration is 14 to 21 days. Treatment of GBS is discussed separately. (See "Group B streptococcal infection in neonates and young infants", section on 'Definitive therapy'.)
Staphylococcus aureus — Meningitis caused by S. aureus is uncommon in children unless there is an underlying anatomic defect (eg, dermal sinus), immune dysfunction, or implanted device (eg, CSF drain or shunt). Management of CSF shunt infections is discussed separately. (See "Infections of cerebrospinal fluid shunts and other devices", section on 'Treatment'.)
Antimicrobial therapy for S. aureus meningitis is as follows:
●MSSA – The standard therapy for methicillin-susceptible S. aureus (MSSA) meningitis is nafcillin or oxacillin (both are dosed at 150 to 200 mg/kg/day IV in four doses [maximum 12 g/day]) [11,17]. Treatment duration is typically 14 days.
●MRSA – The preferred therapy for methicillin-resistant S. aureus (MRSA) meningitis is vancomycin (60 mg/kg/day IV in four divided doses [maximum dose 4 g/day]) [11,17,18]. Treatment duration is at least 14 days. Some experts recommend adding rifampin to vancomycin if the isolate is susceptible to rifampin (20 mg/kg/day orally or IV in two divided doses [maximum dose 600 mg/day]).
Alternative agents for MRSA meningitis include ceftaroline (45 mg/kg/day in three divided doses), trimethoprim-sulfamethoxazole (TMP-SMX; 10 to 12 mg/kg of the TMP component and 50 to 60 mg/kg of the SMX component per day in four divided doses) or linezolid (in patients <12 years old: 30 mg/kg/day IV in three divided doses [maximum dose 1200 mg/day]; in patients ≥12 years old: 600 mg IV twice per day) [11,17,18]:
Inflammation of the meninges does not appear to affect penetration of linezolid into the CSF [19-22]. Rapid penetration has been demonstrated in children and adolescents [22]. However, CSF concentrations are variable and correlation of CSF and plasma levels is inconsistent. Furthermore, linezolid is not bactericidal, but some case reports document successful linezolid treatment of staphylococcal meningitis [17,23].
Treatment of invasive MSSA and MRSA infections in children is discussed in greater detail separately. (See "Staphylococcus aureus in children: Overview of treatment of invasive infections", section on 'Definitive antimicrobial therapy'.)
Gram-negative rods (GNRs) — Consultation with a pediatric infectious diseases specialist is advised for children with meningitis caused by a GNR. Choices for IV therapy are outlined here and discussed in greater detail separately. (See "Infections of cerebrospinal fluid shunts and other devices".)
●Enteric GNR – The usual treatment regimen for susceptible isolates consists of an extended-spectrum cephalosporin (eg, ceftriaxone 100 mg/kg/day IV in two divided doses [maximum dose 4 g/day] or cefotaxime [where available] 200 to 300 mg/kg/day IV in four divided doses [maximum dose 12 g/day]) plus an aminoglycoside (eg, gentamicin 7.5 mg/kg/day IV in three divided doses) [24]. The aminoglycoside often can be discontinued after the first five to seven days, once the CSF is documented to be sterile.
●Pseudomonas aeruginosa – Ceftazidime (150 mg/kg/day IV in three divided doses [maximum dose 6 g/day]) is the most effective cephalosporin for treating susceptible P. aeruginosa infections [25]. For ceftazidime-resistant strains, meropenem (120 mg/kg/day IV in three divided doses [maximum dose 6 g/day]) is an effective treatment.
●Extended-spectrum beta-lactamase (ESBL)-producing organisms – Meropenem (120 mg/kg/day IV in three divided doses [maximum dose 6 g/day]) is the agent of choice in the treatment of meningitis caused by susceptible ESBL-producing GNRs [26,27].
Repeat LP should be performed two to three days after starting therapy to assess the efficacy of treatment. (See 'Repeat lumbar puncture' below.)
Occasionally, IV therapy alone is insufficient and intraventricular administration of an antibiotic (typically an aminoglycoside) is necessary to sterilize the CSF. Intraventricular therapy should be undertaken in consultation with specialists in pediatric infectious diseases and neurosurgery. This issue is discussed in greater detail separately. (See "Infections of cerebrospinal fluid shunts and other devices", section on 'Intraventricular antibiotics'.)
Treatment duration — The duration of antimicrobial therapy depends upon the causative organism and clinical course. We suggest the following durations of therapy for uncomplicated meningitis caused by the following organisms [4,5,11,28]:
●S. pneumoniae – 10 to 14 days
●N. meningitidis – 5 to 7 days
●H. influenzae – 7 to 10 days
●L. monocytogenes – 21 to 28 days
●S. aureus – At least two weeks
●Gram-negative bacilli – Three weeks or a minimum of two weeks beyond the first sterile CSF culture, whichever is longer
Limited observational and clinical trial data suggest that in carefully selected cases, a shorter duration of therapy may be equally efficacious and may reduce hospital duration and health care costs [29-31]. However, due to the limitations of these data, as described below, we view the findings as preliminary and continue to suggest organism-specific durations of therapy, as outlined above.
A 2009 meta-analysis of five randomized trials (383 children) found that treatment for 4 to 7 days resulted in rates of cure similar to treatment for 7 to 14 days (odds ratio 1.24, 95% CI 0.73-2.11) [30]. However, the trials included in the meta-analysis had important limitations, including lack of blinding in all five trials, small number of patients, and relatively short follow-up. In addition, there was considerable variability in the distribution of causative organisms in the different trials, with the most common being S. pneumoniae, N. meningitidis, and H. influenzae type b (Hib). In a subsequent multicenter trial in resource-limited countries involving >1000 children with bacterial meningitis (S. pneumoniae in 33 percent, Hib in 26 percent, N. meningitidis in 7 percent, and no identified cause in 33 percent), outcomes were generally similar among children treated with ceftriaxone for 5 versus 10 days [29]. There were two cases of relapse in the 5-day group versus none in the 10-day group, and there were nine meningitis-related deaths (2 percent) in the 5-day group versus six (1 percent) in the 10-day group. While these differences were not statistically significant, the study may have been underpowered to detect important differences. Furthermore, the setting, methodology, and lack of organism-specific outcome information preclude generalizability to resource-rich settings [29,32].
Outpatient therapy — In selected patients, a portion of parenteral antibiotic therapy may be administered in the outpatient setting [11]. In our practice, we very rarely complete antimicrobial therapy for bacterial meningitis at home; however, it may be a reasonable option for some patients if all of the following criteria are met [33]:
●Patient is clinically stable and afebrile for at least 24 to 48 hours
●Patient has completed at least six days of inpatient therapy – Serious adverse complications of meningitis are uncommon after three or four days of therapy, particularly in children who are clinically well and afebrile [34]
●Patient has normal or nearly normal neurologic function (no focal findings and no seizure activity)
●There is no concern for complications of meningitis on neuroimaging (eg, no abscess or subdural collection)
●Patient is able to take fluids by mouth
●Patient has reliable venous access (ie, a peripherally inserted central catheter or tunneled central venous catheter)
●Caregivers are reliable and have transportation and a telephone
If the outpatient regimen will be different from the regimen given in the hospital, we suggest that the first dose be supervised in the hospital to ensure that the patient tolerates it. Home antibiotic therapy should be administered by a qualified home health nursing professional or a caregiver who has received proper instruction. If the family is not comfortable administering the antibiotics, arrangements can be made to administer antibiotics in the office. In addition, the patient should be examined daily by a clinician (eg, visiting nurse, primary care provider). If any concerns arise (recurrence of fever, new neurologic findings), the patient should be referred for further evaluation.
Potential advantages of completing therapy in the outpatient setting are that it decreases the risk of nosocomial infection, improves quality of life for the patient and family, and decreases health care costs [33,35]. Risks include the potential for missed doses, administration errors, catheter-related complications, adverse drug events, and risks posed by provision of care by caregivers who may lack formal medical training. Careful patient selection and close monitoring are keys to the success and safety of this approach [33,35,36].
Additional details regarding outpatient parenteral antibiotic therapy are provided separately. (See "Outpatient parenteral antimicrobial therapy".)
RESPONSE TO THERAPY — The response to therapy is monitored with clinical and laboratory parameters (eg, fever curve, resolution of symptoms and signs, normalization of inflammatory markers) and by neuroimaging.
Duration of fever — Fevers typically last three to six days after initiating adequate therapy [3]. Fever lasts >5 days in approximately 10 to 15 percent of patients [3,37]; secondary fever (eg, recurrence of fever after being afebrile for at least 24 hours) occurs in approximately 15 to 20 percent [3,37].
Causes of persistent or secondary fever include [3]:
●Inadequate treatment
●Development of nosocomial infection (eg, infected intravenous [IV] catheters, urinary tract infection, viral infection); nosocomial infection is more often associated with secondary fever than with persistent fever
●Discontinuation of dexamethasone (see "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications", section on 'Adverse effects')
●Development of a suppurative complication (pericarditis, pneumonia, arthritis, subdural empyema (image 1 and picture 1))
●Drug fever (a diagnosis of exclusion)
In patients with persistent or secondary fever, suppurative and nosocomial complications should be carefully sought. The evaluation typically includes repeat blood culture, complete blood count, C-reactive protein, and urinalysis. The need for repeat evaluation of the cerebrospinal fluid (CSF) should be considered on an individual basis. In many cases, a specific cause of prolonged fever cannot be determined. In the patient who is improving daily but has unexplained fever despite careful evaluation, it is thought that the individual's host response to infection is responsible for the prolonged fever.
Repeat blood culture — As discussed above, repeat blood culture may be warranted in patients with persistent or secondary fever. In addition, for patients who had a positive blood culture at initial evaluation, blood culture should be repeated to document sterility of the blood stream. The follow-up blood culture is usually obtained when it is known that the initial blood culture is positive.
Repeat lumbar puncture — Reexamination of the CSF is warranted in the following circumstances:
●Poor clinical response – Patients who have a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy should undergo repeat lumbar puncture (LP) [11]. This is particularly important in the following settings:
•Children with cephalosporin-resistant pneumococcal meningitis
•Children with high bacterial burden in CSF (eg, sheets of bacteria on Gram stain)
•Children with pneumococcal meningitis who were treated with dexamethasone (since dexamethasone may interfere with the ability of the clinician to assess clinical response such as resolution of fever) (see "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications", section on 'Adverse effects')
●Gram-negative bacillary meningitis – Patients with gram-negative bacillary meningitis should undergo repeat LP two to three days after beginning treatment to document that the CSF is sterile and to determine treatment duration.
●Persistent or recurrent fever – Repeat LP also may be indicated in children with persistent or recurrent fever. The decision to perform repeat LP in this setting is individualized, as discussed above. (See 'Duration of fever' above.)
Reexamination of the CSF in these settings informs decisions about extending duration of therapy and/or changing the antibiotic regimen. Extension of the duration of therapy is indicated if any of the following are noted:
●CSF cultures from the repeat LP grow a pathogenic organism
●CSF examination at the conclusion of the standard treatment duration shows >30 percent neutrophils
●CSF examination at the conclusion of the standard treatment duration shows CSF glucose of <20 mg/dL (or <20 percent of the blood glucose level)
Neuroimaging — Neuroimaging (with computed tomography or magnetic resonance imaging) may be indicated during the course of treatment to assess for complications such as subdural empyema, brain abscess, cerebral vascular thrombosis, or hydrocephalus. Indications for neuroimaging may include [38]:
●Focal neurologic signs or prolonged obtundation
●Unexplained persistent fever
●Increasing head circumference in young infants
●Seizures occurring >72 hours after the start of treatment
●Persistently positive CSF cultures despite appropriate antibiotic therapy
●Persistent elevation of CSF neutrophils (>30 to 40 percent) at the completion of standard duration of therapy
●Gram-negative meningitis in young infants – Neuroimaging is usually performed sometime during treatment to evaluate for hydrocephalus and other complications of the meningitis (see "Bacterial meningitis in children: Neurologic complications" and "Hydrocephalus in children: Clinical features and diagnosis", section on 'Neuroimaging')
●Meningitis caused by the organism with a propensity to cause abscess (eg, Citrobacter, Cronobacter, Streptococcus anginosus)
In addition, imaging is warranted in children who experience recurrent meningitis to evaluate the possibility of a communication between the nasal passage or ear and the meninges [39].
PROGNOSIS
Mortality — Reported mortality rates among children with bacterial meningitis range from 0 to 15 percent, depending upon the setting, era, and infecting organism [40-46]. In resource-rich settings, mortality rates associated with bacterial meningitis are approximately 4 to 5 percent [43,44]. Reported mortality rates in resource-limited countries are approximately 8 to 10 percent [43].
Case-fatality rates according to the organism isolated are as follows [2,40,41,43,47,48]:
●H. influenzae type b (Hib) – 4 to 5 percent
●N. meningitidis – 7 percent
●S. pneumoniae – 7 to 15 percent
The risk of mortality is increased in children who are comatose or in shock at the time of admission and in those who require mechanical ventilation [41,49,50].
Neurologic sequelae — Persistent neurologic sequelae are common in children who survive an episode of bacterial meningitis. The most common sequelae include hearing loss, seizures, intellectual disability, and spasticity and/or paresis. This is discussed in greater detail separately. (See "Bacterial meningitis in children: Neurologic complications".)
Prognostic factors — Factors related to the outcome of bacterial meningitis in children include [41,51-57].
●Level of consciousness at the time of admission – In an analysis of data from 654 children with bacterial meningitis, the Glasgow Coma Score (GCS) (table 6) at admission was the strongest independent predictor of death or severe neurologic sequelae at the time of hospital discharge [52]. The likelihood of death from severe neurologic disability increased with decreasing GCS (approximately 10-fold higher risk with GCS 7 to 9 and approximately 30-fold higher risk with GCS ≤6).
●Etiologic agent – The risk of death or neurologic sequelae is higher in children with pneumococcal meningitis than with meningococcal or Hib meningitis [41,49].
The risk of hearing impairment is also related to etiologic agent. Hearing loss occurs in approximately 31 percent of children with pneumococcal meningitis, 11 percent of children with meningococcal meningitis, and 6 percent of children with Hib meningitis [41,55,58].
●Seizures – In a multicenter pneumococcal meningitis surveillance study, the occurrence of seizures more than 72 hours after initiation of appropriate antimicrobial therapy was associated with increased risk of neurologic sequelae [41]. In a series of children with Hib meningitis, seizures were associated with subtle cognitive and learning problems [59].
●Cerebrospinal fluid (CSF) glucose concentration – Decreased CSF glucose concentration (<20 mg/dL [1.1 mmol/L]) at the time of admission appears to be associated with increased risk of hearing loss [41,53,54].
●Delayed sterilization of the CSF – Delayed sterilization of the CSF (persistently positive culture 16 to 18 hours after the initiation of therapy) is associated with adverse outcomes, including moderate to profound sensorineural hearing loss, seizures, hemiparesis, and abnormal neurologic findings at the time of discharge [60].
●Underlying conditions – Children with underlying immunodeficiency, malnutrition, malignancy, or preexisting neurologic disease have a higher risk of death or neurologic sequelae [56,57].
FOLLOW-UP
Hearing evaluation — Hearing evaluation should be performed at the time of or shortly after discharge from the hospital [61,62]. Hearing may be assessed by pure tone audiometry; auditory brainstem response may be used in young children or those who cannot cooperate with pure tone audiometry. Hearing evaluation should be repeated if the results of the initial evaluation suggest more than a minor hearing loss. (See "Hearing loss in children: Screening and evaluation".)
Developmental screening — Young children who have been treated for meningitis are at risk for developmental delay. Developmental surveillance should continue throughout childhood. (See "Developmental-behavioral surveillance and screening in primary care".)
Evaluation for immunodeficiency — Children who develop pneumococcal meningitis with a vaccine serotype (table 7) despite having received at least one dose of pneumococcal conjugate vaccine and those who develop Haemophilus influenzae type b (Hib) meningitis despite two or more doses of the Hib vaccine may have an underlying immunodeficiency. In such cases, an evaluation of the child’s immune status with serum immunoglobulin levels and human immunodeficiency virus (HIV) testing can be considered [6,63]. Infections caused by pneumococcal serotype 3 are an exception to this since pneumococcal conjugate vaccines are less protective against this serotype.
In one study of 163 children who underwent immune evaluation after being diagnosed with invasive pneumococcal disease (87 percent had meningitis), 10 percent were found to have an underlying primary immunodeficiency [63]. However, in another study that included 28 children who underwent immune evaluation because they developed invasive pneumococcal disease despite receiving ≥2 doses of pneumococcal conjugate vaccine, only one child was found to have an immunodeficiency [64].
PREVENTION
Chemoprophylaxis — Chemoprophylaxis in the following clinical settings is discussed separately:
●N. meningitidis – Chemoprophylaxis is indicated in close contacts of patients with meningococcal meningitis (table 8). This is discussed in a separate topic review. (See "Treatment and prevention of meningococcal infection", section on 'Antimicrobial chemoprophylaxis'.)
●H. influenzae type b (Hib) – Chemoprophylaxis may be indicated for certain close contacts of a child with Hib meningitis, depending upon individual circumstances. This is discussed in a separate topic review. (See "Prevention of Haemophilus influenzae type b infection", section on 'Postexposure chemoprophylaxis'.)
●S. pneumoniae – Although it does not have a role in preventing the spread of pneumococcal meningitis, chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in children with functional or anatomic asplenia. (See "Overview of the management and prognosis of sickle cell disease", section on 'Infection prevention' and "Prevention of infection in patients with impaired splenic function", section on 'Antibiotic prophylaxis'.)
●Basilar skull fractures – Basilar skull fractures with underlying dural tears are associated with cerebrospinal fluid (CSF) leaks and predispose patients to meningitis because of the potential for direct communication of bacteria in the upper respiratory tract with the central nervous system. The available evidence does not support the routine use of antibiotics prophylactically to prevent meningitis in this setting [65]. Furthermore, the majority of CSF leaks resolve spontaneously within one week of injury. However, the incidence of bacterial meningitis rises substantially if a leak persists past seven days and prophylactic antibiotics may be appropriate in some cases, particularly if the leak cannot be repaired in a timely manner. (See "Skull fractures in children: Clinical manifestations, diagnosis, and management", section on 'Basilar skull fractures'.)
Vaccines — Vaccines directed against each of the major pathogens causing bacterial meningitis in children are discussed separately:
●S. pneumoniae (see "Pneumococcal vaccination in children")
●N. meningitidis (see "Meningococcal vaccination in children and adults")
●Hib (see "Prevention of Haemophilus influenzae type b infection")
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 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 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
●General supportive management – Children with suspected bacterial meningitis should be admitted to the hospital for ongoing management. Supportive management of children with bacterial meningitis includes (table 1) (see 'General management' above):
•Appropriate respiratory and hemodynamic support for patients with respiratory compromise or shock (see "Initial assessment and stabilization of children with respiratory or circulatory compromise")
•Careful management of fluid and electrolyte balance (see 'Fluid management' above)
•Monitoring for complications (eg, seizures, signs of elevated intracranial pressure, development of infected subdural effusions) (see 'Monitoring' above)
•Expert opinion differs on the use of dexamethasone in children with suspected meningitis; this issue is discussed separately (see "Bacterial meningitis in children: Dexamethasone and other measures to prevent neurologic complications")
●Empiric antibiotic therapy – For most patients older than one month with suspected meningitis, we suggest vancomycin plus high doses of a third-generation cephalosporin (eg, ceftriaxone, cefotaxime) rather than other regimens (Grade 2C). This combination provides coverage for antibiotic-resistant Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae (type b [Hib] and non-type b), which are the most common causes of bacterial meningitis in children. Additional coverage may be warranted in select circumstances, as summarized in the table (table 2). Empiric antibiotic therapy should be initiated immediately after lumbar puncture (LP) is performed if the clinical suspicion for meningitis is high (table 1). (See 'Empiric therapy' above and 'Avoidance of delay' above.)
●Specific therapy – Once the causative agent and its in vitro antimicrobial susceptibility pattern are known, empiric antimicrobial therapy can be altered accordingly. The duration of antimicrobial therapy depends upon the causative organism and the clinical course. (See 'Specific therapy' above and 'Treatment duration' above.)
●Response to therapy – The response to therapy is monitored with clinical and laboratory parameters (eg, fever curve, resolution of symptoms and signs, normalization of inflammatory markers). Fevers typically last three to six days after initiating adequate therapy. Repeat LP and/or neuroimaging may be warranted in some patients (see 'Response to therapy' above):
•Repeat LP – Reexamination of cerebrospinal fluid (CSF) is indicated for patients with gram-negative bacillary meningitis (to document that the CSF is sterile) and in patients who have a poor clinical response despite 24 to 36 hours of appropriate antimicrobial therapy. Repeat LP also may be warranted in patients with persistent or recurrent fever. (See 'Repeat lumbar puncture' above.)
•Neuroimaging – Neuroimaging may be indicated during the course of treatment to assess for complications such as subdural empyema, brain abscess, cerebral vascular thrombosis, or hydrocephalus. Indications for neuroimaging may include focal neurologic signs, prolonged obtundation, increasing head circumference, seizures occurring >72 hours after the start of treatment, persistently positive CSF cultures, or persistent CSF neutrophilia despite appropriate antibiotic therapy. (See 'Neuroimaging' above.)
●Prognosis – The mortality rate for children with bacterial meningitis in resource-rich settings is approximately 4 to 5 percent. Neurologic complications are common among survivors. The most common sequelae include hearing loss, seizures, intellectual disability, and spasticity and/or paresis. (See 'Prognosis' above and "Bacterial meningitis in children: Neurologic complications".)
●Follow-up – Children who have been treated for bacterial meningitis should undergo hearing evaluation at the time of or shortly after discharge. They should also be followed closely for other neurologic sequelae including gross motor and cognitive impairment. (See 'Follow-up' above.)
●Chemoprophylaxis – Chemoprophylaxis is indicated for certain close contacts of patients with meningococcal (table 8) and Hib meningitis. (See "Prevention of Haemophilus influenzae type b infection", section on 'Postexposure chemoprophylaxis' and "Treatment and prevention of meningococcal infection", section on 'Antimicrobial chemoprophylaxis'.)
