Acute Bacterial Meningitis

Release Date: March 1, 2012

Expiration Date: March 31, 2014

FACULTY:

Isabel Porto, PharmD
Clinical Assistant Professor
University of Illinois at Chicago College of Pharmacy
Clinical Pharmacist for Pediatrics
Children's Hospital University of Illinois
University of Illinois Hospital & Health Sciences System
Chicago, Illinois

FACULTY DISCLOSURE STATEMENTS:

Dr. Porto has no actual or potential conflicts of interest in relation to this activity.

Postgraduate Healthcare Education, LLC does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced, objective, and scientifically rigorous. Occasionally, authors may express opinions that represent their own viewpoint. Conclusions drawn by participants should be derived from objective analysis of scientific data.

ACCREDITATION STATEMENT:

Pharmacy
acpePostgraduate Healthcare Education, LLC is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.
UAN: 0430-0000-12-005-H01-P
Credits: 2.0 hours (0.20 ceu)
Type of Activity: Knowledge

TARGET AUDIENCE:

This accredited activity is targeted to pharmacists. Estimated time to complete this activity is 120 minutes.

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DISCLAIMER:

Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients' conditions and possible contraindications or dangers in use, review of any applicable manufacturer's product information, and comparison with recommendations of other authorities.

GOAL:

To review common etiologies of bacterial meningitis in different age groups and discuss appropriate selection of empiric antimicrobial therapy, available preventive vaccines, and chemoprophylaxis.

OBJECTIVES:

After completing this activity, the participant should be able to:

  1. Identify common signs and symptoms of bacterial meningitis.
  2. List the most common organisms responsible for bacterial meningitis according to age group and specific risk factors.
  3. Select the appropriate initial empiric antibiotic regimen targeting the most likely organism.
  4. Discuss the role of dexamethasone as adjunctive treatment for bacterial meningitis.
  5. Describe preventive measures used to protect vulnerable populations against common bacterial meningitis pathogens.

Despite the recent advances in management and antimicrobial therapy, meningitis continues to cause significant morbidity and mortality not only in adults, but more dramatically in infants and children. Acute meningitis is characterized by inflammation of the membranes surrounding the brain (meninges) and spinal cord in association with the infiltration of WBCs in the cerebrospinal fluid (CSF). Clinical symptoms typically evolve over a period of hours to several days. Acute bacterial meningitis is a medical emergency. Prompt diagnosis and treatment initiation are crucial not only to prevent mortality, but also to reduce severe neurologic sequelae. This article reviews the common causes of acute bacterial meningitis and the disease's presentation and management.

Causes of Acute Meningitis

Acute meningitis may result from a variety of infectious and noninfectious factors. In community-acquired meningitis, viruses are frequently responsible for aseptic meningitis. Enteroviruses are the leading cause of viral meningitis, with more than 60 different serotypes; subgroups include polioviruses, coxsackieviruses, and echoviruses.1-3 Also associated with viral meningitis are herpesviruses (herpes simplex virus, varicella-zoster virus), mumps virus, arbovirus, HIV, parainfluenzae, and influenza, among others.1,2 Less common causes of infectious acute meningitis include fungi, parasites, Rickettsia, mycobacteria, and Lyme disease (Borrelia burgdorferi).1,3

Noninfectious causes of acute meningitis include systemic lupus erythematosus, neurosurgical procedures, and intracranial tumors, among others. Many drugs have been implicated in the development of aseptic meningitis, more commonly NSAIDs, IV immunoglobulin, and trimethoprim-sulfamethoxazole.1,3

Epidemiology

Bacterial meningitis remains a common disease worldwide and is associated with significant morbidity and mortality. The disease can occur at any age, but infants, the elderly, and immunocompromised patients are at higher risk.4

Thanks to improvements in immunization practices and universal screening of pregnant women for group B streptococcus (GBS), the incidence of bacterial meningitis has declined significantly during the last 20 years. The introduction of childhood immunization with Haemophilus influenzae type b (Hib) conjugate vaccine in early 1990 has resulted in a 55% reduction in meningitis cases. More recently, the literature has reported a decline in overall incidence of meningitis from 2.00 cases/100,000 in 1998–1999 to 1.38 cases/100,000 in 2006–2007, representing another 31% drop.5 Incidence fell significantly in all age groups except infants aged <2 months. Children aged <5 years constitute up to 90% of all reported meningitis cases.6 Overall mortality remained 14.6%.5 Neurologic sequelae are found in 20% to 50% of children who survive meningitis.7

Hib, Streptococcus pneumoniae, Neisseria meningitidis, GBS, and Listeria monocytogenes are responsible for >80% of cases of bacterial meningitis. Etiology is also influenced by the patient's age and underlying disease state (TABLE 1). S pneumoniae and N meningitidis are the most common pathogens in children aged >3 months.4,6 The relative frequency of disease caused by all of these organisms has changed dramatically since early 1990. The routine immunization of infants with Hib conjugate vaccine has virtually eliminated Hib-related meningitis in the United States and other developed countries. The introduction of the seven-valent pneumococcal conjugate vaccine (PCV7) in 2000 has further reduced the incidence of pneumococcal meningitis by >75% in children aged <5 years and by 31% in adults aged >65 years.5,8

Certain factors confer a higher risk of severe invasive pneumococcal disease. These include age <2 years or >50 years, functional or surgical absence of a spleen, chronic immunosuppressive state (e.g., malignancy, hypogammaglobulinemia, HIV), chronic kidney or liver disease, diabetes mellitus, and cochlear implants.9 The incidence of meningococcal meningitis is greatest in infants aged <1 year and in young adults.1,4


During the neonatal period (age <1 month), GBS, Escherichia coli, Klebsiella species, and L monocytogenes are the organisms most frequently detected.4

Frequently, GBS or Streptococcus agalactiae colonizes the genital tract of an asymptomatic pregnant woman, and transmission to the fetus may occur in utero or during birth. GBS disease occurring during the first week of life is considered early-onset disease, whereas late-onset disease occurs in infants aged >1 week to about 3 months.10 GBS disease carries significant morbidity, and mortality can reach 30% in premature neonates. Other risk factors for GBS disease include gestational age <37 weeks, prolonged duration of rupture of membranes, intra-amniotic infection, young maternal age, black race, and previous deliveries affected by GBS infection. Preventive measures, including universal screening and maternal intrapartum antibiotic prophylaxis, reduce the incidence of early-onset invasive disease by as much as 89%. Visit www.cdc.gov/groupbstrep/ guidelines/guidelines.html for the 2010 revised guidelines on the prevention of perinatal GBS disease.

L monocytogenes is a relatively rare cause of meningitis, accounting for about 8% of U.S. cases.1 It is often found as a contaminant in soil, water, and food products. Neonates and adults aged >60 years are the most susceptible.1

Pathophysiology

Bacterial colonization of the upper respiratory tract leads to bacteremia and, eventually, to invasion of and penetration into the central nervous system (CNS). In neonates, pathogens are acquired from maternal genital secretions. Alternatively, CNS invasion can occur by direct inoculation of bacteria as a result of head trauma, skull defects, or spreading from a contiguous infection site (mastoiditis, sinusitis).4

Poor immune host defense allows bacteria to grow and spread to the subarachnoid space. Release of bacterial cell wall products triggers an intense host inflammatory response. The release of inflammatory mediators such as cytokines, tumor necrosis factor (TNF)-alpha, and interleukin 1 and 6 leads to increased blood–brain barrier (BBB) permeability, allowing for the influx of proteins and neutrophils.6,7

Many of the acute and long-term complications of bacterial meningitis are the result of direct brain and neuronal injury caused by this inflammatory process. Cerebral edema, altered cerebral blood flow, and increased intracranial pressure may manifest as altered levels of consciousness. Other neurologic sequelae, including deafness, cerebral palsy, seizures, and motor and cognitive deficits, are thought to be related to tissue damage in different structures of the brain during the inflammatory process.6,7

Clinical Presentation

Clinical features are nonspecific and vary depending upon the patient's age. Only 44% of adult meningitis patients have the classic triad of fever, impaired mental state, and neck stiffness, but virtually all will present with at least one of the three symptoms; and 95% of patients will present with at least two of the following four symptoms: headache, altered mental status, neck stiffness, and fever.1,11 Positive Kernig's and Brudzinski's signs of meningeal irritation have low sensitivity, and their absence does not rule out meningitis.1 Other symptoms include nausea, vomiting, focal neurologic signs, photophobia, seizures, and cardiorespiratory arrest.1,2

In neonates and young children, symptoms can be even more subtle. Fever, poor feeding, vomiting, diarrhea, lethargy, irritability, and apnea may be the only presenting signs. Temperature instability (hypothermia or hyperthermia), along with a bulging fontanel, may be seen in neonates.1 In older children, fever, headaches, photophobia, changes in mental status, nausea, and vomiting may be present. Seizures may be the sole presenting symptom in up to one-third of pediatric patients with pneumococcal meningitis. Rash and petechiae are present in about 50% of cases of invasive disease secondary to N meningitidis.1

Geriatric and immunocompromised patients also may lack specific meningitic signs, with lethargy and altered mental status being the most common initial physical findings.1

Diagnosis

Along with a medical history and physical examination, laboratory findings are essential for the definitive diagnosis of acute bacterial meningitis. All patients in whom meningitis is suspected should undergo a lumbar puncture (LP) and have CSF collected and examined. LP is contraindicated in the presence of cardiopulmonary instability or uncorrected coagulopathy and in the case of signs of increased intracranial pressure (e.g., seizure, focal neurologic deficits, head trauma, space occupying lesions). When LP cannot be performed safely, brain imaging is often recommended.4,12

CSF analysis should include WBC count with differential, protein, and glucose concentration; Gram stain; and culture. The inflammatory process leads to significant leukocytosis, with WBC typically >1,000 cells/mm3, predominantly neutrophils. Commonly, low CSF glucose (usually <40 mg/dL) and high CSF protein (>100 mg/dL) are also present.1,2,6

Specific CSF characteristics will help differentiate between etiologies (TABLE 2). Occasionally, normal or near-normal CSF values occur in immunocompromised patients, young children with neutropenia, and partially treated patients.2,6 The isolation of specific pathogens in CSF culture and Gram stain provide antibiotic susceptibility data essential for optimal antibiotic selection.3,6


Alternative tests, such as latex particle agglutination and polymerase chain reaction, may be employed for the diagnosis of bacterial meningitis in cases in which prior antibiotic use may inhibit CSF culture growth.8

Elevated levels of inflammatory markers such as serum C-reactive protein and procalcitonin, although not diagnostic, may suggest a bacterial infection.9 Peripheral blood counts and serum electrolytes should be evaluated for coagulopathies and the presence of syndrome of inappropriate antidiuretic hormone secretion (manifesting in hyponatremia).3

Treatment

Immediate initiation of antibiotic therapy in cases of suspected or proven bacterial meningitis is recommended to improve clinical outcomes.1,12 Antimicrobial activity against the likely causative pathogen and its ability to achieve bactericidal concentration in the CSF should be considered when the appropriate agent is being selected. Adequate CSF concentration is influenced by BBB characteristics and the antimicrobial's physicochemical properties.

The BBB's tight junctions around the capillaries and the efflux pumps present in the choroid plexus reduce antimicrobials' ability to reach and attain effective bactericidal concentration in the CSF. However, for most antibiotics, meningeal inflammation damages BBB integrity and enables increased permeability. As inflammation subsides, it is important that maximum parenteral doses be given throughout the treatment course to ensure appropriate bactericidal concentrations.1,4,6,8 Initial dosage recommendations for selected antibiotics in patients with normal renal and hepatic function are given in TABLE 3.


High lipid solubility, low molecular weight, low serum protein binding, and low-degree ionization at physiologic pH all increase antibiotic penetration into the CSF. Lipophilic drugs such as fluoroquinolones and rifampin achieve significantly higher CSF concentrations compared with more hydrophilic agents, such as vancomycin and beta-lactams.6,8

Because immune activity in the CSF is poor, the bactericidal properties of antimicrobials are important. Animal models have demonstrated that, to achieve prompt bacterial sterilization, the CSF antibiotic concentration should be ≥10-fold greater than the minimal bactericidal concentration of a specific microorganism.4,6

Pharmacodynamic properties of antibiotics also play an important role in optimizing antimicrobial therapy. Betalactams and vancomycin exhibit time-dependent activity, which means that the bactericidal effect correlates with the time that concentration is maintained above the minimum inhibitory concentration (MIC). For these antimicrobials, a frequent dosing interval is needed to maintain the antibiotic concentration above the MIC for the longest possible time.1,4 Aminoglycoside and fluoroquinolones exhibit concentration-dependent activity, which means that a higher drug concentration leads to greater killing of bacteria.1,4 Often, these drugs can be dosed less frequently.

Empiric selection of antibiotics is made based on likely pathogens according to age and specific risk factors (TABLES 4 and 5). Once individualized cultures and sensitivity data are available, the antibiotic regimen should be adjusted accordingly.4,8

Over the past several years, the development of resistance among S pneumoniae (pneumococcus) and N meningitidis (meningococcus) strains has raised concern and led to the modification of empiric antibiotic recommendations. Up to 35% of pneumococcal strains have been reported to be penicillin resistant in some regions of the U.S., and the rate is as high as 60% to 80% in Latin American and Asian countries.1 Pneumococcus strains with intermediate resistance (MIC 0.1-1 mcg/mL) or high resistance (MIC >2 mcg/mL) to penicillin have shown reduced susceptibility to other classes of antibiotics, including cephalosporins.9,13 Therefore, penicillin should never be used for the empirical treatment of suspected pneumococcal meningitis, but may be used when susceptibility laboratory data show an MIC ≤0.06 mcg/mL.4 Third-generation cephalosporins such as ceftriaxone and cefotaxime remain viable treatment options for penicillin-resistant pneumococci, but treatment failures have been reported. Susceptible strains show an MIC for ceftriaxone and cefotaxime ≤0.5 mcg/mL.

An animal model determined the addition of vancomycin to a third-generation cephalosporin to be synergistic; therefore, it is the currently recommended empiric regimen (TABLES 4 and 5).1,12 Therapeutic serum levels of vancomycin should be maintained between 15 to 20 mcg/mL.12 The addition of rifampin to the regimen has been suggested in cases in which clinical or bacteriologic response is delayed and when ceftriaxone or cefotaxime MIC is >4 mcg/mL.1 Although rifampin has excellent penetration in the CSF, it should never be used as monotherapy, as it rapidly induces
bacterial resistance.12



Other beta-lactams (meropenem, ertapenem, cefepime) and fluoroquinolones are being investigated in the treatment of penicillin-resistant pneumococcal meningitis, and they may offer treatment options in the future.1,8,9

Penicillin G and ampicillin are the agents of choice in documented meningococcal meningitis. However, strains with intermediate penicillin susceptibilities (MIC 0.1-1.0 mcg/mL) have been reported worldwide. Although most patients treated with penicillin were responsive, cases of treatment failure have been reported. For that reason, until individualized susceptibility information is available, the empiric treatment of meningococcal meningitis should include ceftriaxone or cefotaxime.1,9

GBS (S agalactiae) is the organism that predominantly causes neonatal meningitis, but may also be present in the elderly and adults with significant underlying diseases. Treatment should include penicillin or ampicillin, with an aminoglycoside added for synergy.1,9

Ampicillin and penicillin are the drugs of choice for L monocytogenes treatment and should be included in the empiric regimen for neonatal meningitis. Aminoglycosides may be added for possible synergy during the first week of treatment, although clear clinical evidence of a benefit is lacking. Note that cephalosporins are inactive for the treatment of Listeria meningitis. Trimethoprim-sulfamethoxazole is the alternative regimen for patients with penicillin allergy.1,9

Up to 40% to 50% of H influenzae strains are betalactamase–producing and resistant to penicillins; increasing resistance to chloramphenicol also has been observed. Standard therapy for Hib meningitis should include an extended-spectrum cephalosporin such as ceftriaxone or cefotaxime.6,9

According to current guidelines, the duration of antibiotic treatment for bacterial meningitis is 7 days for Neisseria meningitidis, 10 to 14 days for Streptococcus pneumoniae, 14 to 21 days for GBS, 21 days for Listeria monocytogenes, and ≥21 days for gram-negative bacilli.12 Importantly, treatment duration is based mostly on expert consensus rather than on evidence-based studies, and treatment duration may need to be modified based on the patient's clinical response.12

Several trials have evaluated the efficacy of shorter treatment courses. Although results were promising, these studies were limited by their small sample size. In a meta-analysis of randomized, controlled trials comparing short versus long duration of antibiotic treatment in children with bacterial meningitis, no difference was found between short courses (4-7 days) and long courses (7-14 days) in terms of clinical success and long-term complications. Although these results are promising, additional randomized, controlled trials need to be conducted before changes can be applied to standard practice.12

Outpatient antibiotic therapy may be considered in selected patients with close medical follow-up. Patient criteria have been suggested, including ≥6 days of inpatient therapy, absence of fever for ≥24 to 48 hours, ability to take oral fluids, immediate availability of medical care, stable clinical condition, no neurologic dysfunction or seizures, reliable IV access, and compliance.12

Adjunctive Treatment

Many of the neurologic sequelae associated with bacterial meningitis are believed to derive from the intense inflammatory response occurring in the CNS. Dexamethasone has been investigated as a means of reducing inflammation-related complications. Several controlled studies have demonstrated less hearing loss in pediatric patients when dexamethasone is used. The evidence was greatest in cases of Hib meningitis. Beneficial effects in pneumococcal meningitis also occurred when dexamethasone was administered concomitantly with antibiotics or before antibiotics were initiated.15,16 The American Academy of Pediatrics (AAP) Committee on Infectious Diseases recommends that, in infants and children aged ≥6 weeks with pneumococcal meningitis, adjunctive therapy with dexamethasone should be considered after the potential benefits and risks have been weighed.17

In 2004, a meta-analysis concluded that corticosteroids reduced both mortality and neurologic sequelae in adults with pneumococcal bacterial meningitis.11 Presently, the practice guidelines of the Infectious Diseases Society of America recommend the adjunctive use of dexamethasone administered 10 to 20 minutes before or concomitantly with the first dose of antibiotics in adults with suspected pneumococcal meningitis.12

Since corticosteroids can decrease the penetration of antibiotics into the CSF, concerns have been raised that the use of dexamethasone may delay CSF sterilization in patients with pneumococcal strains highly resistant to penicillin and cephalosporin. It has been suggested that rifampin be added to the empirical combination of ceftriaxone or cefotaxime plus vancomycin until in vitro susceptibility testing is available. Also, until more data are available, careful patient follow-up is essential to determine the effects of dexamethasone use in pneumococcal meningitis.8,12 There is no evidence for the use of dexamethasone in neonatal or meningococcal meningitis.12

The currently recommended dexamethasone regimen is 0.15 mg/kg every 6 hours for 2 to 4 days. For optimal results, the first dose should be given before or at the time of the first antibiotic dose.12

Other therapies, including NSAIDs and monoclonal antibodies against TNF-alpha, have been utilized in an attempt to modulate the inflammatory process of meningitis and reduce brain injury. All are considered experimental.6 In a recent multicenter Latin American study, glycerol—a hyperosmolar diuretic—was proposed as an adjunctive treatment to prevent neurologic sequelae in children.18

Complications

The mortality rate for meningitis of all causes has been reported to be between 4% to 14%. Pneumococcal meningitis alone may be responsible for up to 15% of all pediatric fatalities. Mortality rates for meningococcal meningitis are 4% to 8% in children and up to 7% in adults. Common causes of death in pneumococcal meningitis are cardiorespiratory failure, stroke, status epilepticus, and brain herniation. Shock and disseminated intravascular coagulation are frequently associated with meningococcal fatalities.4,9

Neurologic sequelae, including hearing loss, focal neurologic deficits, epilepsy, and cognitive impairment, have been found in up to 50% of pneumococcal meningitis survivors. Hearing loss is present in up to 30% of pneumococcal meningitis survivors and 1% to 8% of meningococcal meningitis survivors.8

The mortality rate for GBS meningitis ranges from 7% to 27% in neonates and up to 30% in adults. Long-term sequelae, present in up to 30% of children, include profound mental retardation, hemiparesis, deafness, blindness, and spastic quadriplegia.9

Chemoprophylaxis

Prophylactic antibiotics should be given to close contacts of patients with invasive Hib and N meningitidis to eliminate carriage state and prevent spread. The attack rate for household contacts exposed to an individual with invasive meningococcal disease is 400 to 800 times higher than in the general population. Chemoprophylaxis should be offered to all close contacts who were directly exposed to a patient's oral secretions, as well as to child care and preschool contacts during the 7 days before disease onset in the index case. Chemoprophylaxis should be initiated ≤24 hours after exposure. Rifampin should be administered at a dosage of 5 mg/kg orally every 12 hours for 2 days in infants aged <1 month, and 10 mg/kg (≤600 mg) orally every 12 hours for 2 days in infants aged ≥1 month. Alternative regimens include ceftriaxone, ciprofloxacin, and azithromycin.17

The risk of contracting Hib is greater among nonimmunized household contacts aged <4 years. Rifampin 20 mg/kg (≤600 mg) should be given orally once daily for 4 days. Some experts recommend lowering the dose to 10 mg/kg in infants aged <1 month.17

Complete recommendations for prophylaxis may be found in the AAP's Red Book: 2009 Report of the Committee on Infectious Diseases.17

Vaccination

In children, immunization against Hib and pneumococcal and meningococcal disease has played a significant role in lessening the incidence of invasive disease caused by these organisms. The introduction of conjugated Hib vaccine in 1987 has reduced the rate of invasive Hib disease by 99%, limiting U.S. occurrences to nonimmunized children and infants too young to have completed the primary immunization series.

Two single-antigen Hib conjugate vaccine products and three combination vaccine products containing Hib conjugate are available in the U.S. Depending upon the product selected, the recommended primary series consists of three doses given at 2, 4, and 6 months or doses given at
2 and 4 months.17

In 2000, a seven-valent pneumococcal polysaccharide protein conjugate vaccine (PCV7; Prevnar, Wyeth) was licensed by the FDA for use in infants and young children. This vaccine consists of seven serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) responsible for up to 82% of meningitis cases
caused by pneumococcus. Since then, the overall incidence of invasive pneumococcal disease in children aged <5 years has fallen by up to 79%. However, an increased occurrence of invasive disease caused by serotypes not covered by the PCV7—in particular, 19A—has been observed.19

In February 2010, the FDA licensed a 13-valent pneumococcal conjugate vaccine (PCV13) for children aged 6 weeks to 71 months. In addition to the seven serotypes included in PCV7, PCV13 contains six additional pneumococcal serotypes (1, 3, 5, 6A, 7F, and 19A). These 13 serotypes are responsible for 63% of invasive pneumococcal disease cases in children aged <5 years.

The CDC Advisory Committee on Immunization Practices (ACIP) recommends the use of PCV13 in all children aged 2 to 59 months and in children aged 60 to 71 months with underlying medical conditions that increase their risk of pneumococcal disease or complications. Examples of underlying conditions include congenital or acquired immunodeficiency, absent or decreased splenic function, chronic lung disease, certain chronic heart diseases, cochlear implants, diabetes, and CSF leaks.19

A 23-valent pneumococcal polysaccharide vaccine (PPSV23) induces antibody responses in children aged ≥2 years to the most common pneumococcal serotypes found in the U.S. PPSV23 immunization does not provide immunologic memory and has no effect on nasopharyngeal carriage. The ACIP recommends that all children aged ≥2 years who have underlying medical conditions receive PPSV23 after completing all recommended doses of PCV13. In children with anatomic or functional asplenia, a second dose of PPSV23 should be administered 5 years after the first dose.19 PPSV23 administration is also recommended for all adults aged ≥65 years without a history of previous pneumococcal vaccination or who had a pneumococcal vaccination >5 years prior. Nursing home residents, smokers, high-risk adults aged <65 years (e.g., chronic lung disease, chronic cardiovascular disease, immunodeficiencies, diabetes) should be considered for PPSV23 vaccine.20

In December 2011, the FDA approved the use of PCV13 (Prevnar 13) in adults aged ≥50 years to prevent pneumonia and invasive pneumococcal disease.21

Two meningococcal vaccines against serotypes A, C, Y, and W-135 are licensed for use in U.S. children and adults. In 1981, meningococcal polysaccharide vaccine (MPSV4) was approved for children aged ≥2 years, and meningococcal conjugate vaccine (MCV4) was approved for children ≥2 years. In April 2011, the FDA approved the use of MCV4 as a two-dose primary series in children aged 9 to 23 months who are at high risk for meningococcal disease. This includes children with persistent complement component deficiency, those who are traveling to or residents of countries in which meningococcal disease is hyperendemic or epidemic, and those who are in a defined risk group during a community or institutional meningococcal outbreak. Vaccination with MPSV4 is not recommended for children aged <2 years because of the low immunogenicity
and short duration of protection in this age group.22

Comprehensive, up-to-date information regarding immunization in children and adults may be found at www.cdc.gov/vaccines/pubs/ACIP-list.htm.

Conclusion

Despite major advances in preventive measures and antimicrobial development, bacterial meningitis continues to cause significant morbidity in susceptible populations. Bacterial meningitis is a medical emergency, and prompt recognition and treatment are imperative. Pharmacists are uniquely positioned to ensure that children and high-risk patients are immunized against common meningitis pathogens in accordance with CDC recommendations. Once meningitis has been diagnosed, pharmacists can use pharmacokinetic and pharmacodynamic principles to ascertain that appropriate antimicrobial therapy is in place.

REFERENCES

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  2. Bamberger DM. Diagnosis, initial management, and prevention of meningitis. Am Fam Physician. 2010;82:1491-1498.
  3. Mann K, Jackson MA. Meningitis. Pediatr Rev. 2008;29:417-430.
  4. Chávez-Bueno S, McCracken GH Jr. Bacterial meningitis in children. Pediatr Clin North Am. 2005;52:795-810.
  5. Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998-2007. N Engl J Med. 2011;364:2016-2025.
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  9. Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev. 2010;23:467-492.
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  11. 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;351:1849-1859.
  12. Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004;39:1267-1284.
  13. Saez-Llorens X, McCracken GH Jr. Acute bacterial meningitis beyond the neonatal period. In: Long SS, Pickering LK, Prober CG, eds. Principles and Practice of Pediatric Infectious Diseases. 3rd ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2008:284-291.
  14. Karageorgopoulos DE, Valkimadi PE, Kapaskelis A, et al. Short versus long duration of antibiotic therapy for bacterial meningitis: a meta-analysis of randomised controlled trials in children. Arch Dis Child. 2009;94:607-614.
  15. Havens PL, Wendelberger KJ, Hoffman GM, et al. Corticosteroids as adjunctive therapy in bacterial meningitis: a meta-analysis of clinical trials. Am J Dis Child. 1989;143:1051-1055.
  16. McIntyre PB, Berkey CS, King SM, et al. Dexamethasone as adjunctive therapy in bacterial meningitis. A metaanalysis of randomized clinical trials since 1988. JAMA. 1997;278:925-931.
  17. Haemophilus influenzae infections. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:314-321.
  18. Peltola H, Roine I, Fernández J, et al. Adjuvant glycerol and/or dexamethasone to improve the outcomes of childhood bacterial meningitis: a prospective, randomized, double-blind, placebo-controlled study. Clin Infect Dis. 2007;45:1277-1286.
  19. Nuorti JP, Whitney CG. Prevention of pneumococcal disease among infants and children—use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine. Recommendations and reports. MMWR. 2010;59:1-18.
  20. CDC. Recommended adult immunization schedule–United States, 2012. MMWR. 2012;61:1-7.
  21. FDA expands use of Prevnar 13 vaccine for people ages 50 and older. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm285431.htm. Accessed February 5, 2012.
  22. CDC. Recommendation of the Advisory Committee on Immunization Practices (ACIP) for use of quadrivalent meningococcal conjugate vaccine (MenACWY-D) among children aged 9 through 23 months at increased risk for invasive meningococcal disease. MMWR. 2011;60: 1391-1392.

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