Topic Editor: Grant E. Fraser, M.D., FRACGP, FACRRM, ASTEM

Review Date: 12/24/2012

Definition

• Meningitis is inflammation of the protective membrane covering the brain and spinal cord (the meninges). This condition is most commonly caused by bacterial, viral, or fungal infection within the cerebrospinal fluid.

Description

• Meningitis is most commonly caused by infection, however non-infectious causes include:
• Cancer
• Drug reactions
• Trauma
• Types of meningitis:
• Bacterial meningitis is a life-threatening condition whose etiology can be predicted based upon patient age and other risk factors
• <1 month of age: Group B strep, E Coli, other gram + or - organism, listeria
• 1 month to 50 years: Streptococcus pneumonia, Neisseria meningitidis or Haemophilus influenzae (listeria rare)
• >50 years or alcoholic: Streptococcus pneumonia, Listeria, other Gram - bacilli
• Note that predicted etiology is used to allow for rationale choice of empiric therapy. Other causes are possible and cultures, gram stain and PCR are important in the definitive diagosis
• Bacterial/Mycobacterial - unusual causes, which may require specialized testing beyond culture to diagnose
• Leptospirosis
• Mycobacterium tuberbulosis
• Mycoplasma (mostly pneumoniae or hominis)
• Neurolyme
• Neurosyphilis
• Viral meningitis may due to enteroviruses, herpesviridae, Lyphocytic Choriomeningitis (LCM) virus, Human Immunodeficiency Virus (HIV), or other viruses
• Fungal meningitis is rare, and is mostly caused by Cryptococcus and Histoplasma
• Parasitic meningitis (also known as Primary Amebic Meningoencephalitis) is caused by parasites such as Naegleria fowleri and results from swimming in warm freshwater where the organism resides. The infection is felt to infect the brain through the cribriform plate and olfactory nerve. There are case reports of sinus irrigation with contaminated water resulting in this condition. It is generally rapidly fatal
• Non-infectious meningitis may be attributable to cancer, systemic lupus erythematosus (lupus), medications (NSAIDs, metronidazole, trimethoprim/sulfamethoxazole, carbamazepine, IVIG), head injury, or post neurosurgery
• All types of meningitis can present with fever with headache, photophobia, and neck stiffness. Common associated symptoms include nausea and vomiting

Epidemiology

Incidence/Prevalence

• Incidence of bacterial meningitis in the U.S. (2003-2007) was 4100, with 500 deaths
• The U.S. has had a decline in cases of meningitis in the period of 1998-2007, which is felt due to immunization
• In 2006-7, there were 1.38 cases/100,000 of confirmed bacterial meningitis
• An estimated 26,000-42,000 hospitalizations/year (U.S.) occur due to aseptic or viral meningitis

• Any age group can be affected by bacterial meningitis
• Infants have a higher risk
• Viral meningitis occurs most commonly in infants (HSV) and in children 5-10 years (Enterovirus and others), but can occur at any age

Gender

• Some data indicates a very slight male predominance ~ 20% higher
• In mump meningitis, there is also a slight male predominance

Risk factors

Risk factors for bacterial meningitis

• Age: Infants are at increased risk
• Immunized individuals with H. influenzae, meningococcal and streptococcal immunizations appear at lower risk
• Young adults living in close quarters (e.g. dormitories and military housing): Increased risk of meningococcal meningitis
• Immunocompromised state and increased risk of invasive infections is present in the following conditions:
• Alcoholism
• Asplenia
• Diabetes mellitus
• Human immunodeficiency virus (HIV) infection
• Immunosuppressive drug use
• Malignancy
• Persons working in laboratories with contact with causative pathogens for meningitis have an increased risk
• Travelers: This increased risk relates to meningococcal meningitis. People visiting the meningitis belt in sub-Saharan Africa due dry weather or travelling to Mecca during the annual Hajj and Umrah pilgrimage have an increased
• Neurosurgery
• Head injury (generally with skull fracture)

• Age: Most common in children 5 years of age
• People in close contact with known cases of viral meningitis have increased risk
• Immunocompromised host

Etiology

Bacterial meningitis

• Newborns: Group B Streptococcus, Escherichia coli (rarely other gram negatives), Listeria monocytogenes
• Infants and children: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b
• Adolescents and adults: N. meningitidis, S. pneumonia
• Older Adults>50 and alcoholics: S. pneumoniae, L. monocytogenes (rare to be N. meningitidis)
• Etiologic organism in a population study including 17.4 million persons in the U.S. from 1998-2007 showed:
• 58% of cases due to S. pneumonia
• 18.1% from Group B. Streptococcus
• 13.9% from N. meningitidis
• 6.7% from H. influenzae
• 3.4% from L. monocytogenes
• PCR testing in one study in which the majority were children and neonates (150 children/neonates and 18 adults) yielded the following:
• H. influenzae 45.2%
• S. pneumoniae 21.4%
• S. agalactiae 2.4%
• E. coli 1.8%
• L. monocytogenes 0.6%
• M. pneumoniae 0.6%

• Enteroviruses: Most common cause of viral meningitis in children
• Mumps virus: Most common in cases of unvaccinated/incomplete vaccination
• West Nile virus
• Herpes virus (Herpes simplex viruses 1 and 2, Varicella Zoster Virus, Epstein Barr Virus, Cytomegalovirus)
• HIV
• Influenza
• Japanese B encephalitis
• LCV (Lympohcytic Choriomeningitis Virus)
• Measles
• Tick-borne encephalitis

[Outline]

• Definition
• Description
• Epidemiology
• Etiology

History

• Patients infected with bacterial meningitis usually develop symptoms within 3-7 days of exposure
• Manifestations of viral meningitis are generally similar to that of bacterial meningitis, but less severe
• A detailed history should be obtained regarding sexual exposure, travel abroad, HIV risks, immunization status, immunocompromise, and exposure to rodents/ticks
• Recent history of upper respiratory tract infection is commonly found in children with bacterial meningitis
• Characteristic features of meningitis (both viral and bacterial) include fever with acute onset, headache, photophobia, altered mental status, and neck stiffness which may be accompanied by nausea and vomiting
• Seizure or coma may occur as a later manifestation in bacterial meningitis (note that seizure is not unusual in young children with viral meningitis)
• Other associated symptoms may be a petechial rash, sore throat, swollen glands, vomiting, and genitourinary symptoms
• Children affected with viral meningitis may have different symptoms than adults
• Newborns and infants with bacterial meningitis may have an absence of the typical feature of bacterial meningitis. Symptoms that are non-specific, such as vomiting, anorexia, irritability or somnolence are typical

Physical findings on examination

• Fever (>100.4°F/38°C)
• Signs of meningeal irritation include:
• Nuchal rigidity
• Brudzinski's and Kernig's sign: Theses signs are insensitive but of reasonable specificity for bacterial meningitis (Kernig's much better than Brudzinski's)
• Such signs are generally of poor diagnostic value, despite being commonly taught. In children, one 2012 review documents the lack of value and poor performance of these tests
• Some reviews indicate as few as 5% of adults with bacterial meningitis have the classical physical findings of meningeal irritation
• Papilledema
• Focal neurologic deficits
• Seizures and hemiparesis are more likely to be present in individuals 65 years
• Altered level of consciousness
• Petechiae and purpural rash: More common in patients with meningococcal meningitis. H. influenzae or S. pneumoniae infection
• Signs in children with bacterial meningitis include fever, apnea, seizures, a bulging fontanel (infant), and rash (petechial- especially in meningococcal disease)
• Systemic examination occasionally reveals co-infection. Recent otitis or sinusitis (25%), pneumonia (12 %) and immunocompromised state (16%) have been reported in adults with community-acquired bacterial meningitis

[Outline]

• History
• Physical findings on examination

Blood test findings

• Complete blood cell count (CBC) with differential: Usually shows increase in white blood cell count (WBC) count and differential has a left shift (80% of neutrophils+bands) in bacterial meningitis. However, WBC count may be normal or depressed in patients at age extremes, septic shock, and in immunosuppressed states
• Cerebral spinal fluid (CSF)/blood glucose ratio: Is expected to be decreased with bacterial meningitis (usually ~0.6, but expected to be decreased with bacterial meningitis)
• Serum electrolytes: For evaluation of electrolyte abnormalities, especially hyponatremia, dehydration, or syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
• Renal function: Testing BUN and creatinine levels assess renal function and any adjustment required in dosing of drugs
• Blood cultures: Recommended in all cases of suspected bacterial meningitis. Such patients generally should have 2 IV's, and with each IV start a culture should be obtained. Where possible, cultures should be obtained prior to starting antibiotics (without delaying administration of antibiotics). Positive results occur in 40-60% of cases

Other laboratory test findings

• Urinalysis: May show urinary tract infection (UTI) rarely

Radiographic findings

• Chest X-ray: May be helpful to identify associated or concomitant conditions (e.g., heart failure or pneumonia)
• Note that up to 50% of patients presenting with pneumococcal meningitis also have pneumonia

Other diagnostic test findings

• Lumbar puncture (LP)
• Is required to make a definitive diagnosis of bacterial meningitis. Advised in all cases of suspected meningitis except where contraindications are present
• The vast majority of patients are appropriate for LP without CT scan
• In cases where there is decreased GCS or suspicion of mass occupying lesion or increased intracranial pressure, LP is delayed until a normal head CT is obtained
• Contraindicated with significant thrombocytopenia, coagulopathy, or use of anticoagulants (heparins, heparinoids, vitamin K antagonists, direct thrombin inhibitors, or factor Xa inhibitors)
• CT head recommended prior to LP in cases where there is:
• Abnormal level of consciousness
• Abnormal visual fields or gaze paresis
• Focal weakness, abnormal speech
• Head trauma
• History of mass lesion, focal infection, or stroke
• History of seizure within the last 7 days
• Immunocompromised state
• Standard CSF analyses consists of gram stain, culture, cell counts (WBC, RBC and differential), and determination of glucose and protein
• Findings in CSF analysis (in cases of bacterial meningitis):
• Typical findings in CSF analysis include pleocytosis, with WBC count >1000 cells/mm3, and predominant polymorphonuclear leukocytes (neutrophils)
• WBC count may be normal when performed early in the course of the disease
• CSF glucose usually is decreased. The normal ratio of CSF-to-serum glucose ratio is 0.6. In cases where the ratio is less than this, serious concern for bacterial meningitis should occur
• Protein level is usually increased
• Gram stain of CSF: 80% to 90% are positive for bacteria in cases of untreated bacterial meningitis
• In cases of viral meningitis, CSF PCR testing for viruses is of value as positive results can alter the need for ongoing antibiotic therapy empirically for bacterial meningitis. Commonly tested viruses include enteroviruses, HSV, and varicella zoster virus. Other viruses can be tested for depending upon location and local epidemiology

[Outline]

• Blood test findings
• Other laboratory test findings
• Radiographic findings
• Other diagnostic test findings

• Acute mononucleosis (Epstein Barr Virus)
• Brain abscess
• Carcinomatous meningitis
• CNS vasculitis
• CytomegalovirusDelirium tremens
• Dengue fever
• Encephalitis
• Endocarditis
• Epidural abscess
• Herpes Simplex (with CNS involvement)
• Influenza
• Intracranial tumor
• Leptospirosis
• Lyme disease (Neurolyme)
• Neuroleptic malignant syndrome
• Noninfectious meningitis
• Rocky Mountain spotted fever
• Seizure disorder (especially post ictal state)
• Stroke
• Subarachnoid Hemorrhage
• Subdural empyema
• Syphilis
• Systemic lupus erythematosus with cerebritis
• Temporal (cranial) arteritis
• Tuberculosis

General treatment items

• Emergently evaluate and treat patients presenting with shock, disseminated intravascular coagulation (DIC), purpura, petechiae, or hypotension
• Treat any seizures which fail to resolve within 5 minutes with benzodiazepines. Repetitive seizures require loading with agents such as phenytoin or fosphenytoin
• Intubation and mechanical ventilation may be required in cases with GCS<8 or expected worsening condition
• Treat other coexisting conditions and take measures to prevent hypothermia and dehydration
• Start antimicrobial therapy urgently in patients with suspected bacterial meningitis. Such patients generally need at least two intravenous lines, with blood cultures being obtained with each of these
• It is important to note that lumbar puncture (LP) generally should occur after the administration of antibiotics (some guidelines indicate, that if the LP can occur within 30 minutes of presentation, that it is reasonable to delay antibiotics for no more than 30 minutes)
• If increased intracranial pressure is suspected, a head CT should be performed prior to lumbar puncture; and only once normal should lumbar puncture occur
• Empiric therapy should be started in all suspected cases of bacterial meningitis. The recommended treatment depends on patient age, risk factors and clinical features
• Infants usually require E. coli, group B streptococcal and listeria coverage. Typical therapy is ampicillin with an aminoglycoside (usually gentamicin) or cefotaxime. In neonates with late onset meningitis, consider an antistaphylococcal antibiotic, such as nafcillin or vancomycin, plus cefotaxime or ceftazidime with or without an aminoglycoside
• Consider vancomycin plus a third-generation cephalosporin (ceftriaxone or cefotaxime) as an initial therapy in children >1 month of age
• Consider vancomycin plus cefepime or ceftazidime or meropenem in patients with predisposing factors such as penetrating trauma, postneurosurgery, or CSF shunt
• For cases of basilar skull fracture, consider vancomycin plus ceftriaxone or cefotaxime
• Therapy may be narrowed based upon gram stain, culture, and susceptibility tests
• Adjunctive dexamethasone therapy (0.15 mg/kg/dose q6 hours x 2-4 days) should be considered in cases of bacterial meningitis. Adjunctive dexamethasone is recommended in all adults with suspected or proven pneumococcal meningitis and in H. influenzae type b meningitis of children. Dexamethasone is generally recommended immediately before (or 10-20 minutes prior to) the first dose of antibiotics
• In cases of aseptic meningitis, the most common causative pathogens are enteroviruses. Such cases do not require specific antimicrobial therapy. Management is usually supportive with adequate analgesia/antipyretics, antiemetics if vomiting, and IV fluids if dehydrated. These cases can be definitively diagnosed with CSF polymerase chain reaction testing, although, in some settings such testing is not available. Positive tests may be used to discontinue antimicrobial therapy started in presumptive cases of bacterial meningitis. Cases of HSV aseptic meningitis are usually self-limited, but must be distinguished from HSV encephalitis
• In patients with tuberculous meningitis, empiric therapy should be started when the diagnosis is made. Treatment should consist of a combination of drugs based upon the resistance pattern in the community and the results of susceptibility testing. Antituberculous therapy is recommended for at least 9-12 months. Adjunctive corticosteroid therapy with dexamethasone for the initial 6-8 weeks is indicated for individuals with stage 2 or stage 3 disease
• Cases of fungal meningitis are treated with a longer duration of high-dose antifungal therapy. The most common fungal meningitis is Cryptococcal meningitis, which is usually found in patients with altered cellular immunity, especially in patients with AIDS. Initial treatment in these cases consists of amphotericin B plus flucytosine
• Cases of mycoplasma, leptospirosis, lyme or syphilis require other specific therapy

Medications indicated with specific doses

Antibiotics

• Ampicillin [IM/IV]
• Adult Dosing
• Pediatric Dosing
• Cefepime [IM/IV]
• Adult Dosing
• Pediatric Dosing
• Cefotaxime [IM/IV]
• Adult Dosing
• Pediatric Dosing
• Ceftazidime [IM/IV]
• Adult Dosing
• Pediatric Dosing
• Ceftriaxone [IM/IV]
• Adult Dosing
• Pediatric Dosing
• Gentamicin [IM/IV]
• Adult Dosing
• Pediatric Dosing
• Meropenem [IV]
• Adult Dosing
• Penicillin G potassium [Injectable]
• Adult Dosing
• Pediatric Dosing
• Vancomycin [IV]
• Adult Dosing
• Pediatric Dosing

Antifungals

• Amphotericin B liposomal [IV]
• Adult Dosing
• Pediatric Dosing
• Flucytosine [IV]
• Adult Dosing
• Pediatric Dosing

Corticosteroids

• Dexamethasone [IM/IV]
• Adult Dosing
• Pediatric Dosing

Disposition

Admission criteria

• All cases of known or suspected bacterial meningitis
• All cases of known or suspected fungal meningitis
• All cases of significantly unwell viral meningitis

Discharge criteria

• Cases of definite viral (or another non serious) cause for symptoms, with well-controlled symptoms

[Outline]

• General treatment items
• Medications indicated with specific doses
• Disposition