1. Description of the problem

What every clinician needs to know

When a patient comes in with fever and headache, it is of urgent importance to discern whether or not he/she may have bacterial meningitis versus another condition. In cases of bacterial meningitis, rapid institution of appropriate antibiotics is vital and should not be delayed while the results of diagnostic procedures are outstanding.

Because of the morbidity and mortality associated with bacterial meningitis, if clinical suspicion exists, erring on the side of aggressive early antimicrobial therapy, which can later be withdrawn and tailored, is appropriate.

In addition to bacterial meningitis, other treatable and less treatable conditions can present with fever, headache, depressed mental status or focal neurologic findings. These conditions include viral encephalitis, viral and “aseptic” meningitis, chronic meningitis (due to TB or other pathogens), brain abscess, septic emboli, mycotic aneurysm and non-infectious conditions such as subarachnoid hemorrhage or cerebral venous thrombosis.

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In immunocompromised hosts with opportunistic infections (such as cryptococcal meningitis, progressive multifocal leukoencephalopathy [PML] or toxoplasmosis), the clinical course is generally more insidious, though an abrupt deterioration can lead to an acute clinical presentation.

Clinical presentation of bacterial meningitis and viral encephalitis

Several case series have examined the signs and symptoms seen with bacterial meningitis. What is considered the classical clinical triad (fever, headache and nuchal rigidity) is present approximately two-thirds of the time. Half the time patients present with altered consciousness. This can be defined as a Glasgow Coma Scale (GCS) score below 14. Photophobia, seizure, neurologic deficits, nausea, vomiting and rash or other skin lesions may also be present.

The presence of petechial rash (or sometimes maculopapular rash), and moreover a rapidly evolving rash, can be a clue to meningococcal meningitis with concomitant meningococcemia.

The clinical presentation of bacterial meningitis overlaps with the presentation of viral encephalitis.

In the elderly and those with even relative immunocompromise, fever may be absent with bacterial meningitis and the presentation may be subtle, with the only sign being an altered mental status. Therefore a high index of suspicion needs to be maintained in the appropriate host with altered mental status, even without fever.

The hallmark clinical presentation of encephalitis is fever, headache and altered consciousness. Other neurologic symptoms such as seizure, focal deficits, odd behavior, personality changes or speech disturbances are also seen.

Many patients with bacterial meningitis have a presentation over several days before deteriorating and as such may have received prior antibiotic therapy (for treatment, for instance, of a presumed bacterial upper respiratory infection).

Risk factors

Risk factors for bacterial meningitis include CSF leak (in which often pneumococcus is the offender) and terminal complement insufficiency (which is risk for meningococcus). History of head trauma or prior sinusitis or mastoiditis may also be present.

Aseptic meningitis is the term used for etiologies of meningitis that are not discernible on initial CSF Gram stain and culture. The clinical presentation of aseptic meningitis overlaps with that of bacterial meningitis symptomatically with fever, headache, stiff neck and photophobia, with headache often being the predominant symptom.

Aseptic meningitis is distinguished from encephalitis by the absence of any neurologic symptoms other than headache, so that while a patient may be lethargic with aseptic meningitis, the presence of altered consciousness suggests encephalitis. Patients may have concomitant meningitis and encephalitis (i.e., meningoencephalitis).

Aseptic meningitis can be caused by a variety of pathogens, with viruses predominating. Pathogens that are ordinarily considered etiologies of chronic meningitis, such as M. tuberculosis and Cryptococcus, can have acute clinical presentation that can be indistinct from that of acute bacterial meningitis and infectious encephalitis.

A recent course of antibiotics can lead to what appears to be aseptic meningitis in a patient who truly has partially treated bacterial meningitis.

Key management points

In patients with fever and altered mental status, rapid decisions need to be made regarding indicated diagnostic studies and therapeutic interventions.

All patients should undergo emergent lumbar puncture if it is not contraindicated by risk of brain herniation.

CT scan of the brain prior to lumbar puncture should be performed in the situations discussed below to attempt to assess intracranial pressure and the risk of herniation with lumbar puncture.

When bacterial meningitis is suspected, empiric antibiotics should be given promptly and should not be delayed while awaiting the completion or results of these diagnostic studies.

Blood cultures should be performed prior to infusing antibiotics if possible.

Empiric corticosteroids are also indicated in acute bacterial meningitis when the pathogen is unknown or suspected to be pneumococcus.

When HSV encephalitis is suspected on clinical grounds, empiric high-dose acyclovir is also indicated.

When a patient with suspected bacterial meningitis has either depressed mental status or focal neurologic deficit, emergent CT scan of the brain is indicated in order to assess intracranial pressure and risk for brain herniation with lumbar puncture.

CT scan does not always adequately rule out elevated intracranial pressure in the case of severe bacterial meningitis (primarily when due to pneumococcus but occasionally when due to other pathogens such as Group B streptococcus), and in this situation, specific intracranial pressure monitoring and the placement of an extraventricular device should be discussed.

Though MRI findings can be helpful in detecting meningitis, in this acute setting MRI is too time-consuming to be practical.

If bacterial meningitis is suspected due to the presence of clinical findings noted above, rapid initiation of empiric antibiotic therapy to cover potential pathogens should be initiated.

The use of corticosteroids adjunctively is associated with decreased morbidity (such as subsequent neurologic sequelae) and in some cases mortality with bacterial meningitis. Therefore, steroids should be given concomitantly or prior to empiric antibiotics.

If bacterial meningitis is not determined to be present, the steroid therapy and antibiotic therapy can be discontinued.

2. Emergency Management

Focus on stabilizing the patient

If a patient’s consciousness is so depressed that he or she is unarousable or unable to produce a gag reflex, emergent intubation for airway protection and the prevention of massive aspiration is appropriate.

If a patient is hemodynamically unstable, which can occur in the case of concomitant bacteremia and meningitis (such as with meningococcemia), measures should be undertaken to treat the patient’s septic shock with antibiotic therapy (see below), high-volume infusions of intravenous fluids (though central catheters and wide-bored peripheral intravenous lines) and vasopressive agents (see chapter “Severe Sepsis and Septic Shock”).

Empiric antibiotics for presumed bacterial meningitis should not be delayed while awaiting diagnostic studies such as lumbar puncture.

CT scan prior to lumbar puncture should be performed in patients with moderate to severely depressed mental status or focal deficits.

Lumbar puncture is important in diagnosing bacterial meningitis and distinguishing it from other serious CNS infections such as HSV encephalitis and less severe infections such as enteroviral meningitis.

In patients with worrisome clinical signs such as worsening consciousness (GCS <=11), papilledema, signs of brainstem pathology including changed pupillary reflexes, posturing and irregular respirations, and acute seizure, CT scan can rarely underappreciate the risk for herniation, and when clinical signs are present that could signal “impending” herniation, LP should be delayed and measures (such as IV mannitol and emergent neurosurgical consultation) should be undertaken to reduce intracranial pressure.

The choice of empiric antibiotic therapy for bacterial meningitis and viral encephalitis should be guided in part by local resistance patterns and the likelihood of a given patient being infected with a given pathogen.

A reasonable philosophy is to give broad empiric therapy when a specific microbiologic diagnosis is not yet known, recognizing that once more data are present, a tailored regimen can be constructed.

Before CSF Gram stain, blood culture or HSV PCR data are available, treatment of pneumococcus, meningococcus and in some cases Listeria should be instituted empirically.

When viral encephalitis is a concern, given HSV is generally the most common pathogen and is treatable, empiric high-dose acyclovir should be initiated.

In the rare case where there is a known recent freshwater exposure, amoebic encephalitis should be considered and CSF should be specifically examined cytologically to visualize organisms.

Clinical trials using dexamethasone in adults with bacterial meningitis have demonstrated clinical benefits, and therefore dexamethasone should be given with or prior to the empiric antibiotic therapy.

Checklist: initial diagnostic and management points not to be missed

1. Initial stabilization of the patient.

  • Airway protected.

  • Intubation if indicated.

  • Hemodynamically stabilize.

  • Goal is normovolemia.

2. Neurologic examination.

  • Assess consciousness and mental status.

  • Assess GCS.

  • Cranial nerve exam including examination of optic discs for papilledema.

  • Pupillary reflex.

  • Gag reflex.

  • Motor, sensory, reflexes, coordination.

  • Meningismus.

3. Physical exam.

4. Blood cultures.

5. Lab work.

  • CBC/coagulation profile for evidence of DIC, bleeding risk.

  • [Na+] for evidence of SIADH or cerebral salt wasting.

  • Renal function, liver function testing.

6. Intravenous line.

7. Institute antibiotic therapy and steroid therapy.

8. Determine if CT scan indicated.

9. CT: evidence of elevated ICP.

  • Neurosurgical consultation –>May require ICP monitoring.

  • Determine if IV mannitol, diuresis, hyperventilation indicated to manage elevated ICP.

10. CT: evidence of hydrocephalus.

  • Neurosurgical consultation –> may require ventriculostomy.

11. CT scan not indicated or demonstrating no evidence of asymmetry or impending herniation.

  • Lumbar puncture

12. Determine if intravenous acyclovir indicated based on clinical history and initial CSF indices.

3. Diagnosis

Diagnostic overview

When bacterial meningitis is suspected on the basis of signs and symptoms, rapid diagnostic testing should be undertaken and empiric therapy should not be delayed while diagnostic testing proceeds. Key historical features can be useful in determining possible causes.

The lumbar puncture is critical to the diagnosis.

Classic physical findings and symptoms (nuchal rigidity, head jolt accentuation of headache, Kernig’s sign and Brudzinski’s sign) have low diagnostic accuracy in predicting who has meningitis, making lumbar puncture more imperative in establishing a diagnosis.

Opening pressure, CSF cell counts, protein, glucose and potentially most importantly CSF Gram stain can be used to diagnose acute bacterial meningitis. Blood cultures can also be helpful and are positive.

Because a delay in performing lumbar puncture can lead to a delay in diagnosis of bacterial meningitis, important questions are when is it appropriate to delay lumbar puncture to perform diagnostic brain imaging (practically speaking, head CT scan) or to delay initial lumbar puncture entirely.

The concern with severe bacterial meningitis is that if significant cerebral edema is present, brain herniation can occur (5% of time) and lumbar puncture can theoretically precipitate uncal herniation.

When cerebral edema is present, early consultation with neurosurgery regarding the necessity of an external ventriculostomy is appropriate, as is consultation regarding the safety of a low-volume spinal tap.

When a patient is presenting with focal neurologic deficits or seizure, a CT scan is more likely to be abnormal and indeed may be useful in beginning to establish alternative diagnoses.

The non-contrast CT scan will also be helpful in determining if subarachnoid hemorrhage is present, which can occur with mycotic (or non-mycotic) aneurysm. Brain abscess may appear as an ill-defined hypodensity on non-contrast CT.

Clinical features should be used to determine which patients are unlikely to have an abnormal CT scan and thus can undergo lumbar puncture without delay.

Generally, patients with coma, papilledema, focal neurologic deficits, recent seizure, known immunocompromise or CNS disease should receive neuroimaging (CT scan) prior to performing lumbar puncture.

Key diagnostic studies

CT scan of the head

A non-contrast head CT scan in bacterial meningitis can range from normal appearance to evidence of sulcal effacement. Later in the course of disease, hydrocephalus can develop and is indicated by enlarged ventricles on CT scan.

Subdural empyema can develop and can be visualized as a subdural collection.

Evidence of sinusitis, mastoiditis or skull fracture can also be seen. If intravenous contrast is given, focal abnormalities such as brain abscess may be better visualized.

When viral encephalitis is suspected, MRI with contrast is more sensitive than CT scan in demonstrating the characteristic orbital-frontal and temporal lobe lesions of HSV encephalitis.

Results from spinal fluid analysis are most helpful in distinguishing bacterial meningitis from other causes of fever and altered mental status:

Opening pressure

Opening pressure is often elevated above 18 cm H2O in bacterial meningitis. Highly elevated opening pressures are seen with cerebral edema.

Appearance of the CSF

The initial appearance of the CSF can also be helpful. In bacterial meningitis, the fluid is cloudy about 80% of the time.

CSF gram stain

A CSF Gram stain on which organisms are seen generally clinches the diagnosis of bacterial meningitis. A Gram stain in which many neutrophils are present is suggestive. The sensitivity of the Gram stain for bacterial meningitis is approximately 50-60%, so that a negative Gram stain does not rule out the diagnosis.

CSF protein and glucose

Total protein is elevated more than 95% of the time in bacterial meningitis and is >200 mg/dL more than half the time. CSF glucose is less than 50 mg/dL about 70% of the time.

In viral encephalitis, generally protein level is elevated and glucose level is normal or slightly low (normal CSF glucose is taken to be approximately 0.6 of the serum level, and a level less than 0.4 of the serum level is often seen with bacterial meningitis).

CSF cell counts

In bacterial meningitis the white cell count often is >1000 cells/mm3.

Neutrophilic predominance with >80% neutrophils is present 80% of the time in bacterial meningitis.

Cases with lymphocyte predominance can be seen in bacterial meningitis, most commonly with
Listeria infection, but generally are more suggestive of meningoencephalitis due to a non-typical bacterial pathogen (such as a viruses, fungi or mycobacteria).

When the absolute neutrophil count is less than 150 cells/mm3 and the neutrophils represent <15% of total WBC, bacterial meningitis is unlikely to be present.

However, in immunocompromised and neutropenic patients, indices may be relatively normal given lack of capacity to mount an inflammatory response, and in these cases repeat lumbar puncture and close observation are warranted in the appropriate clinical scenario.

In viral encephalitis, generally there is a mononuclear cellular predominance (mostly lymphocytes and monocytes) among white blood cells.

The characteristic finding in HSV encephalitis is the presence of red blood cells in the spinal fluid without evidence of a traumatic lumbar puncture, which is reflective of a necrotizing encephalitis.

With a traumatic tap, generally one expects the RBC count to decrease from the first tube sent for cell counts to the fourth tube (sent for a repeated cell count). Thus a lack of decrement in RBC count from tube 1 to tube 4 suggests CNS hemorrhage (due to necrotizing encephalitis or another etiology).


The HSV PCR of the CSF is 98% sensitive and 100% specific for HSV encephalitis and should be performed in any suspected case.

Other tests

In a patient with fever and altered mental status of relatively acute onset, cryptococcal meningitis and tuberculous meningitis are less likely. However, both of these diseases can present acutely.

Cryptococcal meningitis is usually characterized by the non-specific finding of an elevated opening pressure and can be diagnosed with cryptococcal antigen testing (with the CSF test being more sensitive than the serum test), India ink staining of the CSF or fungal culture of the CSF.

While lymphocyte predominance, elevated protein and low glucose are typical CSF findings in tuberculous meningitis, TB meningitis can early on have a neutrophilic predominance (which can last in cases up to 2 weeks) and can be diagnosed with CSF mycobacterial culture. However, when TB meningitis is present, disease is found elsewhere 75% of the time, so that a search for TB in other body sites should be undertaken.

If TB meningitis is suspected on clinical grounds, empiric treatment should be instituted as culture may take several weeks to grow. TB PCR of the CSF can also be attempted but is not highly sensitive.

In terms of other testing that has been investigated to discern bacterial meningitis from aseptic meningitis, some data (though mainly in children) also suggest that elevated procalcitonin levels are also a good predictor of bacterial vs. non-bacterial meningitis. Bacterial antigen testing in the CSF generally has sensitivities of 75% or less and cannot be used to rule out bacterial meningitis.

How do I know what this patient has?

A definitive diagnosis of bacterial meningitis relies on positive CSF Gram stain or culture. Short of that, if the clinical picture and the other CSF indices are consistent with bacterial meningitis (headache, fever, altered consciousness as well as elevated neutrophil count and protein level), it is reasonable to treat presumptively for bacterial meningitis.

Prior antibiotic therapy can alter the CSF indices (leading to increased mononuclear predominance) and lead to negative cultures without adequately treating the infection, so that a history of prior antibiotics should be considered in diagnosing bacterial meningitis in a patient with a negative CSF culture.

What else could it be?

A high CSF neutrophil count is also possible in early viral meningoencephalitis, tuberculous meningitis or fungal meningitis, so that if the diagnosis of bacterial meningitis is in doubt (and the patient is not responding within one to two days on antibacterial therapy or is clinically worsening despite therapy), a repeated lumbar puncture should be performed, after first evaluating for other etiologies of worsening that could be seen on diagnostic imaging (e.g., a communicating hydrocephalus that can develop with bacterial meningitis).

What confirmatory tests should be performed?

When CSF cultures are positive for a particular pathogen, no other specific testing is needed and a diagnosis is made. Repeat lumbar puncture after 48 hours of appropriate treatment may be indicated to see that the antibiotic therapy on which the patient is placed is effective and that the CSF culture has cleared.

If the diagnosis of bacterial meningitis is not definitively made by CSF Gram stain, CSF culture or blood culture, a high index of suspicion for alternative etiologies should be maintained.

MRI with gadolinium is more sensitive than CT scan for visualizing the lesions of a necrotizing viral encephalitis and can occasionally be helpful in seeing inflamed meninges (though this is a nonspecific finding).

If a repeat spinal tap demonstrates a mononuclear predominance (with lymphocytes and monocytes) in the white blood cell differential, testing for viral pathogens (as well as syphilis) should be undertaken.

HSV is the most common cause of encephalitis and should be assessed with PCR.

During the summer and fall months, West Nile virus (WNV) is associated with encephalitis to varying degrees (based on geography and current year), and testing for WNV should be considered.

In the summer and fall, testing for other arboviruses should be considered depending upon geographical location and consultation with local infectious diseases specialists.

If potential for exposure to a rabid animal exists, undertaking direct testing and treatment for rabies is also appropriate.

HIV testing should be performed as a routine part of care for all patients, and if the test is positive, cryptococcal and tuberculous meningitis should be investigated more aggressively .

Even with a CSF neutrophil predominance, if TB is a possibility (particularly if anything is consistent with TB in the lung or elsewhere) and the patient has not responded to antibiotics for bacteria, CSF should be sent for mycobacterial culture and empiric antituberculous therapy should be highly considered.

If there is a history of fresh-water submersion within the prior 2 weeks (or the potential that the patient swam in an underchlorinated pool), CSF cytology should be performed for amoebic encephalitis.

4. Specific Treatment

Treatment overview

Initial antibiotics for bacterial meningitis should cover pneumococcus and meningococcus.

In patients older than 50 or with any immunocompromising conditions, it is reasonable to cover
Listeria as well empirically.

In patients in whom reports of behavioral change are present, if the initial CSF examination demonstrates red blood cells (that do not clear from tubes 1 to 4) with a mononuclear WBC predominance, empiric therapy for HSV encephalitis while awaiting HSV PCR results is also appropriate.

If there is a mononuclear predominance and there is any evidence currently or a recent history of a vesicular rash indicating localized or disseminated zoster, Varicella zoster virus should be considered and covered as well.

If there is any evidence of disseminated Staphylococcus aureus infection (such as skin abscesses or necrotizing pneumonia), MRSA should be covered upfront as well, though staphylococcus is an unusual etiology for isolated bacterial meningitis.

Despite the inflammation and breakdown of the blood-brain barrier in bacterial meningitis, generally antibiotics chosen for treatment should have adequate penetration levels into the CNS. To achieve high serum levels leading to adequate CSF levels, generally high doses of intravenous antibiotics are required in the treatment of bacterial meningitis.

Given the potential morbidity and mortality due to delayed or inappropriate treatment, the initial strategy includes broad therapy aimed at potentially resistant pathogens if they are present in the community, so that, for instance, ceftriaxone is used for initial meningococcal coverage rather than penicillin.

Vancomycin should be added to the empiric ceftriaxone for pneumococcal coverage if pneumococcus with high-level penicillin resistance (and in turn cephalosporin resistance) is seen at all in the community.

Once further microbiologic data on the patient become available, antibiotics can then be judiciously tailored and discontinued. Ampicillin is ideal initial therapy for Listeria.

The role of steroids as adjuvant treatment to antibiotics in bacterial meningitis in adults has been examined in several studies. Particularly in pneumococcal meningitis the use of dexamethasone has been shown to improve mortality.

Generally dexamethasone therapy has been associated with reduced severe hearing loss and other neurologic sequelae in bacterial meningitis, and therefore data generally support the use of adjuvant corticosteroids in presumed bacterial meningitis.

While some controversy surrounds the role of intravenous fluids when cerebral edema is present, fluids are often needed to maintain adequate mean arterial pressure and provide adequate cerebral perfusion pressure, so that the goal should be normovolemia rather than hypovolemia.

Seizures should be treated aggressively with antiepileptics to avoid further increases in intracranial pressure (if seizures occur, give intravenous Ativan and load patient with intravenous phenytoin).

While studies in humans have yet to be performed, slight cooling or limiting fever may have a beneficial role in limiting inflammatory-induced CNS damage.

Drug and antibiotic recommendations and dosing (Please refer to Table I, Table II, Table III, Table IV, Table V, Table VI)

Steroid dosing in bacterial meningitis is based on the dosing used in clinical trials using dexamethasone. The recommended dose is 10 mg of dexamethasone given every 6 hours for 5 days, beginning with or before the first dose of antibiotics.

The dose of acyclovir for HSV encephalitis is generally 10-12.5 mg/kg q8 hours over 14-21 days (with dose adjustment for renal insufficiency). For VZV encephalitis, 12.5mg/kg q8 hours for 21 days is indicated.

Table I. Empiric Therapy for Bacterial Meningitis

Table I.
Host Potential Pathogens Empiric Antibiotics
Normal immunity (>3 months to 18 years old) Neisseria meningitidis, Streptococcus pneumoniae Third-generation intravenous cephalosporin and vancomycin
Age >50 or pregnant S. pneumoniae, Listeria monocytogenes, Gram-negative bacilli Third-generation cephalosporin, vancomycin and ampicillin
Impaired cellular immunity L monocytogenes, Gram-negative bacilli,
S. pneumoniae
Antipseudomonal cephalosporin, ampicillin, vancomycin
Head trauma, neurosurgery, cerebrospinal fluid shunt in place Staphylococcus aureus, Staphylococcus epidermidis, Gram-negative bacilli,
S. pneumoniae
Vancomycin, antipseudomonal cephalosporin

Table II. Antibiotic Recommendations for Bacaterial Meningitis Based on CSF Gram Stain

Table II.
Finding Antibiotic
Gram-positive cocci Vancomycin plus broad-spectrum (third-generation) cephalosporin*
Gram-positive rods Ampicillin +/- gentamicin
Gram-negative rods Antipseudomonal cephalosporin plus aminoglycoside
Gram-negative diplococci or small Gram-negative coccobacilli Broad-spectrum (third-generation) cephalosporin

* Vancomycin should be added to third-generation cephalosporin rather than replacing because cephalosporin is considered to be better therapy when an organism is susceptible.

Table III. Definitive Therapy by Organism of Acute Bacterial Meningitis

Table III.
Organism Treatment
Streptococcus pneumoniae Vancomycin with third-generation cephalosporin
Neisseria meningitidis Ceftriaxone
Listeria monocytogenes Ampicillin and gentamicin
Group B streptococcus Penicillin G
Haemophilus infuenzae Ceftriaxone
Enterobacteriaceae Cefepime and aminoglycoside (need to consider local susceptibility data, and consider infectious diseases consultation)
Pseudomonas aeruginosa, Acinetobacter *Local susceptibility data and infectious diseases consultation needed. Initiate therapy with two potentially active agents.

*Depending on the location, nosocomial or community-acquired may influence which agents may be active, including cefepime, meropenem and aminoglycosides (amikacin, gentamicin).

Table IV. Antibiotic Susceptibility Data for Common Organisms Causing Acute Bacterial Meningitis

Table IV.
Organism First-line therapy
Streptococcus pneumoniae
PCN MIC <0.1 µg/mL Penicillin G or ampicillin
PCN MIC 0.1-1.0 µg/mL Ceftriaxone or cefotaxime
PCN MIC => 2.0 µg/mL Vancomycin plus ceftriaxone or cefotaxime
Neisseria meningitidis
PCN MIC <0.1µg/mL Penicillin G or ampicillin
PCN MIC 0.1-1.0 µg/mL Ceftriaxone or cefotaxime
Listeria monocytogenes Ampicillin +/- gentamicin
Staphylococcus aureus
Methicillin sensitive Nafcillin or oxacillin
Methicillin resistant Vancomycin
Haemophilus influenzae
Beta-lactamase negative Ampicillin
Beta-lactamase positive Ceftriaxone or cefotaxime
Enterobacteriaceae Cefepime plus aminoglycoside*
Pseudomonas aeruginosa Cefepime plus aminoglycoside*
Staphylococcus epidermidis Vancomycin (consider addition rifampin when shunt infection)

*or based on local susceptibility data and infectious diseases consultation

Table V. Dosages of Antibiotics Used to Treat Acute Bacterial Meningitis

Table V.
Drug Daily intravenous dose Dosing interval (hours)
Ampicillin 12 g 4
Cefepime 6 g 8
Cefotaxime 8-12 g 4-6
Ceftriaxone 4 g 12
Chloramphenicol** 4-6 g 6
Gentamicin*** 3-5 mg/kg 8
Nafcillin 12 g 4
Oxacillin 9-12 g 4
Penicillin G 24 million units 4
Rifampin 300 mg 12
Trimethoprim-sulfamethoxazole 10-20 mg/kg 6
Vancomycin**** 2-6 g 8-12

*Adjustments may be needed in renal or hepatic insufficiency.

**Higher dose or alternative regimen recommended for pneumococcus. Used in cases of severe hypersensitivity reactions to penicillins and cephalosporins.

***Monitor serum drug levels.

****With severe infection, consider monitoring CSF levels.

Table VI. Duration of Antibiotic Therapy Depending on Organism Isolated

Table VI.
Organism Duration (days)
Neisseria meningitidis 7
Streptococcus pneumoniae 10-14
Listeria monocytogenes 14-21
Group B streptococci 14-21
Gram-negative bacilli (including
Haemophilus influenzae)
Staphylococcus aureus*


*For Staphylococcus aureus, if concomitant bacteremia or endovascular focus of infection, at least 28 days likely indicated.

Refractory cases

A patient on treatment for presumed bacterial meningitis should have a closely and vigilantly monitored neurologic examination.

If clinical deterioration occurs on therapy, repeat CNS imaging (stat head CT) should be performed.

When cerebral edema is evident, modalities to lower intracranial pressure may be required, such as intravenous mannitol, hypertonic saline and hyperventilation. Additionally, neurosurgical intervention may be required for placement of an intracranial pressure monitor.

If communicating hydrocephalus with elevated ICP and worsened mental status develops (seen most classically in cryptococcal meningitis but also seen in bacterial meningitis), repeated lumbar punctures to reduce opening pressure (typically by half but to under 30 cm H2O) are indicated, and neurosurgical consultation may be appropriate to discuss placement of a lumbar drain or ventriculostomy.

When an initial CSF culture is positive and the patient has not improved over 48 hours, repeat spinal tap is indicated to determine if the culture has cleared. In certain refractory situations there may be a role for specific intrathecal administration of antibiotics.

5. Disease monitoring, follow-up and disposition

Monitoring and complications

Factors that influence prognosis in bacterial meningitis are the patient’s age and premorbid condition, the degree of neurologic impairment at initial presentation and the pathogen isolated.

Delay in institution of appropriate antibiotics for bacterial meningitis results in poorer outcome.

Pneumococcal meningitis is associated with a 20% mortality rate and a similar rate of long-term neurologic morbidity among survivors.

A positive response to therapy is represented by neurologic stabilization followed by improvement in consciousness over the course of a few days.

Once a patient is stabilized and on treatment, very close monitoring of neurologic status is important in order to recognize deterioration or lack of improvement, which could signal a need for further diagnostic and therapeutic interventions.

Several complications can develop in the course of early therapy for bacterial meningitis. These complications are characterized by a non-focal decline in consciousness or development of a focal neurologic deficit:

Decline in the patient’s level of consciousness is an indication to evaluate for these:

Increased cerebral edema: This is due to inflammation and subsequent permeability of the blood-brain barrier. CT findings (decreased ventricular size, effacement of sulci) can aid with diagnosis.

Seizures can occur and result in reduced consciousness, particularly in the post-ictal state. If the mental status does not gradually improve following the seizure, EEG monitoring is indicated in order to detect subclinical seizure activity. Anticonvulsant therapy should be initiated if seizures occur.

Acute hydrocephalus (typically communicating hydrocephalus) can occur, resulting in depressed consciousness. In this situation, lumbar puncture can be both diagnostic (indicating elevated ICP) and therapeutic to reduce ICP. Repeated LPs, a lumbar drain or in some cases a VP shunt may be indicated.

Cerebral venous thrombophlebitis: When this develops, waxing and waning consciousness, seizures and a non-arterial distribution of focal neurologic deficits may be present. Magnetic resonance venography may be diagnostic.

Development of a new focal deficit is an indication to evaluate with imaging for:

  • Cerebral thrombophlebitis resulting in stroke.

  • Subdural empyema due to purulent meningitis (this may be seen particularly in patients with sinusitis or mastoiditis).

  • Cranial nerve abnormalities due to severe meningeal inflammation or elevated pressure (most commonly this effects CN 8 – i.e., hearing).

Wrong diagnosis?

If the initial CSF indices were equivocal for bacterial meningitis and the patient does not demonstrate any improvement on therapy, an alternative diagnosis such as viral encephalitis, tuberculous meningoencephalitis or cryptococcal meningitis should be considered.

Lumbar puncture should be repeated and repeated imaging (including gadolinium enhancing MRI) may be indicated.


Patients who have been adequately treated for bacterial meningitis may require physical and neurocognitive rehabilitation to achieve maximal recovery.

If a patient with meningococcal meningitis is treated with a course of ceftriaxone, no further antibiotics should be necessary to eradicate nasopharyngeal colonization.

Infection control or infectious diseases consultation is appropriate to address who should receive secondary prophylaxis after exposure to the patient.

If a patient is found to have a predisposing condition for development of meningitis (such as invasive sinus disease, otitis or CSF leak), these conditions should be directly addressed.

A patient with recurrent meningococcal disease should be referred to immunology for evidence of terminal complement deficiency.


Mechanism of disease

Meningitis is inflammation of the meninges, which can be caused by various organisms, including bacteria, viruses, fungi and parasites.

Bacterial meningitis is most frequently acquired via the respiratory tract through evasion of the mucosal and submucosal defenses followed by bloodstream invasion and seeding of the CNS. This is the case with Neisseria meningitidis (where infection precedes nasoparyngeal carriage) and with S pneumoniae, in which the organism colonizes the nasopharynx. Organisms such as Staphylococcus aureus, Escherichia coli and many others can seed the meninges during the course of bacteremia from another site of entry.

Bacterial meningitis can also be caused via direct extension into the CNS in cases of severe sinusitis, mastoiditis, otitis media or post-neurosurgical procedure.

In addition to evading mucosal immunity in the respiratory tract, some viral pathogens can evade gastrointestinal tract immunity, disseminate and invade into the CNS.

Because of the limits of localized immunity to opsonize and remove organisms within the subarachnoid space, organisms can replicate and subsequently directly instigate inflammatory cascades involving cytokines that in turn lead to neuronal damage, inflammation and vascular leakage in meningitis due to bacterial, viral and other etiologies.

The increased edema in bacterial meningitis is due to the vascular leakage noted above (blood-brain barrier permeability) as well as edema due to cellular death and obstruction of flow (in the case of hydrocephalus). Raised intracranial pressure can lead in turn to further damage.


Bacterial meningitis is relatively rare, with less than 25,000 cases occurring yearly in the United States. However, the disease occurs with increased frequency in other parts of the world and is of high clinical importance due to its morbidity and mortality, particularly when institution of appropriate antibiotic therapy is delayed. Viral encephalitis is also uncommon, with an estimated 20,000 cases per year in the US.

Streptococcus pneumoniae is responsible for more than 50% of cases of acute bacterial meningitis. The overall incidence has decreased since the pediatric conjugate pneumococcal vaccine was introduced. In adults, it is seen in the highest incidence among those over age 65 but can be seen in all age groups.

Conditions that are associated with increased severity of disease are asplenism, multiple myeloma, alcoholism, malnutrition, cirrhosis and renal disease.

Neisseria meningitidis occurs most frequently in children and young adults and most people acquire the disease through face-to-face contact with an asymptomatic carrier. The introduction of conjugate vaccine meningococcal vaccine has been associated with a decline in reported disease since the mid-1990s.

Vaccination is recommended for those 11-18 years of age and those considered high risk: college freshman, military recruits, microbiology workers, those traveling to endemic regions and those with terminal complement deficiencies.

Among those over age 60, Listeria monocytogenes is the second most common cause of bacterial meningitis. Patients with depressed cellular immunity are at particular risk for infection, although sporadic cases do occur in otherwise healthy adults.

Less common causes of bacterial meningitis include Group B streptococci, Gram-negative bacilli such as Escherichia coli and Klebsiella pneumoniae,
Haemophilus influenzae, Capnocytophaga canimorsus and
Staphylococcus aureus.

HSV is the most common cause of viral encephalitis, accounting for approximately 10% of cases overall.

Both HSV and rabies encephalitis occur throughout the year in the US.

Other etiologies of encephalitis in adults such as West Nile Virus and other arboviruses (such as St. Louis encephalitis, La Crosse encephalitis, and Eastern equine encephalitis) occur with varying yearly and seasonal frequency.


In bacterial meningitis there are several early predictors of outcome. Overall mortality remains in the 20% range. Factors at presentation that have been shown to correlate with either death or poor neurologic outcome are older age, tachycardia, lower Glasgow Coma Scale score, the presence of cranial nerve palsies, 1000 neutrophils/mL CSF and gram-positive cocci on Gram stain.

Long-term prognosis among survivors of bacterial meningitis is worse among those with pneumococcal than meningococcal meningitis, with about 20% experiencing some degree of cognitive dysfunction several years after infection.

Special considerations for nursing and allied health professionals.


What's the evidence?

What every clinician needs to know

Auburtin, M, Wolff, M, Charpentier, J, Varon, E, Le Tulzo, Y. “Detrimental role of delayed antibiotic administration and penicillin-nonsusceptible strains in adult intensive care unit patients with pneumococcal meningitis: the PNEUMOREA prospective multicenter study”. Crit Care Med. vol. 34. 2006. pp. 2758-65.

Sawyer, M, Rotbart, HA, Scheld, M, Whitley, R. “Viral meningitis and the aseptic meningitis syndrome”. Infections of the Central Nervous System. 2004. pp. 75-95.

“CDC: Summary of notifiable diseases, United States”. MMWR Morbid Mortal Wkly Rep. vol. 57. 2008. pp. 1-100.

Tunkel, AR, Van de Beek, D, Scheld, WM, Mandell, GL, Bennett, JE, Dolin, R. “Acute meningitis”. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 2009. pp. 1189-229.

Choi, C. “Bacterial meningitis in aging adults”. Clin Infect Dis. vol. 33. 2001. pp. 1380-5.

Waghdhare, S, Kalantri, A, Joshi, R, Kalantri, S. “Accuracy of physical signs for detecting meningitis: a hospital-based diagnostic accuracy study”. Clin Neurol Neurosurg. vol. 112. 2010. pp. 752-7.

Emergency Management

Van de Beek, D, de Gans, J, Tunkel, A. “Community-acquired bacterial meningitis in adults”. N Engl J Med. vol. 354. 2006. pp. 44-53.

Hasbun, R, Abrahams, J, Jekel, J, Quagliarello, VJ. “Computed tomography of the head before lumbar puncture in adults with suspected meningitis”. N Engl J Med. vol. 345. 2001. pp. 1727-33.


Tokuda, Y, Koizumi, M, Stein, GH, Birrer, RB. “Identifying low-risk patients for bacterial meningitis in adult patients with acute meningitis”. Intern Med. vol. 48. 2009. pp. 537-43.

Viallon, A, Zeni, F, Lambert, C. “High sensitivity and specificity of serum procalcitonin levels in adults with bacterial meningitis”. Clin Infect Dis. vol. 28. 1999. pp. 1313-6.

Specific Treatment

Amorosa, V, Lo Re, V. “Bacterial meningitis”. Hot Topics in Infectious Diseases. 2004. pp. 1-12.

de Gans, J, van de Beek, D. “Dexamethasone in adults with bacterial meningitis”. N Engl J Med. vol. 347. 2002. pp. 1549-56.

Brouwer, MC, McIntyre, P, de Gans, J, Prasad, K, van de Beek, D. “Corticosteroids for acute bacterial meningitis”. Cochrane Database Syst Rev. 2010 Sep 8. pp. CD004405

Lutsar, I, McCracken, G, Friedland, I. “Antibiotic pharmacodynamics in the cerebrospinal fluid”. Clin Infect Dis. vol. 27. 1998. pp. 1117-29.

Tunkel, AR, Hartman, BJ, Kaplan, SL, Kaufman, BA, Roos, KL, Scheld, WM. “Practice guidelines for the management of bacterial meningitis”. Clin Infect Dis. vol. 39. 2004. pp. 1267-84.

Tunkel, AR, Glaser, CA, Bloch, KC, Sejvar, JJ, Marra, CM, Roos, KL, Hartman, BJ, Kaplan, SL, Scheld, WM, Whitley, RJ. “The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America”. Clin Infect Dis. vol. 47. 2008. pp. 303-27.

Disease, follow-up and disposition

Weisfelt, M, van de Beek, D, Spanjaard, L, Reitsma, JB, de Gans, J. “A risk score for unfavorable outcome in adults with bacterial meningitis”. Ann Neurol. vol. 63. 2008 Jan. pp. 90-7.

Weisfelt, M, Hoogman, M, van de Beek, D, de Gans, J, Dreschler, WA, Schmand, BA. “Dexamethasone and long-term outcome in adults with bacterial meningitis”. Ann Neurol. vol. 60. 2006 Oct. pp. 456-68.

Hussein, AS, Shafran, SD. “Acute bacterial meningitis in adults: a 12-year review”. Medicine (Baltimore). vol. 79. 2000. pp. 360-8.

Durand, ML, Calderwood, SB, Weber, DJ. “Acute bacterial meningitis in adults: A review of 493 episodes”. N Engl J Med. vol. 328. 1993. pp. 21-8.