Characteristic features of common causes of bacterial meningitis
Organism	Site of entry	Age range	Predisposing conditions
Neisseria meningitidis	Nasopharynx	All ages	Usually none, rarely complement deficiency
Streptococcus pneumoniae	Nasopharynx, direct extension across skull fracture, or from contiguous or distant foci of infection	All ages	All conditions that predispose to pneumococcal bacteremia, fracture of cribriform plate, cochlear implants, cerebrospinal fluid otorrhea from basilar skull fracture, defects of the ear ossicle (Mondini defect)
Listeria monocytogenes	Gastrointestinal tract, placenta	Older adults and neonates	Defects in cell-mediated immunity (eg, glucocorticoids, transplantation [especially renal transplantation]), pregnancy, liver disease, alcoholism, malignancy
Coagulase-negative staphylococci	Foreign body	All ages	Surgery and foreign body, especially ventricular drains
Staphylococcus aureus	Bacteremia, foreign body, skin	All ages	Endocarditis, surgery and foreign body, especially ventricular drains; cellulitis, decubitus ulcer
Gram-negative bacilli	Various	Older adults and neonates	Advanced medical illness, neurosurgery, ventricular drains, disseminated strongyloidiasis
Haemophilus influenzae	Nasopharynx, contiguous spread from local infection	Adults; infants and children if not vaccinated	Diminished humoral immunity

 

●The major causes of healthcare-associated bacterial meningitis are different (usually staphylococci and aerobic gram-negative bacilli) and, in cases occurring after neurosurgery, may vary with whether or not antimicrobial prophylaxis has been given to prevent surgical site infection. Healthcare-associated bacterial meningitis may also occur in patients with internal or external ventricular drains or following trauma (ie, cranial trauma or after basilar skull fracture with or without clinical evidence of leak of cerebrospinal fluid).

N. meningitis is a medical emergency.

1. Admit in an intensive care unit.

because complications of bacterial meningitis (hypotension, cerebral infarction, seizures, increased ICP) often occur in the first 2 to 3 days of therapy.

2. Draw blood for culture immediately.

3. Empirical antimicrobial and adjunctive dexamethasone therapy initiated without delay. Empiric intravenous antimicrobial therapy once blood cultures have been obtained and prior to head CT.

• Further antimicrobial therapy is guided by cultures and susceptibility testing.

.

Empiric Therapy Regimens based on patient population. 

 All drugs should be administered intravenously (IV). 

Age

Younger than 1 month:

Commonly observed pathogens include group B Streptococcus (GBS) (cases lack characteristic stiff neck of more typical bacterial meningitis), Escherichia coli, Listeria monocytogenes, and Klebsiella species.

• Ampicillin 100 mg/kg plus  cefotaxime 50 mg/kg q6h or
• Ampicillin 100 mg/kg plus an aminoglycoside (gentamicin 2.5 mg/kg or tobramycin 2.5 mg/kg) q8h

One to 23 months:

Commonly observed pathogens include Streptococcus pneumoniae, Neisseria meningitidis (rapidly evolving skin rash indicative of infection with Meningococcusspecies; immediately begin a regimen of benzyl penicillin, ceftriaxone, or cefotaxime), GBS, Haemophilus influenzae type b, and E coli.

• Vancomycin 15 mg/kg q6h plus a third-generation cephalosporin (ceftriaxone 75-100 mg/kg q12-24h or cefotaxime 75-100 mg/kg q6-8h
• Ampicillin is added for empiric Listeria coverage in patients <2 years of age.

Two to 50 years:

Commonly observed pathogens include N meningitides, and S pneumoniae. Adult and pediatric dosing should include vancomycin plus a third-generation cephalosporin (eg, ceftriaxone, cefotaxime).

• Children: Vancomycin 15 mg/kg q6h plus  ceftriaxone 75-100 mg/kg q12-24h orcefotaxime 75-100 mg/kg q6-8h
• Adults: Vancomycin 15 mg/kg q8h (to achieve trough levels of 15-20 ug/mL)plus  ceftriaxone 2 g q12h or cefotaxime 2 g q4h

Older than 50 years:

Commonly observed pathogens include S pneumoniae, N meningitidis, L monocytogenes, and aerobic gram-negative rods.

• Vancomycin 15 mg/kg q8h (to achieve trough levels of 15-20 ug/mL) plus ampicillin 2 g q 4h (hourly if Listeria is suspected) [1] plus  a third-generation cephalosporin (ceftriaxone 2 g q12h or cefotaxime 2 g q4-6h)

Conditions to consider on giving antibiotic therapy

Pregnancy:

Commonly observed pathogens include L monocytogenes.

• Ampicillin 2 g q4h or penicillin G 4 mU q4h

Immunocompromised (eg, chemotherapy, steroids):

Commonly observed pathogens include S pneumoniae, N meningitidis, Listeriaspecies, and anaerobic gram-negative bacilli.

• Vancomycin 15 mg/kg q8h (to achieve trough levels of 15-20 ug/mL) plus ampicillin 2 g q4h plus a third-generation cephalosporin (ceftriaxone 2 g q12h or cefotaxime 2 g q4-6h)

Basilar skull fracture:

Commonly observed pathogens include S pneumoniae, H influenzae, and Streptococcus pyogenes.

• Vancomycin 15 mg/kg q8h (to achieve trough levels of 15-20 ug/mL) plus a third-generation cephalosporin (ceftriaxone 2 g q12h or cefotaxime 2 g q4-6h)

Penetrating trauma or post neurosurgery:

Commonly observed pathogens include Staphylococcus aureus, Staphylococcus epidermidis, and aerobic gram-negative bacilli.

• Vancomycin 15 mg/kg q8h (to achieve trough levels of 15-20 ug/mL) plus cefepime 2 g q8h or  ceftazidime 2 g q8h or meropenem 2 g q8h

Cerebrospinal fluid (CSF) shunt:

Commonly observed pathogens include S epidermidis, S aureus, aerobic gram-negative bacilli, and Propionibacterium acnes.

• Vancomycin 15 mg/kg q8h (to achieve trough levels of 15-20 ug/mL) plus cefepime 2 g q8h or  ceftazidime 2 g q8h or meropenem 2 g q8h

.

Acyclovir should be considered according to the results of the initial cerebrospinal fluid (CSF) evaluation. Doxycycline should also be added during tick season in endemic areas. The treatment duration is 7 days.1

 

Duration of therapy is 10 to 14 days in documented cases of bacterial meningitis.

 

.

4. Give dexamethasone

Given intravenously immediately before or with the first dose of antibiotics if pneumococcal meningitis is suspected (eg, if gram-positive diplococci are seen on CSF Gram stain); similarly, hydrocortisone should be given intravenously immediately if adrenal infarction is suspected in meningococcal meningitis with meningococcemia (eg, gram-negative diplococci are seen on CSF Gram stain; petechiae; shock).

5. Head CT

Indications for CT scan before LP. (CT) scan is performed to exclude a mass lesion or increased intracranial pressure; these abnormalities might rarely lead to cerebral herniation during removal of large amounts of CSF, and have devastating consequences.

—  patients with evidence of raised intracranial pressure (eg, mass effect on CNS imaging or clinical signs of impending herniation), thrombocytopenia or another bleeding diathesis, or spinal epidural abscess.

6. Lumbar Puncture

[The diagnosis of bacterial meningitis is made by examination of the CSF (Table 133-2). The need to obtain neuroimaging studies (CT or MRI) prior to lumbar puncture (LP) requires clinical judgment. In an immunocompetent patient with no known history of recent head trauma, a normal level of consciousness, and no evidence of papilledema or focal neurologic deficits, it is considered safe to perform LP without prior neuroimaging studies. If LP is delayed in order to obtain neuroimaging studies, empirical antibiotic therapy should be initiated after blood cultures are obtained. Antibiotic therapy initiated a few hours prior to LP will not significantly alter the CSF WBC count or glucose concentration, nor is it likely to prevent visualization of organisms by Gram’s stain or detection of bacterial nucleic acid by polymerase chain reaction (PCR) assay.]

5. Fluid and electrolyte resuscitation must be administered to attain appropriate blood pressure and cerebral perfusion.

If the patient does not have hypovolemia or shock upon admission, there may be a role for modest fluid restriction until SIADH can be ruled out, especially if the serum sodium is less than 130 mEq/L (130 mmol/L). SIADH can cause hyponatremia and hypo-osmolality, which could lead to mental confusion, lethargy, seizures, and increased ICP. (20) If SIADH is suspected, serum and urine osmolalities should also be monitored. Fluid restriction can be gradually removed when the sodium concentration reaches 135 mEq/L (135 mmol/L), often within 24 to 48 hours after hospitalization.

The child’s weight, serum electrolytes, urine output, and urine specific gravity should be monitored closely in the first 24 to 36 hours of hospitalization.

Mild early signs of increased ICP can be managed by elevating the head of the bed. However, severe signs of increased ICP (apnea, bradycardia, hypertension, sluggish or dilated pupils) require more aggressive therapy with mannitol and hyperventilation.

Generalized seizures occur early in the disease course in 20% to 25% of meningitis cases and can usually be controlled with standard seizure medications, such as fosphenytoin or phenobarbital. Focal seizures, difficult-to-control seizures, or seizures occurring more than 48 hours after admission should prompt a neurology consultation.

If a subdural empyema develops, drainage is usually necessary. Subdural empyema can present as persistent fever, headache, and nuchal rigidity or new onset of neurologic features, such as seizures, in the setting of appropriate antibiotic treatment.

6. Lumbar Puncture

A CT scan of the head before LP should be performed in adult patients with suspected bacterial meningitis who have one or more of the following risk factors [1-3]:

●Immunocompromised state (eg, HIV infection, immunosuppressive therapy, solid organ or hematopoietic stem cell transplantation)

●History of central nervous system (CNS) disease (mass lesion, stroke, or focal infection)

●New onset seizure (within one week of presentation)

●Papilledema

●Abnormal level of consciousness

●Focal neurologic deficit

• clinical signs of impending herniation (ie, deteriorating level of consciousness, particularly a Glasgow coma scale <11; brainstem signs including pupillary changes, posturing, or irregular respirations; or a very recent seizure) may be predictive of patients in whom an LP should be delayed.

The major drawback to requiring a CT scan before LP is that initiation of antibiotics is often delayed. The bacterial meningitis guidelines in Sweden were revised in 2009 to remove impaired mental status as a contraindication to LP without prior CT scan, and the effect of this change was evaluated in a retrospective study using the Swedish quality registry [31]. After the change to the guidelines was implemented, adequate treatment was started 1.2 hours earlier, and more patients were treated within 2 hours of presentation; in addition, mortality was lower (7 versus 12 percent), and the risk of sequelae at follow-up was decreased (38 versus 49 percent) following the change to the guidelines. Those who underwent immediate LP without CT received antibiotics 1.6 hours earlier than those who underwent CT prior to LP. Treatment delay resulted in a significantly increased risk of fatal outcome, with a relative increase in mortality of 13 percent per hour of delay.

If LP is delayed or deferred, blood cultures should be obtained and antimicrobial therapy should be administered empirically before the imaging study, followed as soon as possible by the LP. In addition, dexamethasone (0.15 mg/kg intravenously [IV] every six hours) should be given shortly before or at the same time as the antimicrobial agents if the preponderance of clinical and laboratory evidence suggests bacterial meningitis with a plan to stop therapy, if indicated, when the evaluation is complete. Adjunctive dexamethasone should not be given to patients who have already received antimicrobial therapy because it is unlikely to improve patient outcome [29]. (See "Dexamethasone to prevent neurologic complications of bacterial meningitis in adults" and "Initial therapy and prognosis of bacterial meningitis in adults", section on 'Avoidance of delay'.)

Prior administration of antimicrobials tends to have minimal effects on the chemistry and cytology findings [24,32] but can reduce the yield of Gram stain and culture [23-25]. However, a pathogen can still be cultured from the CSF in most patients up to several hours after the administration of antimicrobial agents [24,25], with the possible exception of the meningococcus. This issue was addressed in a review of 128 children with bacterial meningitis in whom LP was first performed after initiation of therapy and serial LPs were obtained [25]. Among patients with meningococcal infection, CSF culture was negative in three of nine samples obtained within one hour. In contrast, 4 to 10 hours were required before CSF cultures were sterile in patients with pneumococcal meningitis.

Relative contraindications — Although there are no absolute contraindications to performing an LP, caution should be used in patients with evidence of raised intracranial pressure (eg, mass effect on CNS imaging or clinical signs of impending herniation), thrombocytopenia or another bleeding diathesis, or spinal epidural abscess.

Opening pressure — 

The opening pressure is typically elevated in patients with bacterial meningitis. (normal up to 200 mm H2O) [2].

The opening pressure is measured with the patient lying in the lateral decubitus position.

If the results of the CT reveal that LP is contraindicated, therapy for bacterial meningitis should be continued (if indicated) or

[ evaluation and treatment for an alternative diagnosis should be undertaken (ie, if the CT suggests a different cause for the patient's clinical presentation).]

In patients without any of the risk factors described above, blood cultures and LP may be performed without performing a head CT. Once CSF has been obtained (and before results are available), dexamethasone (if indicated) and empiric antimicrobial therapy should be initiated if bacterial meningitis is suspected.

In an immunocompetent patient with no known history of recent head trauma, a normal level of consciousness, and no evidence of papilledema or focal neurologic deficits, it is considered safe to perform LP without prior neuroimaging studies.

If LP is delayed in order to obtain neuroimaging studies, empirical antibiotic therapy should be initiated after blood cultures are obtained. Antibiotic therapy initiated a few hours prior to LP will not significantly alter the CSF WBC count or glucose concentration, nor is it likely to prevent visualization of organisms by

CSF should be sent for:

•Cell count and differential

•Glucose concentration

•Protein concentration

•Gram stain and bacterial culture

•Other appropriate tests, depending upon the level of concern for other etiologies of meningitis or meningoencephalitis

Characteristic findings in bacterial meningitis include a CSF glucose concentration <40 mg/dL, a CSF to serum glucose ratio of ≤0.4, a protein concentration >200 mg/dL, and a white blood cell count above 1000/microL, usually composed primarily of neutrophils.

 

However, the spectrum of CSF values in bacterial meningitis is so wide that the absence of one or more of these findings is of little value (table 1) [1-3]. This was illustrated in a review of 296 episodes of community-acquired bacterial meningitis: 50 percent had a CSF glucose above 40 mg/dL (2.2 mmol/L), 44 percent had a CSF protein below 200 mg/dL, and 13 percent had a CSF white cell count below 100/microL [3]. In another series of 696 episodes of community-acquired bacterial meningitis, 12 percent had none of the characteristic CSF findings [8]. (See "Clinical features and diagnosis of acute bacterial meningitis in adults", section on 'CSF analysis'.)

 

●The frequent absence of one or more of the expected CSF findings in patients with bacterial meningitis means that there is substantial overlap between bacterial meningitis, which is a life-threatening illness that requires hospital admission and urgent therapy, and viral meningitis, which is a less severe disease that is often monitored in the outpatient setting without antimicrobial therapy. Selected viruses that can cause meningitis are summarized in the Table (table 2). The diagnostic approach to aseptic meningitis is presented separately. (See "Aseptic meningitis in adults".)

 

●Before CSF results are available, it can be difficult to know whether the patient has bacterial or viral meningitis. The decision of which tests to perform on the CSF will depend on patient-specific factors, such as those described above (see 'History' above). In addition to suggesting specific diagnostic tests, we often send an extra tube of CSF if possible to the laboratory to be held for further studies, as the CSF profile and the patient's clinical course may warrant additional testing.

Gram’s stain or detection of bacterial nucleic acid by polymerase chain reaction (PCR) assay.

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TWO TYPES OF MENINGOCOCCAL MENINGITIS VACCINES FOR TEENS AND YOUNG ADULTS

Meningitis ACWY vaccines have been available since the 1980s, but Meningitis B vaccines have been available in the US only since late 2014.

The CDC recommends Meningitis B vaccination for persons 10 years and older in certain groups who are at increased risk for Meningitis B disease. In addition, the CDC says that Meningitis B vaccines may be administered to young adults who are 16–23 years old, but preferably to those who are 16–18 years old.

although vaccines may not result in protection in all recipients. Vaccination does not prevent viral meningitis.

In addition to vaccinating, you can take the following steps to help protect against meningococcal meningitis:

Practice good hygiene

Who's at risk?

Anyone can get meningococcal meningitis—however, certain people face a higher risk:

Infants younger than 1

16–23 year-olds

People with weakened immune systems

People without a spleen

Travelers to areas where meningococcal disease is more common

The mortality rate of untreated bacterial meningitis approaches 100 percent and, even with optimal therapy, morbidity and mortality may occur. Neurologic sequelae are common among survivors.

Despite the effectiveness of current antibiotics in clearing bacteria from the cerebrospinal fluid (CSF), bacterial meningitis continues to cause significant morbidity and mortality worldwide. In two large case series, for example, the case-fatality rate for adults with bacterial meningitis was approximately 25 percent, and transient or permanent neurologic morbidity occurred in 21 to 28 percent of survivors [2,3].

 Unfavorable neurologic outcomes are not the result of treatment with inappropriate antimicrobial agents, since cerebrospinal fluid cultures are sterile 24 to 48 hours after the start of antibiotic therapy.3 Studies in animals have shown that bacterial lysis, induced by treatment with antibiotics, leads to inflammation in the subarachnoid space, which may contribute to an unfavorable outcome.4,5 These studies also show that adjuvant treatment with antiinflammatory agents, such as dexamethasone, reduces both cerebrospinal fluid inflammation and neurologic sequelae.4,5

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