Bacterial Meningitis

Etiology

Bacterial meningitis is caused by a bacterial infection of the meninges, resulting in inflammation. The infection is either community-acquired or nosocomial. Community-acquired bacterial meningitis is the result of the invasion of the bacteria into the meninges from bacteremia or direct extension from local infection. The most common bacterial culprit varies by age. Group B Streptococcus is common in infants less than 2 months of age while Streptococcus pneumoniae is the most common in all other age groups, with the exception of 11 - 17 year old, where Neisseria meningitidis is still the most common cause.  

Listeria monocytogenes and gram-negative bacteria such as Escherichia coli, Klebsiella, Enterobacter, Pseudomonas aeruginosa are other less common causes. Hemophilus influenzae is still occasionally encountered in nonvaccinated individuals. Nosocomial infections are caused by S. pneumonia, Staphylococcus aureus, Staphylococcus albus, and gram-negative bacilli. As per Thigpen etal. out of the 1670 cases reported in the U.S. during 2003–2007, S. pneumoniae was the predominant infective species (58.0%), followed by GBS (18.1%), N. meningitidis (13.9%), H. influenzae (6.7%), and L. monocytogenes (3.4%).[4] Infectious meningitis may also be caused by viruses, fungi, and protozoa. Meningitis may also be non-infectious in etiology and can be caused by cancer, medications, or inflammatory conditions.[5][6]

Epidemiology

Bacterial meningitis was previously more common in pediatric patients. However, as vaccines are developed and utilized, the prevalence of acute bacterial meningitis has decreased and the epidemiology of causative microorganisms has changed. Vaccinations have increased the median age of patients infected. In 2006 there were 72,000 meningitis-related hospitalizations in the United States. The majority of these cases were due to viral infection (54.6%). Bacterial infections accounted for 21.8% of cases, and 7.3% were due to fungi and parasite infections, while 17.2% were due to an unspecified cause. There was an 8% in-hospital mortality rate for patients with bacterial meningitis, and it rose substantially for patients older than 45. [7][8][9] The annual incidence of meningitis in the United States decreased from 2.00 cases per 100,000 population in 1998–1999 to 1.38 cases per 100,000 population in 2006–2007 while the median age of patients increased from 30.3 years in 1998–1999 to 41.9 years in 2006–2007.[4] As per CDC data, rates of meningococcal disease have been declining in the United States since the late 1990s. In 2017, there were about 350 total cases of meningococcal disease reported (incidence rate of 0.11 cases per 100,000 persons).

Several possible risk factors for bacterial meningitis have been identified. Patients with an abnormal communication between the nasopharynx and subarachnoid space are thought to be at increased risk. This abnormal communication can be due to a congenital abnormality or a result of trauma. Patients who have undergone neurosurgery, sustained skull fractures, or have cochlear implants are also at increased risk. Other at-risk patient populations are the immunosuppressed and people that live in close personal contact with others in places like college dorms or military barracks.

Pathophysiology

Bacteria require access to the meninges to cause meningitis. There are several mechanisms for entry. Bacteremia, or bacteria in the blood, can result in bacteria crossing the blood-brain barrier. This can only be accomplished by certain bacteria, most notably N. meningitidis and S. pneumoniae. Direct extension of otitis media or sinusitis to the central nervous system (CNS) may also occur. Dural defects, either congenital or acquired, allow bacteria to enter the CNS. Nosocomial bacterial meningitis is the result of the manipulation of the meninges during neurosurgical procedures. Invasion of bacteria into the subarachnoid space results in inflammation of the meninges.

Although several factors may be involved, lipopolysaccharide in the walls of gram-negative organisms and techoic acid in the walls of gram-positive microorganisms activate brain microglia, leading to a cascade of inflammatory changes that causes cortical microvascular permeability with diffuse cerebral edema, resulting in increased intracranial pressure. This causes the patient to experience headaches and fevers. Blood-brain barrier breakdown occurs secondary to the infection and inflammatory response. Altered mental status, seizures, and focal neurologic deficits occur due to decreased perfusion and increased intracranial pressure. 

History and Physical

Fever, neck stiffness, and altered mental status are the classic triad of symptoms for meningitis; however, all three are only present in 41% of cases of bacterial meningitis. The triad is most commonly seen in elderly patients. Seventy percent of patients will present with at least one of these symptoms. Common early symptoms of the disease include fever, headache, and confusion which can progress to obtundation, focal neuro deficits, and seizures. History should include questioning about any recent neurosurgical procedures, immunization status, and living arrangements. A physical exam may reveal nuchal rigidity or positive Kernig's or Brudzinski's signs. However, the absence of these does not reliably rule out the disease. Brudzinski's sign occurs when passive flexion of the neck causes involuntary flexion of the knee. Kernig's sign is resistance or pain with knee extension when the patient is supine, and their hip is flexed to 90 degrees. These signs are thought to be secondary to meningeal irritation. The fundoscopic exam may reveal papilledema due to increased intracranial pressure. A rapidly spreading petechial rash, known as purpura fulminans, would suggest a Meningococcal infection.

Evaluation

Patients presumed to have bacterial meningitis should receive a lumbar puncture to obtain a cerebrospinal fluid (CSF) sample. The CSF should be sent for Gram stain, culture, complete cell count (CBC), and glucose and protein levels. Bacterial meningitis typically results in low glucose and high protein levels in the cerebrospinal fluid. As CSF glucose levels are dependent on circulating serum glucose levels, the CSF to serum glucose ratio is considered more reliable parameter for the diagnosis of acute bacterial meningitis than absolute CSF glucose levels. A neutrophil predominance on cell count would be expected. 

The diagnosis would be confirmed with bacteria identified on gram stain or culture. A non-contrast CT scan of the head should be performed before lumbar puncture if the patient has a risk of herniation. Risk factors include papilledema on the exam, new onset seizures, focal neurologic deficits, or is immunocompromised. Consider delaying the lumbar puncture if the patient has unstable vital signs, coagulation abnormalities, or has had a recent seizure. Treat with antibiotics empirically if testing is going to be delayed. Blood cultures should be obtained as 53% of patients have concurrent bacteremia. Elevated C-reactive protein or procalcitonin levels would suggest a bacterial rather than viral etiology.[10][11][12]

Treatment / Management

Timely administration of antibiotics is essential. Delays in the administration of 3 to 6 hours are associated with increased mortality. The identified bacteria determine antibiotic selection. Empiric treatment with ceftriaxone and vancomycin should strongly be considered if the diagnosis is going to be delayed. Patients who are immunocompromised or older than 50 should also receive ampicillin. Patients with bacterial meningitis due to head trauma or post-neurosurgical procedure need to be covered for methicillin resistant Staphylococcus aureus and aerobic gram-negative organisms. They should receive vancomycin and ceftazidime or cefepime. Acyclovir can also be administered for HSV coverage. Antibiotics can then be narrowed once the culture and sensitivities have resulted. Dexamethasone may increase survival if given at the time of antibiotic administration for S. pneumoniae infections. It has not been shown to improve outcomes for meningitis caused by other bacteria. Patients suspected of having meningococcal meningitis should be placed in droplet precautions until they have received 24 hours of antibiotics. Close contacts should also be treated prophylactically. Ciprofloxacin, rifampin, or ceftriaxone may be used. Close contacts are defined as people within 3 feet of the patient for more than 8 hours during the seven days before and 24 hours after receiving antibiotics. People exposed to the patient's oral secretions during this time should also be treated.[13][14][15]

Differential Diagnosis

• All causes of altered mental status and coma

• Brain Abscess

• Brain Neoplasms

• Central nervous system (CNS) vasculitis

• Delirium Tremens (DTs)

• Emergent Management of Subarachnoid Hemorrhage

• Encephalitis

• Herpes Simplex Virus (HSV) in Emergency Medicine

• Leptospirosis

• Meningeal carcinomatosis

• Noninfectious meningitis, including medication-induced meningeal inflammation

• Pediatrics, Meningitis and Encephalitis

• Stroke

• Subdural empyema

Prognosis

The mortality for bacterial meningitis varies from 10-15%. Survival depends on early recognition of acute bacterial meningitis, followed by administration of appropriate antibiotic therapy. Delay in treatment can result in increased intracranial pressure causing decreased cerebral perfusion and may rapidly lead to loss of consciousness and death.

Complications

It is estimated that 25% of people with meningococcal disease, will have complications. Complications are not uncommon in other causes of bacterial meningitis. Severity can vary from person to person, and they can be temporary or permanent. Delayed therapy can result in vascular inflammation with cerebral infarction. Other long-term complications include 

• seizures
• problems with memory and concentration
• problems with movement, balance and co-ordination 
• learning difficulties 
• speech problems
• vision loss
• hearing loss