Meningitis: A Clinical Guide
Definition
Meningitis is an inflammation of the leptomeninges—the arachnoid and pia mater—and the cerebrospinal fluid (CSF) within the subarachnoid space that envelops the brain and spinal cord (1). This inflammatory process, most commonly triggered by infection, results in a characteristic clinical syndrome of headache, fever, and meningismus, alongside a diagnostic inflammatory cellular response in the CSF (1). It is crucial to differentiate meningitis from encephalitis, which is inflammation of the brain parenchyma itself, although the two can coexist in a condition termed meningoencephalitis. Acute bacterial meningitis, a purulent infection of the subarachnoid space, is a profound medical emergency. It demands immediate diagnosis and aggressive treatment to prevent devastating rates of morbidity and mortality, which can approach 25% even in the modern era (2).
Epidemiology
In Malaysia, the epidemiology of bacterial meningitis was profoundly reshaped by the introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine into the National Immunisation Programme in 2002 (3). This successful public health measure has drastically reduced the incidence of Hib meningitis, once a primary cause of childhood meningitis. Consequently, Streptococcus pneumoniae has emerged as a leading cause of bacterial meningitis across all age groups in the country, followed by Neisseria meningitidis (3, 4). While national surveillance data for invasive meningococcal disease (IMD) in Malaysia is limited, it is estimated to be responsible for 3.5–13.0% of meningitis cases, with serogroups W, B, Y, and A being reported (5, 6). Specific populations in Malaysia are at higher risk; this includes military recruits living in close quarters and pilgrims traveling for the Hajj/Umrah, for whom quadrivalent meningococcal vaccination is a key preventative strategy (5).
Globally, meningitis remains a significant public health threat. In 2019 alone, it caused an estimated 2.5 million incident cases and 236,000 deaths worldwide, with the highest burden concentrated in children under five years old, particularly in the "meningitis belt" of sub-Saharan Africa (7). This region has historically suffered from large-scale epidemics of meningococcal disease, though the landscape is shifting due to vaccination campaigns like the MenAfriVac® initiative, which has successfully eliminated serogroup A epidemics but has seen the emergence of other serotypes like C, W, and X (7).
Pathophysiology
The development of meningitis is a multi-step process involving a complex interplay between pathogen virulence and the host's immune response. The pathway typically begins with microbial colonization of the host's nasopharynx by encapsulated bacteria such as S. pneumoniae or N. meningitidis (1). For disease to occur, the pathogen must breach the mucosal epithelium, invade the submucosa, and gain access to the bloodstream, leading to high-grade bacteremia. The bacterial polysaccharide capsule is a critical virulence factor at this stage, acting as a shield to help the organism evade host immune defenses like phagocytosis and complement-mediated killing, allowing it to survive and replicate in the blood (8).
Once a sufficient bacteremia is established, the pathogen must cross the blood-brain barrier (BBB) to enter the subarachnoid space (1). This can occur via hematogenous seeding, direct contiguous spread from an adjacent infection (e.g., sinusitis, otitis media), or direct inoculation from trauma or neurosurgery (1).
Inside the relatively immune-privileged CSF, bacteria proliferate rapidly. The release of potent inflammatory triggers—Pathogen-Associated Molecular Patterns (PAMPs) like lipopolysaccharide (LPS) from gram-negative organisms and teichoic acid from gram-positive organisms—is the key event that ignites the host response (8). These molecules are recognized by host receptors (e.g., Toll-like receptors) on microglia and astrocytes, unleashing a massive inflammatory cascade. This "cytokine storm," driven by TNF-α and IL-1, has two devastating consequences: it dramatically increases the permeability of the BBB and it promotes the massive recruitment of neutrophils into the CSF (1, 8).
This cascade directly causes the life-threatening complications of meningitis. The increased BBB permeability leads to vasogenic edema, as protein-rich fluid leaks from capillaries into the brain's extracellular space. Toxins released by bacteria and neutrophils cause direct cellular injury, leading to cytotoxic edema. Finally, the thick, purulent inflammatory exudate can obstruct the normal CSF outflow pathways at the arachnoid villi, causing interstitial edema (8). This triad of edema rapidly increases intracranial pressure (ICP), which in turn reduces cerebral perfusion pressure (CPP = MAP - ICP), leading to global cerebral ischemia. Furthermore, the inflammation can spread to the walls of blood vessels, causing a vasculitis that can lead to thrombosis and focal ischemic stroke, a major contributor to long-term neurological deficits (8).
Clinical Presentation
The classic presentation of meningitis involves a triad of fever, headache, and nuchal rigidity. However, it is a critical clinical lesson that only about 44% of adults with bacterial meningitis present with all three signs simultaneously (9). Relying on the full triad will lead to a missed diagnosis in the majority of cases. A much more sensitive clinical rule is that over 95% of patients will have at least two of the following four features: fever, headache, neck stiffness, and altered mental status (10). The presence of any two should immediately raise suspicion and trigger further workup.
Diagnostic Clues: The presence of a non-blanching petechial or purpuric rash, which does not fade under pressure from a glass tumbler, is a critical red flag for meningococcemia and constitutes a medical emergency requiring immediate antibiotic administration (2). The classic signs of meningeal irritation, Kernig's and Brudzinski's signs, are highly specific (>95%) but have very low sensitivity (~5%). A positive sign is a strong pointer towards meningitis, but their absence is not reassuring and cannot be used to rule out the diagnosis (10).
Common Symptoms:
Headache: Typically described as severe, generalized, throbbing, and unrelenting (~87%) (9).
Fever: A core sign of infection (>38°C), present in ~77% of adults, but may be absent in neonates, the elderly, or the immunocompromised (9).
Nuchal rigidity: Resistance to passive neck flexion is a key sign of meningeal irritation (~83%) (9).
Nausea and Vomiting: Very common (~74%), often associated with headache and raised ICP (9).
Photophobia and Phonophobia: Heightened sensitivity to light and sound are common (1).
⚠️ Red Flag Signs & Symptoms:
Altered mental status: This is an ominous sign indicating more severe disease with cerebral involvement. It ranges from irritability and confusion to delirium, stupor, and coma (~69%) (9).
New-onset seizures: Occurring in 5-30% of patients, seizures are a direct manifestation of cortical irritation and are an independent predictor of mortality and poor neurological outcome (1).
Focal neurological deficits: These include cranial nerve palsies (especially of nerves III, IV, VI, VII), hemiparesis, or aphasia, and strongly suggest a vascular complication like a stroke or direct parenchymal inflammation (meningoencephalitis) (1).
Signs of shock: Hypotension, tachycardia, and poor peripheral perfusion indicate systemic sepsis and are associated with a very poor prognosis.
Complications
Survivors of bacterial meningitis are often left with significant long-term sequelae resulting from the initial inflammatory insult.
Neurological: Acute complications include seizures, cerebral edema leading to brain herniation, and hydrocephalus, which can be either communicating (due to impaired CSF absorption at the arachnoid villi) or obstructive (due to blockage of CSF pathways by exudate). Vascular complications such as arterial or venous sinus thrombosis can lead to permanent stroke. The collection of pus in the subdural space can form a subdural empyema, a neurosurgical emergency (1). Cranial nerve palsies are also common.
Systemic: The systemic inflammatory response can lead to septic shock with multi-organ failure. Disseminated intravascular coagulation (DIC), particularly in meningococcemia, can cause widespread thrombosis and hemorrhage, leading to limb loss. The syndrome of inappropriate antidiuretic hormone (SIADH) is a common metabolic complication that causes hyponatremia and can worsen cerebral edema (2).
Long-term Sequelae: Sensorineural hearing loss is the single most common long-term complication, resulting from direct inflammatory or ischemic damage to the cochlea or auditory nerve. Other major sequelae include epilepsy, significant cognitive impairment (affecting memory, executive function, and processing speed), and persistent focal motor deficits (2).
Prognosis
Despite advances in critical care and antimicrobial therapy, bacterial meningitis remains a devastating disease. The overall mortality rate approaches 25% in some series (1). Among survivors, as many as one in five will experience severe, permanent complications such as deafness, epilepsy, or cognitive deficits (7). Key factors associated with a poor prognosis include delay in diagnosis and treatment, presentation with a low Glasgow Coma Scale (GCS) score, the presence of shock or seizures, a high bacterial load in the CSF, and infection with Streptococcus pneumoniae, which typically elicits a more robust and damaging inflammatory response (1).
Differential Diagnosis
Viral Encephalitis: This is a critical differential, especially when altered mental status is a prominent feature. Encephalitis involves direct inflammation of the brain parenchyma. Its presence is suggested by significant confusion, bizarre behavior, personality changes, or focal neurological signs from the outset. While meningitis and encephalitis can co-exist (meningoencephalitis), a primary presentation of cortical dysfunction points more towards encephalitis, often caused by viruses like Herpes Simplex Virus (HSV), which requires urgent treatment with acyclovir (1).
Subarachnoid Hemorrhage (SAH): SAH can perfectly mimic the symptoms of meningitis, presenting with a sudden, severe "thunderclap" headache, neck stiffness, and photophobia. The key distinguishing feature is the absence of fever at the onset. A non-contrast CT head is the first-line investigation to identify blood. If the CT is negative but suspicion remains high, a lumbar puncture will show a high red cell count and xanthochromia (a yellow tinge to the CSF from bilirubin breakdown), which is diagnostic (10).
Cerebral Abscess: This typically presents more insidiously with headache, fever, and focal neurological deficits that evolve over days to weeks. The headache is often localized and progressively worsens. Neuroimaging (CT with contrast or MRI) is diagnostic, revealing a characteristic ring-enhancing lesion, which clearly distinguishes it from the diffuse meningeal inflammation seen in meningitis (1).
Tuberculous (TB) Meningitis: In the Malaysian context, TB meningitis is a vital differential that must always be considered. It typically presents subacutely over weeks with a prodrome of low-grade fever, headache, malaise, night sweats, and personality changes. Cranial nerve palsies, especially of the 6th nerve, are common. A history of TB contact or immunosuppression is a major clue. The CSF picture is one of lymphocytic pleocytosis with very high protein and very low glucose, providing a strong clue against typical acute bacterial meningitis (2).
Investigations
The diagnostic pathway is a medical emergency and must not delay the initiation of empirical treatment. The mantra is "treat first, investigate safely."
Immediate & Bedside Tests
Blood Cultures: This is mandatory and must be drawn immediately from two different sites, before the first antibiotic dose is administered. It provides the only chance to isolate a pathogen if the CSF culture is negative (e.g., due to prior antibiotic treatment) and is positive in up to 66% of bacterial meningitis cases (2).
Serum Glucose: A contemporaneous blood glucose is essential to calculate the CSF:serum glucose ratio, a critical parameter for differentiating bacterial from viral meningitis (2).
Diagnostic Workup
First-Line Investigation (Lumbar Puncture): A lumbar puncture (LP) for CSF analysis is the definitive investigation to confirm meningitis (2). However, it must be deferred and a CT head performed first in any patient with clinical features suggesting a high risk of cerebral herniation. These features are: an immunocompromised state, a history of prior CNS disease (e.g., tumor, stroke), a new-onset seizure (within one week of presentation), papilledema on fundoscopy, an altered level of consciousness (specifically a GCS < 11), or any focal neurological deficit (10). In these high-risk patients, the sequence is critical: 1) Obtain blood cultures, 2) Administer empirical antibiotics and dexamethasone, 3) Perform the CT scan, and 4) If the CT is clear of contraindications, proceed with the LP.
CSF Analysis:
Opening Pressure: Measured with the patient in the lateral decubitus position. It is typically elevated (>200 mmH₂O) in bacterial, tuberculous, and fungal meningitis due to cerebral edema and provides an immediate clue of raised ICP (10).
Appearance: Normal CSF is crystal clear and colorless. In bacterial meningitis, it may appear turbid, cloudy, or even frankly purulent due to the high concentration of white blood cells (2).
Biochemistry: A CSF:serum glucose ratio <0.4 and a protein level >1.0 g/L are highly suggestive of a bacterial cause. This is because bacteria and the host's inflammatory cells avidly consume glucose, while the inflamed meninges allow protein to leak from the blood into the CSF (10).
Cell Count: A markedly elevated white cell count (typically >1000 cells/µL) with a strong predominance of neutrophils (>80%) is the hallmark of bacterial infection (10).
Gram Stain: This is a crucial rapid microscopy test performed on the centrifuged CSF sediment. Identifying the organism's morphology (e.g., gram-positive diplococci suggesting S. pneumoniae, or gram-negative diplococci suggesting N. meningitidis) allows for early, more targeted therapy while awaiting definitive culture results (2).
Gold Standard:
CSF Culture: This remains the gold standard test. It definitively identifies the bacterial pathogen and, most critically, allows for antimicrobial susceptibility testing (AST) to guide tailored, narrow-spectrum therapy (2).
Monitoring & Staging
Inflammatory Markers: A Full Blood Count (FBC) often shows a neutrophilic leukocytosis, and elevated C-Reactive Protein (CRP) or procalcitonin can further support the suspicion of a bacterial cause. However, a normal result for any of these tests does not exclude the diagnosis and should not provide false reassurance (2).
Renal Profile & Electrolytes: These are essential to monitor for complications like SIADH (which causes hyponatremia) and to ensure renal function is adequate for correct antibiotic dosing and to monitor for nephrotoxicity (2).
Management
Management Principles
The modern management of bacterial meningitis is centered on three synergistic goals: immediate eradication of the pathogen with appropriate antibiotics, aggressive modulation of the host's harmful inflammatory response, and intensive supportive care to prevent secondary brain injury and manage complications (2).
Acute Stabilisation (The First Hour)
This follows the ABCDE approach.
Airway/Breathing: Administer high-flow oxygen via a non-rebreather mask to maintain SpO2 >94% (the action), which is crucial to prevent tissue hypoxia that exacerbates neuronal injury (the rationale). Have a low threshold for intubation in patients with a low or declining GCS (<8) to protect the airway.
Circulation: Secure at least one, preferably two, large-bore IV cannulas. If there are any signs of shock (hypotension, tachycardia, prolonged capillary refill), administer a rapid fluid bolus of isotonic crystalloid (e.g., Normal Saline) (the action) to restore organ perfusion and, most importantly, cerebral perfusion pressure (the rationale) (2).
Disability: Perform a rapid neurological assessment, including GCS and pupillary response. If GCS is <8, this is an indication for urgent anaesthetic review for airway protection.
Definitive Therapy
This is guided by the Malaysian National Antimicrobial Guideline (2). Time is critical; treatment must not be delayed pending LP or CT. The goal is a "door-to-needle" time of under 60 minutes.
First-Line Empirical Treatment (Adults >50 years or with risk factors for Listeria e.g., alcoholism, pregnancy, immunocompromise):
IV Ceftriaxone 2g q12h + IV Ampicillin 2g q4h (2). This combination provides broad coverage for the most common pathogens (S. pneumoniae, N. meningitidis) while the ampicillin adds crucial coverage for Listeria monocytogenes, which has an increased incidence in this age group and for which cephalosporins are ineffective (the rationale).
First-Line Empirical Treatment (Adults <50 years):
IV Ceftriaxone 2g q12h (2). Vancomycin may be added depending on local pneumococcal resistance patterns, but ceftriaxone provides excellent initial coverage for the most likely pathogens (S. pneumoniae, N. meningitidis) in this group (the rationale).
Adjunctive Dexamethasone:
IV Dexamethasone 10mg q6h for 4 days is strongly recommended, particularly in suspected pneumococcal meningitis (2). It is critical that it is given 15-20 minutes before or, at the very latest, concurrently with the first dose of antibiotics. The purpose is to preemptively blunt the massive inflammatory response triggered by bacterial lysis from antibiotics (the rationale). This reduces vasogenic edema, protects the BBB, and has been proven to decrease mortality and neurological sequelae like deafness (the action) (2, 8).
Supportive & Symptomatic Care
Analgesia: Provide adequate pain relief for severe headache, often requiring opioids.
Antiemetics: Aggressively control nausea and vomiting to prevent dehydration and aspiration.
Antipyretics: Administer paracetamol regularly to control fever, as hyperthermia increases cerebral metabolic demand and can worsen outcomes (2).
Seizure management: Treat seizures promptly and aggressively with IV benzodiazepines (e.g., diazepam/lorazepam). Consider loading with an anti-epileptic drug like phenytoin or levetiracetam for seizure prophylaxis, especially in patients with a low GCS or focal brain lesions (1).
Fluid Management: Maintain euvolemia carefully. Avoid both dehydration (which compromises cerebral perfusion) and fluid overload (which can worsen cerebral edema). Monitor for SIADH.
Key Nursing & Monitoring Instructions
Strict hourly neurological observations (GCS, pupil size and reactivity, focal limb power).
Continuous cardiorespiratory monitoring (HR, BP, RR, SpO2, Temperature).
Strict input/output charting to closely monitor fluid balance.
Maintain head of bed elevation at 30 degrees to promote cerebral venous outflow and help lower ICP.
Inform medical staff immediately if GCS drops by 2 points, a new focal deficit develops, pupils become unequal or unreactive, systolic BP drops below 100 mmHg, or urine output is <0.5mL/kg/hr.
Long-Term Plan & Patient Education
All patients who recover from bacterial meningitis require multidisciplinary follow-up. A formal audiology assessment should be scheduled 6-8 weeks after discharge to screen for sensorineural hearing loss, the most common sequela (11). Patients and their families should be educated on the signs of complications and the importance of completing any further prescribed therapies. For those with neurological deficits, early referral to a rehabilitation physician is crucial to coordinate physiotherapy, occupational therapy, and speech therapy to maximize functional recovery.
When to Escalate
A house officer must recognize the signs of a deteriorating patient and escalate care to a senior (Medical Officer or Specialist) in a timely and effective manner.
Call Your Senior (MO/Specialist) if:
The patient's GCS drops by 2 points or more, or if they develop any new signs of brainstem dysfunction (e.g., abnormal posturing, changes in respiratory pattern).
The patient develops any new focal neurological sign (e.g., limb weakness, cranial nerve palsy).
A seizure occurs, especially if it is prolonged or recurrent (status epilepticus).
The patient remains in shock requiring ongoing fluid resuscitation or needs vasopressor support.
There is any concern about the diagnosis, or the patient is not showing signs of clinical improvement after 24-48 hours of appropriate treatment.
Referral Criteria:
Refer to the Infectious Diseases (ID) team for all confirmed cases of bacterial meningitis, for guidance on tailoring therapy, managing complex cases or atypical organisms, and for advice on treatment failure.
Refer to the Neurosurgery team urgently if neuroimaging reveals a complication requiring intervention, such as significant hydrocephalus, a cerebral abscess, or a subdural empyema.
Refer to the Rehabilitation Medicine team prior to discharge for all survivors with new neurological deficits to plan for comprehensive long-term rehabilitation.
References
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Ministry of Health Malaysia. (2017). National Antimicrobial Guideline. https://sites.google.com/moh.gov.my/nag/contents/section-a-adult/a2-central-nervous-infections
Nathan, A. M., & Tee, H. P. (2015). Vaccine preventable meningitis in Malaysia: Epidemiology and management. Human Vaccines & Immunotherapeutics, 11(11), 2737–2743. https://www.researchgate.net/publication/276146702_Vaccine_preventable_meningitis_in_Malaysia_Epidemiology_and_management
Ismail, R., Toh, T. S. M., & Ariffin, F. (2020). Incidence of pneumococcal meningitis in children less than 5 years age in Malaysia, Singapore and Thailand: Review. International Journal of Pediatrics and Adolescent Medicine, 7(3), 121-125. https://www.researchgate.net/publication/275020005_Incidence_of_pneumococcal_meningitis_in_children_less_than_5_years_age_in_Malaysia_Singapore_and_Thailand_Review
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Hoffman, O., & Weber, J. R. (2009). Pathophysiology and treatment of bacterial meningitis. Therapeutic advances in neurological disorders, 2(6), 1–7. https://pmc.ncbi.nlm.nih.gov/articles/PMC3002609/
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