Bacterial Meningitis & Acute Meningoencephalitis

Meet the patient

A 19-year-old university student is brought to casualty at 2am with fever, a thunderous headache, and a neck that will not flex. He is photophobic, vomiting, and increasingly confused. As you examine him you notice a handful of petechial spots on his ankles that do not fade under the glass.[1]

Two questions now run his next hour, and they run every meningitis case: which antibiotic goes in now, before any test? and does he need a CT before the lumbar puncture, or do you tap first? The petechial rash has already made the first decision for you — the clock is running, and the antibiotic is late the moment you hesitate.[1][2]

Overview & Definition

Meningitis is inflammation of the meninges — the membranes (dura mater, arachnoid mater, pia mater) that surround the brain and spinal cord — most often due to infection of the subarachnoid space and the cerebrospinal fluid (CSF) within it.[1]

The clinical skill in suspected meningitis is not the diagnosis (it is clinical, then confirmed by LP) but three time-critical decisions taken in parallel:[1]

1. Recognise the syndrome — fever with headache and neck stiffness (plus photophobia, vomiting, altered mentation, or a petechial rash) is bacterial meningitis (or meningococcal septicaemia) until proven otherwise.
2. Give empirical IV antibiotics immediately on suspicion — before lumbar puncture, before blood cultures, before CT. Every hour of delay increases mortality and neurological disability.[1][2]
3. Decide whether CT is needed before LP — and add adjunctive dexamethasone, Listeria cover (ampicillin), and HSV cover (aciclovir) where appropriate.

Meningitis vs encephalitis vs meningoencephalitis vs aseptic meningitis

• Meningitis — inflammation predominantly of the meninges; brain parenchyma spared. Classic fever + headache + neck stiffness; cognition usually preserved until late.
• Encephalitis — inflammation predominantly of the brain parenchyma; diffuse brain dysfunction dominates (confusion, behaviour change, seizures, focal deficits, coma). Herpes simplex encephalitis is the treatable archetype (temporal lobe changes on MRI/EEG).
• Meningoencephalitis — both meninges and parenchyma inflamed; a combined clinical picture (meningeal signs PLUS encephalopathy). Common with HSV, enterovirus, arboviruses (Japanese encephalitis, West Nile), tuberculous and fungal disease.
• Aseptic meningitis — CSF pleocytosis with negative routine bacterial cultures; the commonest cause is viral (enterovirus, HSV-2, mumps), but the term also encompasses TB, fungal, drug-induced (NSAIDs, trimethoprim, IVIG), and autoimmune causes. "Aseptic" does not mean benign — always exclude the treatable bacterial and viral causes first.[1]

The depth standard for this chapter is the community-acquired acute bacterial meningitis of adults and children, with subtypes (viral, tuberculous, fungal, neonatal, post-neurosurgical) covered in Specific Subtypes.[1]

Classification

Meningitis is classified along three axes that the examiner will probe — aetiology, host, and tempo — because each changes the organism, the CSF picture, and the empirical antibiotic choice.[1]

By aetiology (the axis that drives treatment):[1]

By host / setting:[1]

• Community-acquired — the archetype; organisms dictated by age and vaccination history.
• Post-neurosurgical / CSF-shunt / external ventricular drain — Staphylococcus aureus, coagulase-negative staphylococci, Gram-negative bacilli (including Pseudomonas), and Propionibacterium acnes; empirical therapy is vancomycin + ceftazidime or cefepime (anti-pseudomonal), and infected hardware must be removed or externalised.[1]
• Recurrent meningitis — suspect a CSF leak (cribriform plate, skull-base fracture), complement / properdin deficiency or eculizumab (recurrent meningococcal), anatomical defect (dermal sinus, midline cleft), or Mollaret meningitis (recurrent HSV-2).

By tempo:[1]

• Acute (hours-days) — bacterial, viral, early HSV encephalitis.
• Subacute-chronic (days-weeks) — tuberculous, fungal, carcinomatous, partially-treated bacterial.[1]

Epidemiology & Risk Factors

Bacterial meningitis is uncommon but uniformly life-threatening — contemporary adult series report mortality of about 19% for community-acquired and 23% for hospital-acquired episodes, with permanent neurological sequelae in a further proportion of survivors.[21] The epidemiology has been transformed by conjugate vaccination (Hib, pneumococcal PCV, meningococcal MenACWY/MenB), which is now the single most powerful public-health lever.[13]

Organisms by age — the question most often asked in MCQs:[1]

Risk factors and the organism they favour (high-yield):[1]

Meningococcal epidemiology — peaks at two ages: infants (declining maternal antibody) and adolescents/young adults (colonisation, dormitory/college residence, military barracks). Epidemics occur in the sub-Saharan African "meningitis belt" and during mass gatherings (Hajj). Serogroups B, C, W, Y predominate in high-income countries; serogroup A historically drove the African belt and is now curtailed by MenAfriVac.[1]

Pathophysiology

The pathogenesis of bacterial meningitis is a five-stage cascade from nasopharyngeal colonisation to neuronal injury. Understanding it explains why dexamethasone works, why the CSF glucose falls, and why hearing is lost.[1]

Stage 1 — Mucosal colonisation and invasion. S. pneumoniae and N. meningitidis colonise the nasopharynx (meningococcal carriage is common and usually asymptomatic). Meningococcal pili and IgA1 protease, and the pneumococcal polysaccharide capsule and pneumolysin, allow the organism to evade mucosal defences and invade the epithelium.[1]

Stage 2 — Bacteraemia and crossing the blood-brain barrier. The organism enters the bloodstream (bacteraemia — the cause of the petechial rash and septicaemia in meningococcal disease) and reaches the choroid plexus and cerebral capillaries. It crosses the blood-brain barrier by transcytosis across endothelial cells, by surviving within phagocytes ("Trojan horse", especially Listeria and Mycobacterium tuberculosis), or by direct invasion of the choroid plexus epithelium. Less commonly the organism reaches the CSF by contiguous spread (otitis, mastoiditis, sinusitis), by traumatic breach (skull-base fracture, CSF leak), or iatrogenically (neurosurgery, CSF shunt).[1]

Stage 3 — Multiplication in the CSF. The subarachnoid space is a uniquely permissive site for bacterial growth: it contains low complement, low immunoglobulin, and few phagocytes, with slow opsonisation and turnover. Bacteria multiply rapidly, fuelled by their capsule (resists non-immune phagocytosis) and by available nutrients.[1]

Stage 4 — The inflammatory cascade (the key to the whole clinical picture). Bacterial cell-wall components — pneumococcal peptidoglycan/teichoic acid and meningococcal endotoxin (lipopolysaccharide) — activate complement and toll-like receptors (TLR2, TLR4) on meningeal macrophages and endothelial cells, releasing a cytokine storm (IL-1 beta, TNF-alpha, IL-6, CXCL8/IL-8). This recruits a massive neutrophil influx into the CSF (causing the cloudy, purulent fluid and the neutrophilic pleocytosis). Neutrophils and cytokines together:[1]

• Increase blood-brain barrier permeability → vasogenic oedema (protein leaks into CSF → the high CSF protein).
• Damage the glucose transporter (GLUT-1) and increase glucose consumption by neutrophils and bacteria → low CSF glucose.
• Induce vasospasm and vasculitis of the subarachnoid vessels → cerebral ischaemia and infarction (the cause of strokes and cranial-nerve palsies).
• Impair CSF resorption at the arachnoid granulations (blocked by inflammatory debris) → communicating hydrocephalus and raised intracranial pressure.[1]

Stage 5 — Raised intracranial pressure and neuronal injury. The combination of vasogenic + cytotoxic oedema, hydrocephalus, and impaired autoregulation raises intracranial pressure; combined with vasculitic ischaemia and direct bacterial toxicity, this produces neuronal injury — seizures, focal deficits, decreased conscious level and, if unchecked, transtentorial herniation and death. The cochlea is uniquely vulnerable (its aqueduct allows direct bacterial and inflammatory ingress), which is why sensorineural hearing loss is the commonest long-term complication.[1]

Why dexamethasone works — when bacteria are killed by antibiotics, cell-wall fragments are released in large quantities, amplifying the inflammatory cascade (the Jarisch-Herxheimer-like worsening). Dexamethasone, given with or just before the first antibiotic dose, down-regulates the cytokine/chemokine response, reduces BBB disruption, oedema and neuronal injury, and specifically reduces sensorineural hearing loss in pneumococcal meningitis — hence the timing rule (with/before the first dose).[3]

[1]

Clinical Presentation

The classic adult triad — fever + neck stiffness + altered mental status — is fully present in only about two-thirds of patients, but almost all have at least two of the three; a patient with fever and headache and any sign of meningeal irritation warrants action.[1]

The full classic picture:[1]

• Fever (often high, with rigors) — present in over 95%.
• Severe, diffuse headache — the commonest single symptom.
• Neck stiffness (meningism, nuchal rigidity) — a classic sign that develops over hours; the full classic triad of fever, neck stiffness and altered mental status was present in under half of adults in a contemporary series.[21]
• Photophobia and eye pain on movement.
• Nausea and vomiting.
• Altered mental status — confusion, drowsiness, agitation; coma is a poor prognostic sign.
• Myalgia, arthralgia, malaise.
• Seizures (focal or generalised) — about 15-30%; a marker of parenchymal involvement.[1]

Meningococcal disease adds the rapidly evolving petechial/purpuric rash — classically non-blanching on the glass test — distributed over the trunk, limbs and mucous membranes, that may progress to purpura fulminans (large confluent purpuric areas with skin necrosis) and septic shock with Waterhouse-Friderichsen syndrome (bilateral adrenal haemorrhage, profound shock, hyponatraemia, hyperkalaemia). Meningococcaemia can progress from a febrile, well-looking patient to shock and death within hours.[1]

Raised intracranial pressure features: decreasing GCS, new seizures, focal neurology, Cushing's triad (hypertension, bradycardia, irregular respiration — a pre-terminal sign), and papilloedema (late). These — plus unilateral pupil dilatation and decerebrate posturing — herald transtentorial herniation.[3]

Atypical presentations (always examined):[1]

• Elderly — confusion, falls, functional decline, anorexia; fever may be absent and neck stiffness subtle. A lower threshold to investigate and treat is essential; Listeria must be covered.
• Immunocompromised — presentation is subtle or indolent; consider Listeria, Cryptococcus, TB. Listeria may produce rhombencephalitis (cranial-nerve palsies, cerebellar signs, hydrocephalus).
• Diabetic / uraemic — fever and confusion may be attributed to the chronic disease; meningeal signs blunted.
• Pregnant — Listeria risk; symptoms overlap with hyperemesis or sepsis of another source.
• Neonate — non-specific: poor feeding, lethargy, irritability, fever or hypothermia, apnoea, seizures (often subtle — cycling movements, lip-smacking), high-pitched cry, bulging fontanelle (late). Neck stiffness is often absent. The threshold to investigate a febrile or non-specifically unwell neonate is very low.[1]

[3] [4] [16] [21]

Differential Diagnosis

An acute febrile illness with headache and meningeal signs is not always bacterial meningitis. Distinguish:[1][2]

• Viral (aseptic) meningitis — usually milder, self-limiting, with normal glucose and a lymphocytic CSF. Enterovirus is the commonest cause (summer/autumn, concomitant rash or GI symptoms). In a UK national study of infants under 90 days, enterovirus meningitis caused death or severe neurological complications in under 1%, with no sensorineural hearing loss at 12 months; treat HSV if encephalitis is suspected.[19]
• Encephalitis / meningoencephalitis (HSV) — confusion, behaviour change and seizures dominate over meningeal signs; temporal-lobe changes on MRI and periodic lateralised epileptiform discharges (PLEDs) on EEG. In the landmark comparative trials, mortality was 50-54% in the vidarabine arms versus 19-28% with acyclovir — give IV aciclovir empirically whenever HSV encephalitis is possible. CSF: lymphocytes, sometimes red cells (haemorrhagic), normal/mildly low glucose, HSV PCR positive.[6][7]
• Subarachnoid haemorrhage — thunderclap ("worst ever") headache at onset; blood in the basal cisterns/sulci on CT; xanthochromia and uniform red cells (no clearing) in CSF. May have low-grade fever but is not a febrile-septic illness.
• Tuberculous meningitis — subacute onset (days to weeks), basal meningitis with cranial-nerve palsies, stroke, and hydrocephalus; a disease that kills or disables more than half of those affected. CSF: very low glucose, lymphocytes, cobweb coagulum; Xpert Ultra is the preferred initial CSF test (pooled sensitivity about two-thirds, specificity 100%). HIV co-infection is common.[9][20]
• Cryptococcal meningitis — HIV/AIDS or other immunosuppression; subacute/chronic; CSF shows lymphocytes, low glucose, positive India ink and cryptococcal antigen (CrAg), and often a very high opening pressure whose early recognition and treatment (therapeutic LPs) is a key management principle.[18]
• Brain abscess / subdural empyema — focal neurology predominates; ring-enhancing lesion on imaging; may arise from contiguous otitis/sinusitis/endocarditis or haematogenous (cyanotic heart disease).
• Migraine — severe headache and photophobia but no fever, no septic picture, no meningeal signs.
• Cervical dystonia / mechanical neck pain — no fever, no systemic upset; movement-related.
• Drug-induced aseptic meningitis — NSAIDs, trimethoprim (especially in lupus), IVIG, OKT3; eosinophils may be present in CSF.
• Systemic infection with meningoencephalopathic features — malaria, enteric fever, leptospirosis, rickettsial fever, dengue; CSF usually near-normal but the patient is encephalopathic.
• Autoimmune / neoplastic meningitis — lupus cerebritis, Behcet, carcinomatous/lymphomatous meningitis (cytology positive).[8]

Always specifically consider HSV encephalitis and tuberculous meningitis when the picture is not a straightforward acute bacterial meningitis — both are eminently treatable but missed at great cost.[1]

Clinical & Bedside Assessment

Vital signs and conscious level drive triage. Record temperature, respiratory rate, oxygen saturation, blood pressure, capillary refill, GCS, and blood glucose. Assess for sepsis (qSOFA), shock, and raised ICP.[1]

Meningeal irritation — the named signs (reproduced exactly):[1]

• Kernig sign — with the patient supine and the hip flexed to 90 degrees, passive extension of the knee produces pain or resistance in the back/hamstrings (stretch of the inflamed meninges and nerve roots). Specificity high but sensitivity low (~5%).
• Brudzinski signs:
  • Neck (nuchal) sign — passive flexion of the neck produces involuntary flexion of the hips and knees.
  • Brudzinski of the cheek — pressure on the cheek produces forearm flexion.
  • Contralateral leg sign — passive flexion of one hip and knee produces flexion of the contralateral leg.
• Jolt accentuation of headache — the baseline headache worsens with horizontal rotation of the head two to three times per second; higher sensitivity than Kernig/Brudzinski for meningitis in the alert patient.[1]

Examine the skin for the petechial/purpuric rash of meningococcal disease (perform the glass test — press a glass tumbler against the rash; petechiae/purpura do not blanch), and for purpura fulminans and peripheral gangrene.[1]

Look for the source and the host:[1]

• Ears (otitis media, mastoiditis), nose and throat (sinus tenderness, meningococcal/pharyngeal carriage), skin (cellulitis, infected shunt site), heart (murmur of endocarditis), chest (pneumonia).
• Cranial nerves (III, IV, VI, VII, VIII palsies — VI palsy is a false-localising sign of raised ICP), papilloedema (fundoscopy), and focal motor/sensory deficits.
• CSF shunt / ventricular reservoir — palpate the tubing, look for erythema along the track.
• Stigmata of immunocompromise (oral candidiasis, lymphadenopathy) and head trauma / basal-skull fracture (Battle sign, raccoon eyes, haemotympanum, CSF rhinorrhoea/otorrhoea).[1]

Take blood cultures and a throat swab (for meningococcus) — but do not delay antibiotics if these cannot be obtained instantly.[1]

Investigations

Lumbar puncture (LP) is the diagnostic cornerstone — but the rule of thumb is: antibiotics first, LP when safe. The CSF analysis answers the aetiological question and confirms the diagnosis.[2][22]

Before the LP (and during, in parallel):[2]

• Blood cultures (two sets) — ideally before antibiotics, but never delay antibiotics for them.
• Blood glucose — taken at the same time as the CSF glucose so a CSF-to-serum ratio can be calculated.
• FBC, U&E (watch for SIADH/hyponatraemia), LFT, coagulation, CRP, lactate, and blood gas (acidosis of sepsis).
• Throat swab / EDTA blood for meningococcal/pneumococcal PCR (especially after antibiotics).
• HIV test (cryptococcal and TB risk).
• Coagulation and platelets before LP (correct coagulopathy or significant thrombocytopenia first).[2]

When to obtain CT head BEFORE lumbar puncture

Do NOT delay antibiotics. Obtain CT before LP when any of the following are present (the universally cited indications):[2][22]

• Immunocompromise (HIV, transplant, chemotherapy, immunosuppressants).
• New-onset seizures (within 1 week).
• Papilloedema or other signs of raised ICP.
• Abnormal level of consciousness (decreased GCS / confused).
• Focal neurological deficit (including III, IV, VI, VII, VIII palsies).
• History of CNS disease (mass lesion, stroke, infection).
• Head trauma within the past 1 week.
• Prolonged or unresponsive coma.[2][22]

A normal CT does not fully exclude raised pressure, and a contrast-enhanced CT adds sensitivity for abscess/empyema. If LP must be deferred, start empirical antibiotics immediately and reconsider LP once the patient is stabilised (a delayed LP still helps with aetiology even after antibiotics — PCR and cellular pattern persist for days).[2]

The CSF analysis (reproduced verbatim)

[15] [18] [20]

CSF discriminators — high-yield:[15]

• CSF lactate is the best single CSF discriminator between bacterial and viral meningitis — about four-fold higher in bacterial meningitis, with 92% specificity, outperforming CSF glucose and the CSF-to-blood glucose ratio, and remaining useful when the cell picture is atypical.[15]
• A low CSF-to-blood glucose ratio at admission is an independent predictor of mortality in adults with bacterial meningitis.[23]

Special tests when indicated: multiplex PCR panels (e.g. FilmArray ME — simultaneous detection of the common bacterial, viral and fungal targets within about an hour), CSF cryptococcal antigen, AFB smear and GeneXpert MTB/RIF / Xpert Ultra, enterovirus and HSV-1/2 PCR, meningococcal and pneumococcal PCR (especially valuable after antibiotics have sterilised the culture), VDPR/RPR (syphilis), cytology (malignant), oligoclonal bands (autoimmune). Repeat LP is reserved for patients who fail to improve.[2]

Imaging beyond CT: MRI brain with contrast if abscess, subdural empyema, ventriculitis, cerebral oedema, or basal-exudate of TB meningitis is suspected. MRI temporal-lobe changes (T2/FLAIR hyperintensity, often bilateral but asymmetric) → HSV encephalitis. EEG if seizures or encephalopathy.[2]

Management — Resuscitation

ABCDE first. Secure the airway; give oxygen to keep SpO2 at 94-98% (or 88-92% in chronic CO2 retainers); gain IV access; treat shock, seizures and raised ICP.[2][4]

The non-negotiable rule: give empirical IV antibiotics IMMEDIATELY on suspicion of bacterial meningitis — do NOT delay for blood cultures, LP, or CT. A useful model: if you suspect bacterial meningitis, the antibiotic is given before the patient leaves the bedside.[1][2]

Adjunctive dexamethasone — give IV dexamethasone 10 mg every 6 hours for 4 days, with or 15-20 minutes before the first antibiotic dose. In the European trial this reduced unfavourable outcomes (RR 0.59) and death (RR 0.48), with unfavourable outcomes in the pneumococcal subgroup of 26% versus 52%; a meta-analysis confirmed a mortality reduction in pneumococcal (RR 0.84) but not meningococcal meningitis, and substantial reductions in hearing loss.[3][4]

Empirical antibiotic regimen — adult community-acquired (drug choice; exact doses per current guideline):[2][22]

• A third-generation cephalosporin (ceftriaxone or cefotaxime) is the empiric backbone — ceftriaxone monotherapy was the commonest empiric regimen for community-acquired adult meningitis in a large Thai series, and a Turkish cohort concluded ceftriaxone should be the drug of choice for initial empirical therapy.[21][23]
• PLUS vancomycin where penicillin-resistant pneumococcus is a risk, per local resistance epidemiology.[23]
• PLUS ampicillin/amoxicillin if Listeria is possible — in a nationwide Dutch cohort, every case of community-acquired Listeria meningitis occurred in patients who were immunocompromised or over 50, and 30% of initial regimens did not cover the organism.[5]
• PLUS aciclovir 10 mg/kg 8-hourly if HSV encephalitis is possible (confusion, seizures, temporal features) — the dose and interval proven in the Swedish randomised trial.[7]

Meningococcal septicaemia in shock: treat as sepsis alongside the meningitis therapy — oxygen, blood cultures, lactate, broad-spectrum antibiotics at once, IV fluids and vasopressors for hypotension per your sepsis protocol; early antibiotic treatment improves outcome.[1] Isolate the index case and notify public health so that contact chemoprophylaxis can be arranged.[13]

Raised ICP management (if signs of herniation): elevate the head of the bed, maintain normoxia, normocapnia and normoglycaemia, treat seizures urgently, give osmotherapy (mannitol or hypertonic saline) per local protocol, and obtain urgent CT with neurosurgical involvement for obstructive hydrocephalus or a surgical mass lesion, per the ESCMID guideline.[2] Cerebral infarction complicates about a quarter of adult episodes and is strongly associated with unfavourable outcome.[16]

Management — Definitive & Stepwise

Once the organism and susceptibility are known, de-escalate to directed therapy. The regimens below give the drug choice; exact doses and durations follow current IDSA/ESCMID guidance, and neonatal/paediatric dosing is weight-based (see Special Populations).[2][22]

Directed antimicrobial therapy — common organisms

Dexamethasone — 10 mg IV every 6 hours for 4 days, starting with or 15-20 minutes before the first antibiotic dose. The European trial reduced unfavourable outcomes (RR 0.59) and death (RR 0.48), with the clearest benefit in pneumococcal meningitis (unfavorable outcomes 26% vs 52%); the meta-analysis confirmed a mortality reduction in pneumococcal (RR 0.84) but not meningococcal meningitis, and large reductions in hearing loss, without excess gastrointestinal bleeding.[3][4]

Step-down and oral switch — most meningitis therapy is IV throughout (CSF penetration of oral agents is usually inadequate); oral step-down is reserved for selected, fast-responding patients with susceptible organisms and good bioavailability (e.g. fluoroquinolone for fully sensitive meningococcal disease after clinical response).[3]

Escalation triggers to ICU

Transfer to intensive care if any of: GCS under 8 (intubate and ventilate), seizures or status epilepticus, septic shock, raised intracranial pressure or signs of herniation, respiratory failure, hyponatraemia from SIADH with seizures, or rapidly deteriorating conscious level.[3]

Meningococcal public-health measures (the question that always comes up)

• Isolate the index case with droplet precautions while communicable (until effective antibiotics have been given).
• Notify public health (statutory notification of suspected meningococcal disease).
• Chemoprophylaxis for household and other close contacts is required — the recommended agents are rifampicin, ciprofloxacin or ceftriaxone; agent, dose and timing follow national guidance.[13]
• Vaccinate the at-risk population when the strain is vaccine-preventable — vaccination of the affected population is often necessary in outbreaks, and conjugate vaccines are recommended for adolescents and high-risk groups.[13]

Adjunctive and disease-specific therapy

• Hearing assessment — corticosteroids reduce severe hearing loss (RR 0.67) and any hearing loss (RR 0.74) in bacterial meningitis; survivors need formal audiology follow-up.[4]
• Vaccination history — give missing vaccines before discharge where the strain is vaccine-preventable.[13]
• Thromboprophylaxis per local VTE policy once bleeding risk is acceptable.

Specific Subtypes & Scenarios

Viral meningitis — most cases are enterovirus (echo, coxsackie; summer/autumn, often with a rash or GI illness), HSV-2 (primary genital herpes), mumps (parotitis, orchitis; where unvaccinated), HIV (seroconversion illness — send HIV test), and arboviruses (Japanese encephalitis, West Nile — regional). Management is supportive (analgesia, hydration, antiemetics); give IV aciclovir empirically whenever HSV encephalitis is possible until HSV PCR is negative. Prognosis is excellent in most immunocompetent adults; recovery within days to weeks.[1]

HSV encephalitis — the treatable archetype of viral encephalitis; HSV-1 in adults, often with temporal-lobe features (behaviour change, aphasia, complex partial seizures, anosmia). CSF: lymphocytes, sometimes red cells (haemorrhagic), mildly raised protein; HSV PCR is the diagnostic mainstay, and the IDSA encephalitis guideline should drive the diagnostic algorithm.[8] Treat with IV aciclovir 10 mg/kg 8-hourly — the regimen of the Swedish randomised trial, in which mortality fell from 50% with vidarabine to 19%, and at 12 months 56% of aciclovir recipients had no or mild sequelae versus 13% of comparators. Start empirically in any suspected encephalitis; the American trial found mortality 28% with acyclovir versus 54% with vidarabine.[7][6]

Tuberculous meningitis — subacute-chronic prodrome (malaise, low-grade fever, headache) then meningism, cranial-nerve palsies (especially VI), stroke and hydrocephalus; the disease kills or disables more than half of those affected.[9] CSF: very low glucose, lymphocytes, high protein, cobweb coagulum; Xpert Ultra is the preferred initial test (pooled sensitivity about two-thirds versus about one-third for the older Xpert; specificity 100%) and culture remains the slow reference.[20] Treat with standard first-line antituberculosis chemotherapy plus adjunctive corticosteroids: dexamethasone reduced death (RR 0.69) in the Vietnamese randomised trial, and by about a quarter in meta-analysis — but the benefit in HIV-positive adults is uncertain, and the 2023 ACT HIV trial found no survival benefit (44.1% vs 49.0% deaths at 12 months).[9][10][11]

Cryptococcal meningitis — Cryptococcus neoformans / gattii, classically in HIV/AIDS, transplant recipients and other T-cell-deficient states. Subacute/chronic presentation; CSF is often paucicellular in advanced HIV with a markedly raised opening pressure, lymphocytes, low glucose, high protein. Diagnosis: India ink, cryptococcal antigen (CrAg) and culture. Treat by the three IDSA principles: (1) induction with a fungicidal regimen — a polyene (amphotericin B formulation) plus flucytosine — followed by suppressive regimens using fluconazole; (2) early recognition and treatment of raised intracranial pressure (therapeutic LPs); (3) lipid formulations of amphotericin B when renal function is impaired.[18]

Neonatal meningitis — see Special Populations; organisms GBS, E. coli K1, Listeria; empirical IV ampicillin + cefotaxime (or an aminoglycoside); avoid ceftriaxone in the neonate (biliary sludging, kernicterus — displaces bilirubin).[1]

Post-neurosurgical / CSF-shunt — coagulase-negative staph (S. epidermidis), S. aureus, Gram-negatives including Pseudomonas, and Cutibacterium (Propionibacterium) acnes. Empirical IV vancomycin + ceftazidime or cefepime (anti-pseudomonal); remove or externalise the infected shunt (it is a foreign body — antibiotics alone rarely cure); intraventricular therapy (vancomycin) may be needed if the shunt is retained. CSF from a shunt tap shows the organism.[1]

Recurrent meningitis — every patient with a second episode needs a hunt for a correctable predisposition: CSF leak (high-resolution CT/MRI cisternography, beta-2 transferrin in nasal fluid), complement pathway deficiency (CH50, AP50, individual complement components), asplenia, humoral immunodeficiency, anatomical defect (dermal sinus tract, midline cleft), or Mollaret meningitis (HSV-2). Vaccinate (pneumococcal, meningococcal ACWY + B, Hib) and consider lifelong prophylaxis where appropriate (e.g. eculizumab-receiving patients).[1]

Complications & Pitfalls

Acute / early:[1]

• Septic shock and multi-organ failure (especially meningococcal); DIC and purpura fulminans with peripheral and skin necrosis requiring skin/limb grafting; Waterhouse-Friderichsen (bilateral adrenal haemorrhage — give stress-dose hydrocortisone).
• Seizures (early and late) and status epilepticus.
• Raised intracranial pressure with cerebral oedema and transtentorial herniation — the commonest cause of early death.
• Stroke (arterial vasculitis or venous sinus thrombosis), subdural empyema/effusion, cerebral abscess, ventriculitis.
• Hyponatraemia from SIADH — common; can cause seizures; correct slowly with hypertonic saline if severe.
• Cranial-nerve palsies — III, IV, VI (false-localising), VII, VIII (hearing).[1]

Long-term:[1]

• Sensorineural hearing loss — the commonest long-term complication (~10%, higher in children and pneumococcal disease); reason for dexamethasone and audiology follow-up.
• Cognitive impairment, behavioural change, focal neurological deficits, epilepsy, visual loss.
• Hydrocephalus (communicating or obstructive — may need a shunt).
• Ataxia, developmental delay (children).[3]

Classic pitfalls (the examiner's favourites):[1]

• Delaying antibiotics for LP, blood cultures, or CT — the single most dangerous and most common error.
• Not covering Listeria in the over-50, pregnant, immunocompromised, or neonatal patient (add ampicillin).
• Not adding aciclovir when HSV encephalitis is possible (a treatable, lethal disease).
• Giving dexamethasone too late — the benefit is with/before the first antibiotic dose.
• Missing TB or Cryptococcus in the subacute/immunosuppressed patient.
• Forgetting chemoprophylaxis of meningococcal contacts within 24 hours.
• Over-relying on a normal CT to exclude raised ICP before LP (clinical criteria decide).
• Using ceftriaxone in the neonate (use cefotaxime + ampicillin).
• Not doing an audiology follow-up.
• Attributing confusion in the elderly to dementia or sepsis of another source.[3]

Prognosis & Disposition

Mortality and morbidity — contemporary adult series report mortality of about 19% (community-acquired) and 23% (hospital-acquired), and cerebral infarction — which triples the odds of an unfavourable outcome — complicates about a quarter of adult episodes.[21][16] Adjunctive dexamethasone reduced unfavourable outcome (RR 0.59) and death (RR 0.48) in the European trial, and corticosteroids reduce severe hearing loss (RR 0.67).[3][4] HSV encephalitis mortality was 19-28% on aciclovir versus 50-54% on vidarabine in the comparative trials, with substantial residual morbidity among survivors.[6][7] Tuberculous meningitis kills or disables more than half of those affected despite treatment.[9]

Poor prognostic factors: very young or old age, immunocompromise, delay in antibiotics, coma (low GCS) at presentation, seizures, bacteraemia/pneumococcal aetiology, thrombocytopenia, high CSF bacterial load, low CSF leucocyte count relative to bacterial load (poor host response), and septic shock.[1]

Disposition:[1]

• ICU if GCS under 8, seizures/status, shock, raised ICP, or respiratory failure.
• Ward (with close observation) once stable, neurologically improving, and on directed therapy.
• Discharge when afebrile, neurologically stable, with a plan for IV therapy completion (inpatient or OPAT) and audiology at 6-8 weeks.
• Follow-up with audiology, neuropsychology if cognitive impairment, and review of vaccination status.[1]

Special Populations

[1]

Neonate (0-28 days) — presentation is non-specific (poor feeding, lethargy, irritability, fever or hypothermia, apnoea, seizures, bulging fontanelle late); neck stiffness is often absent, so the threshold to investigate any non-specifically unwell neonate is very low. Group B streptococcus is a leading cause of neonatal sepsis and meningitis, with E. coli and Listeria also targeted; empiric therapy is ampicillin plus a third-generation cephalosporin (cefotaxime) or an aminoglycoside, with ceftriaxone generally avoided in favour of cefotaxime in this age group — follow local neonatal protocols for doses and durations.[24][22]

Pregnancy — physiological immunosuppression of cell-mediated immunity increases Listeria risk, so the empiric regimen adds ampicillin/amoxicillin; involve obstetrics early. For meningococcal chemoprophylaxis the recommended agents are rifampicin, ciprofloxacin or ceftriaxone — choose per national guidance in pregnancy.[13]

Elderly (over 50) — atypical/blunted presentation (confusion, falls, no fever, subtle neck stiffness); in a nationwide cohort, every case of community-acquired Listeria meningitis occurred in a patient who was over 50 or immunocompromised, so always add ampicillin/amoxicillin and lower the threshold to admit, image (CT before LP) and treat.[5]

Immunocompromised (HIV, transplant, anti-TNF, chemotherapy, complement blockade) — broaden empirically: cover Listeria (ampicillin), HSV (aciclovir), and consider TB, Cryptococcus, Gram-negatives; CT before LP (mass lesions common); if cryptococcal is suspected, send CSF and serum CrAg and measure opening pressure (often very high — therapeutic LPs). Complement deficiency or eculizumab/ravulizumab → recurrent meningococcal disease: vaccinate with MenACWY + MenB (4CMenB) AND give meningococcal prophylaxis on any exposure.[1]

Post-neurosurgery / CSF shunt — the IDSA healthcare-associated ventriculitis and meningitis guideline covers shunts, drains, intrathecal pumps and post-neurosurgical infection; empiric therapy must cover staphylococci (including MRSA) and Gram-negatives including Pseudomonas — vancomycin plus an anti-pseudomonal beta-lactam (ceftazidime or cefepime) is the usual approach, and infected hardware usually requires removal or externalisation. Intraventricular dosing and duration are specialist decisions within that guideline.[14]

Anticoagulated patient — warfarin/DOAC is a relative contraindication to LP; reverse (vitamin K + PCC for warfarin; specific reversal agents for DOACs) and confirm normal coagulation before LP. Do not delay antibiotics for reversal.[1]

Evidence, Guidelines & Regional Differences

Landmark trial — dexamethasone (de Gans & van de Beek, NEJM 2002). A prospective, randomised, double-blind, multicentre European trial of adjunctive dexamethasone (10 mg every 6 hours for four days, started 15-20 minutes before or with the first antibiotic dose) in adults with acute bacterial meningitis. It reduced unfavourable outcomes (RR 0.59; 95% CI 0.37-0.94) and mortality (RR 0.48; 95% CI 0.24-0.96), with unfavourable outcomes in the pneumococcal subgroup of 26% versus 52%, and no excess gastrointestinal bleeding (2 vs 5 patients).[3] The 2015 Cochrane meta-analysis found no significant overall mortality reduction (17.8% vs 19.9%) but reductions in severe hearing loss (RR 0.67) and any hearing loss (RR 0.74), a pneumococcal-specific mortality benefit (RR 0.84), and benefit in high-income countries with no demonstrable effect in low-income countries.[4] A Vietnamese trial in suspected bacterial meningitis found benefit confined to microbiologically confirmed cases, with a possible signal of harm when missed tuberculous meningitis received steroids.[12] Current guidelines (ESCMID, IDSA) direct the indications and contraindications in practice.[2][22]

[13] [2]

Key guideline sources:[2]

• ESCMID 2016 (van de Beek et al.) — diagnosis and treatment of acute bacterial meningitis: empirical regimens, LP timing, dexamethasone indications.[2]
• IDSA / Tunkel 2004 — practice guidelines for the management of bacterial meningitis (adults and children, including shunt infection).[4]
• Surviving Sepsis Campaign (SSC) hour-1 bundle — applies to meningococcal septicaemia.
• NICE CG102 / NG51 (UK) — bacterial meningitis and meningococcal septicaemia in children; NICE CKS for adults.
• WHO — integrated management of childhood illness (IMCI); TB and HIV-associated meningitis guidance.

Controversies:[2]

• Dexamethasone in low-income settings and in antibiotic-pretreated patients — the Cochrane meta-analysis found no beneficial effect in low-income countries, and the Vietnamese trial found benefit confined to microbiologically proven disease.[4][12]
• Routine CT before LP — overuse of imaging before LP delays both the LP and the antibiotics; clinical criteria and guideline indications (ESCMID/IDSA) decide.[2][22]
• PCR replacing culture — multiplex panels are fast but expensive; culture still needed for susceptibility.
• ACT HIV 2023 (Donovan et al.) — adjunctive dexamethasone did not improve survival in HIV-positive tuberculous meningitis (44.1% vs 49.0% deaths at 12 months), refining the long-held assumption that steroids always help TBM.[11]
• Adjunctive glycerol, immunoglobulin, and hypothermia — not routine; investigational.

Vaccination (the prevention that examiners reward):[13]

• Hib conjugate — near-elimination of H. influenzae type b meningitis.
• Pneumococcal conjugate (PCV10/13/15/20) — dramatic fall in vaccine-serotype pneumococcal meningitis; non-vaccine serotypes and the 23-valent polysaccharide (PPSV23) in older adults.
• Meningococcal — MenACWY (conjugate) and MenB (4CMenB / Trumenba) — adolescent boosters, complement deficiency, asplenia, Hajj, outbreaks.
• MMR — mumps meningitis prevention.
• Japanese encephalitis, rabies (post-exposure) — regional / risk-based.[13]

Exam Pearls

[3] [5] [7]

• Classic triad: FEVER + NECK STIFFNESS + ALTERED MENTAL STATUS — but two of three is enough to act.
• Meningococcal: NON-BLANCHING PETECHIAL/PURPURAR RASH; antibiotics within 1 hour; isolate 24 h; chemoprophylax contacts.
• Empirical IV antibiotics IMMEDIATELY on suspicion — do NOT delay for LP/CT/blood cultures.
• CSF bacterial: cloudy, NEUTROPHIL-PREDOMINANT, PROTEIN high, GLUCOSE LOW — CSF lactate discriminates bacterial from viral better than glucose measures.[15]
• CSF viral: lymphocytes, NORMAL glucose, mildly raised protein. CSF TB: very low glucose + cobweb coagulum. CSF Cryptococcus: India ink + CrAg, very high opening pressure.
• Add AMPICILLIN for Listeria (over 50, pregnant, immunocompromised, neonate).
• Add ACICLOVIR if HSV encephalitis suspected (temporal changes, seizures, confusion).
• DEXAMETHASONE 10 mg q6h x 4 days, with/before first antibiotic dose — pneumococcal mortality benefit; reduces hearing loss.[3][4]
• CT before LP: immunocompromise, new seizures, papilloedema, altered GCS, focal neurology, trauma, prolonged coma, CNS disease.
• Hearing loss is the commonest complication → dexamethasone + audiology follow-up.
• Organisms by age: neonate GBS/E. coli/Listeria; child pneumo/meningo/Hib; adult pneumo/meningo; over 50 add Listeria.
• Chemoprophylaxis of contacts: rifampicin, ciprofloxacin or ceftriaxone (agent and dose per national guidance).[13]
• Kernig & Brudzinski signs; jolt accentuation.
• Post-neurosurgery/shunt: vancomycin + ceftazidime/cefepime; remove the shunt.
• Complement/properdin deficiency + eculizumab → recurrent meningococcal disease.
• Neonate: avoid ceftriaxone (use ampicillin + cefotaxime).
• Listeria rhombencephalitis; TB basal meningitis + cranial-nerve palsies; HSV temporal-lobe changes.
• Waterhouse-Friderichsen = bilateral adrenal haemorrhage in meningococcal septicaemia → give stress-dose steroids.[3]

Ward-round test — three stems, thirty seconds each

Stem 1 — the student with the non-blanching rash (answer)

The 19-year-old from the top of the topic: fever, headache, neck stiffness, confusion, and petechiae on the ankles that do not blanch. What do you do in the next hour, and in what order? Model: This is meningococcal septicaemia with meningitis until proven otherwise, and the petechial rash is your mandate to move. Give empirical IV antibiotics immediately at the bedside before any test — a third-generation cephalosporin (add vancomycin only if resistant pneumococcus is a local risk; a Listeria risk does not apply here). Give IV dexamethasone 10 mg with or just before the first antibiotic dose. Take blood cultures if they delay nothing, treat the shock as sepsis (fluids, vasopressors, lactate-guided resuscitation), isolate with droplet precautions, notify public health, and arrange chemoprophylaxis for close contacts with rifampicin, ciprofloxacin or ceftriaxone.[3][13]

Stem 2 — the 58-year-old with lymphoma and a normal CT (answer)

A 58-year-old on chemotherapy for lymphoma arrives febrile and confused with mild neck stiffness. CT head is normal. May you proceed straight to lumbar puncture, and what is the one drug the standard regimen is missing? Model: He is immunocompromised, so he must be CT-scanned before LP — done, and normal, so you may tap (a normal CT does not fully exclude raised pressure, but the clinical criteria are now met). The standard cephalosporin-based regimen of ceftriaxone (± vancomycin) misses Listeria, which thrives exactly in this host — in a nationwide Dutch cohort every case of community-acquired Listeria meningitis was over 50 or immunocompromised — so add an ampicillin/amoxicillin-based regimen. Also add IV aciclovir 10 mg/kg 8-hourly while HSV PCR is pending, because encephalopathy plus immunosuppression keeps herpes simplex encephalitis on the list. Send CSF for cell count, glucose and protein paired with a simultaneous blood glucose, Gram stain and culture, and a multiplex PCR panel — and do not forget cryptococcal antigen and Xpert Ultra for TB in this patient.[5][7][18][20]

Stem 3 — the CSF that looks bacterial but is not (answer)

A 25-year-old has three days of fever, behaviour change and a focal seizure. CSF shows 200 lymphocytes, mildly raised protein, glucose two-thirds of serum, and a few red cells. The registrar calls it viral and plans supportive care. What is the diagnosis you cannot miss, and what is the cost of the delay? Model: This is herpes simplex encephalitis until HSV PCR proves otherwise — the temporal-lobe behaviour change, the seizure, the lymphocytic pleocytosis with red cells (haemorrhagic CSF), and the preserved glucose are the signature. Start IV aciclovir 10 mg/kg 8-hourly immediately — do not wait for the MRI temporal-lobe changes or the EEG periodic lateralised discharges to confirm it. In the comparative trials, half of vidarabine-treated patients died versus about a fifth of aciclovir-treated patients, and even among aciclovir survivors only about half were free of sequelae at 12 months — so the only error is waiting for certainty. Continue until HSV PCR returns negative or an alternative diagnosis is proven.[6][7][8]

References

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2. [2]van de Beek D, Cabellos C, Dzupova O, et al. ESCMID guideline: diagnosis and treatment of acute bacterial meningitis. Clinical Microbiology and Infection, 2016.PMID 27062097
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