Meningitis and Encephalitis

In depth

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Pathophysiology, organisms and presentation

Most community-acquired bacterial meningitis starts with nasopharyngeal colonization. The organism enters the blood and crosses the blood–brain barrier, or spreads directly from otitis, sinusitis or a CSF leak after skull fracture or surgery. CSF holds little antibody or complement, so bacteria multiply until their wall products trigger cytokines and a neutrophil influx. The inflammation, more than the bacteria, injures the brain: vasogenic edema through a leaky barrier, cytotoxic edema, interstitial edema when CSF outflow is blocked, and vasculitis and thrombosis of arteries and veins. Antibiotic-induced lysis briefly amplifies it, which is why dexamethasone goes first.

Pneumococcus caused 72% of 1,412 Dutch adult episodes in 2006–14 (Bijlsma 2016), up from 51% (meningococcus 37%) in 1998–2002 (van de Beek 2004) as meningococcal disease declined. Listeria affects older, pregnant and immunocompromised adults; staphylococci and gram-negative bacilli dominate after neurosurgery. Mortality was 21% in the earlier cohort (30% pneumococcal, 7% meningococcal) and 17% in the later one.

In 696 adult episodes the classic triad was present in 44%, but 95% had at least two of headache, fever, neck stiffness and altered mental status, and 33% had focal deficits (van de Beek 2004). Kernig's and Brudzinski's signs were 5% sensitive and nuchal rigidity 30% in 297 adults evaluated for meningitis (Thomas 2002). Older, immunosuppressed and alcohol-dependent patients may show only fever and confusion; Listeria can cause brainstem signs (rhombencephalitis).

The first hour: timing, imaging and lumbar puncture

Outcome tracks how ill the patient is when antibiotics start, so guidelines set a 1-hour target from arrival (ESCMID 2016, UK 2016, WHO 2025). In 123 Canadian adult episodes, a door-to-antibiotic time over 6 h carried an adjusted odds ratio of 8.4 for death (Proulx 2005). Blood cultures come first because they may be the only culture when LP is deferred.

CT looks for a mass that could herniate after LP. Hasbun 2001 scanned 235 adults with suspected meningitis: 24% had an abnormality and 5% mass effect; of 96 without risk features, 93 had a normal CT and none herniated (negative predictive value 97%). In a Swedish national cohort of 815 adults, IDSA criteria would have imaged 65%, ESCMID 32% and Swedish criteria (herniation signs only) 7%, and LP delayed for CT was linked with later treatment and higher mortality (10% vs 4%; Glimåker 2018).

LP is deferred, not abandoned, for respiratory or circulatory instability, a rapidly spreading rash, infection at the site or coagulopathy (UK 2016: platelets under 40 × 10⁹/L, warfarin until INR ≤1.4, 12 h after prophylactic and 24 h after therapeutic LMWH). Tap within about 4 h of the first dose: meningococci cleared from CSF within 2 h of antibiotics and pneumococci began to clear at 4 h in children (Kanegaye 2001).

Reading the CSF

Bacterial CSF typically shows an opening pressure of 20–50 cm H₂O, 1,000–5,000 WBC/µL (range under 100 to over 10,000) with 80–95% neutrophils, glucose under 40 mg/dL in 50–60%, a CSF-to-serum glucose ratio of 0.4 or less, and raised protein in nearly all (IDSA 2004). About 10% of bacterial cases have a lymphocyte predominance.

Gram stain identifies the organism in 60–90% with at least 97% specificity: about 90% of pneumococcal, 75% of meningococcal and a third of Listeria cases. Culture is positive in 70–85% before antibiotics, and Gram stain yield falls about 20% after them. In 422 patients, glucose under 34 mg/dL, a ratio under 0.23, protein over 220 mg/dL, WBC over 2,000 or neutrophils over 1,180/µL each predicted bacterial disease with 99% certainty, and a normal serum CRP argues against it when the Gram stain is negative (all cited in IDSA 2004). WHO 2025 strongly recommends CSF PCR and conditionally CSF lactate; culture with susceptibility testing remains the reference.

Tuberculous meningitis evolves over days to weeks with cranial nerve palsies, basal enhancement, hydrocephalus and infarcts; it needs 2 months of four drugs, then 7–10 months of isoniazid and rifampin, plus dexamethasone or prednisolone tapered over 6–8 weeks (ATS/CDC/IDSA 2016). Cryptococcal meningitis in advanced HIV or transplant recipients raises opening pressure: with symptoms and 25 cm H₂O or more, drain CSF to under 20 and repeat LPs daily until stable; acetazolamide and corticosteroids are avoided and mannitol is unproven (IDSA 2010). Cryptococcal antigen testing is far more sensitive than India ink.

Antibiotics: choices, doses and duration

Ceftriaxone covers pneumococcus, meningococcus and H. influenzae; vancomycin is added for pneumococci with reduced cephalosporin susceptibility until results return (IDSA 2004), while UK 2016 (recent travel) and WHO 2025 add it only for resistance risk. No cephalosporin covers Listeria, so ampicillin is added by age and risk, with gentamicin considered (IDSA 2004). Meningitis doses are high because drug entry into CSF falls as inflammation settles: ceftriaxone 4 g/day, ampicillin 12 g/day, cefepime, ceftazidime or meropenem 6 g/day, and vancomycin 30–45 mg/kg/day in 2–3 doses to a trough of 15–20 (IDSA 2004, 2017); the 2020 vancomycin consensus adds a 20–35 mg/kg load in critical illness and prefers AUC dosing (400–600) to troughs, without meningitis outcome data. All but ceftriaxone need renal adjustment; cefepime neurotoxicity in AKI (confusion, myoclonus, nonconvulsive seizures) can mimic worsening meningitis.

With a severe β-lactam allergy, IDSA 2004 lists moxifloxacin for pneumococcus and meningococcus and TMP-SMX for Listeria; most patients labeled penicillin-allergic tolerate ceftriaxone, so clarify the reaction. Fever and mental status should improve within 48 h; if not, repeat the LP (IDSA 2004) and image for empyema, abscess, hydrocephalus or venous sinus thrombosis. Some add rifampin when resistant pneumococcus is suspected and dexamethasone is given, because steroids may reduce vancomycin entry into CSF (IDSA 2004).

Dexamethasone: evidence and disputes

In the European trial of 301 adults (de Gans 2002), dexamethasone 10 mg every 6 h for 4 days, started 15–20 min before antibiotics, lowered unfavorable outcome from 25% to 15% and death from 15% to 7%; in pneumococcal meningitis, unfavorable outcome fell from 52% to 26% and death from 34% to 14%. The Cochrane review (2015; 25 trials, 4,121 patients) found no overall mortality effect (RR 0.90) but less severe hearing loss (RR 0.67) and fewer neurologic sequelae (RR 0.83), with benefit confined to high-income countries and mortality reduced only in pneumococcal disease (RR 0.84).

Listeria is disputed: in the French MONALISA cohort dexamethasone was linked with higher mortality in neurolisteriosis, while among 162 Dutch adults with Listeria meningitis unfavorable outcome was 46% with it and 72% without (adjusted OR 0.40), and the authors advise not withholding it (Brouwer 2023). Expect hyperglycemia. Rarely, pneumococcal patients deteriorate days after a good recovery from delayed cerebral thrombosis, which UK 2016 notes has not been shown to be caused by dexamethasone.

Encephalitis: HSV, acyclovir and autoimmune causes

Encephalitis inflames the brain itself: altered mental status for 24 h or more, supported by fever, seizures, focal signs, CSF pleocytosis, or imaging or EEG change (International Encephalitis Consortium 2013). HSV-1 is the commonest sporadic cause and the most treatable. Acyclovir cut 6-month mortality to 28% from 54% with vidarabine (Whitley 1986), yet of 93 French adults given acyclovir, 15% died and 20% were severely disabled, and a delay of more than 2 days from admission predicted a poor outcome (Raschilas 2002). EAN/ESCMID 2026 strongly recommends acyclovir as soon as encephalitis is suspected, ideally within 6 h of arrival.

CSF HSV PCR is 96–98% sensitive and 95–99% specific in adults but can miss early disease or CSF with under 10 WBC/µL (IDSA 2008). If the first LP was within 3 days of onset and suspicion persists, repeat it 2–3 days later (EAN/ESCMID 2026; IDSA 2008: 3–7 days). With low suspicion or another diagnosis confirmed, acyclovir can stop once PCR is negative on an LP more than 72 h after onset, CSF WBC is normal and MRI shows no temporal lobe change. MRI with diffusion imaging is preferred within 24 h. Multiplex panels detected HSV-1 with a pooled sensitivity of 76% and should not replace HSV-specific PCR (EAN/ESCMID 2026).

• Dose by ideal body weight in obesity (label); at least 14 days for proven HSV, 21 or even 28 if not improving or immunocompromised (EAN/ESCMID 2026; IDSA 2008: 14–21); the label's 10 days predates this
• Crystals form in renal tubules: infuse over at least 1 h at 7 mg/mL or less, keep the patient hydrated, never bolus (label)
• AKI in 17.8% of 287 patients, more with diabetes, NSAIDs and concurrent vancomycin (OR 4.3) (Lee 2018)
• Renal dosing (label): CrCl 25–50 q12h; 10–25 q24h; under 10 half dose q24h
• Neurotoxicity in about 1% (tremor, agitation, hallucinations, seizures, coma), more in renal failure, can mimic worsening encephalitis

DexEnceph (2026; 94 UK adults; dexamethasone 10 mg every 6 h for 4 days, started a median 7 days after admission) found no difference in verbal memory at 26 weeks and no excess harm; EAN/ESCMID 2026 is unable to recommend for or against corticosteroids. VZV encephalitis takes acyclovir 10–15 mg/kg q8h for 10–14 days (EAN/ESCMID 2026: 10 mg/kg), and doxycycline is added in season when rickettsial or ehrlichial infection is possible (IDSA 2008).

Autoimmune encephalitis is possible with onset over less than 3 months of memory deficits, altered mental status or psychiatric symptoms plus new focal signs, unexplained seizures, CSF WBC over 5/mm³ or suggestive MRI, once other causes are excluded (Graus 2016). Anti-NMDAR encephalitis, mostly in young women and sometimes with an ovarian teratoma, moves from psychiatric symptoms and seizures to orofacial dyskinesias, autonomic instability, falling consciousness and central hypoventilation. In 577 patients, 53% improved within 4 weeks of first-line immunotherapy (steroids, IVIG or plasma exchange) or tumor removal, second-line rituximab or cyclophosphamide helped non-responders, and 81% had a good outcome at 24 months; early treatment and no ICU admission predicted recovery (Titulaer 2013). After HSV encephalitis, 27% developed autoimmune encephalitis, usually within 2 months (Armangue 2018), so new or returning symptoms call for CSF anti-NMDAR testing (EAN/ESCMID 2026).

Meningococcal disease, isolation and contacts

Meningococcemia can kill within hours: petechiae progress to purpura fulminans with DIC, limb ischemia and adrenal hemorrhage. Young adults hold their blood pressure until late, so watch capillary refill and dusky, cold limbs. UK 2016 asks for critical care with a rapidly evolving rash and suggests hydrocortisone 200 mg/day for persisting shock.

Droplet precautions apply to known or suspected meningococcal and H. influenzae type b infection until 24 h after effective therapy starts; other causes need standard precautions, adding airborne only for coexisting pulmonary TB (CDC). Close contacts in the 7 days before onset are household members, child care contacts and anyone exposed to oral secretions. Staff need prophylaxis, whatever their vaccination status, only after unprotected airway exposure such as intubation, ETT management or open suctioning without a mask (CDC). Give it as soon as possible, ideally within 24 h of identifying the case; after 14 days it has little value.

A patient treated with anything other than ceftriaxone needs carriage eradication (UK 2016: ciprofloxacin 500 mg once). Report suspected meningococcal disease to infection prevention and public health at once so contact tracing starts; vaccine is reserved for outbreak control (CDC).

ICU complications and nursing care

Raised ICP comes from edema and hydrocephalus, which affected 5% of 577 Dutch adults with 50% mortality (Kasanmoentalib 2010). Basic measures from the neuro one-pager apply, with hypertonic saline or mannitol as a bridge (WHO 2025); glycerol is not recommended (WHO 2025, UK 2016). UK 2016 advises against routine ICP monitoring, yet in a Swedish intervention–control study ICP-targeted care, mainly CSF drainage, lowered mortality from 30% to 10% (Glimåker 2014). Induced hypothermia to 32–34 °C raised mortality (51% vs 31%) and stopped its trial early (Mourvillier 2013).

Seizures occurred in 17% of 696 episodes and raised mortality (41% vs 16%; Zoons 2008); fluctuating consciousness needs EEG (UK 2016), and WHO 2025 suggests stopping antiseizure drugs within 3 months if none recur. Hyponatremia was present in 30% on admission and below 130 mmol/L in 6% (Brouwer 2007); SIADH and salt wasting both occur, and fluid restriction is not routine: keep patients euvolemic (UK 2016, WHO 2025). Infarction affected 25% (36% of pneumococcal cases) and tripled the odds of a poor outcome (Schut 2012). After pneumococcal meningitis, 54% of 240 Danish survivors had hearing loss on audiometry, profound in 14% (Worsøe 2010); test before discharge or within 4 weeks and fast-track severe loss for cochlear implant assessment (UK 2016).

• Neuro: GCS, pupils, cranial nerves (III, VI, VII, VIII) and limb strength at least hourly while unstable; report a fall of more than 2 points, a new pupil or focal sign, or a seizure
• Airway: consider intubation at GCS under 12 (UK 2016); avoid hypoxemia and hypercapnia
• Circulation: MAP 65 or more with norepinephrine first (UK 2016); check limb perfusion and mark the edges of purpura
• Fluids and labs: euvolemia; sodium and glucose at least daily on dexamethasone; creatinine daily on acyclovir or vancomycin
• Comfort and safety: dim, quiet room for headache and photophobia; treat fever; seizure precautions
• Infection control: droplet sign until 24 h of therapy; document the start time; list unprotected exposures
• Recovery: hearing test, cognitive screen and rehabilitation; vaccination and repair of any CSF leak against recurrence

EVD-associated ventriculitis

External drains became infected at 11.4 per 1,000 catheter-days in pooled data cited by IDSA 2017, mostly with skin flora (coagulase-negative staphylococci, S. aureus, Cutibacterium acnes) or gram-negative bacilli such as Pseudomonas and Acinetobacter. Blood, surgery and the catheter all disturb the CSF, so new or worse mental status, or new fever with a rising CSF WBC, suggests infection, while CSF chemistry neither proves nor excludes it (IDSA 2017). Culture is the key test; hold it 10 days for Cutibacterium. A rising cell index (CSF WBC-to-RBC ratio over the blood ratio) and CSF lactate of 4 mmol/L or more support treatment but are not fully validated.

Empiric therapy is vancomycin plus cefepime, ceftazidime or meropenem; meropenem for ESBL producers; IV plus intraventricular colistin or polymyxin B for carbapenem-resistant Acinetobacter. Intraventricular doses are given by the neurosurgical team when systemic therapy fails, with the drain clamped 15–60 min afterward. Remove or replace the infected drain. Treat 10 days for coagulase-negative staphylococci or Cutibacterium with minimal CSF change and 10–14 days otherwise, some experts using 21 for gram-negative bacilli (IDSA 2017). Prevention (IDSA 2017): one periprocedural antibiotic dose, antimicrobial-impregnated catheters, no scheduled exchange and CSF sampling only when clinically indicated.

Exam pearls

• Antibiotics within 1 h of arrival; blood cultures first; never wait for CT or LP
• Dexamethasone 10 mg q6h for 4 days, first dose before or with antibiotics; the benefit is in pneumococcal meningitis
• Ampicillin for Listeria over 50 (60 in UK and WHO guidance), in pregnancy and immunosuppression; cephalosporins never cover it
• CT first for immunocompromise, CNS disease, new seizure, papilledema, altered consciousness or focal deficit (IDSA)
• Bacterial CSF: high pressure, neutrophils, glucose ratio ≤0.4, high protein; viral: lymphocytes, normal glucose
• Lymphocytes with low glucose: TB or fungal; very high opening pressure: Cryptococcus
• HSV encephalitis: temporal lobes, RBCs in CSF, acyclovir 10 mg/kg q8h for 14–21 days with hydration
• Droplet precautions for meningococcus and Hib until 24 h of therapy; prophylaxis for unprotected airway exposure
• Complications: raised ICP, seizures, hyponatremia, infarction and hearing loss; audiology before discharge