Acute pyogenic infection of the meninges — neurologic emergency requiring empiric antibiotics within 1 hour.
Also known as: bacterial meningitis, meningococcal meningitis, pneumococcal meningitis, acute meningitis
Overview
Acute pyogenic infection of the leptomeninges and subarachnoid space, characterized by inflammation, neutrophilic CSF pleocytosis, and high morbidity/mortality without prompt antibiotic therapy.
Epidemiology
Incidence in the US ~1-2 per 100,000 adults annually; higher in infants and young children. Vaccination has dramatically reduced Haemophilus influenzae type b and Streptococcus pneumoniae meningitis. Outbreaks of Neisseria meningitidis occur in close-contact settings (college dormitories, military barracks).
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Question 1NeurologyMedium
A 60-year-old man who underwent splenectomy after a motor vehicle crash presents with 12 hours of high fever, severe headache, photophobia, and neck stiffness. Temperature is 39.6 C and he is lethargic. Cerebrospinal fluid shows a neutrophilic pleocytosis, low glucose, and gram-positive diplococci. He is started on ceftriaxone for the most likely pathogen. Which of the following best describes the mechanism of action of this antibiotic?
AInhibition of the 50S ribosomal peptidyltransferase
BInhibition of the penicillin-binding transpeptidases
CInhibition of bacterial DNA gyrase and topoisomerase
DDisruption of the bacterial cytoplasmic cell membrane
Reveal answer & full explanation
Correct answer: B — Inhibition of the penicillin-binding transpeptidases
AInhibition of the 50S ribosomal peptidyltransferase
BInhibition of the penicillin-binding transpeptidases✓
CInhibition of bacterial DNA gyrase and topoisomerase
DDisruption of the bacterial cytoplasmic cell membrane
Why Inhibition of the penicillin-binding transpeptidases is correct
This is Streptococcus pneumoniae bacterial meningitis, the most common cause of community-acquired bacterial meningitis in adults and especially dangerous in asplenic patients because the spleen normally clears opsonized encapsulated organisms.
The gram-positive diplococci in a neutrophilic, low-glucose CSF confirm the pathogen.
Empiric therapy includes ceftriaxone, a third-generation cephalosporin.
Cephalosporins are beta-lactams that bind and inhibit penicillin-binding proteins, the transpeptidase enzymes that cross-link peptidoglycan; blocking cross-linking weakens the cell wall and causes bacterial lysis.
Why the others are wrong
Inhibition of the 50S ribosomal peptidyltransferase — is the mechanism of macrolides, clindamycin, and linezolid, which impair protein synthesis, not the beta-lactam target.
Inhibition of bacterial DNA gyrase and topoisomerase — is the mechanism of fluoroquinolones, which block bacterial DNA replication rather than cell-wall synthesis.
Disruption of the bacterial cytoplasmic cell membrane — describes agents such as daptomycin and polymyxins, which are not the mechanism of ceftriaxone.
Question 2NeurologyMedium
A 68-year-old man develops fever, headache, neck stiffness, and confusion. Which of the following is the most appropriate initial diagnostic test after assessing the need for immediate imaging?
ANoncontrast CT angiography of the head
BSerum procalcitonin and lactate
CLumbar puncture for CSF analysis
DElectroencephalography with video
Reveal answer & full explanation
Correct answer: C — Lumbar puncture for CSF analysis
ANoncontrast CT angiography of the head
BSerum procalcitonin and lactate
CLumbar puncture for CSF analysis✓
DElectroencephalography with video
Why Lumbar puncture for CSF analysis is correct
Fever, headache, neck stiffness, and confusion are the meningitis syndrome, and CSF analysis is the definitive test.
CSF cell count, glucose, protein, Gram stain, and culture establish bacterial meningitis and guide therapy.
Empiric antibiotics and dexamethasone should precede the LP if it must be delayed for imaging.
Why the others are wrong
Electroencephalography with video — EEG evaluates seizures/encephalopathy and cannot diagnose meningeal infection (altered-mental-status trap).
Noncontrast CT angiography of the head — CT before LP only screens for mass effect or herniation risk; it does not diagnose meningitis, which still needs CSF (imaging-substitution trap).
Serum procalcitonin and lactate — These only suggest bacterial infection in general and cannot localize or confirm meningitis the way CSF can (nonspecific-biomarker trap).
Start empiric antibiotics immediately -- do not delay for CT or LP -- and add dexamethasone with or just before the first dose.
For adults over 50 (as here), empiric therapy is vancomycin + ceftriaxone PLUS ampicillin to cover Listeria monocytogenes.
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Viral (aseptic) meningitis — Less ill-appearing; lymphocytic CSF, normal glucose, mildly elevated protein, negative gram stain; enterovirus most common
Encephalitis (HSV, arboviral) — Prominent altered mental status, seizures, focal deficits; HSV with temporal lobe involvement on MRI
Subarachnoid hemorrhage — Thunderclap headache; LP with RBCs and xanthochromia; CT head before LP if clinical suspicion
Brain abscess — Focal deficits, ring-enhancing lesion on imaging; LP often contraindicated due to mass effect
Tuberculous meningitis — Subacute course (1-2 weeks), basilar meningitis, cranial nerve palsies, lymphocytic CSF with high protein, very low glucose, AFB smear/PCR/culture
LP CSF studies: opening pressure, cell count and differential, protein, glucose (with simultaneous serum glucose), Gram stain, culture, latex agglutination/multiplex PCR (meningitis/encephalitis panel), HSV PCR, cryptococcal antigen if at risk, AFB stain/culture/PCR if TB suspected, cytology in older patients
Typical bacterial CSF: WBC >1000 (PMN predominant), glucose <40 (or CSF:serum ratio <0.4), protein >200, opening pressure elevated (>250 mm H2O)
Imaging
CT head BEFORE LP only if any of: immunocompromise, history of CNS disease (mass, stroke, focal infection), new seizure within 1 week, papilledema, abnormal level of consciousness, focal neurologic deficit, age >60 — to exclude mass effect and risk of herniation
DO NOT delay antibiotics for imaging or LP — give empiric antibiotics immediately if any delay anticipated
MRI brain if focal findings, suspected complications (abscess, ventriculitis, infarct)
Diagnostic algorithm
Parameter
Bacterial
Viral
Fungal/TB
Normal
Opening pressure (mm H2O)
Elevated (>250)
Normal or mildly elevated
Elevated
70-180
WBC (cells/µL)
>1000 (often 1000-5000)
10-500
100-500
0-5
WBC predominance
Neutrophils (PMN)
Lymphocytes
Lymphocytes
—
Glucose (mg/dL)
Low (<40) or CSF:serum <0.4
Normal
Low
50-80 (~2/3 serum)
Protein (mg/dL)
High (>200)
Mildly elevated (50-150)
Very high (>250)
<45
Gram stain
Often positive
Negative
Negative (AFB/India ink)
Negative
Typical CSF profiles by etiology of meningitis.
Treatment
First-line
Empiric antibiotics within 1 hour of presentation — do not delay for imaging or LP if not immediately available:
Adults 18-50: ceftriaxone 2 g IV q12h + vancomycin 15-20 mg/kg IV q8-12h (covers pneumococcus with ceftriaxone resistance)
Adults >50 or immunocompromised, alcoholic, pregnant: ADD ampicillin 2 g IV q4h to cover Listeria monocytogenes
Children 1 month-18 years: ceftriaxone + vancomycin
Post-neurosurgery/penetrating head trauma: vancomycin + cefepime (or ceftazidime or meropenem) — covers Pseudomonas, MRSA, gram-negatives
Dexamethasone 0.15 mg/kg IV q6h x 4 days, FIRST DOSE 10-20 minutes BEFORE OR WITH first antibiotic dose — reduces mortality and neurologic sequelae (especially hearing loss) in pneumococcal meningitis (de Gans & van de Beek NEJM 2002); continue if pneumococcus confirmed
Acyclovir IV 10 mg/kg q8h if HSV encephalitis cannot be excluded
Second-line / adjunct
Narrow antibiotics once Gram stain/culture/sensitivities return:
S. pneumoniae (gram-positive diplococci): ceftriaxone (continue vancomycin until sensitivities confirm)
N. meningitidis (gram-negative diplococci): ceftriaxone or penicillin G
H. influenzae (gram-negative coccobacilli): ceftriaxone
L. monocytogenes (gram-positive rods): ampicillin ± gentamicin
Group B Streptococcus: penicillin G or ampicillin
Standard duration: meningococcus 7 days, H. influenzae 7-10 days, pneumococcus 10-14 days, GBS 14-21 days, Listeria 21 days, gram-negative bacilli 21 days
Chemoprophylaxis for close contacts of meningococcus: rifampin 600 mg PO BID x 2 days, ciprofloxacin 500 mg PO x 1, or ceftriaxone 250 mg IM x 1 (preferred in pregnancy)
Vaccinate close contacts of vaccine-preventable cases (meningococcal, Hib, pneumococcal); update routine vaccinations in survivors and high-risk patients
Audiology screening on recovery (CN VIII injury, especially pneumococcal)
Complications
Death (mortality ~10-30% adults; up to 50% pneumococcal in elderly)
Sensorineural hearing loss (~10-30%, especially pneumococcal)
Cognitive impairment, memory deficits
Seizure disorder
Cranial nerve palsies
Hydrocephalus, cerebral infarction
Subdural empyema, brain abscess
Septic shock, DIC, adrenal hemorrhage (Waterhouse-Friderichsen with meningococcemia)
Limb necrosis from purpura fulminans
PANCE pearls
Empiric antibiotics within 1 hour. If CT before LP is needed, give blood cultures and antibiotics FIRST.
Add ampicillin for Listeria in patients >50, immunocompromised, alcoholic, or pregnant.
Dexamethasone before/with first antibiotic in suspected pneumococcal meningitis — reduces mortality and hearing loss.
Petechial rash with meningismus = meningococcemia until proven otherwise; isolate, treat, and notify public health.
Vaccination: MenACWY (preteens, college students, military, asplenia, complement deficiency); MenB (high-risk patients and during outbreaks); PCV13/15/20 and PPSV23; Hib in children.
Close contacts of meningococcus require chemoprophylaxis within 24 hours.
In suspected partially treated meningitis (prior antibiotics), Gram stain and culture may be negative — multiplex PCR helpful.
Recurrent meningitis suggests anatomic defect (CSF leak from basilar skull fracture, dermal sinus tract) or complement deficiency.
References
IDSA 2004 — Practice Guidelines for the Management of Bacterial Meningitis (Tunkel et al., Clin Infect Dis 2004; updates pending)
ESCMID 2016 — Diagnosis and Treatment of Acute Community-Acquired Bacterial Meningitis (van de Beek et al., Clin Microbiol Infect 2016)
de Gans NEJM 2002 — Dexamethasone in Adults with Bacterial Meningitis (de Gans & van de Beek, NEJM 2002)
CDC ACIP — ACIP Recommendations for Meningococcal Vaccination
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