What is the differential diagnosis and management for a patient with neutrophilic pleocytosis on lumbar puncture (LP)?

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Neutrophilic Pleocytosis on Lumbar Puncture: Differential Diagnosis

Neutrophilic pleocytosis on LP most commonly indicates acute bacterial meningitis, but can also occur in early viral meningitis (especially enteroviral), partially treated bacterial meningitis, fungal infections (particularly blastomycosis), and rarely in early tuberculous meningitis. 1

Primary Differential Diagnosis

Acute Bacterial Meningitis

  • Most common cause with typical CSF showing raised WCC (typically >100 cells/μL), neutrophil predominance, raised protein, and very low glucose/CSF-plasma glucose ratio 1
  • Common organisms include Streptococcus pneumoniae, Neisseria meningitidis, and Listeria monocytogenes 2
  • Opening pressure typically raised (>20 cm CSF), appearance turbid/cloudy/purulent 1
  • Critical caveat: 10% of bacterial meningitis cases may have <100 cells/mm³, especially early in illness 1

Partially Treated Bacterial Meningitis

  • Lymphocytic predominance may shift to neutrophilic if antibiotics given before LP 1
  • CSF sterilization occurs within 2 hours for meningococci and 4 hours for pneumococci after antibiotic administration 1
  • PCR remains useful with 87-100% sensitivity even after antibiotics 1

Early Viral Meningitis

  • Neutrophilic pleocytosis can occur early in enteroviral meningitis, though lymphocytic predominance typically develops later 1
  • Total CSF WCC unlikely to exceed 2000 cells/mm³ in viral disease 3
  • CSF protein only mildly raised, glucose normal or slightly low 1, 3
  • Approximately 50% of enterovirus infections show CSF pleocytosis 3

Fungal Meningitis

  • Blastomycotic meningitis can present with marked neutrophilic pleocytosis (>5,000 PMNs/mm³ reported) 4
  • More commonly shows lymphocytic predominance with raised protein and low glucose 1
  • Cytologic examination of CSF useful for establishing diagnosis 4

Other Considerations

  • Tuberculous meningitis: May show neutrophils early in disease course, though typically lymphocytic with markedly raised protein and very low glucose 1
  • Human Monocytic Ehrlichiosis: Neutrophilic pleocytosis sometimes seen early, though lymphocytic more common 3

Critical Management Pitfalls

Absence of Pleocytosis Does NOT Exclude Meningitis

  • Bacterial meningitis can occur without pleocytosis, especially early in illness or in immunocompromised patients 1, 5
  • Review of 124 cases showed primarily bacterial organisms (99 cases) with 31% mortality 5
  • Blood cultures positive in 71% of cases without CSF pleocytosis - always obtain as adjunct 5
  • If meningitis suspected, empiric antibiotics must be administered regardless of initial WBC count 5

Timing of Lumbar Puncture

  • LP should be performed within 1 hour of hospital arrival if no contraindications present 1
  • Contraindications requiring neuroimaging first: focal neurological signs, papilledema, continuous seizures, GCS ≤12 1
  • If LP delayed, start antibiotics immediately after blood cultures - do not wait 1
  • LP remains diagnostically useful even after several days of illness 3

Treatment Cannot Be Delayed

  • Most deaths occur within first 24 hours, often before specialist care begins 6
  • Treatment delay increases mortality - antibiotics should be given within first hour 1
  • In community settings, immediate IM benzylpenicillin or ceftriaxone upon suspicion without waiting for investigations 6

Diagnostic Algorithm

  1. Obtain blood cultures immediately (within 1 hour) 1
  2. Assess for LP contraindications - if present, obtain neuroimaging first then LP 1
  3. Perform LP within 1 hour if safe, documenting opening pressure, cell count with differential, protein, glucose (with concurrent plasma glucose) 1
  4. Send CSF for: Gram stain, culture, PCR (especially if prior antibiotics), and store additional CSF for further testing 1
  5. Start empiric antibiotics immediately after LP (or before if LP delayed): ceftriaxone + ampicillin + dexamethasone 7
  6. Add vancomycin or rifampicin in regions with critical pneumococcal resistance to third-generation cephalosporins 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Bacterial meningitis in the absence of cerebrospinal fluid pleocytosis: A case report and review of the literature.

The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale, 2014

Guideline

Cerebrospinal Fluid Analysis in Aseptic Meningitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Marked polymorphonuclear pleocytosis due to blastomycotic meningitis: case report and review.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 1994

Guideline

Meningococcemia Recognition and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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