Bacterial meningitis

Background

• Bacterial infection of meninges

Microbiology

• Adults 1
  • Streptococcus pneumoniae (70%)
  • Neisseria meningitidis (15%): more in young adults
  • Group B Streptococcus (10%)
  • Haemophilus influenzae (10%)
  • Listeria monocytogenes (5%): more in elderly ≥65 years, immunocompromised, alcoholics, and diabetes
• Infants ≤2 months old 1
  • Group B Streptococcus (90%)
  • Listeria monocytogenes, Streptococcus pneumoniae, others including Gram-negative bacilli
• Infants 2 months to 2 years 1
  • Streptococcus pneumoniae (50%)
  • Group B Streptococcus (20%)
  • Neisseria meningitidis (15%)
  • Haemophilus influenzae (10%)
• Head trauma or neurosurgery
  • Staphylococcus aureus
  • Gram-negative bacilli

Risk factors

• Immunosuppression
• Diabetes
• Splenic dysfunction or splenectomy (e.g. sickle cell)
• Alcoholism
• Recent neurosurgery
• CSF leak
• Shunt infections
• Head trauma
• Chronic otitis media

Clinical Presentation

• Typically, an acute onset of headache with fever and vomiting after viral prodrome
• Bacterial vs. aseptic/viral meningitis
• Headache or neck pain (70-80%)
• Fever (75%)
• Altered level of consciousness (70%)
• Clinical signs
  • Brudzinski's sign (unhelpful)
  • Kernig's sign (may be specific)
  • Jolt test (very sensitive)
  • Seizures or focal neurological deficits (rare, poor prognosis)
  • Rash (purpuric with Neisseria)
• Ask about recent travel and sick contacts

Investigations

• Lab
  • CBC with differential
  • Electrolytes
  • Liver enzymes
  • Blood cultures
• Imaging
  • CT head to rule out abscess or increased ICP
  • MRI head if suspicion for herpes encephalitis
    • Temporal lobe enhancement (usually unilateral)
• Other
  • Lumbar puncture after CT head

CSF Interpretation

• Gram stain positive
• Glucose <1.0
• CSF:blood glucose <0.23
• Protein >2.2
• WBC >2000
• PMNs >1180

Management

• Blood cultures before antibiotics
• Start empiric antibiotics and dexamethasone
  • Infants
  • Children
  • Adults
    • Ceftriaxone 2g bid
    • vancomycin 1g q12h
    • +/- ampicillin 2g 14h if >50
    • Dexamethasone 10mg q6h x72h
    • +/- acyclovir
  • >65 years old
    • Treat like immunocompromised
• CT head if reduced or altered level of consciousness
• Lumbar puncture
• Adjust antibiotics based on Gram stain and cultures

First- and second-line antimicrobials by organism

Organism	First-line	Second-line
Streptococcus pneumoniae (penicillin MIC ≤0.06)	penicillin G or ampicillin	third-generation cephalosporin or chloramphenicol
Streptococcus pneumoniae (penicillin MIC ≥0.12)	third-generation cephalosporin	cefipime or meropenem
Streptococcus pneumoniae (ceftriaxone MIC ≥1)	vancomycin plus a third-generation cephalosporin	fluoroquinolone
Neisseria meningitidis (penicillin MIC ≤0.06)	penicillin G or ampicillin	third-generation cephalosporin or chloramphenicol
Neisseria meningitidis (penicillin MIC ≥0.12)	third-generation cephalosporin	chloramphenicol, fluoroquinolone, or meropenem
Listeria monocytogenes	ampicillin or penicillin G	[[TMP-SMX] or meropenem
Streptococcus agalactiae	ampicillin or penicillin G	third-generation cephalosporin
E. coli and other Enterobacteriaceae	third-generation cephalosporin	ampicillin, meropenem, aztreonam, TMP-SMX, or ciprofloxacin
Pseudomonas aeruginosa	cefipime or ceftazidime	meropenem, aztreonam, or ciprofloxacin
ESBL Gram-negative bacillus	meropenem	cefepime or a fluoroquinolone
Haemophilus influenzae (β-lactamase negative)	ampicillin	third-generation cephalosporin, cefepime, chloramphenicol, or a fluoroquinolone
Haemophilus influenzae (β-lactamase positive)	third-generation cephalosporin	cefepime, chloramphenicol, or a fluoroquinolone
Staphylococcus aureus (methicillin-susceptible)	nafcillin or oxacillin	vancomycin
Staphylococcus aureus (methicillin-resistant)	vancomycin	daptomycin, TMP-SMX, or linezolid
Staphylococcus epidermidis	vancomycin	linezolid
Enterococcus species (ampicillin susceptible)	ampicillin plus gentamicin
Enterococcus species (ampicillin resistant)	vancomycin plus gentamicin
Enterococcus species (ampicillin and vancomycin resistant)	linezolid

Recommended antimicrobial dosages

Antimicrobial	Neonate (≤7 days)	Neonate (8 to 28 days)	Infants and children	Adults
amikacin	15-20 mg/kg divided q12h	30 mg/kg divided q8h	20-30 mg/kg divided q8h	15 mg/kg divided q8h
ampicillin	150 mg/kg divided q8h	200 mg/kg divided q6-8h	300 mg/kg divided q6h	12 g divided q4h
aztreonam				6-8 g divided q6-8g)
cefepime			150 mg/kg divided q8h	6 g divided q8h
cefotaxime	100-150 mg/kg divided q8-12h	150-200 mg/kg divided q6-8h	225-300 mg/kg divided q6-8h	8-12 g divided q4-6h
ceftazidime	100-150 mg/kg divided q8-12h	150 mg/kg divided q8h	150 mg/kg divided q8h	6 g divided q8h
ceftriaxone			80-100 mg/kg divided q12-24h	4 g divided q12-24h
chloramphenicol	25 mg/kg divided q24h	50 mg/kg divided q12-24h	75-100 mg/kg divided q6h	4-6 g divided q6h
ciprofloxacin				800-1200 mg divided q8-12h
gatifloxacin				400 mg divided q24h
gentamicin	5 mg/kg divided q12h	7.5 mg/kg divided q8h	7.5 mg/kg divided q8h	5 mg/kg divided q8h
meropenem			120 mg/kg divided q8h	6 g divided q8h
moxifloxacin				400 mg divided q24h
nafcillin	75 mg/kg divided q8-12h	100-150 mg/kg divided q6-8h	200 mg/kg divided q6h	9-12 g divided q4h
oxacillin	75 mg/kg divided q8-12h	150-200 mg/kg divided q6-8h	200 mg/kg divided q6h	9-12 g divided q4h
penicillin G	0.15 mU/kg divided q8-12h	0.2 mU/kg divided q6-8h	0.3 mU/kg divided q4-6h	24 mU divided q4h
rifampin		10-20 mg/kg divided q12h	10-20 mg/kg divided q12-24h	600 mg divided q24h
tobramycin	5 mg/kg divided q12h	7.5 mg/kg divided q8h	7.5 mg/kg divided q8h	5 mg/kg divided q8h
TMP-SMX			10-20 mg/kg divided q6-12h	10-20 mg/kg divided q6-12h
vancomycin	20-30 mg/kg divided q8-12h	30-45 mg/kg divided q6-8h	60 mg/kg divided q6h	30-45 mg/kg divided q8-12h

Complications

• Cerebral edema with raised ICP
• Hydrocephalus
• Seizures
• Arterial ischemia or infarction
• SIADH
• Subdural effusion or subdural empyema
• Venous sinus thrombosis
• Cranial nerve palsies, especially deafness