Bacterial meningitis: Difference between revisions

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==Background==
==Background==

* Bacterial infection of meninges
*Bacterial infection of meninges and subarachnoid space (i.e. [[meningitis]])


===Microbiology===
===Microbiology===

* Adults [[CiteRef::thigpen2011ba]]
*Adults [[CiteRef::thigpen2011ba]]
** ''[[Streptococcus pneumoniae]]'' (70%)
** ''[[Neisseria meningitidis]]'' (15%): more in young adults
**''[[Streptococcus pneumoniae]]'' (70%)
**''[[Neisseria meningitidis]]'' (15%): more in young adults
** [[Group B Streptococcus]] (10%)
** ''[[Haemophilus influenzae]]'' (10%)
**[[Group B Streptococcus]] (10%)
**''[[Haemophilus influenzae]]'' (10%)
** ''[[Listeria monocytogenes]]'' (5%): more in elderly ≥65 years, immunocompromised, alcoholics, and diabetes
**''[[Listeria monocytogenes]]'' (5%): more in elderly ≥65 years, immunocompromised, alcoholics, and diabetes
* Infants ≤2 months old [[CiteRef::thigpen2011ba]]
*Infants ≤2 months old [[CiteRef::thigpen2011ba]]
** [[Group B Streptococcus]] (90%)
** [[Listeria monocytogenes]], [[Streptococcus pneumoniae]], others including Gram-negative bacilli
**[[Group B Streptococcus]] (90%)
**[[Listeria monocytogenes]], [[Streptococcus pneumoniae]], others including Gram-negative bacilli
* Infants 2 months to 2 years [[CiteRef::thigpen2011ba]]
*Infants 2 months to 2 years [[CiteRef::thigpen2011ba]]
** ''[[Streptococcus pneumoniae]]'' (50%)
** [[Group B Streptococcus]] (20%)
**''[[Streptococcus pneumoniae]]'' (50%)
** ''[[Neisseria meningitidis]]'' (15%)
**[[Group B Streptococcus]] (20%)
** ''[[Haemophilus influenzae]]'' (10%)
**''[[Neisseria meningitidis]]'' (15%)
**''[[Haemophilus influenzae]]'' (10%)
* Head trauma or neurosurgery
*Neurosurgery
** ''[[Staphylococcus aureus]]''
**''[[Staphylococcus aureus]]''
** Gram-negative bacilli
**[[Gram-negative bacilli]], including [[Pseudomonas aeruginosa]]
*Basal skull fracture
**[[Streptococcus pneumoniae]]
**[[Haemophilus influenzae]]
**[[Streptococcus pyogenes]]
*Asplenia
**[[Streptococcus pneumoniae]]
**[[Neisseria meningitidis]]
**[[Haemophilus influenzae]]
*Relatively immunocompromised (alcohol use disorder, diabetes, malignancy, chemotherapy)
**[[Listeria monocytogenes]]
**[[Gram-negative bacilli]]
*[[Strongyloides]] hyperinfection
**Gut flora


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


*Immunosuppression
==Clinical Presentation==
*[[Diabetes]]
* Typically, an acute onset of headache with fever and vomiting after viral prodrome
*[[Hyposplenism]] or [[splenectomy]] (e.g. sickle cell)
* Bacterial vs. aseptic/viral meningitis
*[[Alcohol use disorder]]
* Headache or neck pain (70-80%)
*Recent neurosurgery
* Fever (75%)
*[[CSF leak]]
* Altered level of consciousness (70%)
*[[Ventricular shunt infection]]
* Clinical signs
*Head trauma
** Brudzinski's sign (unhelpful)
*[[Otitis media|Chronic otitis media]]
** Kernig's sign (may be specific)

** Jolt test (very sensitive)
==Clinical Manifestations==
** Seizures or focal neurological deficits (rare, poor prognosis)

** Rash (purpuric with ''Neisseria'')
*Typically, an acute onset of headache, neck stiffness, fever, and photophobia
* Ask about recent travel and sick contacts
**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 (petechial or purpuric with ''Neisseria'')
*Ask about recent travel and sick contacts


==Investigations==
==Investigations==

* Lab
*[[Lumbar puncture]] after CT head (if needed), sent for Gram stain, culture, viral PCR, cell count with differential, protein, ± cryptococcal antigen, ± fungal cultures
** CBC with differential
*Lab
** Electrolytes
**CBC with differential
** Liver enzymes
**Electrolytes
** Blood cultures
**Liver enzymes
* Imaging
**Blood cultures
** CT head to rule out abscess or increased ICP
*Imaging
** MRI head if suspicion for herpes encephalitis
**CT head to rule out abscess or increased ICP
*** Temporal lobe enhancement (usually unilateral)
**MRI head if suspicion for herpes encephalitis
* Other
***Temporal lobe enhancement (usually unilateral)
** Lumbar puncture after CT head


===CSF Interpretation===
===CSF Interpretation===

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


==Management==
==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


*Blood cultures before antibiotics, if possible
===Recommended antimicrobial dosages===
*Start empiric antibiotics and dexamethasone
**Infants
**Children
**Adults
***[[Ceftriaxone]] 2g bid plus [[vancomycin]] 1g q12h +/- [[ampicillin]] 2g 14h if >50
***[[Dexamethasone]] 10mg q6h x72h (stopped if not [[Streptococcus pneumoniae]] or [[Haemophilus influenzae]])
****Prevents severe hearing loss, neurologic sequelae, and mortality in pneumococcal meningitis
****Continue for 3-4 days
***Consider empiric [[acyclovir]], as well, until confirmed to be bacterial
**>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

===Antimicrobials By Organism===
{| class="wikitable sortable"
!Organism!!First-line!!Second-line
!Duration
|-
|''[[Streptococcus pneumoniae]]'' ([[penicillin]] MIC ≤0.06)||[[penicillin G]] or [[ampicillin]]||third-generation cephalosporin or [[chloramphenicol]]
| rowspan="3" |10-14 days
|-
|''[[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]]
| rowspan="2" |7 days
|-
|''[[Neisseria meningitidis]]'' (penicillin MIC ≥0.12)||third-generation cephalosporin||[[chloramphenicol]], fluoroquinolone, or [[meropenem]]
|-
|''[[Listeria monocytogenes]]''||[[ampicillin]] or [[penicillin G]]||[[TMP-SMX]] or [[meropenem]]
|≥21 days
|-
|''[[Streptococcus agalactiae]]''||[[ampicillin]] or [[penicillin G]]||third-generation cephalosporin
|14-21 days
|-
|''[[E. coli]]'' and other [[Enterobacteriaceae]]||third-generation cephalosporin||[[ampicillin]], [[meropenem]], [[aztreonam]], [[TMP-SMX]], or [[ciprofloxacin]]
| rowspan="3" |21 days
|-
|''[[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
| rowspan="2" |7 days
|-
|''[[Haemophilus influenzae]]'' (β-lactamase positive)||third-generation cephalosporin||[[cefepime]], [[chloramphenicol]], or a fluoroquinolone
|-
|''[[Staphylococcus aureus]]'' (methicillin-susceptible)||[[nafcillin]] or [[oxacillin]]||[[vancomycin]]
| rowspan="2" |
|-
|''[[Staphylococcus aureus]]'' (methicillin-resistant)||[[vancomycin]]||[[daptomycin]], [[TMP-SMX]], or [[linezolid]]
|-
|''[[Staphylococcus epidermidis]]''||[[vancomycin]]||[[linezolid]]
|
|-
|''[[Enterococcus]]'' species (ampicillin susceptible)||[[ampicillin]] plus [[gentamicin]]||
| rowspan="3" |
|-
|''[[Enterococcus]]'' species (ampicillin resistant)||[[vancomycin]] plus [[gentamicin]]||
|-
|''[[Enterococcus]]'' species (ampicillin and vancomycin resistant)||[[linezolid]]||
|-
|No organism identified
|[[ceftriaxone]]
|
|10 days
|}

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


==Complications==
==Complications==

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


[[Category:CNS infections]]
[[Category:CNS infections]]

Latest revision as of 13:35, 27 October 2023

Background

  • Bacterial infection of meninges and subarachnoid space (i.e. meningitis)

Microbiology

Risk factors

Clinical Manifestations

  • Typically, an acute onset of headache, neck stiffness, fever, and photophobia
    • 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 (petechial or purpuric with Neisseria)
  • Ask about recent travel and sick contacts

Investigations

  • Lumbar puncture after CT head (if needed), sent for Gram stain, culture, viral PCR, cell count with differential, protein, ± cryptococcal antigen, ± fungal cultures
  • 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)

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, if possible
  • Start empiric antibiotics and dexamethasone
  • CT head if reduced or altered level of consciousness
  • Lumbar puncture
  • Adjust antibiotics based on Gram stain and cultures

Antimicrobials By Organism

Organism First-line Second-line Duration
Streptococcus pneumoniae (penicillin MIC ≤0.06) penicillin G or ampicillin third-generation cephalosporin or chloramphenicol 10-14 days
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 7 days
Neisseria meningitidis (penicillin MIC ≥0.12) third-generation cephalosporin chloramphenicol, fluoroquinolone, or meropenem
Listeria monocytogenes ampicillin or penicillin G TMP-SMX or meropenem ≥21 days
Streptococcus agalactiae ampicillin or penicillin G third-generation cephalosporin 14-21 days
E. coli and other Enterobacteriaceae third-generation cephalosporin ampicillin, meropenem, aztreonam, TMP-SMX, or ciprofloxacin 21 days
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 7 days
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
No organism identified ceftriaxone 10 days

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

References

  1. a b c  Michael C. Thigpen, Cynthia G. Whitney, Nancy E. Messonnier, Elizabeth R. Zell, Ruth Lynfield, James L. Hadler, Lee H. Harrison, Monica M. Farley, Arthur Reingold, Nancy M. Bennett, Allen S. Craig, William Schaffner, Ann Thomas, Melissa M. Lewis, Elaine Scallan, Anne Schuchat. Bacterial Meningitis in the United States, 1998–2007. New England Journal of Medicine. 2011;364(21):2016-2025. doi:10.1056/nejmoa1005384.

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