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bacterial meningitis

Inflammation of the membranes of the brain or spinal cord. Etiology: 1) neonates a) group B streptococcus b) Escherichia coli c) Listeria monocytogenes d) Gm- rods vs Gm+ cocci associated with antepartum antibiotics [6] 2) Infants & toddlers (3 months - 2 years, the highest incidence of meningitis is in this age-group) a) Streptococcus pneumonia (most common) [20] b) Haemophilus influenzae uncommon since introduction of HiB vaccine [20] c) Neisseria meningitidis 3) older children & adolescents a) Streptococcus pneumoniae b) Neisseria meningitis c) Haemophilus influenzae 4) adults a) Streptococcus pneumoniae 58% d) Streptococcus agalactiae 18% c) Neisseria meningitis 14% d) Haemophilus influenzae 7% b) Listeria monocytogenes 3% 5) hospital-acquired - Staphylococcus - gram negative rods [8] 6) complication of surgical procedures or trauma a) craniotomy b) external lumbar catheters c) head trauma (basilar skull fracture) d) infection rates may be as high as 25% [9] Epidemiology: - < 75/100,000 per year in children age <1 year - 21% decrease in annual incidence from 1993 to 2011 - decrease mainly due to N meningitidis, H influenzae & S pneumoniae - 41% of all cases in 1993 but only 24% in 2011 - increases in meningitis (1993 to 2011) due to - Staphylococcus aureus - gram-negative bacteria - Klebsiella pneumoniae - Escherichia coli - Pseudomonas aeruginosa Clinical manifestations: 1) headache 2) fever 3) nausea/vomiting 4) photophobia 5) stiff neck, nuchal rigidity 6) seizures 7) Kernig's sign 8) Brudzinski's sign 9) purpura or petechiae 10) tachycardia 11) altered mental status - irritability, lethargy 12) recent infection may be noted - otitis, sinusitis, URI Laboratory: 1) blood cultures: - prior to antibiotics* - positive in 50% of bacterial meningitis cases 2) cerebrospinal fluid (head CT prior to lumbar puncture)* a) increased opening pressure of 200-500 mm Hg b) decreased CSF glucose (< 40 mg/dL) c) increased CSF protein (100-500 mg/dL) d) WBC count 1000-5,000/mm3, predominantly neutrophils - neoates (median) 1217/mm3 gram-negative rods vs. 167/mm3 gram-positive cocci [6] e) gram stain positive for organisms 60-90% of time f) culture positive in 70-85% of cases [8] - up to 50% of hospital-acquired infections may be culture negative [8] g) Streptococcus pneumoniae antigen in CSF [8] h) multiplex PCR assay can detect 14 pathogens in 1 hour [8] i) latex agglutination for CSF antigens: 1] indications: a] CSF findings consistent with bacterial meningitis b] gram stain is negative c] not recommended, rarely affects management [8] 2] organisms detected a] Streptococcus pneumonia b] Haemophilus influenzae c] Neisseria meningitidis j) heparin-binding protein k) tuberculosis 1] WBC < 300/mm3, predominantly lymphocytes 2] CSF protein < 300 mg/dL [8] 3] CSF glucose < 40 mg/dL 3) CH50 for repeated episodes of Neisseria meningitidis 4) serum CRP > 20 mg/L, serum procalcitonin > 0.5 mg/mL, CSF protein > 0.5 g/L, positive CSF gram stain best predicators of bacterial meningitis [8] 5) see ARUP consult [12] * sequence in managing patient with suspected bacterial meningitis: - blood cultures, empiric antibiotics +/- dexamethasone, head CT, lumbar puncture (if cleared by head CT) - blood cultures, lumbar puncture, empiric antibiotics +/- dexamethasone * Conflicting sequences reported in NEJM knowledge+ - the 2nd of the 2, reported in Neurology module, the 1st of the 2 may have been reported in Infectious disease module Radiology: - computed tomography (head CT) prior to lumbar puncture - identify potential for brain stem herniation* - may identify site(s) of CSF leakage [9] * risk factors for brain stem herniation - focal neurologic signs - immunocompromised patient - history of CNS disease - hypertension & bradycardia - papilledema - respiratory abnormalities - new onset seizures - moderate-severe impairment of consciousness Differential diagnosis: 1) brain abscess 2) subarachnoid hemorrhage 3) epidural abscess 4) viral encephalitis 5) CNS symptoms may occur with connective tissue disease, including lupus erythematosus & polyarteritis nodosa Management: 1) neonates a) ampicillin 100-200 mg/kg/day divided every 6 hours b) gentamicin 7.5 mg/kg/day divided every 8 hours c) cefotaxime 50-100 mg/kg/day divided every 12 hours d) prognosis: higher mortality with gram-negative rods than gram-positive cocci (13% vs 4%) 2) children & adolescents a) vancomycin b) 3rd generation cephalosporin 1] cefotaxime 50-100 mg/kg/day divided every 12 hours 2] ceftriaxone 100 mg/kg/day divided every 12 hours c) ampicillin 100-200 mg/kg/day divided every 6 hours (Listeria) 3) adults (double or triple antibiotic therapy + dexamethasone) [8] a) vancomycin + 3rd generation cephalosporin +/- ampicillin* + dexamethasone for empiric therapy [8] - *ampicillin coverage for Listeria not necessary for immunocompetent patients < 50 years of age [8] - include gentamicin with ampicillin if Listeria likely (Gram-positive rods) - include acyclovir if Herpes encephalitis is a concern [24] - for beta-lactam allergy - moxifloxacin instead of cephalosporin - trimethoprim/sulfamethoxazole instead of ampicillin [8] - treat as nosocomial meningitis if Pseudomonas suspected b) vancomycin + 3rd generation cephalosporin + dexamethasone (4 days) with antimicrobials for Streptococcus pneumoniae [8,14] - risk of ceftriaxone-resistant Streptococcus pneumoniae [24] c) 3rd generation cephalosporin for Neisseria meningitidis or Haemophilus influenzae [8] 1] cefotaxime 1 gram every 8 hours 2] ceftriaxone 1 g every 12 hours 3] ceftazidime 1.5 grams every 8 hours if Pseudomonas suspected d) ampicillin 2 grams every 6 hours (Listeria) 1] optional as empiric therapy in patients < 50 years of age 2] not indicated for empiric therapy if basilar skull fracture [8] e) dexamethasone reduces mortality - recommended as adjunctive therapy for all patients [8] 4) nosocomial or post neurosurgery or CSF shunt a) vancomycin plus ceftazidime, cefepime or meropenem [8,9] - gram-negative coverage for Pseudomonas aeruginosa & Acinetobacter baumannii [8,9] - piperacillin-tazobactam (Zosyn) has poor penetration into CSF b) intravenous & intraventricular antimicrobial therapy (usually vancomycin or gentamicin) may be required to eradicate infection, especially in patients with multidrug-resistant gram-negative bacilli (e.g., Acinetobacter baumannii) c) removal of infected external or internal ventricular catheter 5) duration of therapy a) intravenous (IV) antibiotics for 10-14 days b) IV antibiotics for 21 days if pathogen in Gm- bacillus 6) if patient does not improve clinically within 24 hours a) chloramphenicol b) vancomycin 7) repeat lumbar puncture (LP) unnecessary if patient is clinically improving 8) limit IV fluids in infants & children to <2/3 maintenance to diminish risk of cerebral edema 9) maintain head of bed > 30 degrees may diminish increased intracranial pressure [8] 10) dexamethasone 10 mg IV every 6 hours for 4 days - diminishes morbidity & mortality [3,8] - non-significant reduction in mortality [13] - significant reduction in mortality for S pneumoniae meningitis (RR=0.84) [13] - reduces risk of severe hearing loss for H influenzae meningitis (RR=0.34) [13] - begin 15 minutes prior to antibiotic administration [8] - consider discontinuing if S pneumoniae not isolated from CSF or blood [18] - no beneficial effect of glucocorticoids in low-income countries [13] - increases risk of recurrent fever [13] 11) prophylaxis: a) meningococcal polysaccharide vaccine, especially students living in dormatories or other situations where contagious disease may spread rapidly - not effective against serogroup B b) meningococcal serogroup B vaccine c) pediatric immunization programs that include the Haemophilus influenzae type B vaccine & heptavalent protein-polysaccharide pneumococcal conjugate vaccines have reduced incidence of bacterial meningitis but not mortality [11] 12) tuberculosis a) isoniazid 1] 15-20 mg/kg/day (max 500 mg/day) in children 2] 8-10 mg/kg/day (max 300 mg/day) in adults 3] QD or BID b) rifampin 1] 15-20 mg/kg/day (max 600 mg/day) 2] QD or BID c) dexamethasone for 4-6 weeks may be of benefit [5] Follow-up: 1) adults do not need follow-up because neurologic sequellae are rare with appropriate therapy 2) test hearing in children

Interactions

disease interactions

Related

meningococcal polysaccharide vaccine (Menomune-A/C/Y/W-135, MenACWY-CRM, Menactra, MenACYW-D) meningococcal serogroup B vaccine (Bexsero, Trumenba, 4CMenB)

Specific

tuberculous meningitis

General

bacterial infection meningitis

References

  1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1063-64
  2. Contributions from Robert Libke, MD, Dept of Medicine, UCSF Fresno
  3. Journal Watch 22(24):179, 2002 de Gans J & van de Beek D Dexamethasone in adults with bacterial meningitis. N Engl J Med 347:1549, 2002 PMID: 12432041 Tunkel AR & Scheld WM N Engl J Med 347:1613, 2002 (commentary)
  4. Journal Watch 24(24):184, 2004 van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB, Vermeulen M. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med. 2004 Oct 28;351(18):1849-59. PMID: 15509818 - Swartz MN Bacterial meningitis--a view of the past 90 years. N Engl J Med. 2004 Oct 28;351(18):1826-8. No abstract. PMID: 15509815
  5. Journal Watch 24(24):185, 2004 Thwaites GE, Nguyen DB, Nguyen HD, Hoang TQ, Do TT, Nguyen TC, Nguyen QH, Nguyen TT, Nguyen NH, Nguyen TN, Nguyen NL, Nguyen HD, Vu NT, Cao HH, Tran TH, Pham PM, Nguyen TD, Stepniewska K, White NJ, Tran TH, Farrar JJ. Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults. N Engl J Med. 2004 Oct 21;351(17):1741-51. PMID: 15496623
  6. Smith PB et al, A comparison of neonatal gram-negative rod and gram-positive cocci meningitis. J Perinatol 2006; 26:111 PMID: 16435007
  7. Dubos F et al, Serum procalcitonin and other biologic markers to distinguish between bacterial and aseptic meningitis J Pediatr 2006, 149:71 PMID: 16860131
  8. Medical Knowledge Self Assessment Program (MKSAP) 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 2006, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  9. van de Beek D et al Nosocomial bacterial meningitis. N Engl J Med 2010 Jan 14; 362:146. PMID: 20071704
  10. Linder A et al. Heparin-binding protein: A diagnostic marker of acute bacterial meningitis. Crit Care Med 2011 Apr; 39:812. PMID: 21200320
  11. Thigpen MC et al. Bacterial meningitis in the United States, 1998-2007. N Engl J Med 2011, May 26; 364:2016. PMID: 21612470
  12. ARUP Consult: Meningitis, Acute deprecated reference
  13. The NNT: Glucocorticoid Steroids for Bacterial Meningitis. http://www.thennt.com/nnt/steroids-for-meningitis/ - Brouwer MC, McIntyre P, de Gans J, Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2010 Sep 8;(9):CD004405 PMID: 20824838 - Brouwer MC, McIntyre P, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2013 Jun 4;6:CD004405 PMID: 23733364
  14. Brouwer MC, Tunkel AR, van de Beek D. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev. 2010 Jul;23(3):467-92 PMID: 20610819
  15. Pellegrino P et al. Epidemiological analysis on two decades of hospitalisations for meningitis in the United States. Eur J Clin Microbiol Infect Dis 2014 Apr 23 PMID: 24756210 http://link.springer.com/article/10.1007%2Fs10096-014-2102-2
  16. Manian FA, Alame D Case records of the Massachusetts General Hospital. Case 11-2015. A 28-year-old woman with headache, fever, and a rash. N Engl J Med. 2015 Apr 9;372(15):1454-62 PMID: 25853750 http://www.nejm.org/doi/full/10.1056/NEJMcpc1415165
  17. van de Beek D, Brouwer MC, Thwaites GE, Tunkel AR. Advances in treatment of bacterial meningitis. Lancet. 2012 Nov 10;380(9854):1693-702. Review. PMID: 23141618
  18. Hamnvik OPR How Do You Approach a Patient with Suspected Bacterial Meningitis? NEJM Knowledge+. July 26, 2018 https://knowledgeplus.nejm.org/blog/suspected-bacterial-meningitis/
  19. van de Beek D, Brouwer M, Hasbun R, Koedel U, Whitney CG, Wijdicks E. Community-acquired bacterial meningitis. Nat Rev Dis Primers. 2016 Nov 3;2:16074. Review. PMID: 27808261
  20. NEJM Knowledge+ Question of the Week. Dec 17, 2019 https://knowledgeplus.nejm.org/question-of-week/4763/ - Ku LC, Boggess KA, Cohen-Wolkowiez M. Bacterial meningitis in infants. Clin Perinatol 2015 Mar; 42:29 PMID: 25677995 Free PMC Article
  21. Hasbun R Progress and Challenges in Bacterial Meningitis. A Review. JAMA. 2022;328(21):2147-2154. Dec 6 PMID: 36472590 https://jamanetwork.com/journals/jama/fullarticle/2799148
  22. van de Beek D, de Gans J, Tunkel AR, Wijdicks EF. Community-acquired bacterial meningitis in adults. N Engl J Med. 2006 Jan 5;354(1):44-53 PMID: 16394301 Review.
  23. Hasbun R. Update and advances in community acquired bacterial meningitis. Curr Opin Infect Dis. 2019 Jun;32(3):233-238. PMID: 31021955 Review.
  24. NEJM Knowledge+
  25. NINDS Encephalitis and Meningitis Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Meningitis-and-Encephalitis-Information-Page