Diagnostic Considerations

Diagnoses to consider aside from meningitis include the following:

Noninfectious meningitis, including medication-induced meningeal inflammation
Meningeal carcinomatosis
Central nervous system (CNS) vasculitis
Stroke
Encephalitis
All causes of altered mental status and coma
Leptospirosis
Subdural empyema
Parameningeal foci of infection
Seizures
Migraine
Infective endocarditis

Differential Diagnoses

Brain Abscess
Brain Neoplasms
Delirium Tremens (DTs)
Emergent Management of Subarachnoid Hemorrhage
Encephalitis
Febrile Seizures
Herpes Simplex Encephalitis
Herpes Simplex Virus (HSV) in Emergency Medicine
Pediatrics, Meningitis and Encephalitis

Differential Diagnoses

Brain Abscess
Brain Neoplasms
Delirium Tremens (DTs)
Emergent Management of Subarachnoid Hemorrhage
Encephalitis
Febrile Seizures
Herpes Simplex Encephalitis
Herpes Simplex Virus (HSV) in Emergency Medicine
Pediatrics, Meningitis and Encephalitis

Workup

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Media Gallery

Pneumococcal meningitis in a patient with alcoholism. Courtesy of the CDC/Dr. Edwin P. Ewing, Jr.
Acute bacterial meningitis. This axial nonenhanced computed tomography scan shows mild ventriculomegaly and sulcal effacement.
Acute bacterial meningitis. This axial T2-weighted magnetic resonance image shows only mild ventriculomegaly.
Acute bacterial meningitis. This contrast-enhanced, axial T1-weighted magnetic resonance image shows leptomeningeal enhancement (arrows).
Chronic mastoiditis and epidural empyema in a patient with bacterial meningitis. This axial computed tomography scan shows sclerosis of the temporal bone (chronic mastoiditis), an adjacent epidural empyema with marked dural enhancement (arrow), and the absence of left mastoid air.
Subdural empyema and arterial infarct in a patient with bacterial meningitis. This contrast-enhanced axial computed tomography scan shows left-sided parenchymal hypoattenuation in the middle cerebral artery territory, with marked herniation and a prominent subdural empyema.

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Table 1. Most Common Bacterial Pathogens on Basis of Age and Predisposing Risks

Risk or Predisposing Factor	Bacterial Pathogen
Age 0-4 weeks	Streptococcus agalactiae (GBS) Escherichia coli K1 Listeria monocytogenes
Age 4-12 weeks	S agalactiae E coli Haemophilus influenzae Streptococcus pneumoniae Neisseria meningitidis
Age 3 months to 18 years	N meningitidis S pneumoniae H influenzae
Age 18-50 years	S pneumoniae N meningitidis H influenzae
Age >50 years	S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli
Immunocompromised state	S pneumoniae N meningitidis L monocytogenes Aerobic gram-negative bacilli
Intracranial manipulation, including neurosurgery	Staphylococcus aureus Coagulase-negative staphylococci Aerobic gram-negative bacilli, including Pseudomonas aeruginosa
Basilar skull fracture	S pneumoniae H influenzae Group A streptococci
CSF shunts	Coagulase-negative staphylococci S aureus Aerobic gram-negative bacilli Propionibacterium acnes
CSF = cerebrospinal fluid; GBS = group B streptococcus.

Table 2. Infectious Agents Causing Aseptic Meningitis

Category	Agent
Bacteria	Partially treated bacterial meningitis Listeria monocytogenes Brucella spp Rickettsia rickettsii Ehrlichia spp Mycoplasma pneumoniae Borrelia burgdorferi Treponema pallidum Leptospira spp Mycobacterium tuberculosis Nocardia spp
Parasites	Naegleria fowleri Acanthamoeba spp Balamuthia spp Angiostrongylus cantonensis Gnathostoma spinigerum Baylisascaris procyonis Strongyloides stercoralis Taenia solium (cysticercosis) Toxocara spp
Fungi	Cryptococcus neoformans Coccidioides immitis Blastomyces dermatitidis Histoplasma capsulatum Candida spp Aspergillus spp
Viruses	Enterovirus	Poliovirus Echovirus Coxsackievirus A Coxsackievirus B Enterovirus 68-71
	Herpesvirus (HSV)	HSV-1 and HSV-2 Varicella-zoster virus Epstein-Barr virus Cytomegalovirus HHV-6 and HHV-7
	Paramyxovirus	Mumps virus Measles virus
	Togavirus	Rubella virus
	Flavivirus	West Nile virus Japanese encephalitis virus St Louis encephalitis virus
	Bunyavirus	California encephalitis virus La Crosse encephalitis virus
	Alphavirus	Eastern equine encephalitis virus Western equine encephalitis virus Venezuelan encephalitis virus
	Reovirus	Colorado tick fever virus
	Arenavirus		LCM virus
	Rhabdovirus		Rabies virus
	Retrovirus		HIV
HHV = human herpesvirus; HSV = herpes simplex virus; LCM = lymphocytic choriomeningitis.

Table 3. Causes of Chronic Meningitis

Category	Agent
Bacteria	Mycobacterium tuberculosis Borrelia burgdorferi Treponema pallidum Brucella spp Francisella tularensis Nocardia spp Actinomyces spp
Fungi	Cryptococcus neoformans Coccidioides immitis Blastomyces dermatitidis Histoplasma capsulatum Candida albicans Aspergillus spp Sporothrix schenckii
Parasites	Acanthamoeba spp Naegleria fowleri Angiostrongylus cantonensis Gnathostoma spinigerum Baylisascarisprocyonis Schistosoma spp Strongyloides stercoralis Echinococcus granulosus

Table 4. Changing Epidemiology of Acute Bacterial Meningitis in United States*

Bacteria	1978-1981	1986	1995	1998-2007
Haemophilus influenzae	48%	45%	7%	6.7%
Listeria monocytogenes	2%	3%	8%	3.4%
Neisseria meningitidis	20%	14%	25%	13.9%
Streptococcus agalactiae (group B streptococcus)	3%	6%	12%	18.1%
Streptococcus pneumoniae	13%	18%	47%	58%
*Nosocomial meningitis is not included; these data include only the 5 major meningeal pathogens.

Other Exposures and Organisms Associated with Meningitis

Animal exposure	Organism associated with meningitis
Dog	Brucella B henselae C canimorus C cynodegmi Leptospira M avium P multocida Rabies
Cat	B henselae C canimorsus C cynodegmi M avium P multocida
Cow	B anthracis Brucella C fetus C burnetii Leptospira M bovis
Sheep	Brucella C fetus C burnetii
Pig	Brucella Leptospira M avium M bovis P multocida S suis
Goat	Brucella C fetus C burnetiid S equi
Horse	Leptospira M avium S equi
Rabbits/squirrel	F tularensis Leptospira M avium Yersinia pestis
Fish	Streptococcus iniae
Rodents (hamster, rats, mice)	Lymphocytic choriomeningitis virus
Mosquito	Yellow fever Plasmodium sp ( Malaria ) Japanese encephalitis West Nile Virus St Louis California encephalitis group of viruses Dengue virus Chikungunya virus Zika virus
Bats	Rabies Australian Bat Lyssavirus Nipah Virus
Ticks	Borrelia burgdorferi (Lyme’s disease) Ehrlichia Rocky Mountain spotted fever Anaplasma Powassan virus Coltivirus (Colarado tick fever)
Sandflies	Toscana virus

Table 6. CSF Findings in Meningitis by Etiologic Agent

Agent	Opening Pressure (mm H₂O)	WBC count (cells/µL)	Glucose (mg/dL)	Protein (mg/dL)	Microbiology
Bacterial meningitis	200-300	100-5000; >80% PMNs	< 40	>100	Specific pathogen demonstrated in 60% of Gram stains and 80% of cultures
Viral meningitis	90-200	10-300; lymphocytes	Normal, reduced in LCM and mumps	Normal but may be slightly elevated	Viral isolation, PCR assays
Tuberculous meningitis	180-300	100-500; lymphocytes	Reduced, < 40	Elevated, >100	Acid-fast bacillus stain, culture, PCR
Cryptococcal meningitis	180-300	10-200; lymphocytes	Reduced	50-200	India ink, cryptococcal antigen, culture
Aseptic meningitis	90-200	10-300; lymphocytes	Normal	Normal but may be slightly elevated	Negative findings on workup
Normal values	80-200	0-5; lymphocytes	50-75	15-40	Negative findings on workup
LCM = lymphocytic choriomeningitis; PCR = polymerase chain reaction; PMN = polymorphonuclear leukocyte; WBC = white blood cell.

Table 7. Comparison of CSF Findings by Type of Organism

Normal Finding	Bacterial Meningitis	Viral Meningitis*	Fungal Meningitis**
Pressure (mm H₂O) 50-150	Increased	Normal or mildly increased	Normal or mildly increased in tuberculous meningitis; may be increased in fungal; AIDS patients with cryptococcal meningitis have increased risk of blindness and death unless kept below 300 mm H₂O
Cell count (mononuclear cells/µL) Preterm: 0-25 Term: 0-22 >6 months: 0-5	No cell count result can exclude bacterial meningitis; PMN count typically in 1000s but may be less dramatic or even normal (classically, in very early meningococcal meningitis and in extremely ill neonates); lymphocytosis with normal CSF chemistries seen in 15-25%, especially when cell counts < 1000 or with partial treatment; ~90% of patients with ventriculoperitoneal shunts who have CSF WBC count >100 are infected; CSF glucose is usually normal, and organisms are less pathogenic; cell count and chemistries normalize slowly (over days) with antibiotics	Cell count usually < 500, nearly 100% mononuclear; up to 48 hours, significant PMN pleocytosis may be indistinguishable from early bacterial meningitis; this is particularly true with eastern equine encephalitis; presence of nontraumatic RBCs in 80% of HSV meningoencephalitis, though 10% have normal CSF results	Hundreds of mononuclear cells
Microscopy No organisms	Gram stain 80% sensitive; inadequate decolorization may mistake Haemophilus influenzae for gram-positive cocci; pretreatment with antibiotics may affect stain uptake, causing gram-positive organisms to appear gram-negative and decrease culture yield by average of 20%	No organism	India ink is 50% sensitive for fungi; cryptococcal antigen is 95% sensitive; AFB stain is 40% sensitive for tuberculosis (increase yield by staining supernatant from at least 5 mL CSF)
Glucose Euglycemia: >50% serum Hyperglycemia: >30% serum Wait 4 hr after glucose load	Decreased	Normal	Sometimes decreased; aside from fulminant bacterial meningitis, lowest levels of CSF glucose are seen in tuberculous meningitis, primary amebic meningoencephalitis, and neurocysticercosis
Protein (mg/dL) Preterm: 65-150 Term: 20-170 >6 months: 15-45	Usually >150, may be >1000	Mildly increased	Increased; >1000 with relatively benign clinical presentation suggestive of fungal disease
AFB = acid-fast bacillus; CSF = cerebrospinal fluid; HSV = herpes simplex virus; RBC = red blood cell; PMN = polymorphonuclear leukocyte. Some bacteria (eg, Mycoplasma, Listeria, Leptospira spp, Borrelia burgdorferi [Lyme], and spirochetes) produce spinal fluid alterations that resemble the viral profile. An aseptic profile also is typical of partially treated bacterial infections (>33% of patients have received antimicrobial treatment, especially children) and the 2 most common causes of encephalitis—the potentially curable HSV and arboviruses. *In contrast, tuberculous meningitis and parasites resemble the fungal profile more closely.

Table 7. Recommended Empiric Antibiotics for Suspected Bacterial Meningitis, According to Age or Predisposing Factors ^[43]

Age or Predisposing Feature	Antibiotics
Age 0-4 wk	Ampicillin plus either cefotaxime or an aminoglycoside
Age 1 mo-50 y	Vancomycin plus cefotaxime or ceftriaxone*
Age >50 y	Vancomycin plus ampicillin plus ceftriaxone or cefotaxime plus vancomycin*
Impaired cellular immunity	Vancomycin plus ampicillin plus either cefepime or meropenem
Recurrent meningitis	Vancomycin plus cefotaxime or ceftriaxone
Basilar skull fracture	Vancomycin plus cefotaxime or ceftriaxone
Head trauma, neurosurgery, or CSF shunt	Vancomycin plus ceftazidime, cefepime, or meropenem
CSF = cerebrospinal fluid. Add ampicillin if Listeria monocytogenes* is a suspected pathogen.

Table 8. Specific Antibiotics and Duration of Therapy for Acute Bacterial Meningitis

Bacteria	Susceptibility	Antibiotic(s)	Duration (days)
Streptococcus pneumoniae	Penicillin MIC ≤0.06 μg/mL	Recommended: Penicillin G or ampicillin Alternatives: Cefotaxime, ceftriaxone, chloramphenicol	10-14
	Penicillin MIC ≥0.12 μg/mL Cefotaxime or ceftriaxone MIC ≥0.12 μg/mL	Recommended: Cefotaxime or ceftriaxone Alternatives: Cefepime, meropenem
	Cefotaxime or ceftriaxone MIC ≥1.0 μg/mL	Recommended: Vancomycin plus cefotaxime or ceftriaxone Alternatives: Vancomycin plus moxifloxacin
Haemophilus influenzae	Beta-lactamase−negative	Recommended: Ampicillin Alternatives: Cefotaxime, ceftriaxone, cefepime, chloramphenicol, aztreonam, a fluoroquinolone	7
	Beta-lactamase−positive	Recommended: Cefotaxime or ceftriaxone Alternatives: Cefepime, chloramphenicol, aztreonam, a fluoroquinolone
	Beta-lactamase−negative, ampicillin-resistant	Recommended: Meropenem Alternatives: Cefepime, chloramphenicol, aztreonam, a fluoroquinolone
Neisseria meningitidis	Penicillin MIC < 0.1 μg/mL	Recommended: Penicillin G or ampicillin Alternatives: Cefotaxime, ceftriaxone, chloramphenicol	7
Neisseria meningitidis	Penicillin MIC ≥0.1 μg/mL	Recommended: Cefotaxime or ceftriaxone Alternatives: Cefepime, chloramphenicol, a fluoroquinolone, meropenem	7
Listeria monocytogenes	...	Recommended: Ampicillin or penicillin G Alternative: TMP-SMX	14-21
Streptococcus agalactiae	...	Recommended: Ampicillin or penicillin G Alternatives: Cefotaxime, ceftriaxone, vancomycin	14-21
Enterobacteriaceae	...	Recommended: Cefotaxime or ceftriaxone Alternatives: Aztreonam, a fluoroquinolone, TMP-SMX, meropenem, ampicillin	21
Pseudomonas aeruginosa	...	Recommended: Ceftazidime or cefepime Alternatives: Aztreonam, meropenem, ciprofloxacin	21
Staphylococcus epidermidis		Recommended: Vancomycin Alternative: Linezolid Consider addition of rifampin
MIC= minimal inhibitory concentration; TMP-SMX = trimethoprim-sulfamethoxazole.

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Author

Shikha S Vasudeva, MBBS Assistant Professor of Internal Medicine, Virginia Tech Carilion School of Medicine; Assistant Professor of Internal Medicine, Edward Via Virginia College of Osteopathic Medicine; Infectious Disease Consultant, Department of Medicine, Veterans Affair Medical Center

Shikha S Vasudeva, MBBS is a member of the following medical societies: Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America; Fellow of the Royal College of Physicians, London

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Medical Association, Association of Professors of Medicine, Infectious Diseases Society of America, Oklahoma State Medical Association, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Rodrigo Hasbun, MD, MPH Associate Professor of Medicine, Section of Infectious Diseases, University of Texas Medical School at Houston

Disclosure: Received research grant from: Biofire<br/> Speaker for Biofire.

Acknowledgements

Suur Biliciler, MD Neuromuscular Fellow, Department of Neurology, Baylor College of Medicine