Meningitis

Resident Survival Guide

Meningitis Main Page
Patient Information
Overview
Causes
Classification Viral Meningitis Bacterial Meningitis Fungal Meningitis
Differential Diagnosis
Diagnosis
Treatment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Niloofarsadaat Eshaghhosseiny, MD[2]Seyedmahdi Pahlavani, M.D. [3]
Synonyms and keywords: Leptomeningitis, Inflammation of meninges

Overview

The meninges (singular meninx) is the system of membranes which envelop the central nervous system. The meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. The primary function of the meninges and of the cerebrospinal fluid is to protect the central nervous system. Meningitis is the inflammation of these protective membranes.
Meningitis may have been described in the Middle Ages, but it was first accurately identified by the Swiss Vieusseux (a scientific-literary association) during an outbreak in Geneva, Switzerland in 1805. In 1661, Thomas Willis first described the inflammation of meninges and an epidemic of meningitis. In the 17th century, Robert Whytt provided a detailed explanation of tuberculous meningitis and its stages. This was further elaborated by John Cheyne in the same century. Meningococcal meningitis was than described by Gaspard Vieusseux, Andre Matthey in Geneva and Elisa North in Massachussetes.
Meningitis may develop in response to a number of causes, including infectious agents (bacteria, viruses, fungi, or other organisms) or non-infectious causes, such as systemic illnesses that may involve CNS (e.g. neoplasms or connective tissue diseases, such as sarcoidosis, systemic lupus erythematosus (SLE), and wegener's) or certain drugs (e.g. nonsteroidal antiinflammatory drugs, intravenous immunoglobulin, intrathecal agents, and trimethoprim-sulfamethoxazole). While some forms of meningitis are mild and resolve spontaneously (e.g. viral meningitis), meningitis is a potentially serious condition owing to the proximity of the inflammation to the brain and spinal cord. The potential for serious neurologic damage or even death necessitates prompt medical attention and evaluation. The common presenting features of meningitis are, fever, neck stiffness and headache. Other symptoms include, photophobia (inability to tolerate bright light), phonophobia (inability to tolerate loud noises), irritability, altered mental status (in small children), and seizure. Physical examination of meningitis may vary in adults and infants. In adults, physical examination findings may include bradycardia, disorientation, papilledema, neck stiffness, positive brudzinski's and kernig's sign. However, petechial rash, bulging fontanelle, neck stiffness, jaundice, and convulsions are physical examination findings in infants. Diagnosis is based on clinical findings and CSF analysis. Treatment options are based on etiology and varies from supportive care and observing the patient (viral meningitis) to antibiotic therapy for bacterial meningitis or chemotherapy and/or irradiation for neoplastic meningitis.

Causes

Etiology Common causes Less common causes Bacterial Streptococcus pneumoniae Neisseria meningitis Hemophilus influenza Group B streptococcus Listeria monocytogenes Staphylococcus aureus Klebsiella Pseudomonas E. coli Kingella Kingae Mycobacterium tuberculosis Diphtheroids Propionibacterium acnes Serratia marcescens Salmonella species Brucella sp Nocardia Francisella tularensis Streptococcus suis Ehrlichia chaffeensis Viral Enteroviruses Herpes simplex viruses 1 and 2 Arboviruses Influenza virus Herpes zoster Human Herpes Virus 6 Epstein barr virus (EBV) Lymphocytic choriomeningitis virus Mumps Cytomegalo virus (CMV) Human immunodeficiency virus (HIV) West nile virus Human T cell lymphotrophic virus I and II Varicella zoster virus SARS-CoV-2 virus (corona virus) Fungal Cryptococcus neoformans Aspergillus sp. Blastomyces dermatitidis Coccidioides immitis Candida spp. Histoplasma capsulatum Sporothrix schencki Xylohypha (formerly Cladosporium) trichoides and other dark-walled (demateaceous) fungi such as Curvularia and Drechslera Mucor Arthrographis kalrae Pneumocystis jirovecii Cryptococcus albidus Alternaria spp Rhodotorula spp Acremonium spp. Dreschlera spp Malassezia spp Scedosporium spp Arthrographis spp Blastoschizomyces Paecilomyces Aureobasidium Clavispora Ustilago Exophiala (Wangiella) Exserohilum Spirochetal Treponema pallidum Borrelia burgdoferi -- Protozoal and Helminthic Amebas (Naegleria, Acanthamoeba, and Balamuthia) Angiostrongylus cantonensis Gnathostoma species Baylisascaris procyonis Toxocara species Taenia solium Noninfectious conditions Neoplastic Sarcoidosis Systemic lupus erythematosus Granulomatosis with polyangiitis (Wegener's) Behçet's disease Fabry disease Central nervous system vasculitis Vogt-Koyanagi-Harada disease Chemical or drug-induced meningitis Nonsteroidal antiinflammatory drugs Intravenous immunoglobulin Intrathecal agents Certain antibiotics (eg, trimethoprim-sulfamethoxazole)

Classification

Meningitis could be classified to two main groups based on etiology:

• Infectious
• Non-infectious

Infectious meningitis

Infectious meningitis may be classified as the following algorithm based on chronicity of symptoms.

Infectious Meningitis

Viral

Bacterial

Fungal

Acute

Chronic

Recurrent

Acute

Subacute

Chronic

Recurrent

Non-infectious meningitis

Systemic illnesses, such as malignancies and connective tissue diseases (e.g. sarcoidosis, SLE, and wegener's) may involve meninges in their course and present as chronic meningitis.

Certain drugs may cause meningeal irritation and resemble as meningitis including:

• Nonsteroidal antiinflammatory drugs (NSAIDs)
• Intravenous immunoglobulin
• Intrathecal agents
• Certain antibiotics (eg, trimethoprim-sulfamethoxazole)

Differential diagnosis

Diseases	Symptoms				Physical Examination					Past medical history	Diagnostic tests			Other Findings
	Headache	↓LOC	Motor weakness	Abnormal sensory	Motor Deficit	Sensory deficit	Speech difficulty	Gait abnormality	Cranial nerves		CT /MRI	CSF Findings	Gold standard test
Meningitis	+	-	-	-	-	+	+	-	-	History of fever and malaise	-	↑ Leukocytes, ↑ Protein ↓ Glucose	CSF analysis	Fever, neck rigidity
Encephalitis	+	+	+/-	+/-	-	-	+	+/-	+	History of fever and malaise	+	↑ Leukocytes, ↓ Glucose	CSF PCR	Fever, seizures, focal neurologic abnormalities
Brain tumor	+	-	-	-	+	+	+	-	+	Weight loss, fatigue	+	Cancer cells	MRI	Cachexia, gradual progression of symptoms
Hemorrhagic stroke	+	+	+	+	+	+	+	+	-	Hypertension	+	-	CT scan without contrast	Neck stiffness
Subdural hemorrhage	+	+	+	+	+	-	-	-	+	Trauma, fall	+	Xanthochromia	CT scan without contrast	Confusion, dizziness, nausea, vomiting
Neurosyphilis	+	-	+	+	+	+	-	+	-	STIs	+	↑ Leukocytes and protein	CSF VDRL-specifc CSF FTA-Ab -sensitive	Blindness, confusion, depression, Abnormal gait
Complex or atypical migraine	+	-	+	+	-	-	+	-	-	Family history of migraine	-	-	Clinical assesment	Presence of aura, nausea, vomiting
Hypertensive encephalopathy	+	+	-	-	-	-	+	+	-	Hypertension	+	-	Clinical assesment	Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy	-	+	-	-	-	+	+	+	+	History of alcohal abuse	-	-	Clinical assesment and lab findings	Ophthalmoplegia, confusion
CNS abscess	+	+	-	-	+	+	+	-	-	History of drug abuse, endocarditis, immunosupression	+	↑ leukocytes, ↓ glucose and ↑ protien	MRI is more sensitive and specific	High grade fever, fatigue,nausea, vomiting
Drug toxicity	-	+	-	+	+	+	-	+	-	-	-	-	Drug screen test	Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder	+	+	+	+	+	+	+	+		History of emotional stress	-	-	Diagnosis of exclusion	Tremors, blindness, difficulty swallowing
Metabolic disturbances (electrolyte imbalance, hypoglycemia)	-	+	+	+	+	+	-	-	+	-	-	Hypoglycemia, hypo and hypernatremia, hypo and hyperkalemia	Depends on the cause	Confusion, seizure, palpitations, sweating, dizziness, hypoglycemia
Multiple sclerosis exacerbation	-	-	+	+	-	+	+	+	+	History of relapses and remissions	+	↑ CSF IgG levels (monoclonal bands)	Clinical assesment and MRI	Blurry vision, urinary incontinence, fatigue
Seizure	+	+	-	-	+	+	-	-	+	Previous history of seizures	-	Mass lesion	Clinical assesment and EEG	Confusion, apathy, irritability,

Diagnosis

Diagnosis of meningitis, is based on clinical presentation in combination with CSF analysis. CSF analysis has major role for diagnosis and rule out other possibilities. The following table summarizes the CSF findings in different types of meningitis.

Cerebrospinal fluid level	Normal level	Bacterial meningitis	Viral meningitis (except SARS-CoV-2 meningitis)	SARS-CoV-2 associated meningitis	Fungal meningitis	Tuberculous meningitis	Neoplastic meningitis
Cells/ul	< 5	>300	10-1000	10-1000	10-500	50-500	>4
Cells	Lymphocyte	Leukocyte > Lymphocyte	Lymphocyte > Leukocyte	Lymphocyte > Neutrophil	Lymphocyte > Leukocyte	Lymphocyte > Leukocyte	Lymphocyte > Leukocyte
Total protein (mg/dl)	45-60	Typically 100-500	Normal or slightly high	Normal or slightly high	High	Typically 100-200	>50
Glucose ratio (CSF/plasma)	> 0.5	< 0.3	> 0.6	> 0.6	<0.3	< 0.5	<0.5
Lactate (mmols/l)	< 2.1	> 2.1	< 2.1	NA	>3.2	> 2.1	>2.1
Others	Intra-cranial pressure (ICP) = 6-12 (cm H2O)	CSF gram stain, CSF culture, CSF bacterial antigen	PCR of HSV-DNA, VZV	RT-PCR for detection of viral RNA i n CSF ( not approved by FDA)	CSF gram stain, CSF india ink	PCR of TB-DNA	CSF tumour markers such as alpha fetoprotein, CEA

Treatment

Medical Therapy

• Empiric therapy for meningitis must be initiated after CSF obtained.
• The choice of empiric antibiotic therapy is depend on patient age and underlying comorbid disease.
• Adapted from IDSA guidlines.

Predisposing factor	Common bacterial pathogen	Antimicrobial therapy
1 month	Streptococcus agalactiae, Escherichia coli, Listeriamonocytogenes, Klebsiellaspecie	Ampicillin plus cefotaxime or ampicillin plus anaminoglycoside
1–23 months	Streptococcus pneumoniae, Neisseria meningitidis,S. agalactiae, Haemophilus influenzae, E. coli	Ampicillin plus cefotaxime or ampicillin plus anaminoglycoside
2–50 years,150 years	N . meningitidis, S. pneumoniae,S. pneumoniae, N. meningitidis, L. monocytogenes,aerobic gram-negative bacill	Vancomycin plus a third-generation cephalosporin,Vancomycin plus ampicillin plus a third-generationcephalosporina,
Head traumaBasilar skull fracture	S. pneumoniae, H. influenzae,group Ab-hemolyticstreptococci	Vancomycin plus a third-generation cephalospori
Penetrating trauma	Staphylococcus aureus,coagulase-negative staphylo-cocci (especiallyStaphylococcus epidermidis),aer-obic gram-negative bacilli (includingPseudomonasaeruginosa)	Vancomycin plus cefepime, vancomycin plus ceftazi-dime, or vancomycin plus meropenem
Postneurosurgery	Aerobic gram-negative bacilli (includingP. aeruginosa),S . aureus, coagulase-negative staphylococci (es-peciallyS. epidermidis)	ancomycin plus cefepime, vancomycin plus ceftazi-dime, or vancomycin plus meropenem
CSF shunt	Coagulase-negative staphylococci (especiallyS. epi-dermidis), S. aureus,aerobic gram-negative bacilli(includingP. aeruginosa), Propionibacterium acnes	ancomycin plus cefepime, vancomycin plus ceftazi-dime, or vancomycin plus meropenem

• Recommendations for antimicrobial therapy in adult patients with presumptive pathogen identification by positive Gram stain.
• Adapted from IDSA guidlines.

Microorganism	Recommended therapy	Alternative therapies	Duration oftherapy, days
Streptococcus pneumoniae	Vancomycin plus a third-generationcephalosporina,	Meropenem , fluoroquinolonec	7
Neisseria meningitidis	Third-generation cephalospori	Penicillin G, ampicillin, chloramphenicol, fluoro-quinolone, aztreonam	7
Listeria monocytogenes	Ampicillindor penicillin G	Trimethoprim-sulfamethoxazole, meropenem	10-14
Streptococcus agalactiae	Ampicillindor penicillin G	Third-generation cephalosporin	14-21
Haemophilus influenzae	Third-generation cephalospori	Chloramphenicol, cefepime , meropenem ,fluoroquinolon	21
Escherichia coli	Third-generation cephalospori	Cefepime, meropenem, aztreonam, fluoroquino-lone, trimethoprim-sulfamethoxazole	>21

Surgery

• Surgical intervention is not recommended for the management of meningitis.

Primary Prevention

• Adapted from the recommendations of the United States Centers for Disease Control and Prevention's (CDC's) Advisory Committee on Immunization Practices (ACIP) for the use of meningococcal vaccines.

Targeted group by age and/or risk factor	Primary dose(s)	Booster dose(s)
For ages 11 through 18 years	Give one dose of Menactra or Menveo, preferably at age 11 or 12 years. Discuss serogroup B meningococcus vaccination (Trumenba or Bexsero)*, which may be administered to adolescents and young adults 16 through 23 years of age; the preferred age for vaccination is 16 through 18 years of age (perhaps at the time of Menactra or Menveo booster).	If primary dose was given at age ≤12 years, give Menactra or Menveo booster at age 16 years. If primary dose was given at age 13 to 15 years, give Menactra or Menveo booster at age 16 to 18 years
For individuals ages 19 through 21 years who are first year college students living in residence halls	If not yet received a dose of vaccine, give one dose of Menactra or Menveo. Discuss serogroup B meningococcus vaccination (Trumenba or Bexsero)*, which may be administered to adolescents and young adults 16 through 23 years of age; the preferred age for vaccination is 16 through 18 years of age.	Give Menactra or Menveo booster if previous dose given at age younger than 16 years.
|Patients with HIV infection
For age <2 years	Give four doses of Menveo (at ages 2, 4, 6, and 12 to 15 months) or give two doses of MenactraΔ (at age 9 to 23 months, 12 weeks apart).	Give additional dose of Menveo or Menactra three years after primary series. Booster doses should be repeated every five years thereafter.
For age ≥2 years	Give two doses of Menveo or Menactra 8 to 12 weeks apart.	For individuals age <7 years at previous dose, give additional dose of Menveo or Menactra three years after primary series. If the most recent dose was received before age 7 years, a booster dose should be readministered three years later. Booster doses should be repeated every five years thereafter. For individuals age ≥7 years at previous dose, give additional dose of Menveo or Menactra five years after primary series; booster doses should be repeated every five years thereafter
Travelers to or residents of countries where meningococcal disease is hyperendemic or epidemic
For age 2 months through 18 months	Give Menveo at ages 2, 4, 6, and 12 to 15 months	If risk continues, give initial booster after three years followed by boosters every five years.
For children age 7 months through 23 months who have not initiated a series of Menveo	Give Menveo (if age 7 to 23 months)§ or Menactra (if age 9 to 23 months); administer two doses separated by three months	If risk continues, give initial booster after three years followed by boosters every five years.
For age 2 years through 55 years	Give one dose of Menactra or Menveo.	Boost every five years with Menactra or Menveo
For age 56 years and older	Give one dose of Menactra or Menveo	Boost every five years with Menactra or Menveo
People with prolonged increased risk for exposure (eg, military recruits, microbiologists routinely working with Neisseria meningitidis)
For age 10 years and older	Give one dose of Menactra or Menveo. Give either Trumenba (three doses administered at 0, 1 to 2, and 6 months) or Bexsero (two doses administered at least one month apart)	Boost every five years with Menactra or Menveo. Boost with one dose MenB (Trumenba or Bexsero) one year after primary series; revaccinate every 2 to 3 years if risk remains.
People present during outbreaks caused by a meningococcal vaccine serogroup
For age 2 months through 18 months	Give Menveo at ages 2, 4, 6, and 12 to 15 months.	'
For children age 7 months through 23 months who have not initiated a series of Menveo	Give Menveo (if age 7 to 23 months)§ or Menactra (if age 9 to 23 months); administer two doses separated by 3 months	'
For age 2 years through 9 years	Give one dose of Menactra or Menveo	'
For age 10 years through 55 years	Give one dose of Menactra or Menveo. Give either Trumenba (three doses administered at 0, 1 to 2, and 6 months) or Bexsero (two doses administered at least one month apart)	'
For age 56 years and older	Give one dose of Menactra or Menveo. Give either Trumenba (three doses administered at 0, 1 to 2, and 6 months) or Bexsero (two doses administered at least one month apart)	'
People with persistent complement component deficiencies
For age 2 months through 18 months	Give Menveo at ages 2, 4, 6, and 12 to 15 months.	Give Menactra or Menveo booster after three years followed by boosters every five years thereafter.
For children age 7 months through 23 months who have not initiated a series of Menveo	Give Menveo (if age 7 to 23 months)§ or Menactra (if age 9 to 23 months); administer two doses separated by three months.	'
For age 2 years through 9 years	Give two doses of Menactra or Menveo two months apart.	Boost every five years with Menactra or Menveo
For age 10 years through 55 years	ive two doses of Menactra or Menveo two months apart and either Trumenba (three doses administered at 0, 1 to 2, and 6 months) or Bexsero (two doses administered at least one month apart)	Boost every five years with Menactra or Menveo. Boost with one dose MenB (Trumenba or Bexsero) one year after primary series; revaccinate every 2 to 3 years if risk remains.
For age 56 years and older	Give two doses of Menactra or Menveo two months apart and either Trumenba (three doses administered at 0, 1 to 2, and 6 months) or Bexsero (two doses administered at least one month apart)	Boost every five years with Menactra or Menveo. Boost with one dose MenB (Trumenba or Bexsero) one year after primary series; revaccinate every 2 to 3 years if risk remains.
People with functional or anatomic asplenia, including sickle cell disease
For age 2 months through 18 months	Give Menveo at ages 2, 4, 6, and 12 months.	Give Menactra or Menveo booster after three years followed by boosters every five years thereafter.
For children age 19 months through 23 months who have not initiated a series of Menveo	Give two doses of Menveo three months apart.	Give Menactra or Menveo booster after three years followed by boosters every five years thereafter.
For age 2 years through 9 years	Give two doses of Menactra or Menveo two months apart	Boost every five years with Menactra or Menveo
For age 10 years through 55 years	Give two doses of Menactra or Menveo two months apart and either Trumenba (three doses administered at 0, 1 to 2, and 6 months) or Bexsero (two doses administered at least one month apart)	Boost every five years with Menactra or Menveo. Boost with one dose MenB (Trumenba or Bexsero) one year after primary series; revaccinate every 2 to 3 years if risk remains
For age 56 years and older	Give two doses of Menactra or Menveo two months apart and either Trumenba (three doses administered at 0, 1 to 2, and 6 months) or Bexsero (two doses administered at least one month apart).	Boost every five years with Menactra or Menveo. Boost with one dose MenB (Trumenba or Bexsero) one year after primary series; revaccinate every 2 to 3 years if risk remains.

The quadrivalent meningococcal conjugate vaccines (MenACWY) are Menactra (MenACWY-DT) and Menveo (MenACWY-CRM); these have replaced the quadrivalent meningococcal polysaccharide vaccine Menomune (MPSV4). MenHibrix (HibMenCY), a combination conjugate vaccine against meningococcus serogroups C and Y and Haemophilus influenzae type b, was discontinued in 2017. Trumenba (MenB-FHbp) and Bexsero (MenB-4C) are meningococcus serogroup B vaccines.

Secondary Prevention

• Secondary prevention with Antimicrobial chemoprophylaxis is necessary for individuals who have close contact with patients with invasive meningococcal disease. Close contacts include:
• 1.household members , 2.child-care center contacts ,3.anyone directly exposed to the patient's oral secretions (e.g., through kissing, mouth-to-mouth resuscitation, endotracheal intubation, or endotracheal tube management) in the 7 days before symptom onset. Health-care personnel should receive chemoprophylaxis if they were managing an airway or exposed to respiratory secretions of a patient with meningococcal disease. For travelers, antimicrobial chemoprophylaxis should be considered for any passenger who had direct contact with respiratory secretions from an index-patient or for anyone seated directly next to an index-patient on a prolonged flight (i.e., one lasting ≥8 hours)

• Recommended chemoprophylaxis regimens for protection against meningococcal disease — Advisory Committee on Immunization Practices (ACIP), United States, 2012

Drug	Age group	Dosage	Duration and route of administration
Rifampin	Children aged <1 mo	5 mg/kg every 12 hrs	2 days
Rifampin	Children aged ≥1 mo	10 mg/kg every 12 hrs	2 days
Rifampin	Adults	600 mg every 12 hrs	2 days
Ciprofloxacin	Adults	500 mg	Single dose
Ceftriaxone	Children age <15 yrs	125 mg	Single IM dose
Ceftriaxone	Adults	250 mg	Single IM dose

References

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