Meningitis (Clinical)

Overview

Definition

Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis is inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the protective membranes of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and the spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy, collectively called the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy, that is commonly caused by an acute infection.

Epidemiology^[3]

• A significant decrease in frequency occurred after introduction of routine infant vaccinations against Haemophilus influenzae Haemophilus Influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through viii. Haemophilus and Pneumococcus.
• Since 2010, the peak incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis shifted from children < 5 years of age to adults.
• Meningococcal meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis is observed in crowded accommodations.
• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency is higher in developing countries owing to the lack of access to preventive measures.
• Viral meningitis Viral meningitis Viral infections of the leptomeninges and subarachnoid space. Togaviridae infections; flaviviridae infections; rubella; bunyaviridae infections; orbivirus infections; picornaviridae infections; orthomyxoviridae infections; rhabdoviridae infections; arenaviridae infections; herpesviridae infections; adenoviridae infections; JC virus infections; and retroviridae infections may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, photophobia, and signs of meningeal irritation. Meningitis peaks in early fall and summer.
• Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis can occur at any age and affects both sexes equally.

Etiology

Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis can be of infectious (most common) or noninfectious origin. Infectious meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis can be community- or hospital-acquired.

Infectious meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis^[1–6,15]

Bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis:

• The most common cause of bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis is Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pneumoniae.
• Relative frequency Relative frequency Basics of Probability of occurrence varies according to the age group:
  • Neonates: Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli, Listeria Listeria Listeria spp. are motile, flagellated, gram-positive, facultative intracellular bacilli. The major pathogenic species is Listeria monocytogenes. Listeria are part of the normal gastrointestinal flora of domestic mammals and poultry and are transmitted to humans through the ingestion of contaminated food, especially unpasteurized dairy products. Listeria Monocytogenes/Listeriosis monocytogenes, group B streptococci 
  • Infants and children: Haemophilus influenzae Haemophilus Influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through viii. Haemophilus, Neisseria meningitidis Neisseria meningitidis A species of gram-negative, aerobic bacteria. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the nasopharynx. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis. It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being a, b, c, y, and w-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype. Neisseria 
  • Adults: S. pneumoniae, N. meningitidis N. meningitidis A species of gram-negative, aerobic bacteria. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the nasopharynx. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis. It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being a, b, c, y, and w-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype. Neisseria (Meningococcus), L. monocytogenes L. monocytogenes A species of gram-positive, rod-shaped bacteria widely distributed in nature. It has been isolated from sewage, soil, silage, and from feces of healthy animals and man. Infection with this bacterium leads to encephalitis, meningitis, endocarditis, and abortion. Listeria Monocytogenes/Listeriosis  
• Community-acquired bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis is mainly caused by 5 organisms:
  • S. pneumoniae (50%)
  • N. meningitidis N. meningitidis A species of gram-negative, aerobic bacteria. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the nasopharynx. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis. It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being a, b, c, y, and w-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype. Neisseria (15%)
  • Group B streptococci (15%)
  • L. monocytogenes L. monocytogenes A species of gram-positive, rod-shaped bacteria widely distributed in nature. It has been isolated from sewage, soil, silage, and from feces of healthy animals and man. Infection with this bacterium leads to encephalitis, meningitis, endocarditis, and abortion. Listeria Monocytogenes/Listeriosis (10%)
  • H. influenzae H. influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. Haemophilus (10%) 
• Tubercular meningitis Tubercular meningitis A form of bacterial meningitis caused by Mycobacterium tuberculosis or rarely Mycobacterium bovis. The organism seeds the meninges and forms microtuberculomas which subsequently rupture. The clinical course tends to be subacute, with progressions occurring over a period of several days or longer. Headache and meningeal irritation may be followed by seizures, cranial neuropathies, focal neurologic deficits, somnolence, and eventually coma. The illness may occur in immunocompetent individuals or as an opportunistic infection in the acquired immunodeficiency syndrome and other immunodeficiency syndromes. Meningitis:
  • Caused by Mycobacterium tuberculosis Mycobacterium tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
  • Prevalent in developing countries
  • Predisposing conditions are:
    • History of previous exposure to tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
    • AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS
    • Young age (children)

Viral meningitis Viral meningitis Viral infections of the leptomeninges and subarachnoid space. Togaviridae infections; flaviviridae infections; rubella; bunyaviridae infections; orbivirus infections; picornaviridae infections; orthomyxoviridae infections; rhabdoviridae infections; arenaviridae infections; herpesviridae infections; adenoviridae infections; JC virus infections; and retroviridae infections may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, photophobia, and signs of meningeal irritation. Meningitis:

• Enteroviruses:
  • Coxsackievirus Coxsackievirus Coxsackievirus is a member of a family of viruses called Picornaviridae and the genus Enterovirus. Coxsackieviruses are single-stranded, positive-sense RNA viruses, and are divided into coxsackie group A and B viruses. Both groups of viruses cause upper respiratory infections, rashes, aseptic meningitis, or encephalitis. Coxsackievirus
  • Echovirus Echovirus Echoviruses are single-stranded positive-sense RNA viruses belonging to the genus Enterovirus. Transmission is most commonly through the fecal-oral route. The majority of patients are asymptomatic. Patients who are symptomatic can exhibit a wide range of illnesses ranging from nonspecific URIs and exanthems to severe and life-threatening illnesses. Echovirus
  • Human enterovirus Enterovirus A genus of the family picornaviridae whose members preferentially inhabit the intestinal tract of a variety of hosts. The genus contains many species. Newly described members of human enteroviruses are assigned continuous numbers with the species designated ‘human enterovirus’. Coxsackievirus
• HSV-2 
• Arthropod-borne viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology
• HIV HIV Anti-HIV Drugs
• Mumps Mumps Mumps is caused by a single-stranded, linear, negative-sense RNA virus of the family Paramyxoviridae. Mumps is typically a disease of childhood, which manifests initially with fever, muscle pain, headache, poor appetite, and a general feeling of malaise, and is classically followed by parotitis. Mumps Virus/Mumps

Fungal meningitis Fungal meningitis Meningitis caused by fungal agents which may occur as opportunistic infections or arise in immunocompetent hosts. Meningitis:

• Cryptococcus Cryptococcus Cryptococcosis is an opportunistic, fungal infection caused by the Cryptococcus species. The principal pathogens in humans are C. neoformans (primary) and C. gattii. Cryptococcus neoformans is typically found in pigeon droppings and acquired by inhaling dust from contaminated soil. The majority of affected patients are immunocompromised. Cryptococcus/Cryptococcosis neoformans: most common cause of fungal meningitis Fungal meningitis Meningitis caused by fungal agents which may occur as opportunistic infections or arise in immunocompetent hosts. Meningitis
• Coccidioides immitis Coccidioides immitis Coccidioides/Coccidioidomycosis
• Histoplasma capsulatum Histoplasma capsulatum Histoplasma/Histoplasmosis
• Blastomyces dermatitidis Blastomyces dermatitidis Blastomyces/Blastomycosis
• Candida Candida Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis species

Parasitic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis:

• Angiostrongylus cantonensis
• Gnathostoma spinigerum 
• Acanthamoeba spp.
• Naegleria fowleri 
• Taenia Taenia Taenia belong to the Cestoda class of helminths. Humans are infected with these tapeworms by eating undercooked beef (T. saginata) or pork (T. solium and T. asiatica). Taeniasis is often asymptomatic, but the ingestion of larvae can cause abdominal discomfort, nausea, and constipation or diarrhea. Taenia/Taeniasis solium 
• Strongyloides stercoralis Strongyloides stercoralis A species of parasitic nematode widely distributed in tropical and subtropical countries. The females and their larvae inhabit the mucosa of the intestinal tract, where they cause ulceration and diarrhea. Strongyloidiasis

Noninfectious meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis

• Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus ( SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus)
• Malignancy Malignancy Hemothorax
• Sarcoidosis Sarcoidosis Sarcoidosis is a multisystem inflammatory disease that causes noncaseating granulomas. The exact etiology is unknown. Sarcoidosis usually affects the lungs and thoracic lymph nodes, but it can also affect almost every system in the body, including the skin, heart, and eyes, most commonly. Sarcoidosis 
• NSAIDs NSAIDS Primary vs Secondary Headaches
• IV immunoglobulins IV immunoglobulins Immunoglobulin preparations used in intravenous infusion, containing primarily immunoglobulin g. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric aids; primary hypergammaglobulinemia; scid; cytomegalovirus infections in transplant recipients, lymphocytic leukemia, chronic; kawasaki syndrome, infection in neonates, and idiopathic thrombocytopenic purpura. DiGeorge Syndrome 
• Behçet’s disease Behçet’s disease Rare chronic inflammatory disease involving the small blood vessels. It is of unknown etiology and characterized by mucocutaneous ulceration in the mouth and genital region and uveitis with hypopyon. The neuro-ocular form may cause blindness and death. Synovitis; thrombophlebitis; gastrointestinal ulcerations; retinal vasculitis; and optic atrophy may occur as well. Vasculitides

Risk factors^[8]

• Unvaccinated individuals or those who have skipped vaccinations
• Children < 5 years 
• Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis individuals with conditions like AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS, diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, SLE SLE Systemic lupus erythematosus (SLE) is a chronic autoimmune, inflammatory condition that causes immune-complex deposition in organs, resulting in systemic manifestations. Women, particularly those of African American descent, are more commonly affected. Systemic Lupus Erythematosus
• Immunosuppressant drugs
• Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care 
• Outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza commonly occur in community accommodation Accommodation Refractive Errors settings. 
• Pneumococci:
  • Other pneumococcal infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease: pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia, sinusitis Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis, otitis media
  • Splenectomy Splenectomy Surgical procedure involving either partial or entire removal of the spleen. Rupture of the Spleen, asplenia Asplenia Asplenia is the absence of splenic tissue or function and can stem from several factors ranging from congenital to iatrogenic. There is a distinction between anatomic asplenia, which is due to the surgical removal of the spleen, and functional asplenia, which is due to a condition that leads to splenic atrophy, infarct, congestion, or infiltrative disease. Asplenia 
  • Hypogammaglobulinemia Hypogammaglobulinemia Selective IgA Deficiency
  • Complement deficiency 
• N. meningitidis N. meningitidis A species of gram-negative, aerobic bacteria. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the nasopharynx. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis. It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being a, b, c, y, and w-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype. Neisseria: 
  • Complement deficiency
  • B serotype
• L. monocytogenes L. monocytogenes A species of gram-positive, rod-shaped bacteria widely distributed in nature. It has been isolated from sewage, soil, silage, and from feces of healthy animals and man. Infection with this bacterium leads to encephalitis, meningitis, endocarditis, and abortion. Listeria Monocytogenes/Listeriosis: 
  • Neonates < 1 month
  • Pregnant women 
  • Individuals > 60 years 
  • Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis individuals

Pathophysiology

Direct inoculation of the infectious agent into the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy is rare in meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis. Usually, infection at an adjacent or remote site spreads to the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification.

Onset^[4]

Acute meningitis Acute Meningitis Meningitis: 

• Etiology: predominantly bacterial or viral
• Symptoms develop in a few hours or within a day. 

Chronic meningitis Chronic Meningitis Meningitis:  

• Etiology: bacterial, viral, parasitic, fungal, or noninfectious 
• Symptoms persist for > 4 weeks  
• When taking a history, questions should be asked about recent travel, immune status, and animal exposure.

Pathogenesis of infectious meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis^[1,3]

• 1st step is usually mucosal colonization Colonization Bacteriology.
• Sites of colonization Colonization Bacteriology:
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions
  • Nasopharynx Nasopharynx The top portion of the pharynx situated posterior to the nose and superior to the soft palate. The nasopharynx is the posterior extension of the nasal cavities and has a respiratory function. Pharynx: Anatomy
  • Respiratory tract
  • GI tract 
  • Genitourinary tract 
• Mechanisms of mucosal attachment vary depending on the organism:
  • N. meningitidis N. meningitidis A species of gram-negative, aerobic bacteria. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the nasopharynx. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis. It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being a, b, c, y, and w-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype. Neisseria: type 4 Type 4 Spinal Muscular Atrophy pili Pili Filamentous or elongated proteinaceous structures which extend from the cell surface in gram-negative bacteria that contain certain types of conjugative plasmid. These pili are the organs associated with genetic transfer and have essential roles in conjugation. Normally, only one or a few pili occur on a given donor cell. This preferred use of ‘pili’ refers to the sexual appendage, to be distinguished from bacterial fimbriae, also known as common pili, which are usually concerned with adhesion. Salmonella 
  • S. pneumoniae: platelet-activating factor receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors, laminin Laminin Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. Connective Tissue: Histology, polymeric immunoglobulin receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
• Secretion Secretion Coagulation Studies of IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions protease Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Infection and AIDS by pathogens inactivates mucosal IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions and also helps epithelial attachment.
• Organism invades the submucosa at the site of colonization Colonization Bacteriology and disrupts host defenses. The capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides is an important virulence Virulence The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its virulence factors. Proteus factor in this process.
• Viral pathogens usually multiply in regional lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy before invading the bloodstream.
• Invasion of the bloodstream and hematogenous Hematogenous Hepatocellular Carcinoma (HCC) and Liver Metastases spread to the CNS is the most common pathway Common pathway Hemostasis:
  • Polysaccharide capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides of the main pathogens inhibits complement attachment and phagocytosis Phagocytosis The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (phagocytes). Innate Immunity: Phagocytes and Antigen Presentation.
  • Capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides is the major factor in intravascular survival. 
• Other CNS access pathways:
  • Retrograde neuronal transmission through olfactory or peripheral nerves Peripheral Nerves The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. Nervous System: Histology 
  • Direct contiguous spread (due to otitis, sinusitis Sinusitis Sinusitis refers to inflammation of the mucosal lining of the paranasal sinuses. The condition usually occurs concurrently with inflammation of the nasal mucosa (rhinitis), a condition known as rhinosinusitis. Acute sinusitis is due to an upper respiratory infection caused by a viral, bacterial, or fungal agent. Sinusitis) 
  • Direct inoculation (rare)
  • Vertical transmission Vertical transmission The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. Congenital TORCH Infections in newborns (from mother)
• Organism seeds the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy. 
• Body defenses act against the pathogen to induce inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, causing a cascade of events, including edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema of the meninges Meninges The brain and the spinal cord are enveloped by 3 overlapping layers of connective tissue called the meninges. The layers are, from the most external layer to the most internal layer, the dura mater, arachnoid mater, and pia mater. Between these layers are 3 potential spaces called the epidural, subdural, and subarachnoid spaces. Meninges: Anatomy and brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification parenchyma.
• Parenchymal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema increases the intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension, which worsens the symptoms.

Clinical Presentation

The clinical features of bacterial and viral meningitis Viral meningitis Viral infections of the leptomeninges and subarachnoid space. Togaviridae infections; flaviviridae infections; rubella; bunyaviridae infections; orbivirus infections; picornaviridae infections; orthomyxoviridae infections; rhabdoviridae infections; arenaviridae infections; herpesviridae infections; adenoviridae infections; JC virus infections; and retroviridae infections may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, photophobia, and signs of meningeal irritation. Meningitis are similar. Viral meningitis Viral meningitis Viral infections of the leptomeninges and subarachnoid space. Togaviridae infections; flaviviridae infections; rubella; bunyaviridae infections; orbivirus infections; picornaviridae infections; orthomyxoviridae infections; rhabdoviridae infections; arenaviridae infections; herpesviridae infections; adenoviridae infections; JC virus infections; and retroviridae infections may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, photophobia, and signs of meningeal irritation. Meningitis tends to be less acute and usually self-limits within 7–10 days.

The classic triad presenting in ~50% of bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis cases is:^[2–8]

• Altered mental status Altered Mental Status Sepsis in Children (Glasgow coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma scale Scale Dermatologic Examination score, < 14)
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever > 38℃
• Stiff neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess

Symptoms^[2–8]

• Severe headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
• Lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia and drowsiness 
• Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia 
• Photophobia Photophobia Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. Migraine Headache 

Signs^[2–8,15] 

• Signs of meningeal irritation Meningeal Irritation Subarachnoid Hemorrhage:
  • Stick neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess ( nuchal rigidity Nuchal Rigidity Meningitis): patient is supine; patient is unable to move the chin Chin The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. Melasma toward the sternum Sternum A long, narrow, and flat bone commonly known as breastbone occurring in the midsection of the anterior thoracic segment or chest region, which stabilizes the rib cage and serves as the point of origin for several muscles that move the arms, head, and neck. Chest Wall: Anatomy owing to reflex contraction of neck muscles Neck muscles The muscles of the neck can be divided into 3 groups: anterior, lateral, and posterior neck muscles. Each of the groups is subdivided according to function and the precise location of the muscles. Muscles of the Neck: Anatomy.
  • Kernig sign Kernig Sign Meningitis
    • Patient is supine; hip flexion Flexion Examination of the Upper Limbs followed by knee extension Extension Examination of the Upper Limbs causes pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways and resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing.
    • Due to meningeal or root irritation 
  • Brudzinski sign Brudzinski Sign Meningitis: forced neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess flexion Flexion Examination of the Upper Limbs while the patient is supine causes involuntary flexion Flexion Examination of the Upper Limbs of the knees.
• Signs of raised intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension; papilloedema ( swelling Swelling Inflammation of the optic disk)
• Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions manifestations:
  • Non-blanching, palpable, petechial rash Rash Rocky Mountain Spotted Fever: N. meningitidis N. meningitidis A species of gram-negative, aerobic bacteria. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the nasopharynx. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis. It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being a, b, c, y, and w-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype. Neisseria
  • Maculopapular Maculopapular Dermatologic Examination rash Rash Rocky Mountain Spotted Fever: some viral meningitis Viral meningitis Viral infections of the leptomeninges and subarachnoid space. Togaviridae infections; flaviviridae infections; rubella; bunyaviridae infections; orbivirus infections; picornaviridae infections; orthomyxoviridae infections; rhabdoviridae infections; arenaviridae infections; herpesviridae infections; adenoviridae infections; JC virus infections; and retroviridae infections may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, photophobia, and signs of meningeal irritation. Meningitis 
• Signs of meningoencephalitis Meningoencephalitis Encephalitis ( meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis + inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification parenchyma ( encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis)):
  • Focal neurologic deficits Neurologic Deficits High-Risk Headaches, such as:
    • Paresis Paresis A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. ‘general paresis’ and ‘general paralysis’ may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. Spinal Disk Herniation 
    • Aphasia Aphasia A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. Ischemic Stroke 
    • Ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia
  • Cranial nerve abnormalities 
  • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures 
  • Behavioral changes
• Signs of systemic inflammation Systemic Inflammation Surgical Site Infections
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever 
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension 
  • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children 
• Signs of underlying infection: bulging, red tympanic membrane Tympanic membrane An oval semitransparent membrane separating the external ear canal from the tympanic cavity. It contains three layers: the skin of the external ear canal; the core of radially and circularly arranged collagen fibers; and the mucosa of the middle ear. Ear: Anatomy: acute otitis media Acute Otitis Media Acute otitis media is an infection in the middle ear characterized by mucosal inflammation and retention of fluid. The most common pathogens are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The condition can present with fever, otalgia, and diminished hearing. Acute Otitis Media

Diagnosis

Commence empiric antibiotics immediately after obtaining blood cultures and CSF samples. If lumbar puncture Lumbar Puncture Febrile Infant is delayed, obtain blood cultures and administer antibiotics until it can safely be performed. 

Laboratory analysis^[3,7]

• CBC:
  • Elevated WBC count
  • Differential diagnosis may help determine etiology:
    • Neutrophil proliferation in bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis
    • Increase in lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology in viral or fungal meningitis Fungal meningitis Meningitis caused by fungal agents which may occur as opportunistic infections or arise in immunocompetent hosts. Meningitis
• Blood cultures
  • To identify the cause of meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis and test for antibiotic sensitivity
  • Two sets to be taken before starting antibiotic therapy 
• CMP:
  • Compare serum glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance with CSF glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance levels
  • Assess for metabolic disturbances.
  • Assess for organ dysfunction. 
• HIV HIV Anti-HIV Drugs test:
  • Test for immune status if there is no history of other immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis conditions.
• Coagulation profile (PT, PTT) prior to lumbar puncture Lumbar Puncture Febrile Infant:
  • Chronic alcohol use
  • Chronic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease
  • Suspected DIC DIC Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation

CSF analysis CSF analysis Meningitis^{[3,7–9,12,15]}

• Lumbar puncture Lumbar Puncture Febrile Infant (LP) is performed in all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with suspected meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis unless contraindicated, such as with increased intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension or suspicion of a mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast lesion.
• CSF analysis CSF analysis Meningitis establishes a definite diagnosis and aids AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS in the provision of appropriate treatment. CSF is tested for:
  • Opening pressure:
    • Typically > 20 cm H₂O in bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis
    • Lower pressure noted in infants and children
  • Leukocyte count
  • Differential leukocyte count
  • Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance levels:
    • Normal CSF-to-blood glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance ratio: 0.6.
    • Viral meningitis Viral meningitis Viral infections of the leptomeninges and subarachnoid space. Togaviridae infections; flaviviridae infections; rubella; bunyaviridae infections; orbivirus infections; picornaviridae infections; orthomyxoviridae infections; rhabdoviridae infections; arenaviridae infections; herpesviridae infections; adenoviridae infections; JC virus infections; and retroviridae infections may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, photophobia, and signs of meningeal irritation. Meningitis: normal ratio
    • Bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis: ratio of ≤ 0.5 (≤ 0.6 in neonates), with high likelihood if ratio is < 0.23
    • Hypoglycorrhachia (low CSF glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance) points to a bacterial etiology.
    • Ratio becomes less helpful in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus.
  • Lactate levels: ≥ 35 mg/dL consistent with bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis
  • Protein: elevated in bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis 
  • RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology 
  • Culture and sensitivity
  • Microbiologic staining (e.g., Gram stain Gram stain Klebsiella, acid-fast stain Acid-Fast Stain Meningitis in Children):
    • Allows rapid identification Identification Defense Mechanisms of the causative agent in up to 90% of cases of bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis
    • Gram-positive Gram-Positive Penicillins cocci Cocci Bacteriology → S. pneumoniae
    • Gram-negative diplococci Gram-negative diplococci Neisseria → N. meningitidis N. meningitidis A species of gram-negative, aerobic bacteria. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the nasopharynx. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis. It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being a, b, c, y, and w-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype. Neisseria
    • Gram-positive Gram-Positive Penicillins bacilli Bacilli Shigella →  L. monocytogenes L. monocytogenes A species of gram-positive, rod-shaped bacteria widely distributed in nature. It has been isolated from sewage, soil, silage, and from feces of healthy animals and man. Infection with this bacterium leads to encephalitis, meningitis, endocarditis, and abortion. Listeria Monocytogenes/Listeriosis 
  • Latex agglutination test:
    • Checks for antigens and antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions
    • Negative result does not completely rule out the pathogen.
    • Most useful in cases with a negative Gram stain Gram stain Klebsiella or CSF culture
• Ideally taken before commencing antibiotics:
  • US and UK guidelines recommend LP within 1 hour after presentation unless contraindicated.
  • CSF sterilization Sterilization Procedures to block or remove all or part of the genital tract for the purpose of rendering individuals sterile, incapable of reproduction. Surgical sterilization procedures are the most commonly used. There are also sterilization procedures involving chemical or physical means. Reproductive Ethical Issues may occur after 2 and 4 hours of antibiotic administration for Meningococcus and Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus, respectively.
• Note on healthcare-associated meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis:
  • CSF cell count, glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance, and protein may be normal.
  • CSF Gram stain Gram stain Klebsiella may be negative.
  • CSF cultures are very important in identifying the organism (and will need to be monitored for ≥ 10 days, especially in infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease from Propionibacterium acnes Propionibacterium acnes A bacteria isolated from normal skin, intestinal contents, wounds, blood, pus, and soft tissue abscesses. It is a common contaminant of clinical specimens, presumably from the skin of patients or attendants. Acne Vulgaris).
  • In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship in whom infection is suspected, cultures of shunt and drain components (if removed) are recommended.
• Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to LP:
  • Anticoagulation Anticoagulation Pulmonary Hypertension Drugs
  • Antiplatelet agents Antiplatelet agents Antiplatelet agents are medications that inhibit platelet aggregation, a critical step in the formation of the initial platelet plug. Abnormal, or inappropriate, platelet aggregation is a key step in the pathophysiology of arterial ischemic events. The primary categories of antiplatelet agents include aspirin, ADP inhibitors, phosphodiesterase/adenosine uptake inhibitors, and glycoprotein IIb/IIIa inhibitors. Antiplatelet Drugs, except aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs)
  • Presence of disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation
  • Infection or loss of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions integrity at the puncture site
  • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock or rapidly evolving rash Rash Rocky Mountain Spotted Fever (UK)
  • Cardiac or respiratory compromise (UK)
  • Signs of increased intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension ( ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP)) may necessitate CT prior to LP.

Imaging^{[3,7–9,12,13]}

Imaging is not required for diagnosis but is usually indicated before performing a lumbar puncture Lumbar Puncture Febrile Infant if there is a concern about high intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension and to detect complications. 

• CT or MRI can be performed, but treatment with antibiotics and dexamethasone Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Antiemetics should not be delayed.
• Guidelines differ between US, Europe, and UK; US is the most liberal in using imaging prior to LP.
• According to guidelines by the Infectious Diseases Society of America, neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant is indicated in:^[12]
  • Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • History of CNS disease (lesion/stroke/focal infection)
  • Seizure within 1 week of presentation 
  • Papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension 
  • Altered consciousness 
  • Focal neurologic deficit Focal Neurologic Deficit Intracerebral Hemorrhage
  • Healthcare-associated meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis and ventriculitis
  • To detect complications:
    • Hydrocephalus Hydrocephalus Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial. Subarachnoid Hemorrhage 
    • Cerebral infarct Infarct Area of necrotic cells in an organ, arising mainly from hypoxia and ischemia Ischemic Cell Damage 
    • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease 
    • Subdural empyema Empyema Presence of pus in a hollow organ or body cavity. Pneumonia 
    • Venous sinus thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus
• Supportive findings:
  • May be normal 
  • Mild degree of meningeal enhancement 
  • May identify sources of infection e.g. mastoiditis Mastoiditis Inflammation of the honeycomb-like mastoid bone in the skull just behind the ear. It is usually a complication of otitis media. Mumps Virus/Mumps
  • May identify complications (e.g., abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease)

Management and Prevention

Treatment is based on the type of meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis. The patient should always be stabilized first using the A-E approach. Supportive care is common for most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship. Broad-spectrum Broad-Spectrum Fluoroquinolones antibiotics are usually administered as an immediate measure while the cause is being determined.

Prehospital management^[8,11,16]

US guidelines:

• Role of prehospital antibiotics remains unclear.
• There is a concern for rapid bacteriolysis that may precipitate shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock (unproven).
• Antibiotics should be administered in rural or remote settings where patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may be facing prolonged transportation times to secondary facilities.

 UK guidelines:

• Arrange emergency medical transfer to hospital. 
• If the patient has suspected bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis with a nonblanching rash Rash Rocky Mountain Spotted Fever or meningococcal septicemia:
  • Administer a single dose of parenteral benzylpenicillin (IV or IM) 1200 mg for adults and children > 10 years.
  • Withhold benzylpenicillin if the patient has a history of severe penicillin Penicillin Rheumatic Fever allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction. 
• If the patient does not have a nonblanching rash Rash Rocky Mountain Spotted Fever: administer parenteral antibiotics only if urgent transfer to hospital is not possible. 

Hospital management^[8,9,15]

Initial supportive measures:

• Droplet precautions
• Early consultation with an infectious disease specialist
• Adequate oxygenation
• Maintain stable cerebral blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure and provide measures to decrease intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension.
• IV fluids IV fluids Intravenous fluids are one of the most common interventions administered in medicine to approximate physiologic bodily fluids. Intravenous fluids are divided into 2 categories: crystalloid and colloid solutions. Intravenous fluids have a wide variety of indications, including intravascular volume expansion, electrolyte manipulation, and maintenance fluids. Intravenous Fluids:
  • Administer cautiously in those with elevated intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension, acute respiratory distress syndrome Acute Respiratory Distress Syndrome Acute respiratory distress syndrome is characterized by the sudden onset of hypoxemia and bilateral pulmonary edema without cardiac failure. Sepsis is the most common cause of ARDS. The underlying mechanism and histologic correlate is diffuse alveolar damage (DAD). Acute Respiratory Distress Syndrome (ARDS), or myocardial dysfunction.
  • Use vasopressors Vasopressors Sepsis in Children in those presenting with hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension/ shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock.
• Prevent hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia and hyponatremia Hyponatremia Hyponatremia is defined as a decreased serum sodium (sNa+) concentration less than 135 mmol/L. Serum sodium is the greatest contributor to plasma osmolality, which is very tightly controlled via antidiuretic hormone (ADH) release from the hypothalamus and by the thirst mechanism. Hyponatremia. 
• Bed rest 
• Analgesics 
• Antipyretics 
• Anticonvulsants in care of seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
• Immunoglobulin administration in immunodeficient patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship

Bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis:

• Timing
  • Antibiotics should be commenced after taking blood cultures and, ideally, after lumbar puncture Lumbar Puncture Febrile Infant
  • Do not delay antibiotics while awaiting results of CT scan or lumbar puncture Lumbar Puncture Febrile Infant.
  • Delays of > 2 hours are associated with doubling of mortality Mortality All deaths reported in a given population. Measures of Health Status.
  • Duration depends on the patient’s response and the pathogen.
• Antibiotic choice
  • Initially, broad-spectrum Broad-Spectrum Fluoroquinolones antibiotics are given empirically.
    • Antibiotic choice depends on local resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing patterns and patient factors.
    • North American guidelines generally recommend ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins 2 g IV every 12 hours) + vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides 15–20 mg/kg IV every 8–12 hours.
    • In adults > 50 years of age, also add ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins 2 g IV every 4 hours (agent with activity against L. monocytogenes L. monocytogenes A species of gram-positive, rod-shaped bacteria widely distributed in nature. It has been isolated from sewage, soil, silage, and from feces of healthy animals and man. Infection with this bacterium leads to encephalitis, meningitis, endocarditis, and abortion. Listeria Monocytogenes/Listeriosis).
  • Later, antibiotics are adjusted based on Gram stain Gram stain Klebsiella results, then culture and sensitivity:
    • S. pneumoniae: vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides + ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins for 10–14 days; vancomycin Vancomycin Antibacterial obtained from streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. Glycopeptides can be stopped if S. pneumoniae is susceptible to ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins.
    • N. meningitidis N. meningitidis A species of gram-negative, aerobic bacteria. It is a commensal and pathogen only of humans, and can be carried asymptomatically in the nasopharynx. When found in cerebrospinal fluid it is the causative agent of cerebrospinal meningitis. It is also found in venereal discharges and blood. There are at least 13 serogroups based on antigenic differences in the capsular polysaccharides; the ones causing most meningitis infections being a, b, c, y, and w-135. Each serogroup can be further classified by serotype, serosubtype, and immunotype. Neisseria: 3rd-generation cephalosporin Cephalosporin Multidrug-resistant Organisms and Nosocomial Infections; penicillin Penicillin Rheumatic Fever G or ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins if susceptible, given for 7 days
    • H. influenzae H. influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. Haemophilus: 3rd-generation cephalosporin Cephalosporin Multidrug-resistant Organisms and Nosocomial Infections; penicillin Penicillin Rheumatic Fever G or ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins if susceptible
    • L. monocytogenes L. monocytogenes A species of gram-positive, rod-shaped bacteria widely distributed in nature. It has been isolated from sewage, soil, silage, and from feces of healthy animals and man. Infection with this bacterium leads to encephalitis, meningitis, endocarditis, and abortion. Listeria Monocytogenes/Listeriosis: ampicillin Ampicillin Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic. Penicillins or penicillin Penicillin Rheumatic Fever G + gentamicin Gentamicin Aminoglycosides  for 21 days; sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim + trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim can be used if penicillin-allergic
    • Gram-negative bacilli Bacilli Shigella (usually nosocomial): 3rd-generation cephalosporin Cephalosporin Multidrug-resistant Organisms and Nosocomial Infections
• Route
  • IV administration is used for maximum efficacy.
  • Penetration Penetration X-rays of blood–brain barrier Blood–Brain Barrier Meningitis in Children is facilitated by active meningeal inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation. 
  • Intrathecal administration of antibiotics is considered in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are unresponsive to IV antibiotics or in nosocomial meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis.
• Dexamethasone Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Antiemetics administration:
  • Initially administered to all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (10 mg IV every 6 hours)
  • Should be started prior to or simultaneously with antibiotics
  • Beneficial for suspected or proven meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis caused by S. pneumoniae or H. influenzae H. influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. Haemophilus:
    • In experimental models, associated with decreased cerebral inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension
    • Decreases mortality Mortality All deaths reported in a given population. Measures of Health Status
    • Decreases rate of neurologic complications (e.g., hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss)
  • Continue for 4 days if streptococcal meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis is confirmed.
  • Stop if Meningococcus or Listeria Listeria Listeria spp. are motile, flagellated, gram-positive, facultative intracellular bacilli. The major pathogenic species is Listeria monocytogenes. Listeria are part of the normal gastrointestinal flora of domestic mammals and poultry and are transmitted to humans through the ingestion of contaminated food, especially unpasteurized dairy products. Listeria Monocytogenes/Listeriosis is confirmed (associated with increased mortality Mortality All deaths reported in a given population. Measures of Health Status in Listeria Listeria Listeria spp. are motile, flagellated, gram-positive, facultative intracellular bacilli. The major pathogenic species is Listeria monocytogenes. Listeria are part of the normal gastrointestinal flora of domestic mammals and poultry and are transmitted to humans through the ingestion of contaminated food, especially unpasteurized dairy products. Listeria Monocytogenes/Listeriosis meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis).

Treatment considerations in bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis ^[8,12–15]

• Infected CSF shunts and drains:
  • Treat with IV antibiotics and remove the infected CSF shunt or drain. 
  • Similarly, an infected intrathecal infusion pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols or hardware with deep brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification stimulation should be removed. 
• Repeat LP is not necessary if patient is responding clinically.
• Consider repeat LP:
  • If no improvement 48 hours after initiating treatment
  • In pneumococcal meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis due to penicillin- or cephalosporin-resistant strains, especially in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship given adjunctive dexamethasone Dexamethasone An anti-inflammatory 9-fluoro-glucocorticoid. Antiemetics therapy
  • In meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis due to gram-negative bacilli Bacilli Shigella (e.g., in neonates, documentation Documentation Systematic organization, storage, retrieval, and dissemination of specialized information, especially of a scientific or technical nature. It often involves authenticating or validating information. Advance Directives of CSF sterilization Sterilization Procedures to block or remove all or part of the genital tract for the purpose of rendering individuals sterile, incapable of reproduction. Surgical sterilization procedures are the most commonly used. There are also sterilization procedures involving chemical or physical means. Reproductive Ethical Issues by repeat LP helps determine treatment duration)
  • In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with CSF shunt infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease in whom shunt removal was performed (a drainage catheter allows for monitoring CSF parameters and response to antibiotics) 
  • If fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever persists > 8 days without obvious causes
• Neuroimaging Neuroimaging Non-invasive methods of visualizing the central nervous system, especially the brain, by various imaging modalities. Febrile Infant is indicated when there is no improvement in 48 hours or new neurologic deficits Neurologic Deficits High-Risk Headaches develop (check for other etiology or complications).
• Complications:
  • Short-term or variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables onset:
    • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease
    • Shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock
    • Hydrocephalus Hydrocephalus Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial. Subarachnoid Hemorrhage
    • Increased intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures
    • Subdural effusion
    • Septic deep vein thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus
  • Long-term:
    • Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss
    • Cognitive and/or behavioral problems
• In children treated for bacterial meningitis Bacterial meningitis Bacterial infections of the leptomeninges and subarachnoid space, frequently involving the cerebral cortex, cranial nerves, cerebral blood vessels, spinal cord, and nerve roots. Meningitis:
  • Test hearing before discharge or within 4 weeks after discharge. 
  • In those with severe to profound hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss, consider a cochlear implant Cochlear implant Electronic hearing devices typically used for patients with normal outer and middle ear function, but defective inner ear function. In the cochlea, the hair cells may be absent or damaged but there are residual nerve fibers. The device electrically stimulates the cochlear nerve to create sound sensation. Hearing Loss as soon as the patient is over the acute stage of meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis. 
• In select patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, continued treatment as an outpatient can be considered in the following cases:
  • ≥ 6 days of inpatient antimicrobial therapy
  • No fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever for at least 24–48 hours prior to switching to outpatient therapy
  • No significant neurologic deficit or seizure activity
  • Improved condition
  • Able to feed and take fluids by mouth
  • IV line Iv Line Central Venous Catheter and device, with access to home health services for antibiotic administration
  • Availability of physician, with established plan for visits and monitoring
  • Patient compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology
  • Safe environment (with access to phone, utilities, food, refrigerator)

Nonbacterial meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis management^{[3,8–10,13]}

Viral meningitis Viral meningitis Viral infections of the leptomeninges and subarachnoid space. Togaviridae infections; flaviviridae infections; rubella; bunyaviridae infections; orbivirus infections; picornaviridae infections; orthomyxoviridae infections; rhabdoviridae infections; arenaviridae infections; herpesviridae infections; adenoviridae infections; JC virus infections; and retroviridae infections may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, photophobia, and signs of meningeal irritation. Meningitis: 

Viral meningitis Viral meningitis Viral infections of the leptomeninges and subarachnoid space. Togaviridae infections; flaviviridae infections; rubella; bunyaviridae infections; orbivirus infections; picornaviridae infections; orthomyxoviridae infections; rhabdoviridae infections; arenaviridae infections; herpesviridae infections; adenoviridae infections; JC virus infections; and retroviridae infections may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, photophobia, and signs of meningeal irritation. Meningitis is usually self-limiting Self-Limiting Meningitis in Children and requires only supportive management. Antiviral Antiviral Antivirals for Hepatitis B therapy is indicated only if viral encephalitis Viral encephalitis Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of togaviridae infections; herpesviridae infections; adenoviridae infections; flaviviridae infections; bunyaviridae infections; picornaviridae infections; paramyxoviridae infections; orthomyxoviridae infections; retroviridae infections; and arenaviridae infections. Encephalitis is also suspected; in selected and/or severe cases. 

• Indications for antiviral Antiviral Antivirals for Hepatitis B therapy (concern for viral encephalitis Viral encephalitis Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of togaviridae infections; herpesviridae infections; adenoviridae infections; flaviviridae infections; bunyaviridae infections; picornaviridae infections; paramyxoviridae infections; orthomyxoviridae infections; retroviridae infections; and arenaviridae infections. Encephalitis):
  • Risk factors
    • HIV HIV Anti-HIV Drugs (or immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis) patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
    • Neonates with mother with active HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2 lesions 
  • Clinical features of encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis 
  • Characteristic imaging findings for encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis 
  • Characteristic lumbar findings for viral meningitis Viral meningitis Viral infections of the leptomeninges and subarachnoid space. Togaviridae infections; flaviviridae infections; rubella; bunyaviridae infections; orbivirus infections; picornaviridae infections; orthomyxoviridae infections; rhabdoviridae infections; arenaviridae infections; herpesviridae infections; adenoviridae infections; JC virus infections; and retroviridae infections may cause this form of meningitis. Clinical manifestations include fever, headache, neck pain, vomiting, photophobia, and signs of meningeal irritation. Meningitis 
• Choice of antiviral Antiviral Antivirals for Hepatitis B
  • HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2: acyclovir Acyclovir A guanosine analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes. Herpes Zoster (Shingles) 10 mg/kg IV every 8 hours
  • CMV: ganciclovir Ganciclovir An acyclovir analog that is a potent inhibitor of the herpesvirus family including cytomegalovirus. Ganciclovir is used to treat complications from aids-associated cytomegalovirus infections. Antivirals for Herpes Virus 5 mg/kg/dose IV every 12 hours, foscarnet Foscarnet An antiviral agent used in the treatment of cytomegalovirus retinitis. Foscarnet also shows activity against human herpesviruses and HIV. Antivirals for Herpes Virus 60 mg/kg/dose IV every 8 hours
• Duration: 7–10 days

Fungal meningitis Fungal meningitis Meningitis caused by fungal agents which may occur as opportunistic infections or arise in immunocompetent hosts. Meningitis: 

• The most common type is cryptococcal meningitis Cryptococcal meningitis Meningeal inflammation produced by cryptococcus neoformans, an encapsulated yeast that tends to infect individuals with acquired immunodeficiency syndrome and other immunocompromised states. The organism enters the body through the respiratory tract, but symptomatic infections are usually limited to the lungs and nervous system. The organism may also produce parenchymal brain lesions (torulomas). Clinically, the course is subacute and may feature headache; nausea; photophobia; focal neurologic deficits; seizures; cranial neuropathies; and hydrocephalus. Cryptococcus/Cryptococcosis.
• Antifungal Antifungal Azoles drugs administered are:
  • Amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes 
  • Fluconazole Fluconazole Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in aids. Azoles 
  • Itraconazole Itraconazole A triazole antifungal agent that inhibits cytochrome p-450-dependent enzymes required for ergosterol synthesis. Azoles 
• Raised intracranial pressure Intracranial Pressure Idiopathic Intracranial Hypertension is a common complication of fungal meningitis Fungal meningitis Meningitis caused by fungal agents which may occur as opportunistic infections or arise in immunocompetent hosts. Meningitis and is managed by:
  • Regular Regular Insulin lumbar punctures to drain the excess fluid 
  • Placement of a lumbar drain 

Other types of meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis: 

• Tubercular meningitis Tubercular meningitis A form of bacterial meningitis caused by Mycobacterium tuberculosis or rarely Mycobacterium bovis. The organism seeds the meninges and forms microtuberculomas which subsequently rupture. The clinical course tends to be subacute, with progressions occurring over a period of several days or longer. Headache and meningeal irritation may be followed by seizures, cranial neuropathies, focal neurologic deficits, somnolence, and eventually coma. The illness may occur in immunocompetent individuals or as an opportunistic infection in the acquired immunodeficiency syndrome and other immunodeficiency syndromes. Meningitis is treated with antitubercular therapy:
  • Isoniazid Isoniazid Antibacterial agent used primarily as a tuberculostatic. It remains the treatment of choice for tuberculosis. Antimycobacterial Drugs, rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis, pyrazinamide Pyrazinamide A pyrazine that is used therapeutically as an antitubercular agent. Antimycobacterial Drugs, ethambutol Ethambutol An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle Bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. Antimycobacterial Drugs, streptomycin 
  • Recommended duration of treatment is 9–12 months.
• Parasitic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis:
  • Antimicrobials: amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes, miconazole Miconazole An imidazole antifungal agent that is used topically and by intravenous infusion. Azoles, rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis, miltefosine Miltefosine Leishmania/Leishmaniasis
  • Parasitic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis is fatal, and immediate treatment is essential.
  • The drugs are administered in high doses, and some are administered intrathecally. 
• Noninfectious meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis:
  • Allergic or autoimmune meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis is managed with corticosteroids Corticosteroids Chorioretinitis.
  • Meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis due to cancer is managed by treating the underlying condition.

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas^[1,3]

• Mortality Mortality All deaths reported in a given population. Measures of Health Status increases with age:
  • 18–34 years old: Case fatality is 8.9%.
  • > 65 years old: Case fatality is 22.7%.
• Neurologic complications ( hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss, intellectual impairment, focal deficits) affect up to 28% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.

Prevention^[10,15]

Vaccinations can protect against certain types of meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis: 

• Haemophilus influenzae Haemophilus Influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through viii. Haemophilus type B (Hib) vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination 
• Pneumococcal conjugate vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination 
• Meningococcal vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination

Routine vaccination Vaccination Vaccination is the administration of a substance to induce the immune system to develop protection against a disease. Unlike passive immunization, which involves the administration of pre-performed antibodies, active immunization constitutes the administration of a vaccine to stimulate the body to produce its own antibodies. Vaccination schedule:

• Hib:
  • Primary series at 2, 4 and 6 months
  • Booster at 12–15 months
• Pneumococcus:
  • 4-dose series at 2, 4, 6, and 12–15 months 
  • Adults ≥ 65
• Meningococcus:
  • 2-dose series at 11–12 and 16 years
  • 1st-year college students living in residential areas if not vaccinated at age 16
• Additional vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination doses may be indicated in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with anatomic or functional asplenia Functional Asplenia Asplenia, prior to elective splenectomy Splenectomy Surgical procedure involving either partial or entire removal of the spleen. Rupture of the Spleen or with immunocompromise. 

Chemoprophylaxis Chemoprophylaxis Meningitis in Children:^[11,15,17]

• Meningococcal and H. influenzae H. influenzae A species of Haemophilus found on the mucous membranes of humans and a variety of animals. The species is further divided into biotypes I through VIII. Haemophilus meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis are reportable cases.
• For close contacts of a patient with meningococcal meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis, antibiotic chemoprophylaxis Chemoprophylaxis Meningitis in Children is recommended:
  • To remove established carriage from the exposed/close contact group
  • To reduce transmission
• Chemoprophylaxis Chemoprophylaxis Meningitis in Children should be given to the following (exposed in the 7 days before symptom onset):
  • Household members
  • Daycare contacts
  • Other close contacts (those directly exposed to oral secretions) of a patient with meningococcal meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis
• Chemoprophylaxis Chemoprophylaxis Meningitis in Children options:
  • Ciprofloxacin Ciprofloxacin A broad-spectrum antimicrobial carboxyfluoroquinoline. Fluoroquinolones 500 mg (20 mg/kg in children) orally once
  • Ceftriaxone Ceftriaxone A broad-spectrum cephalosporin antibiotic and cefotaxime derivative with a very long half-life and high penetrability to meninges, eyes and inner ears. Cephalosporins 250 mg (125 mg if < 15 years of age) IM once
  • Rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis 600 mg (5 mg/kg/dose in children < 1 month, 10 mg/kg/dose in children ≥ 1 month) orally every 12 hours for 2 days (total of 4 doses)
  • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides 500 mg (10 mg/kg in children) orally once

Differential Diagnosis

• Stroke: damage to the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification due to interrupted blood supply: Stroke presents with neurologic defects, blurred vision Blurred Vision Retinal Detachment, slurred speech Slurred Speech Cerebellar Disorders, and paresthesia. Stroke is diagnosed by history, neurologic examination, and imaging. Management depends on the type of stroke. 
• Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease: collection of pus in response to an infection or trauma: Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia. Diagnosed by evaluation of signs and symptoms, blood tests, and imaging. Management includes antibiotic therapy and surgery to drain the abscess Abscess Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. Chronic Granulomatous Disease. 
• Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis: inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification parenchyma due to infection: Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways in muscles and joints, and fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia. Diagnosed by imaging, CSF analysis CSF analysis Meningitis, lab tests, and electroencephalography Electroencephalography Seizures. Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis rarely presents with nuchal rigidity Nuchal Rigidity Meningitis and photophobia Photophobia Abnormal sensitivity to light. This may occur as a manifestation of eye diseases; migraine; subarachnoid hemorrhage; meningitis; and other disorders. Photophobia may also occur in association with depression and other mental disorders. Migraine Headache. Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures are common. Supportive management, anti-inflammatory drugs, and antiviral Antiviral Antivirals for Hepatitis B drugs are used to manage encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis. 
• Subdural empyema Empyema Presence of pus in a hollow organ or body cavity. Pneumonia: collection of pus between the dura mater Dura mater The outermost of the three meninges, a fibrous membrane of connective tissue that covers the brain and the spinal cord. Meninges: Anatomy and the arachnoid mater Arachnoid mater A delicate membrane enveloping the brain and spinal cord. It lies between the pia mater and the dura mater. It is separated from the pia mater by the subarachnoid cavity which is filled with cerebrospinal fluid. Meninges: Anatomy: Subdural empyema Empyema Presence of pus in a hollow organ or body cavity. Pneumonia presents with fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia, focal neurologic deficits Neurologic Deficits High-Risk Headaches, and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures. This condition is diagnosed by imaging, most commonly with contrast-enhanced MRI Contrast-enhanced MRI Imaging of the Head and Brain. Subdural empyema Empyema Presence of pus in a hollow organ or body cavity. Pneumonia is managed surgically and with antibiotics.
• Delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium tremens: severe form of ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism withdrawal that presents clinically with global confusion, agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus, hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and diaphoresis. Diagnosis of delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium tremens is made by history and signs and symptoms and management is with supportive therapy and thiamine Thiamine Also known as thiamine or thiamin, it is a vitamin C12H17N4OSCl of the vitamin B complex that is essential to normal metabolism and nerve function and is widespread in plants and animals Water-soluble Vitamins and their Deficiencies. 
• Subarachnoid hemorrhage Subarachnoid Hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage: bleeding within the subarachnoid space Subarachnoid space The space between the arachnoid membrane and pia mater, filled with cerebrospinal fluid. It contains large blood vessels that supply the brain and spinal cord. Subarachnoid Hemorrhage that occurs spontaneously or following head trauma Head trauma Head trauma occurs when external forces are directed to the skull and brain structures, resulting in damage to the skull, brain, and intracranial structures. Head injuries can be classified as open (penetrating) or closed (blunt), and primary (from the initial trauma) or secondary (indirect brain injury), and range from mild to severe and life-threatening. Head Trauma: Subarachnoid hemorrhage Subarachnoid Hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage presents with neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess and shoulder pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, numbness throughout the body, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, confusion and irritability, diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis, and sudden headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess. Diagnosis is by history, signs and symptoms, imaging, and cerebral angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery. Subarachnoid hemorrhage Subarachnoid Hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage is managed surgically. Antihypertensive agents are recommended.