CNS Infections_Amboss_2024-1-32.pdf

Meningitis Summary Meningitis is an infection of the meninges in the brain or spinal cord. Common causes include viruses and bacteria, although fungal, parasitic, and non-infectious causes of meningitis are possible. The most common bacterial pathogens (N. meningiti...

Meningitis Summary Meningitis is an infection of the meninges in the brain or spinal cord. Common causes include viruses and bacteria, although fungal, parasitic, and non-infectious causes of meningitis are possible. The most common bacterial pathogens (N. meningitidis, S. pneumoniae, H. influenzae, Group B streptococcus, and L. monocytogenes) vary depending on age and underlying medical conditions. Enteroviruses and herpes simplex virus (HSV) are the leading causes of viral meningitis. The classic triad of meningitis (fever, meningismus, altered mental state) occurs in less than half of adult patients and meningitis in infants and children frequently presents with nonspecific symptoms. Advanced infection includes signs of increased intracranial pressure (ICP), neurological deficits, altered mental status, and seizures. Diagnosis is confirmed with CSF analysis and microbiological studies (e.g., PCR, culture). If increased ICP is suspected, a CT of the head is recommended prior to lumbar puncture (LP). Antibiotic therapy should not be delayed for diagnostic testing. Bacterial meningitis requires rapid initiation of empiric antimicrobials and sometimes glucocorticoids to prevent complications, which include neurological deficits (e.g., hearing loss) and end-organ damage (e.g., Waterhouse-Friderichsen syndrome in patients with meningococcal meningitis). While most cases of viral meningitis are self- limiting, herpesvirus infections (e.g., HSV, VZV) must be promptly recognized and treated with IV acyclovir to prevent serious complications and death. Prevention is through vaccination against common causes of meningitis, and chemoprophylaxis for exposed contacts. Epidemiology In the paediatric population, meningitis most often occurs in children < 1 year of age. The median age for meningitis in the adult population is 43 years. Sub-Saharan Africa has the worldwide highest incidence of meningitis caused by N. meningitidis. Aetiology Common causes Otitis media 1|Page  Sinusitis CSF leak after head trauma or neurosurgery Maternal group B streptococcal infection during birth Sepsis Risk factors Immunocompromise (e.g., due to AIDS, asplenia, heavy alcohol use disorder, chronic illness, cancer, sickle cell anaemia, old age, pregnancy) Crowded occupational or living conditions (e.g., college dormitories, military barracks, retirement homes, kindergartens) Close contact with an infected person Most common causative agents of bacterial meningitis by age group and underlying condition Patient population Pathogen By age Streptococcus agalactiae (Group B streptococcus): most common cause of early-onset bacterial meningitis < 1 month Gram-negative bacilli: Escherichia coli (very common), Klebsiella species, Enterobacter species Listeria monocytogenes Streptococcus pneumoniae Neisseria meningitidis (meningococcal disease)(first peak: < 2 years of 1 month–2 years age) Group B streptococcus (esp. Streptococcus agalactiae) Hemophilus influenzae type b (if not immunized) Neisseria meningitidis (second peak: 16–20 years of age) 2–50 years Streptococcus pneumoniae (most common in adults) Streptococcus pneumoniae (most common) > 50 years Aerobic gram-negative bacilli (e.g., Escherichia coli) 2|Page  Listeria monocytogenes Haemophilus influenzae type b (if not immunized) Neisseria meningitidis Group B streptococcus By underlying condition Listeria monocytogenes Streptococcus pneumoniae Immunocompromise Haemophilus influenzae type b Gram-negative bacilli (e.g., Escherichia coli, Salmonella spp.) Streptococcus pneumoniae Basilar skull fracture Haemophilus influenzae type b Group A beta-hemolytic streptococci Staphylococcus aureus Penetrating trauma Coagulase-negative staphylococci (e.g., Staphylococcus epidermidis) Aerobic gram-negative bacilli (including Pseudomonas aeruginosa) Coagulase-negative staphylococci (e.g., Staphylococcus epidermidis) Staphylococcus aureus Health care- Gram-negative bacteria (e.g., Pseudomonas associated aeruginosa, Enterobacter cloacae, Serratia marcescens, Klebsiella spp.) Propionibacterium acnes Less common bacterial pathogens Borrelia spp. (Lyme meningitis) Treponema pallidum (syphilitic meningitis) Mycobacterium tuberculosis (tuberculous meningitis) Actinomyces israelii Leptospira (leptospirosis) Other aetiologies Viral meningitis: often associated with encephalitis (meningoencephalitis) 3|Page  o Enteroviruses (especially coxsackieviruses and echoviruses): the most common cause of all types of meningitis in all patient groups o Herpesviruses: HSV (meningitis is more commonly caused by HSV2 than HSV1) , CMV, EBV, VZV o Lymphocytic choriomeningitis virus (LCMV) o Mumps virus o Measles virus o Some arboviruses (e.g., West Nile virus, TBEV in Eurasia) o Poliovirus (nonparalytic poliomyelitis: aseptic meningitic form) o St. Louis encephalitis virus o California encephalitis virus o Western equine encephalitis virus o Influenza virus o HIV o JC virus Fungal meningitis o Coccidioides o Candida spp. o Aspergillus spp. Parasitic meningitis o Helminths (e.g., Echinococcus spp., Strongyloides stercoralis, Angiostrongyliasis cantonensis, Baylisascaris procyonis) o Protozoa (e.g., Naegleria fowleri, Acanthamoeba) Noninfectious meningitis o Sarcoidosis o Tumor metastases (meningeal carcinomatosis and meningeal leukaemia) o Medication (e.g., NSAIDs, sulpha drugs) Causes of meningitis in immunocompromised individuals Bacterial o Certain immune deficiencies can predispose to certain types of meningitis.  Defects in humoral immunity (including splenectomy): encapsulated bacteria (N. meningitidis, S. pneumoniae, H. influenzae, etc.)  Defects in cell-mediated immunity (e.g., in HIV, drug- induced immunosuppression): M. tuberculosis, L. monocytogenes 4|Page  o Immunocompromised individuals are at increased risk of recurrent bacterial meningitis compared to those with intact immunity. Viral: Risk is higher in individuals with cell-mediated immune deficiencies (e.g., in HIV infection). o Herpesviruses: CMV, EBV, VZV, and HSV6 o HIV o Adenovirus o JC virus Fungal: Risk is higher in individuals with cell-mediated immune deficiencies (e.g., HIV infection). o Cryptococcus spp. o Candida spp. o Histoplasma capsulatum o Aspergillus spp. Protozoal: Toxoplasma gondii (rare) Pathophysiology Pathways of infection Most pathogens that cause meningitis colonize the nasopharynx or the upper airways before entering the CNS via: o Hematogenous dissemination o Contiguous spread of infections in nose, eyes, and ears o Retrograde transport along or within peripheral or cranial nerves Direct infection (e.g., due to trauma or head surgery) Incubation periods Bacterial meningitis: usually 3–7 days Viral meningitis: usually 2–14 days, depending on the type of virus Clinical features Clinical features of bacterial and viral meningitis are similar, although viral meningitis is less acute and usually self-limiting within 5–14 days. 5|Page Symptoms of meningitis Classic triad of meningitis o Fever o Meningismus  Headache  Neck stiffness  Photophobia o Altered mental state Nausea, vomiting Malaise Seizures Neonates and young children often present with nonspecific symptoms. Pathogen-specific symptoms Patients with N. meningitidis: signs of meningococcemia o Myalgia: more common in children o Possibly petechial or purpuric rash: more common in children o Possibly Waterhouse-Friderichsen syndrome: more common in adults Patients with viral meningitis o Prodrome with flu-like symptoms  Low-grade fever  Malaise and fatigue  Myalgia  Upper respiratory symptoms (e.g., sore throat) o Pharyngitis, herpangina, and/or rash Less than half of adult patients have all three features of the classic triad of meningitis; the percentage is even lower in neonates and young infants, who typically present with nonspecific symptoms Subarachnoid haemorrhage manifests with the classic triad of meningitis, but it typically has a more sudden onset and affected individuals often lose consciousness. 6|Page Physical examination Signs of meningeal irritation o Neck stiffness o Kernig sign o Brudzinski sign Systemic signs of inflammation o Fever o Hypotension o Tachycardia Signs of increased intracranial pressure (< 5% of cases), e.g., cranial nerve palsies, papilledema Signs of underlying infections o Bulging and redness of tympanic membrane: acute otitis media o Skin manifestations  Cutaneous petechiae in meningococcal meningitis: suggestive of meningococcemia  Maculopapular rash in some viral meningitis types (e.g., West Nile virus, enterovirus)  Non-blanching rash: raises suspicion for meningococcal meningitis Features suggestive of meningoencephalitis In addition to the features of meningitis, meningoencephalitis is characterized by signs of inflammation of the brain parenchyma (encephalitis). Focal neurological signs (e.g., paresis, extrapyramidal symptoms, aphasia) Seizures (focal-onset or generalized) Behavioural changes, psychosis Altered consciousness 7|Page  Kernig sign The Kernig sign can be assessed using two methods. In the first method (A), the extended leg is passively elevated at the hip joint. If there is pain, there is reflex flexion of the knee. Alternatively (B), the Kernig sign can be assessed by flexing the hip and knee at a 90° angle. Subsequent extension of the leg causes stretching of the nerve roots or meninges, which can result in pain and muscle guarding against extension. Brudzinski sign Passive flexion of the neck (A) leads to spontaneous flexion of the hips (B) as a reflex, which provides relief of painful strain on the meninges. 8|Page Initial management Bacterial meningitis is a medical emergency and requires immediate treatment. Diagnostic and treatment steps should be initiated simultaneously and empiric treatment should not be delayed for diagnostic steps. o If the patient is stable and has no LP contraindications: Perform LP as soon as possible before starting empiric antibiotics. o If the patient is unstable, requires neuroimaging, or has relative contraindications to LP (e.g., coagulopathy): Defer LP and start empiric antibiotic treatment. Management of meningitis 9|Page  Do not delay empiric antibiotic therapy in patients suspected of having bacterial meningitis. Diagnostics Approach Obtain samples immediately for blood cultures, routine laboratory tests, and screening for organ dysfunction. Confirm the diagnosis with LP and CSF analysis (if no LP contraindications are present). Start empiric antibiotics immediately after obtaining blood cultures and CSF samples. If LP is delayed for any reason (e.g., the need for a CT or hemodynamic stabilization), obtain blood cultures and administer antibiotics until it can be performed. Laboratory studies Routine tests o Blood cultures (two sets): obtain before starting antibiotic therapy o FBC  Normal/↑ WBC count  In severe infections, ↓ WBC count and thrombocytopenia o BMP: Blood glucose is needed to analyze CSF glucose.  Common finding: mild electrolyte disturbances (e.g., hyponatremia from SIADH)  In critically ill patients: possible signs of acute kidney injury o CRP: elevated Additional tests o Assess for organ damage and complications.  Coagulation panel: especially if there is suspicion for disseminated intravascular coagulation (e.g., petechiae, purpura)  Blood gas: metabolic acidosis may be present in critically ill patients o Consider testing for atypical infections 10 | P a g e Neuroimaging Imaging is not necessary to establish the diagnosis of meningitis in most patients and should only be considered in patients with significant risk factors for complications. Indications o To assess the risk of brain herniation precipitated by LP o Identify abscesses or other localized lesions (e.g., in postsurgical patients in whom infection is suspected) o Suspected healthcare-associated ventriculitis/meningitis o Patients with devices (e.g., CSF shunts) Recommended criteria for imaging prior to LP in suspected meningitis o Focal neurological deficits o Altered mental status o Immunocompromised status (e.g., HIV, post-transplant, taking immunosuppressants) o Papilledema o History of CNS disease (e.g., mass, stroke, abscess) o Seizures (new-onset) Modalities o CT head (with or without IV contrast): before LP if increased ICP is suspected o MRI brain with IV contrast and diffusion: especially useful in patients with devices or after surgery Supportive findings o Usually normal or showing mild meningeal enhancement o May identify predisposing factors for the infection (e.g., fractures, mastoiditis) or complications (e.g., abscess) 11 | P a g e Cerebrospinal fluid analysis Lumbar puncture is indicated in all patients with suspected meningitis. Lumbar puncture (1/2): materials, patient positioning, and puncture site Sterile materials (upper left): (a) Local anaesthetic (b) Syringe for application of local anaesthetic (c) and (d) Syringe and needles for superficial and deep application of local anaesthetic (e) Gauze (f) CSF collection tubes (4) (g) Forceps (h) Sterile gloves (i) Antiseptic (j) Spinal needle Nonsterile materials (lower left): (k) Surgical mask Patient positioning: The patient is typically seated and flexed forward (upper right) or placed in a flexed lateral recumbent position with the head supported (lower right). Flexion increases the interspinous space and facilitates access to the subarachnoid space. Puncture site (far right): For lumbar puncture (including spinal anaesthesia), the spinal needle is typically inserted in the L3–4 or L4–5 interspace and directed toward the umbilicus. 12 | P a g e  Lumbar puncture (2/2): procedure 1. The skin is prepped widely with antiseptic in a spiral motion outwards from the intended needle insertion site. A sterile fenestrated drape is typically applied over the antiseptic prep (not shown). 2. Local anesthesia is injected subcutaneously with a small gauge needle, creating a skin wheal over the intended needle insertion site. Local anesthesia is then infiltrated into the deeper tissue through this skin wheal, anesthetizing the entire intended needle tract (2a). 3. The spinal needle is inserted with the tip directed towards the umbilicus and advanced until a loss of resistance is felt. Failure to direct the needle toward the umbilicus may result in the needle encountering bone before reaching the subarachnoid space (3a). 4. The stylet is withdrawn and the needle hub is observed for CSF flow. If flow is present, CSF is collected in four collection vials. 5. The stylet is replaced after the collection of CSF is complete. 6. The spinal needle and stylet are removed and a dressing is applied to the puncture site (not shown). 13 | P a g e Routine testing Cerebrospinal fluid analysis in meningitis Normal Bacterial meningitis Viral meningitis Appearance Clear fluid Cloudy, purulent fluid Clear fluid Elevated cell count Variable cell count (leukocyte Cell count and with significant pleocytosis Cell count < 5/mm3 count 10–500/mm3) differential (leukocyte count > 1000/mm3) ↑ Lymphocytes ↑ Granulocytes (> 80%) Opening 5–18 cm H2O ↑↑ Normal or ↑ pressure Lactate 1.2–2.1 mmol/L ↑↑ Variable Protein 15–45 mg/dL ↑ Normal or ↑ Glucose 40–75 mg/dL ↓ Normal 14 | P a g e  Positive gram stain and culture o Meningococci: gram- negative diplococci Gram stain and o Pneumococci: gram- No organisms present No organisms present culture positive diplococci o Listeria: gram-positive rods o Haemophilus influenzae: gram- negative coccobacilli Atypical pathogen testing Atypical pathogen testing is not necessary for all patients and should be performed as directed by clinical suspicion. Cerebrospinal fluid analysis in meningitis due to atypical pathogens Tuberculous meningitis Lyme meningitis Cryptococcal meningitis Appearance Clear fluid with a spiderweb clot Clear fluid Cloudy fluid Cell count Variable cell count (30–300/mm3) Variable cell count (10–1000/mm3) and Pleocytosis (predominantly lymphocytes Variable cell count (20–200/mm3) Pleocytosis (lymphocytes, mononuclear differential but also granulocytes and mononuclear Pleocytosis (lymphocytes) cells) cells) 15 | P a g e Opening ↑↑ ↑↑ ↑↑ pressure Lactate ↑ Variable ↑ Protein ↑ Normal or ↑ ↑ Glucose ↓ Normal or ↓ ↓ 16 | P a g e Additional microbiological testing Special microbiological stains o Acid-fast staining: if there is suspicion for tuberculous meningitis o India ink preparation: if there is suspicion for cryptococcus o Wright or Giemsa stain: if there is suspicion for toxoplasmosis Special cultures o Viral culture  Not typically recommended  May confirm enterovirus, herpes simplex virus infection o M. tuberculosis cultures: Results can take up to 6 weeks. o Fungal cultures: for the identification of Candida spp., Cryptococcus spp. o For patients with CSF shunts or drains: Extend CSF cultures for at least 10 days. PCR for viral meningitis and specific bacterial subtypes o Indications  Confirmation of viral meningitis/encephalitis (e.g., HSV)  Detection of intracellular bacteria (e.g., TB, rickettsial infections) o Disadvantages  No antibiotic sensitivity data for bacterial infections  Not readily available for unusual pathogens (especially bacteria) Latex agglutination test o Bacterial antigen detection  Not routinely used because of variable accuracy  Consider in patients in whom there is strong suspicion for bacterial meningitis despite negative Gram stain or culture after 48 hours o Fungal latex agglutinations: especially relevant for cryptococcal antigen testing (see cryptococcal meningitis) Treatment Approach Apply appropriate isolation precautions. Stabilize the patient as needed. Administer empiric antibiotics as soon as possible, preferably within 1 hour. 17 | P a g e  o If LP can be performed rapidly, administer antibiotics and adjuvant therapy (e.g., dexamethasone) after obtaining CSF. o If LP is delayed (e.g., because neuroimaging is required), administer antibiotics and adjuvant therapy (e.g., dexamethasone) immediately. o Add other antimicrobial therapy (e.g., antivirals, antifungals) as needed. Tailor antimicrobial therapy once the pathogen is identified. Provide postexposure prophylaxis for close contacts if indicated Do not delay administering antibiotics if neuroimaging is indicated prior to LP. Obtain blood cultures, start antibiotics (and steroids, if needed) immediately, then proceed with the CT and LP. Immediate stabilization for meningitis Airway management: Secure the airway (e.g., intubate) if GCS < 8, the patient has intractable seizures, or there are signs of cerebral herniation. Provide hemodynamic support with fluids and/or vasopressors. Identify and reverse any coagulopathy. Identify and treat elevated ICP. Intracranial pressure (ICP) is the pressure that exists within the cranium, including its compartments (e.g., the subarachnoid space and the ventricles). ICP varies as the position of the head changes relative to the body and is periodically influenced by normal physiological factors (e.g., cardiac contractions). Adults in the supine position typically have a physiological ICP of ≤ 15 mm Hg; an ICP of ≥ 20 mm Hg indicates pathological intracranial hypertension. ICP may be elevated in a variety of conditions (e.g., intracranial tumours) and can result in a decrease in cerebral perfusion pressure (CPP) and/or herniation of cerebral structures. Symptoms of elevated ICP are generally nonspecific (e.g., impaired consciousness, headache, vomiting); however, more specific symptoms may be present depending on the affected structures (e.g., Cushing triad if the brainstem is compressed). Findings from brain imaging (e.g., a midline shift) and physical examination (e.g., papilledema) can indicate ICP elevation but may not be able to rule it out. Therefore, ICP monitoring and quantification are vital in at- risk patients. Management usually involves expedited surgery of resectable or drainable lesions, conservative measures (e.g., positioning, sedation, analgesia, and antipyretics), and medical therapy (e.g., hyperosmolar therapy such as mannitol or hypertonic saline, or glucocorticoids). Treatment options for refractory intracranial hypertension include temporary controlled hyperventilation, CSF drainage, and decompressive 18 | P a g e  craniectomy (DC), as well as other advanced medical therapies (e.g., barbiturate coma, therapeutic hypothermia). Antimicrobial therapy Empiric antibiotic therapy The choice of initial empiric therapy depends primarily on the prevalence of organisms in certain age groups and individual patient risk factors for resistant organisms. Factors to consider: o Epidemiological factors (e.g., local flora, resistance patterns) o Bioavailability: Antimicrobial agents should cross the blood-brain barrier and higher doses may be needed. o Individual patient risk factors and comorbidities Empiric antibiotic therapy for bacterial meningitis Patient characteristics Recommended regimen Age 50 years PLUS one of the following third-generation cephalosporins: o Cefotaxime o Ceftriaxone Vancomycin Immunocompromised PLUS ampicillin PLUS one of the following: 19 | P a g e  o Cefepime o Meropenem Ampicillin is added if patients are at risk of Listeria spp. infection (e.g., newborns, pregnant women, adults > 50 years of age, or immunocompromised patients) because cephalosporins are ineffective against Listeria spp. Empiric therapy for viral meningitis Most cases of viral meningitis (e.g., caused by enteroviruses) can be treated supportively. Specific antiviral therapy is only warranted if viral encephalitis is also suspected. Indications o Concern for HSV encephalitis, for example:  Suggestive clinical features (e.g., focal neurological deficits, altered mental status, seizures, behavioural changes, coma)  Imaging findings (e.g., temporal lobe enhancement)  CSF: ↑ RBCs despite a nontraumatic LP (suggestive of haemorrhagic encephalitis) o Concern for other herpesviruses, e.g., VZV, EBV Recommended empiric antiviral agent: acyclovir o Continue treatment if either HSV or VZV is detected, otherwise discontinue. Treatment with acyclovir should be started in all patients who present with typical clinical signs of viral meningoencephalitis and only discontinued after PCR and antibody tests are negative for HSV and VZV, even if CSF is initially normal. Pathogen-specific therapy The decision to narrow therapy should be guided by final culture and sensitivity results, as well as local resistance patterns. We list a few examples of antimicrobial agents that may be used against specific pathogens. 20 | P a g e  Pathogen-specific therapy in meningitis Pathogen Examples of antimicrobial agents S. pneumoniae (penicillin- resistant strains) Vancomycin MRSA S. epidermidis H. influenzae Third- N. meningitidis generation cephalosporin (e.g., cefotaxime OR ceftriaxone) For E. coli in neonates, add gentamicin. E. coli L. monocytogenes Ampicillin Consider the addition of gentamicin. S. agalactiae Gentamicin Enterococcus spp. PLUS either ampicillin OR vancomycin P. aeruginosa Cefepime R. rickettsii Doxycycline Herpes viruses Acyclovir Corticosteroids Indication: suspected or proven meningitis due to S. pneumoniae or H. influenzae Mechanism: reduces the local and systemic inflammation seen in bacterial meningitis and improves outcomes 21 | P a g e  Recommended agent: dexamethasone o Should be administered before or concomitant to antibiotics for optimal result o Discontinue if a pathogen other than S. pneumoniae or H. influenzae is identified. Disadvantages: side effects, e.g., hyperglycaemia, GI bleeding Do not delay antibiotics to administer adjuvant therapy. If dexamethasone is not readily available, start antibiotics immediately. Subtypes and variants Tuberculous meningitis Pathogen: Mycobacterium tuberculosis Incubation period: approximately 2–8 weeks Risk factors: immunocompromise (e.g., HIV infection) Clinical course o Subacute course over several weeks or months o Gradual manifestation with intermittent fever Clinical features o Typical symptoms of meningitis, including fever, headache, neck stiffness, and altered mental status o Focal neurological deficits (e.g., hemiparesis) due to hematogenous dissemination of cranial arteritis o Cranial nerve deficits are most commonly seen in basal meningitis and predominantly involve the abducens nerve Diagnostics o CSF fluid  Presence of acid-fast bacilli on CSF Gram stain  Culture is the gold standard for diagnosis, but results may take weeks.  Analysis of adenosine deaminase (ADA) activity  ↑↑ Activity in CSF of individuals with tuberculous meningitis compared to CSF of individuals with other types of meningitis (e.g., cryptococcal or bacterial meningitis)  For the differentiation of tuberculous from other types of meningitis, combining serum and CSF ADA activity can increase sensitivity and specificity. 22 | P a g e   However, reported sensitivity and specificity vary greatly in the literature; confounding factors include the CSF ADA cut-offs, assay types, and comorbidities (especially HIV). o CT/MRI: possible hydrocephalus, basilar meningeal thickening, tuberculomas, oedema, infarcts Complications o Communicating (malabsorptive) hydrocephalus o Pituitary gland insufficiency Treatment o Treatment for Tuberculosis. o Adjunctive glucocorticoid therapy with dexamethasone or prednisolone tapered over 6–8 weeks VIEW CAPTION Tuberculous meningitis 12-month-old infant with HIV and mycobacterium tuberculosis The child's body presents a position typical for a seizure. The head is overextended and the feet reach out for the head. Neck stiffness and general tension in hands and feet are also present. These findings are suggestive of meningoencephalitis. Cryptococcal meningitis Pathogen: Cryptococcus neoformans (a type of encapsulated yeast) Risk factors o AIDS o Exposure to pigeon droppings Clinical course: subacute onset with (low) fever, fatigue, and headaches Clinical features o See section on “Clinical features” above 23 | P a g e  o Meningeal symptoms are often absent Diagnostics o Cryptococcal antigen testing of CSF and serum  Highly specific and sensitive  Typically performed via latex agglutination or enzyme immunoassay o CSF culture (Sabouraud agar) o CSF gram staining: India Ink (clear halo), mucicarmine (red inner capsule) o MRI: gelatinous pseudocysts (soap bubble appearance) Treatment o Induction: Intravenous amphotericin B PLUS flucytosine for at least 2 weeks o Consolidation: fluconazole for at least 8 weeks o Maintenance: fluconazole for at least 1 year o Manage raised ICP with therapeutic lumbar puncture. o Important consideration: Delay initiation of cART for 4–6 weeks after starting antifungal therapy to reduce the risk of immune reconstitution syndrome. Cryptococcal meningitis MRI head (with contrast; T1-weighted; axial plane) of a 58-year-old patient with monoclonal gammopathy and polycythemia vera who presented with confusion, fatigue, and auditory hallucinations for one week. Mild meningeal enhancement is seen (see arrows), which is suspicious for an infectious event and caused by cryptococcosis in this case. 24 | P a g e  Cryptococcosis MRI head (with contrast; axial plane) A small contrast-enhancing lesion (indicated by arrow) resulting from cryptococcosis is visible in the right basal ganglia. In unspecific findings like this one, an inflammatory etiology should be considered as a differential on the basis of contrast enhancement and localization. Primary amoebic meningoencephalitis Pathogen: Naegleria fowleri (colloquially referred to as “brain- eating amoeba”), found in warm freshwater (e.g., ponds, hot springs) Route of infection: via contaminated water entering the nose (e.g., while swimming) → invades the CNS directly via the olfactory nerve (perforates the cribriform plate) Clinical features: causes fulminant meningoencephalitis with rapid onset Diagnosis o CSF analysis  Findings similar to those of bacterial meningitis (e.g., neutrophilic pleocytosis, hypoglycorrhachia, increased CSF protein)  CSF erythrocytosis (due to haemorrhagic necrosis)  Microscopy shows trophozoites Treatment: amphotericin B, miltefosine Prognosis: nearly always fatal 25 | P a g e Complications Neurologic Most common: sensorineural hearing loss (transient or permanent) Focal neurological deficits Seizures [Especially during acute infection, but the risk remains slightly elevated after recovery.] Cognitive impairment Spasticity or paresis Cerebral oedema and elevated ICP Communicating hydrocephalus Cerebrovascular disease Rare: brain abscess, subdural empyema, arteritis (risk of cerebral infarction and cerebral venous sinus thrombosis), ventriculitis, cerebritis Waterhouse-Friderichsen syndrome Epidemiology: predominantly affects small children and asplenic individuals Description: acute primary insufficiency of the adrenal gland most commonly caused by adrenal haemorrhage o Dangerous complication of a number of diseases but most commonly associated with meningococcal meningitis o Rarer causes include DIC, endotoxic shock, and septicemia due to other pathogens (e.g., S. pneumoniae) Pathophysiology: coagulopathy triggered by endotoxins, which often leads to haemorrhagic necrosis of the adrenal glands Clinical features o Fever o Myalgia o Non-blanching, petechial rash (mostly on trunk and legs); in severe cases, even purpura fulminans with extensive necrosis of the skin o Severe malaise o Hypotension or even shock o Findings of disseminated intravascular coagulation o Findings of acute adrenal gland failure o Respiratory failure 26 | P a g e  Treatment o Treatment of the underlying cause o Parenteral fluid therapy and management of disorders of sodium balance o Coagulopathy treatment Prognosis: fatal without treatment and often fatal even with treatment, particularly if associated with meningococcal infection (> 40% mortality rate) Purpura Bluish-red, round or oval maculae (approx. 0.2 mm–1 cm in diameter) are distributed over the right lower leg. There is also an irregularly shaped macula of the same color lateral to the patella (approx. 4 × 2 cm in diameter). This appearance is characteristic of purpura. Purpura in Waterhouse-Friderichsen syndrome Purple nonblanching macules of various sizes, consistent with purpura (larger macules) and petechiae (smaller macules), are visible. These findings are consistent with purpura in Waterhouse-Friderichsen syndrome. 27 | P a g e  Skin haemorrhages in Waterhouse-Friderichsen syndrome There are multiple small, nonblanching purple macules on the upper thigh, medial aspect of the knee, and anterior lower leg. This appearance is consistent with purpura due to Waterhouse-Friderichsen syndrome. Prognosis Bacterial meningitis o Fatal if left untreated o Prognosis in treated patients depends on age, overall condition, immune status and the pathogen(s) involved. Viral meningitis o Resolves spontaneously in the majority of cases o Residual symptoms such as sensorineural hearing loss, epilepsy, and cognitive deficits are rare. Fungal meningitis o Associated with neurological sequelae and a high mortality rate o Treatment adherence is very important to avoid relapse. Prevention Primary prevention Promptly treat infections that can spread to the CNS (e.g., mastoiditis, sepsis). Meningococcal vaccine There are three types of meningococcal vaccine. The meningococcal vaccination schedule varies widely between countries. 28 | P a g e Prevention of onward transmission Follow empiric droplet precautions and then adjust based on the identified pathogen. Provide postexposure chemoprophylaxis for close contacts. Postexposure chemoprophylaxis Administer chemoprophylaxis as soon as possible, preferably within 24 hours of symptom onset in the index patient. Postexposure chemoprophylaxis for bacterial meningitis Pathogen Indications Recommended regimens Rifampin OR ceftriaxone All close contacts within 7 days of OR ciprofloxacin, should be avoided symptom onset, i.e.: in: o Household members o Pregnant patients (ceftriaxone is preferred) N. o Individuals exposed in a meningitidis childcare setting o Children (unless there are contraindications to other o Individuals directly exposed to options) respiratory secretions o Patients residing in areas o Passengers on long flights where fluoroquinolone- resistant N. meningitidis has been detected Close contacts All household contacts if anyone in the household meets any of the Rifampin for 4 days H. following criteria: Childcare facility outbreaks : Also influenzae o < 12 months of age and has offer Hib vaccine if not up to date. not completed the primary course of Hib vaccines 29 | P a g e  o ≤ 4 years of age and not up-to- date on age-recommended Hib vaccine o A child of any age who is immunocompromised Childcare facility members (all children and possibly caregivers) if: o ≥ 2 cases occur within 60 days o AND any child is not up to date on age-recommended Hib vaccine Special patient groups Meningitis in infants and children Aetiology Bacterial o < 1 month old  Commonly: Group B streptococcus, E. coli  Other gram-negative organisms: Klebsiella or Enterobacter species  L. monocytogenes o ≥ 1 month old: S. pneumonia, N. meningitidis o See also “Most common causative agents of bacterial meningitis by age group and underlying condition.” Viral o Most common: enterovirus o Herpes simplex virus (life-threatening; more common in neonates 1–3 weeks old) o Parechovirus Rates of bacterial meningitis in infants and children are declining due to a combination of vaccination against Hib and Streptococcus pneumoniae and prenatal GBS screening and prophylaxis. 30 | P a g e Clinical features Children < 2 years old often have nonspecific symptoms without meningismus. o Poor appetite, vomiting o Neurological signs  Altered mental status (most common): lethargy, irritability, seizures  Signs of increased intracranial pressure: bulging fontanelle (in infants), cranial nerve palsies  Hypotonia, high-pitched crying, abnormal breathing patterns o Changes in vital signs  Temperature instability: hyperthermia, hypothermia  Abnormal breathing patterns: tachypnoea, apnoea  Heart rate changes: tachycardia, bradycardia For children ≥ 2 years of age, see “Clinical features of meningitis.” Diagnostics for meningitis in children Diagnostics for meningitis do not differ significantly between adults and children. Treatment for meningitis in children Initial management of meningitis does not differ between children and adults. For unstable patients, initiate immediate stabilization for meningitis. Start empiric antimicrobial therapy as appropriate. Empiric antibiotic therapy Neonates ≤ 28 days o Always initiate empiric antibiotic therapy. o Recommended empiric antibiotics are ampicillin PLUS either or both:  Gentamicin  Cefotaxime Infants and children ≥ 29 days of age o Suspected bacterial meningitis: Start empiric antibiotic therapy with vancomycin PLUS ceftriaxone. o Suspected viral meningitis in otherwise healthy children : Consider using a meningitis scoring system, e.g., the bacterial meningitis score. 31 | P a g e Avoid ceftriaxone in neonates because of the risk of kernicterus; use cefotaxime or ceftazidime when possible. 32 | P a g e