(4/6) Itokazu Lecture: Central Nervous System Infections Central Nervous System infections include inflammation of the meninges and formation of abscesses. Inflammation of the meninges, also known as Meningitis, is far more common and is the topic for this lecture. As with any infection, the goal is to (1) cure infection with antimicrobial therapy and to (2) minimize the risk for complications, or drug-related toxicity. Meningitis: Inflammation of the meninges - Pathogenesis: Colonial bacteria of the respiratory tract, depending on their virulence, may enter the blood stream and in some cases the CNS. The meninges are the set of tissues layering the brain and spinal cord responsible for maintaining the cerebral spinal fluid (CSF) within the subarachnoid space. The tissue layers are: dura, arachnoid, and pia. The CSF is most common site for infections in the brain. - Bacterial Causes: The predisposing causes and infective pathogens are heavily reliant on patient age o Age 1-23mo: S. pneumoniae, N. meningitidis, H. influenzae o Age 2-50years: N. meningitidis, S. pneumoniae. With age, H. flu comes off due to vaccination. o à In both cases, the empiric abx choice is Vancomycin + 3 rd -generation cephalosporin o Listeria monocytogenes: In the very young, and the very old, Listeria is the major player, thus requiring alternative empiric therapy. o H. influenzae: 30% produce sufficient beta-lactamases to exhibit ampicillin-resistance o N. meningitidis: Infection very often presents with a ‘petechial rash’ - Clinical Presentation: The prevalent s/sx of meningitis in both adults and infants are fever and seizures. Likely due to a more advanced ability to articulate, adults convey s/sx: headache, visual disturbances, neck stiffness, and confusion. Whereas younger infants present as irritable, vomiting, and have decreased oral intake o Acute Infection: Bacterial and Viral § Symptoms present within hours to days, progress, and may rapidly become fatal o Chronic Infection: M. tuberculosis and Fungal § Symptoms occur over a long period of time, sometimes as long as 4 weeks o There are multiple causes of meningitis, many of which are fatal. Thus, it is critical to accurately diagnose patients to initiate life-saving treatment as soon as possible - Diagnostics & Labs o CSF Sample: Confirmation of bacterial meningitis consists of: § WBCÝ: Represents fighting infection, or inflammatory process § PolysÝ: A ‘left shift’ of PMN suggests ongoing infection to fight § Protein ContentÝ: Due to a break in the BBB, protein can move in § Glucoseß: The WBC quickly consume glucose as energy to battle o CSF Gram-Stain: Helps with preliminary pathogen identification § G(-) Cocco-bacilli: H. influenzae § G(+) Diplococci: S. pneuomoniae § G(+) Cocci-clusters: Methicillin-resistant S. aureus (MRSA). Looks like a buncha grapes Supportive Measures of Meningitis - Hydration therapy, replenish electrolytes, facilitate enteral feedings Pharmacologic Approach for the Treatment of Bacterial Meningitis - Prophylaxis o Vaccination: Decreases the risk for H. influenzae type b meningitis § Unconjugated-23-valent: For Adults. Includes serotypes to PCN-non-susceptible strains § Conjugated-13-valent: For Adults/Kids ~produces a more robust immune response o Close Contact Chemoprophylaxis: PCN (S. pneumo), Rifampin (H. inf), Rif/Cipro/Ceft (N. meningitidis) § Eliminates the initial step in meningitis pathophysiology: Nasopharyngeal carriage § Thus, chemoprophylaxis prevents transmission and the development of invasive disease in colonized persons. Additionally, the CDC recommends limit time & proximity w/ those infected - Role of Steroids: The brain cavity is an enclosed space sensitive to changes in pressure. Given antibiotics, bacteria will “explode,” releasing their pro-inflammatory contents within the CNS, causing Ýpressure leading to neurologic damage. Therefore, the role of steroids in treating meningitis is to prevent the adverse effects of inflammation. All studies have shown major benefit in reducing unfavorable outcomes by using steroids