Meningitis Siva PPT

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Pharmacotherapeutics of Meningitis Siva Reddy Challa, M.Pharm, Ph.D. HOD at Dept. of Pharmacology KVSR Siddhartha College of Pharmaceutical Sciences, Siddhartha Nagar, Vijayawada

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Definitions Meningitis – inflammation of the meninges Encephalitis – infection of the brain parenchyma Meningoencephalitis – inflammation of brain + meninges Aseptic meningitis – inflammation of meninges with sterile CSF

Encephalitis Brain: 

Encephalitis Brain

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Bacterial meningitis Presence of neutrophils in the CSF is associated with infection by N. meningitidis , S. pneumoniae etc. CSF protein level reflects the degree of meningeal inflammation:- 10 X in bacterial infections CSF glucose levels :- very low in bacterial infections Viral meningitis Presence of lymphocytes is associated with infection by viruses or mycobacteria. CSF protein level reflects the degree of meningeal inflammation:- 2-3 X in viral CNS infection CSF glucose levels :- n ormal with viral infections Bacterial meningitis Vs Viral meningitis

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Normal Bacterial Viral Fungal TB other WBC (TNC) 0-5 100-10,000 5-3000 5-500 5-500 paraneo Cell type >50% PMN >50% lymphs >50% lymphs >50% lymphs Monoclonal, atypia Protein 50-80 mg/dL >200 Nl/slight increase Nl/slight increase Increase increased Glucose 70-80 mg/dL >60% serum <40, <60% of serum glucose Normal normal <40 or nl decrease Gm stain 60% + Neg 50% india ink + crypto AFB + 25-35% Pressure 75-200 mm Hg Inc Nl Inc Nl /inc

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Neonates Most caused by Group B Streptococci E coli, enterococci, Klebsiella, Enterobacter, Samonella , Serratia , Listeria Older infants and children Neisseria meningitidis, S. pneumoniae, tuberculosis, H. influenzae Bacterial meningitis - Organisms

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gram-negative diplococcus and cultures of the bacteria test positive for the enzyme oxidase Children younger than 5 years are at greatest risk, followed by teenagers of high school age Neisseria meningitidis

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Neisseria meningitidis causes rash

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Haemophilus influenzae type b Gram-negative, rod-shaped bacterium , it is generally aerobic, but can grow as a facultative anaerobe

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Streptococcus pneumoniae pneumococcus is the most common bacterial etiology of meningitis in children beyond 2 months of age (1-3 per 100,000). Streptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic , aerotolerant anaerobic member of the genus Streptococcus

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Listeria monocytogenes Gram-positive bacterium and facultative anaerobe, intracellular bacterium

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Use of bactericidal agents Bactericidal therapy is generally necessary to cure meningitis Bacteriostatic drugs, such as clindamycin and tetracycline, are inadequate for meningitis Chloramphenicol is a bacteriostatic drug for most enteric Gram negative rods; however, it is usually bactericidal for H. influenzae, N. meningitidis, and S. pneumoniae and has been extensively and successfully used to treat meningitis caused by these organisms

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Choice of agent Selected third generation cephalosporins such as cefotaxime and ceftriaxone, have emerged as the beta- lactams of choice in the empiric treatment of meningitis These drugs have potent activity against the major pathogens of bacterial meningitis with the notable exception of listeria Ceftazidime , another third generation cephalosporin, is much less active against penicillin-resistant pneumococci than cefotaxime and ceftriaxone

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Treatment - Empiric Ceftriaxone 2 gm IV q12h or Cefotaxime 2 gm IV q4-6h plus Vancomycin 15 mg/kg q6h If > 50 years, also add Ampicillin 2 gm IV q4h (for Listeria)

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THERAPY FOR SPECIFIC PATHOGENS Streptococcus pneumoniae The conventional approach to the treatment of pneumococcal meningitis was the administration of penicillin alone for two weeks at a dose of four million units intravenously every four hours Good results have also been obtained with third generation cephalosporins However, the problem of treating pneumococcal meningitis has recently been compounded by the widespread and increasingly common reports of pneumococcal strains resistant to penicillin

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Cefotaxime or ceftriaxone can be used if the MIC for these drugs is less than 0.5 µg/ mL It is recommended that vancomycin (2 g/day) should be given with cefotaxime or ceftriaxone in the initial treatment of pneumococcal meningitis if there has been beta- lactam resistance noted locally Vancomycin should be continued if there is high level penicillin resistance and an MIC >0.5 µg/ mL to third generation cephalosporins If corticosteroids are given, rifampin should be added as a third agent since it increases the efficacy of the other two drugs The usual duration of therapy is two weeks

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Haemophilus influenzae A third generation cephalosporin is the drug of choice for H. influenzae meningitis Patients with H. influenzae meningitis should be treated for five to seven days For adults, a dose of 2 g every six hours of cefotaxime and 2 g every 12 hours of ceftriaxone is more than adequate therapy Pharyngeal colonization persists after curative therapy and may require a short course of rifampin if there are other children in the household at risk for invasive Haemophilus infection The recommended dose is 20 mg/kg per day (to a maximum of 600 mg/day) for four days

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Neisseria meningitidis This infection is best treated with penicillin Although there are scattered case reports of N. meningitidis resistant to penicillin, such strains are still very rare A third-generation cephalosporin is an effective alternative to penicillin for meningococcal meningitis A five day duration of therapy is adequate However, when penicillin is used, there may still be pharyngeal colonization with the infecting strain. As a result, the index patient may need to take rifampin, a fluoroquinolone, or a cephalosporin

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Listeria monocytogenes Listeria has been traditionally treated with ampicillin and gentamicin , as resistance to these drugs is quite rare Ampicillin is given in typical meningitis doses (2 g intravenously every four to six hours in adults) and gentamicin is used for synergy An alternative in penicillin-allergic patients is trimethoprim-sulfamethoxazole (dose of 10/50 mg/kg per day in two or three divided doses) The usual duration of therapy is at least three weeks

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Meningococcemia - Prophylaxis Rifampin Urine, tears, soft contact lenses orange; OCP’s ineffective <1 mo 5 mg/kg PO Q 12 x 2 days >1 mo 10 mg/kg (max 600 mg) PO Q 12 x 2 days Ceftriaxone  12 y 125 mg IM x 1 dose >12 y 250 mg IM x 1 dose Ciprofloxacin  18 y 500 mg PO x 1 dose

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Pneumococcal meningitis – Mgmt Vancomycin + cefotaxime or ceftriaxone, if > 1 month old If hypersensitive (allergic) to  -lactam antibiotics, use vancomycin + rifampin D/C vancomycin once testing shows PCN-susceptibility Consider adding rifampin if susceptible & condition not improving, or cefotaxime or ceftriaxone MIC high Not vancomycin alone

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Bacterial Meningitis - Treatment Neonatal (<3 mo) Ampicillin (covers Listeria ) + Cefotaxime High CSF levels Less toxicity than aminoglycosides No drug levels to follow Not excreted in bile  not inhibit bowel flora

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Meningitis - Treatment duration Neonates: 14 – 21 days Gram negative meningitis: 21 days Pneumococcal, H flu: 10 days Meningococcal: 7 days

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Meningitis: Antimicrobials Empirical Microorganism Directed

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Empirical Antimicrobials Early-onset acquisition Late-onset acquisition 1- 3 month > 3 month Amp + Cefotax Nafcillin + ceftaz Amp + cefotax (ceftriax) Cefotax (ceftr) + vanco

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Duration of Treatment Neonates GBS GN Listeria ≥ 14 days ≥ 21 days 10 days Infants & Children N. meningitides H. influenzae S. pneumoniae 7 days 10 days >10 days

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Meningitis: Dexamethasone Indicated H. influenzae S. pneumoniae Not indicated Aseptic meningitis Neonatal meningitis Partially treated meningitis Doses 0.15 mg / kg /dose Q 6h (4 days) 0.4 mg / kg / dose Q 12h (2 days)

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HIB vaccine (Pedvax HIB) is a polysaccharide-protein conjugate vaccine which has been shown to produce antibody to the capsular polysaccharide of Haemophilus influenzae type b. (Hib)

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Meningococcal Meningitis: PH measures To avoid further exposure advise individuals to: Avoid sharing eating/drinking utensils Avoid sharing food, drinks, cigarettes, or musical mouth pieces. Cover mouth when sneezing/coughing WASH HANDS FREQUENTLY To prevent additional cases: Refer close contacts for chemoprophylaxis Advise contacts to seek medical attention if symptoms of MM appear Other preventive measures to protect individuals: Avoid smoking and smoky environment Get plenty of sleep and exercise regularly Eat balanced diet and avoid excessive alcohol consumption Meningococcal Vaccine is available and should be offered to persons > 2 yrs of age with: Complement deficiency Functional or anatomical asplenia Travelers visiting meningitis belt Persons who may be exposed to bacteria

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Thank You This presentation is dedicated to my parents