Infective meningitis

Pharmacotherapeutics of Meningitis

1. V.S.Swathi Assistant Professor VIPT, Duvvada INFECTIVE MENINGITIS

2. Definition According to CDC, Infective meningitis is an inflammation of protecting membranes of brain and spinal cord caused by microorganisms such as bacteria, virus, fungus, and amoeba.

3. Epidemiology Over 1.2 millon cases of bacterial meningitis are estimated to occur worldwide each year Between 2014 and 2015, a total of 16,217 cases and 300 deaths due to meningitis were recorded in India

4. Types Bacterial meningitis It is a predominant disease in young children Caused by: Neisseria meningitides Haemophilus influenzae Escheria coli Enterobactericiae Listeria monocytogenes Staphylococcus aureus Enterococcus species

5. Viral Meningitis Caused by: Herpes simplex virus Human Enterovirus ( Echo virus, Coxsackie virus) Varicella zoster Mumps HIV

6. Fungal Meningitis Caused by: Candida Cryptococcus neoformans Histoplasma   Parasitic Meningitis caused by: Ameoba  

7. Risk factors Children Elders Students Immune compromised patients ( HIV, TB, SLE and Cancer) Family members Health care workers Patients underwent surgeries Pregnant women

8. Etiology Bacteria Viruses Fungi Protozoa See in detail in Types

9. Pathogenesis Bacteria/ Virus/Fungi/Parasite ↓ Risk Factors Enter in to body via Abnormal communication (Trauma and Congenital anomaly) Other source of infections (Ear infections like Otitis media or Sinusitis) Direct spread from nasopharynx ↓ Attach to host mucosal surface ↓ Invade in to meningitis by disrupting BBB ↓

10. Induction of pathophysiological changes in CSF ↓ Vascular leakage ↓ Entry of blood components in subarachnoid space ↓ Cerebral edema , cerebral protein ↑, glucose↓ ,WBC ↑ ↓ Intracranial Hypertension ↓ Ischemia ↓ Neurological dysfunction and injury  

11. Cellular changes and biochemical responses in different forms of Infective Meningitis Type of meningitis Cell count and type of WBC Protein(g/d) Glucose Bacterial 500-2000μL -1 Polymorphs 1-3 Less than 50% of blood glucose Viral 50-500 μL -1 Lymphocytes 0.5-1 Normal Fungal 50-1000 μL -1 Lymphocytes 1-3 Less than 50% of blood glucose Tubercular 100-600 μL -1 Lymphocytes 1-6 Less than 50% of blood glucose

12. Clinical Presentation Bacterial Meningitis in children Sudden onset of headache Neck stiffness Photophobia Fever and vomiting Kerning’s sign positive Seizures Haemorrhagic skin rash

13. Bacterial Meningitis in Infants Fever Diarrhea Lethargy Feeding difficulty Respiratory distress Seizures Bulging Fontanalle

14. Viral Meningitis Acute onset of low grade fever Head ache Photophobia Neck stiffness Lack of orientation

15. Fungal and Tubercular Meningitis Malaise Apathy Anorexia  

16. Complications Hearing loss Recurrent seizures Problems with memory and concentration Problems with co ordination, movement and balance Learning difficulties and behavioural problems Vision loss Arthritis Kidney damage

17. Diagnosis CSF analysis CT scan PCR

18. Non Pharmacological Treatment Vaccination Avoid sharing of needles Maintain good diet Surgery in case of cerebral oedema and spinal abnormalities

19. Treatment Algorithm

20. Adjunctive therapy with Dexamethasone to reduce inflammation in brain Adults-10mg-QID for 4 days adults Paediatrics-0.15mg/kg- QID for 4 days Viral Meningitis Acyclovir-10mg/kg-TID for 10 days Fungal Meningitis Amphotericin B –IV-0.7-1mg/kg/day or Flucytosine-100mg/kg/day for 6-10 weeks or Fluconazole-400mg/day- 10 weeks    

21. Tubercular Meningitis Isoniazid , Rifampicin , Pyrizinamide and Ethambutal for 2 months ↓ Isoniazid and Rifampicin for 8 months + Prednisolone 20-40mg if on Rifampicin otherwise 10-20mg (Adults) Prednisolone 1-2mg/ Kg (Children)

22. Drugs used in treatment of Meningitis Drug Category Mode of action Dose Adverse effects Ampicillin Pencillin Inhibit cell wall synthesis in bacteria 50mg/kg-BD/ TID Hypokelemia Hypomagnesemia Chills Anemia Nephrotoxicity Amoxicillin Pencillin Inhibit cell wall synthesis in bacteria 25mg/kg-BD/ TID Anaphylaxis Anemia Hepatotoxicity Colitis Candidiasis Cefotaxime Cephalosporin Inhibit cell wall synthesis in bacteria 50mg/kg-BD/ TID Hepatotoxicity Colitis Candidiasis Thrombocytopenia Anemia Ceftazidime Cephalosporin Inhibit cell wall synthesis in bacteria 50mg/kg- BD/TID Hepatotoxicity Eosinophilia Diarrhea Phlebitis GI disturbances Ceftrioxone Cephalosporin Inhibit cell wall synthesis in bacteria 75-100mg/kg-BD Induration after injection Eosinophilia Hepatotoxicity Leukopenia Anemia

23. Amphotericin B Anti Fungal agent Inhibit cell membrane synthesis of bacteria 0.7-1mg/kg/day IV 6-10 weeks Hypokelemia Hypomagnesemia Anemia Chills Nephrotoxicity Flucytosine Anti Fungal agent Inhibit DNA synthesis in bacteria 100/kg/day for 6-10 weeks Confusion Headache Hallucination Pruritis Photosensitivity Fluconazole Anti Fungal agent Inhibit DNA and lipid synthesis in bacteria 400mg/day for 10 weeks Headache Nausea Abdominal pain Diarrhea Rash Vomiting Acyclovir Anti viral drug Inhibit DNA replication in bacteria 100mg/kg-TID Malaise Inflammation at injection site Phlebitis GI disturbances Hepatotoxicity Dexamethasone Corticosteroid Reduces inflammation 10mg-QID -4 days Dry skin Hyperglycaemia Cushing syndrome Abdominal fat deposition Glaucoma

24. Resources https://www.ncbi.nlm.nih.gov/pubmed/24440644 https://www.ncbi.nlm.nih.gov/pubmed/23013403 https://www.ncbi.nlm.nih.gov/pubmed/20046106 https://www.ncbi.nlm.nih.gov/pubmed/29642927 https://www.ncbi.nlm.nih.gov/pubmed/24440644