Bacterial meningitis

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2 Bacterial meningitis Is an acute purulent infection in the subarachnoid space that is associated with inflammation reaction in the brain and cerebral blood vessels that causes decreased conciuosness, seizure, raised intracranial pressure, and stroke. Is inflammation of the meningens caused by a bacterial pathogen.

3 Incidence In Asia, there is increasing incidence of H influenzae type b (Hib). Previously, Salmonella, S pneumoniae and M tuberculosis. In USA, 2.5 to 3.5 cases per 100,000 population H influenzae type b declined 421 cases 1987 to 0,7 per 100,000 in Today the most common bacterial: Streptococcus pneumoniae, N meningitidis, and H influenzae

4 Meningitis Classified into two syndromes: Septic or purulent meningitis is caused by bacterial or fungal organism Aseptic meningitis is caused by viral, neoplastic, protozoal, spirochetal or other non septic causes.

5 Pooled information from 1853 case of meningitis E coli Group B strep 30 % 34 % Listeria spp 6 % Other gram negative Other streptococci Staphylococci Salmonella spp Pneumococcus Haemophilus Pseudomonas spp Meningococcus Others 4% 4.5 % 1 % 3 % 2 % 3 % 2 % 3 % 8 % Fig. Distribution of the most common causes of neonatal meningitis

6 TABLE. Estimated age-specifik incidence of bacterial meningitis (cases per 100,000 population), United States, 1995 Haemophilus Streptococcus Neiseria Group B Age group influenzae pneumoniae meningitis Streptococcus Listeria < 1 mo mo yr Adapted from Schuchat A, Robinson K, Wenger JD, et al. Bacterial meningitis in the United States in N Engl J Med 1997;337;970

7 Clinical presentation There are two patterns of presentation: The first is more insidious and develops over one or several days. The other is more acute and fulminant. Usually with severe brain edema and herniation

8 Signs and Symptoms of Bacterial Meningitis Fever Depression of consciousness Full fontanel Irritability Stiff neck Seizures Headache Focal neurologic deficits Petechial skin rash

9 Table 3. Clinical signs of neonatal bacterial meningitis Symtoms Percentage Sign Percentage Lethargy 50 Fever or hypothermia 61 Anorexia Respiratory distress 47 Vomiting 49 Irritability 32 Diarrhea Jaundice 28 Convulsions 40 Full/bulging fontanelle 28 Apnea 7 Neck stiffness 15 Altered sleep pattern High-pitched cry Hipotonia Petechiae Hypotension, shock Bradycardia Source : Frequencies from Klein & Marcy (1995)

10 Table 1. INCIDENCE AND MORTALITY RATES IN ACUTE BACTERIAL MENINGITIS Children Incidence Mortality rate Organism (%) (%) S. pneumoniae N. meningitidis H. influenzae Gram negative bacilli 1-2 NA S. aureus 1-2 NA Streptococci 2-4 NA L. monocytogenes Anaerobes 1-2 NA NA = not avilable

11 EVALUATION OF THE PATIENT WITH ACUTE BACTERIAL MENINGITIS BACTERIAL CELL WALL COMPONENTS Endothelial Cells CNS-Macrophages Endotoxin Shock IL-1 PGE 2 TNF,IL-1, PAF Thrombosis CSF pleocytosis Impaired BBB Infarction Hydrocephalus Perfusion Edema ICP CBF Microcirculatory Failure

12 CSF Examinations in Suspected Bacterial Meningitis Routine test Gram s stain (60 90%) Bacterial culture and sensitivities (70 85%) Cell count and differential Glucose Protein Bacterial antigen (50 100%) Special test Culture for tuberculosis, fungus, virus Additional bacterial antigen studies Serology Cryptococcus antigen India ink Coccidioidomycosis antibody Polymerase chain reaction

13 Table 3. CEREBROSPINAL FLUID FINDINGS IN BACTERIAL MENINGITIS Normal Bacterial meningitis Opening pressure mm CSF > 200 mm CSF (3,8-15 mm Hg) Cell count < 5 cells/mm ,000 cells/mm3 (15% neutrophils (86% neutrophils) Protein mg/dl 100 to 500 mg/dl Glucose mg/dl usually <20-40 mg/dl CSF : Glucose Ratio > 0,5 < 0,4 CSF = Cerebrospinal fluid; NL = normal

14 Treatment Two critical decisions must be consider: The first concern the choice of antibiotic therapy The second, the benefits versus the risk of doing a lumbar puncture.

15 EVALUATION OF THE PATIENT WITH ACUTE BACTERIAL MENINGITIS Mild Irritibility Lethargy Headache Vomiting Nurchal rigidity Lumbar Puncture; Start Antibiotics And Steroids ICP NL ICP CT or MRI Scan and Treat Observe Moderate Seizures Focal deficit Consciousness Papilledema Severe Status epilepticus Persistent deficit Coma Herniation Start Antibiotics And Steroids And Do CT or MRI Scan Lumbar Puncture ICP NL ICP Treat Observe

16 Delayed LP Intravenous antibiotics used for 2 to 3 days prior to lumbar puncture do not alter the CSF cell count, or protein or glucose concentrations Substantially decrease the chance of demostrating bacteria on Gram stain or culture

17 TABLE 3. RECOMMENDATIONS FOR ANTIBIOTIC THERAPY IN PATIENTS WITH BACTERIAL MENINGITIS TYPE BACTERIA CHOICE OF ANTIBIOTIC On Gram s staining Cocci Gram-positive Gram-negative Bacilli Gram-positive Gram-negative Vancomycin plus broad-spectrum cephalosporin Penicilin G Ampicillin (or penicillin G) plus aminoglycoside Broad-spectrum cephalosporin plus aminoglycoside

18 TABLE 3. RECOMMENDATIONS FOR ANTIBIOTIC THERAPY IN PATIENTS WITH BACTERIAL MENINGITIS TYPE BACTERIA CHOICE OF ANTIBIOTIC On culture S. pneumoniae Vancomycin plus broad-spectrum cephalosporin H. influenzae Ceftriaxone N. meningitidis Penicillin G L. monocytogenes Ampicillin plus gentamicin S. agalactiae Penicillin G Enterobacteriaceae Pseudomonas aeru- ginosa, acinetobacter Broad-spectrum cephalosporin plus aminoglycoside Ceftazidime plus aminoglycoside

19 The American Academic of Pediatrics recommended Dexamethasone, 0,6 mg/kg per day in four divided doses for the first two days of antibiotic treatment. The first dose should be given at the time of, or shortly before the first dose of antibiotic

20 Empiric therapy for acute bacterial meningitis in neonatus 0-7 hari Ampisilin 150 mg/kg/hari dibagi setiap 8 jam IV plus cefotaksim 100 mg/kg/hari setiap 12 jam IV atau Ceftriaxone 50 mg/kg/hari diberikan setiap 24 jam IV atau Ampisilin 150 mg/kg/hari dibagi setiap 8 jam IV plus gentamisin 5 mg/kg/hari IV setiap 12 jam.

21 > 7 hari Ampisilin 200 mg/kg/d divided dose every 6 hours IV AND Cefotaxime 150 mg/kg/d divided dose every 8 hours IV or Cetriaxone 75 mg/kg every 24 hours IV

22 Table 2. Empiric therapy for acute bacterial meningitis 1-3 months Ampicilin mg/kg/d divided dose every 6 hours IV AND Cefotaxime 200 mg/kg/d divided dose every 6 hours IV or Cetriaxone 100 mg/kg/d divided dose every 12 hours IV or 80 mg/kg daily IV/IM; Add vancomycin 60 mg/k/d IV divided dose every penicillin-resistant S pneumococcus suspected

23 Table 2. Empiric therapy for acute bacterial meningitis > 3 months Cefotaxime 200 mg/kg/d divided dose every 6-8 hours IV OR Ceftriaxone 100 mg/kg/d divided dose every 12 hours IV or 80 mg/kg IV/IM every day OR Ampicillin 200 mg/kg/d divided dose every 6 hours IV PLUS Chloramphenicol 100 mg/kg/d divided dose every 6 hours IV; Add vancomycin 60 mg/kg/d divided dose every 6 hours IV if penicillin-resistant S pneumococcus suspected

24 TABLE 4. GUIDELINES FOR THE DURATION OF ANTIBIOTIC THERAPY PATHOGEN SUGGESTED DURATION OF THERAPHY (DAYS) H. influenzae 7 N. meningitis 7 S. Pneumoniae I. monocytogenes Group B streptococci Gram negative bacilli (other than 21 H. influenzae

25 Complications during Acute Bacterial Meningitis Common Increased intracranial pressure SIADH Ventriculomegaly Seizures Extra-axial fluid collection Infarction and necrosis Cranial nerve involvement (deafness) Disseminated intravascular coagulation Uncommon Subdural empyema Brain abscess Cranial nerve deficits other than VIII

26 Table Treatment of the Seriously III Patient with Meningitis INTRACRANIAL PRESSURE MEASUREMENT SCAN RESULTS INCREASED Normal Hyperventilate to reduce increased cerebral blood volume Edema Do not hyperventilate; use furosemide or mannitol and restrict fluids Acute ventriculomegaly, Remove CSF by ventricular tap or drain; de hydrocephalus or en- crease CSF production (Diamox or digo larged subarachnoid xin); increase CSF reabsorption (stero - spaces ids) Subdural effusions Subdural drainage Infarcts Steroids to reduce peri-infarct edema

27 Fundamental principles to the management of meningitis Antibiotic therapy should be prompt and appropriate Cerebral metabolisme should be protected Increased intracranial pressure should be monitor Seizure should be prevented or controlled Fluid management Hyperpyrexia should be controlled

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29 Penetration of antibacterials into CNS CSF Antibiotics Normal meninges Meningitis Penicillins Penicillins G Poor Fair-good Ampicillin Poor Fair-good Methicillin Poor - Nafcillin - Fair Cephalosporins Cefazolin Poor Fair-good Cefotaximes Good Good Ceftriaxone Good Good Ceftazidime Good Good Tetracyclines Tetracycline - Fair Oxytetracycline - Fair Chlortetracycline - Poor Sources : Infectious Disease in Emergency Medicine Judith C. Brillman & Ronald

30 Table. Complication and outcome of patient with acute bacterial meningitis Complications Children (%) Acute seizures 31 Cranial nerve palsies 3 5 Deafness 10 Focal neurologic deficits 4 15 Hydrocephalus 2 20 Cerebrovascular Involvement 2 12 Cerebral edema 2 8 Central nervous system hemorrhage 2 Herniation 2 6 Mental retardartion 4 6 Epilepsy 4 7 Outcome Good recovery/mild disability Severe/moderate disability 8 14 Persistent vegetative state 1 2 Dead 2 5

31 Penetration of antibacterials into CNS CSF Antibiotics Normal meninges Meningitis Aminoglycosides Gentamycin Poor Fair Amikacin - Poor Rifampin Fair Good Cyprofloxacin Fair Fair Miscellaneus antibacterials Chloramphenicol Good Good Clindamycin Poor Fair Metronidazole - Good Trimetrophin Good Good Vancomycin Poor Good Sources : Infectious Disease in Emergency Medicine Judith C. Brillman & Ronald

32 Guidelines for acceptable CSF values At the end of therapy 1. The percentage of polymorphonuclear leukocytes (PMNs) in the CSF is more important than the absolute white blood cell (WBC) count and is usually 5 percent, but should not exceed percent of the total WBC. 2. The CSF glucose concentration should exceed 20 mg/dl and be more than 20 percent of a concomitantly obtained serum glucose.

33 Table 1. INCIDENCE AND MORTALITY RATES IN ACUTE BACTERIAL MENINGITIS Children Incidence Mortality rate Organism (%) (%) S. pneumoniae N. meningitidis H. influenzae Gram negative bacilli 1-2 NA S. aureus 1-2 NA Streptococci 2-4 NA L. monocytogenes Anaerobes 1-2 NA NA = not avilable

34 Cell damage Bacteria Peptidoglycan Teichoic acid Endotoxin Permeability blood-brain barrier Immune modulators Edema Glucose Intracranial pressure Lactate Blood flow Hypoxia Figure 33.1 Pathophysiology of bacterial meningitis

35 Lethal to infants Meningitis infects the membranes covering the brain, and it is always treated as a medical emergency National Health and Medical Research Council (AUS) suggest that doctors should give the first doses of antibiotic before a child goes to hospital Important to be a ware of the sign of meningitis and act quickly

36 Acute bacterial meningitis A high index of suspicion is required to diagnose this condition which, if undetected and untreated, can lead to significant morbidity or death.

37 Table 33.3 clinical signs of bacterial meningitis Symtoms Percentage Sign Percentage Lethargy 50 Fever or hypothermia 61 Anorexia Respiratory distress 47 Vomiting 49 Irritability 32 Diarrhea Jaundice 28 Convulsions 40 Full/bulging fontanelle 28 Apnea 7 Neck stiffness 15 Altered sleep pattern High-pitched cry Hipotonia Petechiae Hypotension, shock Bradycardia Source : Frequencies from Klein & Marcy (1995)

38 Table 1. Complication and Outcome In Acute Bacterial Meningitis Complications Children (%) Acute seizures 31 Cranial nerve palsies 3 5 Deafness 10 Focal neurologic deficits 4 15 Hydrocephalus 2 20 Cerebrovascular Involvement 2 12 Cerebral edema 2 8 Central nervous system hemorrhage 2 Herniation 2 6 Mental retardartion 4 6 Epilepsy 4 7 Outcome Good recovery/mild disability Severe/moderate disability 8 14 Persistent vegetative state 1 2 Dead 2 5

39 TABLE 1. chronic complications of bacterial meningitis Hearing loss Behavior disorders Mental retardation Neuropsychiatric dysfunction Seizures Auditory dysfunction Spasticity, paresis Diabetes insipidus Hydrocephalus Transverse myelitis Blindness Polyarteritis

40 Table 2. ANTIBIOTICS RECOMMENDED FOR EMPIRICAL THERAPY IN PATIENTS WITH SUSPECTED BACTERIAL MENINGITIS WHO HAVE A NONDIAGNOSTIC GRAM S STAIN OF CEREBROSPINAL FLUID GROUP OF PATIENTS LIKELY PATHOGEN CHOICE OF ANTIBIOTIC Immunocomperent Age, < 3 mo S. agalactiae, E. coli, or Ampicillin plus broad-spectrum L. monocytogenes cephalosporin Age, 3 mo to < 18 yr N. meningitidis, S. pneumoniae Broad-spectrum cephalosporin H. influenzae With impaired cellular L. monocytogenes or gram- Ampicillin plus ceftazidine negative bacilli With head trauma, neuro Staphylococci, gram-negative Vancomycin plus ceftazidime surgery, or cerebrospi bacilli, or S pneumoniae nal fluid shunt

41 The American Academy of Pediatrics (AAP) recommended in 1997 : Vancomycin plus Cefotaxim or ceftriaxone Vancomycin plus Cefotaxim or ceftriaxone should be administered initially to all children older than 1 month with definite or probable bacterial meningitis.