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![Cont’d…
31
Early intravenous administration of glucocorticoids (usually
dexamethasone) has been evaluated as adjuvant therapy in an attempt
to diminish the rate of hearing loss and other neurologic
complications as well as mortality in selected patients with bacterial
meningitis.
The rationale for this approach is provided by animal studies
showing that hearing loss is temporally associated with the severe
inflammatory changes induced by bacterial meningitis and that
dexamethasone reduces cerebrospinal fluid (CSF) concentrations of
cytokines (such as tumor necrosis factor [TNF]-alpha and interleukin
[IL]-1), CSF inflammation, and cerebral edema.
The efficacy of dexamethasone therapy has been reported to vary in
developed and developing countries.](https://image.slidesharecdn.com/meningitis-pedibydesalegnd-230301125854-98235599/75/Meningitis-Pedi-by-Desalegn-D-pptx-31-2048.jpg)
![Partially treated meningitis
50% cases prior antibiotic - alters the findings in bacterial
meningitis.
Accurate history vital
CSF mainly lymphocytic [not usual polys]
Can have normal glucose.
+ve cultures reduced by 30%
Gram stain reduced by 20%
35](https://image.slidesharecdn.com/meningitis-pedibydesalegnd-230301125854-98235599/75/Meningitis-Pedi-by-Desalegn-D-pptx-35-2048.jpg)
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Meningitis-Pedi ( by Desalegn D.).pptx
- 1. Central Nervous SystemInfections By Desalegn D.
- 2. Introduction Infection ofthe central nervous system (CNS) is a significant cause of morbidity and mortality in children. Identification of CNS infections can be problematic for clinicians because symptoms can be nonspecific in younger infants, and a delayed or missed diagnosis contributes to the morbidity and mortality rates associated with these diseases. Viral infections remain a significant cause of CNS disease, with atypical bacterial, fungal, and parasitic pathogens also contributing to a smaller number of pediatric CNS infections. 2
- 3. Cont’d… Regardless ofthe etiology, many patients with CNS infection have similar clinical manifestations. Common symptoms include headache, nausea, vomiting, anorexia, photophobia, restlessness, altered state of consciousness, and irritability. Common signs of CNS infection include fever, neck pain and rigidity, focal neurologic deficits, seizures, and coma. The severity and constellation of signs are determined by host–pathogen interactions and the affected region of the CNS. 3
- 4. Cont’d… The skulland vertebrae protect the CNS from blunt or penetrating trauma. The brain is suspended in these structures by cerebrospinal fluid (CSF) and is surrounded by the meninges. The meninges are made up of three separate membranes: dura mater, arachnoid, and pia mater. Dura mater, or pachymeninges, lies directly beneath and is adherent to the skull. Pia mater lies directly over brain tissue. Arachnoid, the middle layer, lies between the dura mater and the pia mater. The subarachnoid space, located between the arachnoid and the pia mater, is the conduit for CSF. 4
- 5. Meningitis By definition,meningitis refers to inflammation of the subarachnoid space of meninges or spinal fluid, Whereas encephalitis is an inflammation of the brain itself or brain parenchyma. Meningoencephalitis may better describe diffuse infections of the CNS by pathogens such as viruses. Brain abscess is the most common example of a focal infection of the CNS. 5
- 6. Cont’d… Cerebrospinal Fluid Clear, protein content 50 mg/dL, a glucose concentration of 50% to 66% of the simultaneous peripheral serum glucose concentration, and a pH of approximately 7.4; Contains fewer than five WBCs/mm3, all lymphocytes. 6
- 7. Cerebrospinal Fluid Findingsin Central Nervous System Disorders Types Normal Acute Bacterial Viral Fungal TB- M Brain abscess Pressure (Cm H2O) < 28 Usually elevated Normal or slightly elevated Usually elevated Usually elevated Usually elevated WBC(cells /mm3) <5 100 - 10,000 Rarely, >1,000 5 - 500 10 - 500 5 - 200 Protein (mg/dL) 20 - 45 100 – 500 Usually, 50 - 200 25 - 500 100 – 3,000 75 - 500 Glucose (mg/dL) >50 ( or 75% of serum glucose) Decreased, <40 (<50% of serum glucose) Generally normal; may be < 40 in some viral diseases. <50, decreases with time Decreased, < 50 in most cases Normal unless abscess ruptures into ventricular system 7
- 8. Cont’d… Acute infectionsof the nervous system are among the most important problems in therapeutics because early recognition, efficient decision-making, and rapid institution of therapy can be lifesaving These distinct clinical syndromes include: Acute bacterial meningitis, Viral meningitis, Encephalitis, Focal infections such as brain abscess and subdural empyema 8
- 9. I. Acute BacterialMeningitis in Pediatrics Bacterial meningitis is one of the most serious pediatric infections, as it is associated with a high rate of acute complications and a risk of long-term morbidity and mortality Bacterial meningitis is an acute purulent infection within the subarachnoid space of the meninges. It is associated with a CNS inflammatory reaction that may result in: Decreased consciousness Seizures Raised intracranial pressure (ICP) Stroke The meninges, the subarachnoid space, and the brain parenchyma are frequently involved in the inflammatory rxn (meningoencephalitis). 9
- 10. Etiology Currently, theorganisms most commonly responsible for community- acquired bacterial meningitis are: Streptococcus pneumoniae: Causes Pneumococcal Meningitis (~50%) N. meningitidis: Causes Meningococcal Meningitis (~25%) Group B streptococci (~15%) Listeria monocytogenes (~10%) H. influenzae (<10% ) 10
- 11. Causes based onthe age and immune status of the patient Predisposing Factor Bacterial Pathogen Age <1 month GBS(S. agalacticae), E. coli, L. monocytogenes, K. pneumoniae 1 - 23 month GBS(S. agalacticae), E.coli, H. influenzae, S. pneumoniae, N. meningitidis 2 - 50 years S.pneumoniae, N.meningitidis >50 year S.pneumoniae, N.meningitidis, L.monocytogenes, Gram negative bacilli. Immunodeficiency S.pneumoniae, N.meningitidis, L.monocytogenes, Gram negative bacilli, P. aeruginosa, M. tuberculosis, Cryptococcosis Skull fracture S.pneumoniae, H.influenzae, Group A streptococci Post neurosurgery S. aureus, coagulase negative staphylococci, Gram negative bacilli, P. aeruginosa 11
- 12. Pathogenesis Source of Infection Contiguous spread: URTI(Sinusitis, OM), birth defect Hematogenous: bacteremia seeding meninges Direct inoculation: Trauma, neurosurgical complications Reactivation of latent disease: HSV, TB 12
- 13. Cont’d… CNS Response toInfection Contact with bacterial cell wall components triggers cytokine releases (TNF, PAF, IL-1) Platelet activating factor (PAF) triggers clotting cascade, forming microthrombi Cytokine cascade stimulates vasodilation and vascular permeability Compromised BBB allows entry of neutrophils and other blood components 13
- 14. Cont’d… Increased ICP Decreased CerebralBlood Flow Signs/Sx of Meningitis •Headache •Fever •Neck stiffness •Altered mental status •Seizures •Abnormal CSF findings Ischemia and Direct Tissue Damage 14
- 15. Clinical Presentation New-born& Infants: non-specific Fever, vomting Irritability Lethargy Poor feeding or unable to suck breast High pitched cry, Bulging fontanel Apneas: a temporary suspension or absence of breathing Purpuric rash Convulsions or seizure 15
- 16. Cont’d… In olderchildren's 16
- 17. Cont’d… Signs andSymptoms in children The classic triad: fever, neck stiffness, altered mental status or headache. Chills, vomiting, photophobia, and severe headache; Kernig's and Brudzinski's signs may also be present but are poorly sensitive and frequently are absent in children Other signs and symptoms include irritability, delirium, drowsiness, lethargy, and coma. 17
- 18.
- 19.
- 20. Cont’d… Differential Signs andSymptoms Purpuric and petechial skin lesions typically indicate meningococcal involvement, although the lesions may be present with H. influenzae meningitis. Rashes rarely occur with pneumococcal meningitis. A rapid eruption of multiple hemorrhagic lesions associated with a shock-like state, is associated with meningococcal meningitis H influenza meningitis and meningococcal meningitis both can cause involvement of the joints during the illness. A history of head trauma with or without skull fracture or presence of a chronically draining ear is associated with pneumococcal involvement. 20
- 21.
- 22. Laboratory Tests CSFvia lumbar puncture (LP) for chemistry, microbiology, and hematology tests. An elevated CSF WBC(Leukocytes) & protein CSF glucose concentration Gram stain and culture of the CSF Blood cultures( two sets) & other specimens. CBC with differential & platelet count. PT, aPTT(particularly in patients with petechiae or purpura) Serum electrolyte, BUN, creatinine & glucose. Magnetic resonance imaging (MRI) or cranial computed tomography (CT) 22
- 23. TREATMENT Desired Outcome Eradication of infection Amelioration of signs and symptoms Prevention of neurologic sequelae, such as seizures, deafness, coma, and death. 23
- 24. Approach to Treatment Administration of fluids, electrolytes, antipyretics, analgesics. Appropriate antibiotic therapy (empirical or definitive) should be started as soon as possible. Therapy should last at least 48 to 72 hours or until the diagnosis of bacterial meningitis can be ruled out. The empiric antibiotic(s) used must be: Bactericidal against the infecting organism. Broad spectrum Lipophilic to easily penetrate BBB Parenteral(IV or IM) Given at high dose 24
- 25. Cont’d… ABC PaediatricICU Supportive care: adequate oxygenation, prevention of hypoglycemia, effective anticonvulsant therapy, nutritional support, control of intracranial hypertension, and prevention of fluctuations in cerebral blood flow are considered crucial parts of the management. Fluid management: aggressive resuscitation Dexamethasone: only in Pneumococcal & H. influenza type b, given before or immediately after antibiotics. Inotropes: increasing aortic diastolic pressure & improving myocardial contractility. 25
- 26. Antibiotics Used inEmpirical Therapy of Bacterial Meningitis Indication Antibiotic 1. Preterm infants to infants <1 month -------- Ampicillin + cefotaxime/aminoglycoside 2. Infants 1 - 3 month ---------------------------- Ampicillin + cefotaxime or ceftriaxone 3. Immunocompetent children >3 month & -- adults <55 Cefotaxime or ceftriaxone + vancomycin 4. Adults >55 and adults of any age with ----- alcoholism or other debilitating illnesses Ampicillin + cefotaxime or ceftriaxone + vancomycin 5. Hospital-acquired meningitis, post- traumatic or post-neurosurgery meningitis, neutropenic patients, or patients with impaired cell-mediated immunity. Ampicillin + ceftazidime + vancomycin Note: the duration of 26
- 27. Cont’d… S.N Name ofthe antibiotics Their Meningeal doses 1. Penicillin G 250,000 to 300,000 U/kg per day IV in 4 or 6 divided doses 2. Ampicillin 300 mg/kg/day IV BID or QID 3. Gentamycin 7.5 mg/kg/day IV QD or TID 4. Cefotaxime 225 - 300 mg/kg/day IV TID or QID 5. Ceftriaxone 100 mg/kg/day IV QD or BID 6. Ceftazidime 150 mg/kg/day IV TID 7. Vancomycin 60 mg/kg/day IV TID 8. Cefepime 150 mg/kg/day IV TID 9. Meropenem 120 mg/kg/day IV TID 10. Metronidazole 30 mg/kg/day IV TID (when brain abscess & Ventriculitis is suspected.) Adjuvant therapy(steroid) 11. Dexamethasone 0.15 mg/kg/dose IV QID for 2 – 4 days, in the treatment of H. influenzae type b meningitis in children older than 6 wk of age. 27
- 28. Duration of therapy The duration of antimicrobial therapy depends upon the causative organism and the clinical course. We suggest the following durations of therapy for uncomplicated meningitis caused by the following organisms. S. pneumoniae – 10 to 14 days N. meningitidis – 5 to 7 days H. influenzae type b (Hib) – 7 to 10 days L. monocytogenes – 14 to 21 days S. aureus – at least 2 weeks Gram-negative bacilli – 3 weeks or a minimum of 2 weeks beyond the first sterile CSF culture, whichever is longer. 28
- 29. Dexamethasone as anAdjunctive Treatment for Meningitis The release of bacterial cell-wall components by bactericidal antibiotics production of the inflammatory cytokines IL-1 and TNF in the subarachnoid space. Dexamethasone inhibits the synthesis of IL-1 and TNF at the level of mRNA, decreasing CSF outflow resistance, and stabilizing the blood-brain barrier. Dexamethasone should be given 15 - 20 min before or immediately after, the first dose of antimicrobial therapy. So that dexamethasone inhibits the production of TNF by macrophages & microglia before the cells are activated by endotoxin. Dexamethasone does not alter TNF production once it has been induced. 29
- 30. Cont’d… Dexamethasone, 0.15mg/kg/dose given every 6 hr for 2 days, in the treatment of H. influenzae type b meningitis in children older than 6 wk of age. Corticosteroids appear to have maximum benefit if given 1-2 hr before antibiotics are initiated. They also may be effective if given concurrently with or soon after the first dose of antibiotics. Pediatric data regarding benefits, if any, of corticosteroids in the treatment of meningitis caused by other bacteria remain inconclusive. 30
- 31. Cont’d… 31 Early intravenousadministration of glucocorticoids (usually dexamethasone) has been evaluated as adjuvant therapy in an attempt to diminish the rate of hearing loss and other neurologic complications as well as mortality in selected patients with bacterial meningitis. The rationale for this approach is provided by animal studies showing that hearing loss is temporally associated with the severe inflammatory changes induced by bacterial meningitis and that dexamethasone reduces cerebrospinal fluid (CSF) concentrations of cytokines (such as tumor necrosis factor [TNF]-alpha and interleukin [IL]-1), CSF inflammation, and cerebral edema. The efficacy of dexamethasone therapy has been reported to vary in developed and developing countries.
- 32. Chemoprophylaxis For N.meningitidis: indicated in close contacts of patients with meningococcal meningitis. Rifampicin: 5 mg/kg/dose PO Bid for 2 days(Children aged <1 month) Rifampicin: 10 mg/kg/dose PO Bid for 2 days(Children aged ≥1 month) Ceftriaxone 125 mg/250 mg IM stat dose for Children age <15 year/>15 years. Ciprofloxacillin 20 mg/kg PO (Max 500 mg) stat For Hib – may be indicated for certain close contacts of a child with Hib meningitis, depending upon individual circumstances. Rifampicin: 10 mg/kg/day PO QD for 4 days(Children aged <1 month) Rifampicin: 20 mg/kg/day PO QD for 4 days(Children aged ≥1month) For S. pneumoniae – Although it does not have a role in preventing the spread of pneumococcal meningitis, chemoprophylaxis is an important aspect of prevention of invasive pneumococcal infections in children with functional or anatomic asplenia. 32
- 33. Vaccines Vaccines directedagainst each of the major pathogens causing bacterial meningitis in children are: S. pneumoniae N. meningitidis Hib 33
- 34. Bacterial Meningitis -Complications Acute Complications Chronic Complications Cerebral edema (vasogenic & cytotoxic) Developmental delay in ~(25 – 50%) Increased intracranial pressure Late-onset seizures ~(10 – 20%) Ventriculitis Cerebral palsy ~(15 – 20%) Hydrocephalus Hearing loss ~(5 – 10%) Brain abscess Cortical blindness in <10% Cerebritis Low B.P Cerebral infarction Septic shock Arteritis/Cerebral venous thrombosis DIC Arterial stroke Purpura Subdural effusion or empyema adreno-cortical insufficiency 34
- 35. Partially treated meningitis 50% cases prior antibiotic - alters the findings in bacterial meningitis. Accurate history vital CSF mainly lymphocytic [not usual polys] Can have normal glucose. +ve cultures reduced by 30% Gram stain reduced by 20% 35
- 36. II. Viral meningitis Most common infection of CNS especially in <1yr Usually clears up in a week or two with no specific treatment. Common; rarely serious infection of fluid in the spinal cord or fluid that surrounds the brain Also called aseptic meningitis 36
- 37. Causes of ViralMeningitis Caused by a number of different viruses mosquito-borne viruses occasionally seen after strep throat in young adults common intestinal viruses account for half of cases. Causes: enterovirus (commonest, meningitis occurring in 50% of children <3mth ) Enteroviruses(polio, echo, coxsackie), HSV type 2, arbo, influenza, rubella,, EBV, adenovirus. Mononuclear lymphocytes in CSF Symptomatic treatment. Complications associated with encephalitis and ICP 37
- 38. Signs and Symptoms Clinical features of viral meningitis in children vary with age, immune status, and etiologic agent. The manifestations of viral meningitis are generally similar to those of bacterial meningitis, but often are less severe. Usually occur one week after exposure Fever Headache Stiff neck Tiredness Rash Sore Throat Vomiting 38
- 39. Treatment and Prevention No specific treatment for viral meningitis Antibiotics do not work on viruses Pay careful attention to personal hygiene Good hand-washing helps prevent spread of infection & viruses. For most causes of viral meningoencephalitis, no effective antiviral agents exist; therefore, treatment is primarily supportive care. Intravenous fluids are typically administered because of poor oral intake. NSAIDs are often used for symptomatic relief of headache. It is important to monitor patients with severe encephalitis closely for seizures, cerebral edema, disturbed fluid and electrolyte balance, aspiration, respiratory failure, and cardiac arrest. 39
- 40. T/t Cont’d…. Herpessimplex virus (HSV): the outcome of HSV meningitis without encephalitis is usually excellent even without antiviral therapy, acyclovir can be used to hasten recovery. For neonatal HSV, 60 mg/kg per day IV divided every 8 hours, for a minimum of 21 days For CNS infections in children aged 3 months - 11 years, 30 to 45 mg/kg per day IV, divided every 8 hours, for a minimum of 14 to 21 days. For CNS infections in children ≥12 years old, 30 mg/kg per day IV, divided every 8 hours, for a minimum of 14 to 21 days 40
- 41. T/t Cont’d…. Varicella-zostervirus (VZV) – Treatment with acyclovir may improve outcomes, although data are limited in pediatric patients. Cytomegalovirus (CMV) – CMV infection in immunocompromised children is treated with ganciclovir. Treatment may also be warranted in immunocompetent children with serious symptomatic CMV infection; however, data are limited. Ebstein-Barr virus (EBV) – EBV infection rarely requires more than supportive therapy 41
- 42. III. Tuberculous Meningitis Usually insidious: difficult to diagnose in early stages (fever 30%, URTI 20%) Rare in children in developed countries If untreated is usually fatal Meningitis usually occurs 3-6mths after primary infection Stage I: lasts 1-2wk, fever malaise, headache Stage II: +/- suddenly, meningeal signs Stage III: worsening neurological condition, death. M.tuberculosis is the primary cause of tuberculous meningitis. 42
- 43. Cont’d… Although upto 40% of patients may present with evidence of pulmonary involvement with hilar adenopathy. Tuberculous meningitis still may exist in the absence of disease in the lung or extrapulmonary sites. 43
- 44. Treatment of Tb-M It is recommended that an initial regimen of four drugs for empirical treatment of M. tuberculosis. This regimen consists of isoniazid, rifampin, pyrazinamide, and ethambutol for the first 2 months, generally followed by isoniazid plus rifampin for the remaining duration of therapy. Patients with M. tuberculosis meningitis should be treated for 9 months or longer with multiple-drug therapy, and patients with rifampin-resistant strains should receive 18 to 24 months of therapy. The management of TBM in children should be 12 months or more (>2RHZE/10RH). 44
- 45. Recommended doses ofpediatric treatment To reduce the risk for drug-induced hepatotoxicity in children, follow the recommended dosages: Isoniazid (H): 10 mg/kg (range, 10–15 mg/kg); maximum dose, 300 mg/day Rifampicin (R): 15 mg/kg (range, 10–20 mg/kg); maximum dose, 600 mg/ kg per day Pyrazinamide (Z): 35 mg/kg (range, 30–40 mg/kg) Ethambutol (E): 20 mg/kg (range, 15–25 mg/kg). 45
- 46. Corticosteroid therapy inTBM Corticosteroid therapy is indicated for patients with stage 2 or stage 3 disease(i.e. those with evidence of neurologic deficits or deterioration in mental function The rationale lies in the reduction of inflammatory effects associated with mycobacterial killing by the antimicrobial agents. The agent usually chosen are: Prednisolone 2 mg/kg/day for 4 – 6 weeks, which may be tapered after 2- 3 weeks of therapy. Or Dexamethasone 60 – 80 mg/day for 4 – 6 weeks. 46
- 47. Treatment regimens Ifnational recommendations are not available, follow the WHO guidelines according to the regimens given below: Four-drug regimen: HRZE for 2 months, followed by a two-drug (HR) regimen for 4 months for all children with suspected or confirmed pulmonary TB or peripheral lymphadenitis living in an area of high HIV prevalence or where resistance to H is high or children with extensive pulmonary disease living in areas of low HIV prevalence or low H resistance; Three-drug regimen: HRZ for 2 months, followed by a two-drug (HR) regimen for 4 months for children with suspected or confirmed pulmonary TB or tuberculous peripheral lymphadenitis living in areas of low HIV prevalence or low H resistance or HIV-negative; In cases of suspected or confirmed tuberculous meningitis, spinal TB with neurological signs or osteo-articular TB, treat for 12 months with a four-drug regimen (HRZE) for 2 months, followed by a two-drug (HR) regimen for 10 months; In infants (aged 0–3 months) with suspected or confirmed pulmonary TB or tuberculous peripheral lymphadenitis, treat promptly with the standard regimens described above, with adjustment of doses to reconcile the effect of age and possible toxicity in young infants. 47
- 48. Cont’d… Note: All anti-TBdrugs should be administered daily & intermittent therapy is not recommended. Streptomycin is not advised for children as it may cause ototoxicity(irreversible auditory nerve damage) and nephrotoxicity, and the injections are painful. So it should not be used as part of first-line treatment regimens for children & reserved for the treatment of multidrug-resistant TB in children with known susceptibility to this medicine. Children < 5 years of age who are household or close contact of people with TB and who, after an appropriate clinical evaluation, are found not to have active TB should be given 6 months of isoniazed preventive therapy (IPT) (10 mg/kg/day, range 7 -15 mg/kg, maximum dose 300 mg/day) 48
- 49. IV. Cryptococcal meningitis Cryptococcal meningitis is the most common form of fungal CNS infection and is a major cause of morbidity and mortality in immunosuppressed patients. 85% of cases occur in HIV-infected patients. C.neoformans is a soil fungus acquired by inhalation of spores from the environment leading to pneumonia, which is usually asymptomatic. 49
- 50. Cont’d… Induction phase:Amphotericin B 0.7 – 1.5 mg/kg/day +/- flucytosine 100 mg/kg/day for 2 weeks of therapy, Followed By: Consolidation phase: fluconazole 6 - 12 mg/day for 8 weeks, Then Thereafter Secondary prophylaxis with fluconazole 3 -6 mg/ day until immune reconstitution occurs. 50
- 51. Mortality/Morbidity Bacterial meningitis:Overall mortality 5 -10% Neonatal meningitis: 15 - 20% Older children: 3 -10% Strep. pneumonia: 26 - 30% H. influenza type B: 7 - 10% N. meningitidis: 3.5 - 10% 30% neurological complications. 4% Profound hearing loss (sensorineural) in all bactreial meningitis 51
- 52.
Editor's Notes
- #16 Apnea: brief pause in breathing: a temporary suspension or absence of breathing
- #19 Kerning's sign – a symptom of meningitis in which the hamstring muscles in the legs are so stiff that the patient is unable to extend his legs at the knee when the thighs are held at a right angle on the body.
- #20 Brudzinski's sign – as the neck is pulled forward, the hips and knees bend involuntarily.