Professor of microbiology and immunology Royal College of Pediatricians of Thailand

Transcription

1 Professor of microbiology and immunology Royal College of Pediatricians of Thailand Researching field New vaccines, new antibiotics, nosocomial infection, pediatric AIDS,immunologic deficiency diseases, epidemiology of infectious diseases Academic Activities President of the Medical Council of Thailand Executive Committee of Western Pacific Society for Chemotherapy and Infectious Diseases Professor Somsak Lolekha

2 Meningitis in Children Suggestion for Asian Guideline Somsak Lolekha M.D.,Ph.D.

3 Acute Central Nervous System Bacterial meningitis Infections Viral meningitis / encephalitis/ meningoencephalitis TB meningitis Rickettsial infection e.g. Scrub typhus Parasitic meningitis e.g. Amebic meningoencephalitis Fungal meningitis e.g. Cryptococcal meningitis Brain abscess

4 When should we suspect a child has meningitis? Newborn Infants Children

5 Neonatal Meningitis Meningitis in newborn and premature baby are extremely difficult to recognize. Clinical manifestations are non specific. Meningitis should be suspected, if a baby has signs of sepsis. Not doing well, looking and doing poorly Fever may or may not be present. Hypothermia may be present.

6 Neonatal Meningitis Common signs and symptoms Irritability Poor feeding Increased sleepiness or drowsiness Vomiting, diarrhea The fontanel may be full, tense, or bulging Respiratory are usually irregular Jaundice may present in sepsis The neck is supple

7 Neonatal Meningitis Irritable when picked up, with a high pitch or moaning cry Blotchy skin, getting paler or turning blue Extreme shivering A stiff body with jerky movements, or else floppy / lifeless 'Pin prick' rash / marks or purple bruises on the body Cold hands and feet

8 Risk factors for neonatal sepsis and meningitis Premature baby Prolonged rupture of amniotic membrane Maternal fever GBS in mother Complicated delivery Poor environmental hygiene

9 Meningitis in infancy Fever/vomiting Marked irritability Severe headache Stiff neck (Less common in young children) Dislike of bright lights (Less common in young children) Very sleepy / vacant / difficult to wake Confused / delirious Rash (anywhere on the body) (Not present in all cases) Seizures

10 Meningitis in infancy Refusing to eat/feed Irritable, not wanting to be held/touched A stiff body, with jerky movements, or floppy, unable to stand up Can not sit with their leg straight Tense bulging anterior fontanel Kernig sign may be positive Brudzinski sign

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12 Bacterial Meningitis by Age Group and Causative Organisms, Children s Hospital, Bangkok, Hib S. pneumo Salmonella N. meninitidis 0 <1m 1m 2-5m 6-11m 12-23m 24-35m >3-15y

13 Meningitis in Children Fever Throwing up repeatedly Severe headache Stiff neck Dislike of bright lights Confusion / deliriousness Severe sleepiness / losing consciousness Rash Seizures

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15 Chotpitayasunondh T et al Bacterial Meningitis in Children s Hospital Bangkok (Pre-Hib vaccine era) Organism No. of cases H. influenzae b % S. pneumoniae % Salmonella spp % N. meningitides % E. coli % Pseudomonas spp % Gr. B Streptococcus % Others % No growth % Total %

16 Cumulative Number of Hib Meningitis Children s Hospital Age range Number Percent 0-6 months % 0-12 months % 0-24 months % 0-36 months % 0-15 years % Chotpitayasunondh T et al

17 ACUTE BACTERIAL MENINGITIS Children's Hospital ( ) Neonates (N=77) Beyond neonate (N=541) Total (N=618) Hib (42.3%) 229 (37%) S. pneumoniae 2 (2.6%) 120 (22.2%) 122 (19.7%) Salmonella 2 (2.6%) 67 (12.4%) 69 (11.1%) N. meningitidis 1 (1.3%) 19 (3.5%) 20 (3.2%) E coli 8 (10.4%) 12 (12.2%) 20 (3.2%) Others 64 (83%) 94 (17.4%) 158 (25.6%) Total 77 (100%) 541 (100%) 618 (100%) ( T.Chotpitayasunondh. Southeast Asian J Trop Med Public Health 1994;25: )

18 ACUTE BACTERIAL MENINGITIS Ramathibodi Hospital 96 Patients ( ,7-year period) Neonates 35 cases (36%) GBS: 9 (43%) Staphylococcus or streptococcus: 5 (24%) E coli: 3 (14%), GNB: 4 (19%) Fatality rate 11.4% Beyond neonatal period 61 cases (64%) Hib: 18 (48.6%) S. pneumoniae: 9 (24.3%) Salmonella: 8 (21.6%) N.meningitidis: 1 (2.7%), S.aureus: 1 (2.7%) Fatality rate 1.8% (A.Yuensrikul. Thai Journal of Pediatrics 1991;30: )

19 BACTERIAL PATHOGENS (proved) IN MENINGITIS Children < 14 years - Thailand C.H. (N=540) Study gr. (N=389) Rama.H. (N=58) Hib 42.4% 43% 31.0% S. pneumoniae 22.6% 30% 15.5% Salmonella spp. 12.8% 12% 13.8% N. meningitidis 3.7% 5% 1.7% Other 18.5% 10% 38% C.H. = Children's Hospital Study gr. = 16 Large hospital in Thailand Rama.H. = Ramathibodi Hospital

20 Laboratory diagnosis of meningitis Lumbar puncture (If there is no sign of increased intracranial pressure) CSF culture and sensitivity (MIC) CSF gram stain, CSF cytology and chemistry (protein, glucose) Antigen detection (CIE, Latex agglutination, coagglutination, PCR) Culture from throat, petichiae, blood MRI, CT scan, ultrasound

21 Host Defense in CSF Lack of surface phagocytosis Reduced bactericidal and opsonic activity Low complement activity Low concentration of immunoglobulin Blood brain barrier S. Lolekha

22 Factors Influence the Penetration of Antibiotics into the CSF Serum drug concentration The status of blood brain barrier Molecular weight Degree of ionization at physiologic ph Lipid solubility Protein binding in serum Active transport mechanisms

23 Factors influence the activity of antibiotic in CSF ph Exit pump Metabolites Other drugs Growth rate Innoculum size Protein binding

24 Relative Diffusion of Antibiotics from Blood into CSF Excellent with Good only with Minimal or No passage with or without inflammation not good with inflammation inflammation inflammation Sulfonamide Penicillin Aminoglycoside Polymyxin B Chloramphenicol Ampicillin Tetracycline Trimethoprim 3rd Cephalosporin Erythromycin INH Rifampicin Lincomycin Quinolone Cefoxitin Meropenem Cephalothin

25 Antimicrobial Concentration in CSF Optimal management of bacterial meningitis Concentration of antibiotic in CSF should be >= 1:8 fold of bactericidal level J Infect Dis 1981;143:

26 Treatment of Neonatal Meningitis Initial Empiric Regimens Early onset: Ampicillin + aminoglycoside or cefotaxime Late onset: Term infant: Ampicillin + aminoglycoside or cefotaxime LBW/preterm: Vancomycin + amikacin or cefotaxime When Etiology Known Group B strep: Ampicillin +/- aminoglucoside Coliforms: Cefotaxime +/- aminoglycoside Pseudomonas: Ceftazidime + aminoglycoside Listeria: Ampicillin +/- aminoglycoside

27 Empiric antibiotic in bacterial meningitis >2mo.-14 yrs Cefotaxime or Ceftriaxone Alternate Ampicillin (PGS) + chloramphenicol Suspected Pneumococcal meningitis Cefotaxime or ceftriaxone+ Vancomycin

28 Dosage of 3rd Generation Cephalosporins in Bacterial Meningitis Ceftriaxone 100 mg/kg/d once or twice daily Cefotaxime mg/kg/d q 6 hr Ceftazidime 150 mg/kg/d q 6 hr Ceftriaxone 100 mg/kg/d CSF level 0.9 to 30 mcg/ml 2.8 hr after IV dose Antimicrob Agents Chemother 1995;39:

29 Treatment of DRSP meningitis Vancomycin 60 mg/kg/d q 6-8 hr CSF concentration 2.0 to 5.9 mcg/ml at 2.8 hr after IV dose (20% of serum level) Combination of Vancomycin and cefotaxime or ceftriaxone Combination of Rifampicin with vancomycin or Rifampicin with ceftriaxone Pediatr 1997;99:

30 Antimicrobial Therapy for Infants and Children with Pneumococcal Meningitis Cefotaxime + Vancomycin Penicillin susceptible Discontinue vancomycin Begin penicillin or continue cefotaxime or ceftriaxone alone Nonsusceptible to Penicillin Susceptible to cefotaxime Discontinue vancomycin continue cefotaxime or ceftriaxone Nonsusceptible to cefotaxime Continue vancomycin and cefotaxime rifampicin may be added

31 Duration of Treatment for Uncomplicated Bacterial Meningitis Neonates GBS and other strep Gram neg. enteric Listeria Infants and Children Meningococcus Haemophilus Pneumococcus days 21 days > 21 days 7 days 7-10 days days

32 Dexamethasone Therapy for Meningitis Regimen: mg/kg daily in 2, 3 or 4 divided doses for 2-4 days First dose should be given before or at the time of the first parenteral antibiotic dose It is doubtful that dexamethasone will be effective if given more than min, after the first parenteral antibiotic dose

33 Complication of bacterial meningitis Increased intracranial pressure Seizure SIADH Focal neurological deficits Hyponatremia Hydrocephalus Subdural effusion and ventriculitis

34 Second Lumbar Puncture in Meningitis Indicated for All neonates at hrs Lack of clinical improvement with hrs of starting treatmemnt Resistant pneumococcal meningitis Prolonged or secondary fever Not indicated At completion of therapy in uncomplicated patient except for neonates

35 Increased Intracranial Pressure (ICP) Rational in treating To avoid large elevation in intracranial pressure Herniation Signs & symptoms Papilledema Decrease level of consciousness Dilated or non-reactive pupils Cushing reflexes

36 Treatment of increase ICP Head elevation 30⁰ Judicious hyperventilation (goal PaCO₂ mmhg) Mannitol children g/kg (goal serum Osm between ) Pentobarbital 5-10 mg/kg at 1 mg/kg/min initial dose 1-3 mg/kg/hour maintenance dose

37 Siezures 30%-40% in children Treatment Short acting anticonvulsant with rapid onset of action Lorazepam 0.05 mg/kg Diazepam mg/kg (maximum mg/dose) Long acting Phenytoin mg/kg (loading dose) 5-8 mg/day (maintenance) Other anticonvulsants Phenobarbital mg/kg/dose Valproic acid mg/kg/d

38 Hyponatremia Treatment Fluid restriction Recommendation Intravenous fluid rate 3/4 of normal maintenance requirement ( ml/sqm daily) Gradual increase of volume if Na rises above 135 mmol/l ( ml/sqm/day (does not apply to patients in shock and dehydrated)

39 Treatment Hydrocephalus Avoid lumbar puncture Consider measures to decrease ICP Venticulostomy and drainage Indication Hydrocephalus caused by occlusion of foramen of Monro Rapidly decreasing clinical status Arbitrary (moderate to severe degree of hydrocephalus)

40 Subdural Effusion Occurs in 1/3 of children Treatment Conservative (most of them resolves) Surgical if it enlarges dramatically or get infected

41 Acute Complications of Bacterial Meningitis, Children s Hospital, Bangkok Complications (%) Neonates > 1 month old (N=77) (N=541) Subdural effusion Ventriculitis Hydrocephalus Cerebral palsy Relapsing meningitis Recurrent meningitis Recrudescence meningitis ( T.Chotpitayasunondh. Southeast Asian J Trop Med Public Health 1994;25: )

42 Fatality Rate of Meningitis by Organisms, Children s Hospital, Bangkok Organism Deaths/Cases (% fatality) Haemophilus influenzae type b 25/229 (10.9) Streptococcus pneumoniae 29/122 (23.8) Salmonella sp 16/69 (23.2) Neisseria meningitidis 2/20 (10.0) Escherichia coli 9/20 (45.0) Pseudomonas aeruginosa 15/19 (78.9) Klebsiella pneumoniae 6/14 (42.8) Staphylococcus sp 3/9 (33.3) Enterobacter sp 6/9 (66.7) Others 4/11 (36.4) No bacterial growth 12/79 (15.2) Total 129/619 (20.8) Southeast Asian J Trop Med Public Health 1994;25:

43 Causes of persistent fever after therapy of bacterial meningitis In effective antimicrobial therapy Subdural effusion Suppurative neurologic complications Nosocomial infection Drug fever Phlebitis Unknown or others

44 Prolonged Fever in Meningitis Be familiar with usual fever patterns Check details of antibiotic regimen Examine for focal neurological signs, phlebitis, arthritis, URI and UTI Consider CBC, CRP, LP, imaging studies If above is unrevealing, drug fever is possible

45 Recurrent Meningitis Congenital malformation congenital dermal sinus cribriform plate defect pericranial air sinus defect temporal bone defect Skull fracture Immunodeficiency Ventriculostomy Brain abscess Post splenectomy Undetermined

46 When is a CT or MRI indicated? When usual course of disease is altered Prolonged obtundation Seizures >72 hr after diagnosis Excessive irritability Focal neurological findings Enlarging head circumference Neonatal meningitis, especially caused by Citrobacter diversus Persistently abnormal CSF value(s) Relapse or recurrence

47 Haemophilus influenzae chemoprophylaxis Secondary cases in household contact and day care, highest in children under 2 years of age Most secondary cases (75%) occur within 6 days but may be as long as one month Rifampicin 20 mg/kg daily for 4 days for all individuals, including adult, in households with at least one child younger than 48 months of age. The index case should also receive rifampicin prophylaxis.

48 Chemoprophylaxis for meningococcemia Rifampicin 600 mg bid for 2 days Children 10 mg/kg bid Ceftriaxone 250 mg IM Ciprofloxacin mg single dose

49 Prevention of Meningitis Hemophilus type b conjugate vaccine Pneumococcal conjugate vaccine (7, 10, 13 serotypes) Meningococcal conjugate vaccine (A,C, Y, W135)

50 Thank You