BACTEREMIA, SEPSIS, AND MENINGITIS IN CHILDREN 林口急診醫學部 吳孟書 醫師

BACTEREMIA AND SERIOUS BACTERIAL INFECTION Children between ages of birth and 3 years old Children between ages of birth and 3 years old Bacteremia Bacteremia Occult bacteremia (OB): Streptococcus pneumoniae Occult bacteremia (OB): Streptococcus pneumoniae Septicemia Septicemia Serious bacterial infection (SBI) Serious bacterial infection (SBI) Early-onset disease Early-onset disease Late-onset disease Late-onset disease Immunization for Hib and pneumococcus Immunization for Hib and pneumococcus

Age-Related Risk Groups and Causes of Bacteremia in Children GroupRiskPathogens Neonates High risk Group B Streptococcus Escherichia Coli Listeria monocytogenes Enterococcus sp. Young infants days Intermediate risk Neonatal pathogens (above) Community-acquired pathogens (below) Older infants 3-36 months Low risk Streptococcus pneumoniae Neisseria meningitidis Haemophilus influenza b (unimmunized) Group A Streptococcus Escherichia coli (pyelonephritis) Salmonella sp. (gastroenteritis) Staphylococcus aureus (osteomyelitis)

Serious Bacterial Infections Associated with Bacteremia MeningitisMeningitis PneumoniaPneumonia PyelonephritisPyelonephritis Bacterial enteritisBacterial enteritis Facial cellulitisFacial cellulitis Septic arthritisSeptic arthritis OsteomyelitisOsteomyelitis

Clinical Features Risk for neonatally acquired bacterial infection: premature delivery, ruptured amniotic membranes for more than 24 h prior to delivery, and maternal amnionitisRisk for neonatally acquired bacterial infection: premature delivery, ruptured amniotic membranes for more than 24 h prior to delivery, and maternal amnionitis An overall ill appearance (TICLS) and assess children with PATAn overall ill appearance (TICLS) and assess children with PAT Persist lethargy or irritability with associated feverPersist lethargy or irritability with associated fever Immunization satusImmunization satus Prior infection and underlying diseasesPrior infection and underlying diseases By definition, it is impossible to distinguish children with OB from those without bacteremia by clinical feature alone, especially when rectal temperature is more than 39 ℃.

Diagnosis (neonates and young infants) Sepsis workup: CBC/DC CBC/DC U/A and U/C U/A and U/C B/C B/C CSF studies and culture (selective in infants aged days) CSF studies and culture (selective in infants aged days) CxR for respiratory signs or symptoms CxR for respiratory signs or symptoms S/A for diarrhea S/A for diarrhea

Low-Risk Criteria for Febrile Infants Days of Age (Rochester) History: Full term Full term No underlying medical problems No underlying medical problems No prior antibiotics No prior antibiotics Physical examination: “ Well appearance ” “ Well appearance ” No focus of infection (otitis, soft tissue, bone, or joint) No focus of infection (otitis, soft tissue, bone, or joint)Laboratory: WBC /μL with <1500 bands/μL WBC /μL with <1500 bands/μL Urinalysis < 10 WBCs/hpf, negative for leukocyte esterase, nitrite Urinalysis < 10 WBCs/hpf, negative for leukocyte esterase, nitrite Stool smear < 5 WBCs/hpf (if diarrhea present) Stool smear < 5 WBCs/hpf (if diarrhea present) Normal chest x-ray (if clinical indicated) Normal chest x-ray (if clinical indicated)Follow-up: Reliable parents Reliable parents Home telephone and transportation Home telephone and transportation

Diagnosis (children 3-36 months of age) Overall appearanceOverall appearance HistoryHistory Physical examinationPhysical examination Individualized laboratory assessmentIndividualized laboratory assessment An ill-appearance febrile child, regardless of age, should be stabilized and comprehensively evaluated for sepsis.An ill-appearance febrile child, regardless of age, should be stabilized and comprehensively evaluated for sepsis. A well-appearance febrile infant should have laboratory evaluation base on clinically identified risk factors for SBI with bacteremia.A well-appearance febrile infant should have laboratory evaluation base on clinically identified risk factors for SBI with bacteremia. The pursuit of OB should not distract emergency physicians from carefully evaluating febrile infants for focal serious bacterial infections, including UTI, pneumonia, meningitis, and soft tissue, bone, or joint infection.The pursuit of OB should not distract emergency physicians from carefully evaluating febrile infants for focal serious bacterial infections, including UTI, pneumonia, meningitis, and soft tissue, bone, or joint infection.

Indications for Blood Cultures in Children Unexplained ill appearance, regardless of age or feverUnexplained ill appearance, regardless of age or fever Febrile neonatesFebrile neonates “ High-risk ” febrile infants aged days“ High-risk ” febrile infants aged days MeningitisMeningitis Pneumonia (required admission)Pneumonia (required admission) Pyelonephritis (age ≦ 6 months or febrile requiring admission)Pyelonephritis (age ≦ 6 months or febrile requiring admission) Bacterial enteritis (age ≦ 2 years)Bacterial enteritis (age ≦ 2 years) Facial cellulitisFacial cellulitis Septic arthritisSeptic arthritis OsteomyelitisOsteomyelitis Underlying immune deficiency with feverUnderlying immune deficiency with fever

Management scheme for febrile infants aged 0 to 90 days Documented fever, age ≦ 90days Age ＜ 30 days Full sepsis workup Antibiotics in ED Admit Yes No High-risk factors? -History -Physical exam -Laboratory -Follow-up Yes Outpatient management - Follow-up in 24 h No Option 1 Full sepsis workup Ceftriaxone 50 mg/kg IM If negative LP Option 2 Selective lumbar puncture No antibiotic if negative LP

Antibiotic Dosages for Bacteremia and Meningitis Age Group Bacteremia/SepsisMeningitis Neonates Ampicillin 100 mg/kg plus plus Cefotaxime 50 mg/kg or or Ceftriaxone 50 mg/kg Ampicillin 100 mg/kg plus plus Cefotaxime 50 mg/kg or or Ceftriaxone 50 mg/kg Young infants days days Ampicillin 100 mg/kg plus plus Cefotaxime 50 mg/kg or or Ceftriaxone 50 mg/kg Ampicillin 100 mg/kg plus plus Cefotaxime 100 mg/kg plus vancomycin 15 mg/kg or or Ceftriaxone 100 mk/kg plus vancomycin 15 mg/kg Older children Cefotaxime 50 mg/kg or or Ceftriaxone 50 mg/kg plus consider plus consider Vancomycin 15 mg/kg Cefotaxime 100 mg/kg plus vancomycin 15 mg/kg or or Ceftriaxone 100mg/kg plus vancomycin 15 mg/kg

Admission All febrile neonatesAll febrile neonates Ill-appearance infantsIll-appearance infants Young infants fail to meet low-risk criteriaYoung infants fail to meet low-risk criteria Positive blood culturePositive blood culture Follow-up within 24 h and clear instructions regarding indications for return are the cornerstones of outpatient management of well- appearing febrile infants 3 to 36 months of age.

SEPSIS A clinical syndrome defined by bacteremia with clinical evidence of invasive, systemic infection that can progress with variable rapidity to circulatory failure.A clinical syndrome defined by bacteremia with clinical evidence of invasive, systemic infection that can progress with variable rapidity to circulatory failure. 1)Clonization with a bacterial pathogen 2)Invasion of the blood by encapsulated organisms and release of inflammatory mediators 3)Host defense-response failure

SEPSIS HOST RISK FACTORS:HOST RISK FACTORS: 1)Impaired splenic function – congenital absence, surgical removal, or functional impairment in sickle hemoglobulinemia 2)Congenital metabolic disease – e.g., galactosemia 3)Primary humoral and cellular immunodeficiency stats 4)Acquired humoral and cellular immunodeficiency stats The likely pathogens for sepsis demonstrate an age-related distribution.

SEPSIS Clinical features:Clinical features: 1.Neurogenic symptoms – alternated mental status with irritable, confusion, or lethargy 2.Poor feeding, lack of spontaneous motor activity, and hypotonia 3.Hyperpyrexia or hypothermia 4.Tachypnea and retractions 5.Cutaneous findings – petechiae, or progressed to coalescent pupura Early septic shock – resting tachycardia, widened pulse pressure, warm distal extremities, and brisk capillary refill. Late septic shock – weak distal pulses, delayed capillary refill, cool extremities, and eventually followed by decreased sensorium and hypotension.

SEPSIS Diagnosis:Diagnosis: 1.A clinical diagnosis of exclusion 2.Should be considered in any febrile or ill-looking child 3.No laboratory test is diagnostic 4.D.D. includes – infectious, cardiac, metabolic and traumatic diseases.

SEPSIS Treatment:Treatment: 1)Restoration of oxygenation and perfusion. 2)I.V., O 2, and monitors – 20 mL/kg N/S for fluid resuscitation and high flow oxygen 3)Foley catheter – 1-2 mL/kg/h 4)Treat hypoglycemia with dextrose if needed – 0.5g/kg bolus 5)ET + MV if indicated 6)Inotropic agents if need – dopamine or epinephrine 7)Antibiotic therapy Antibiotic therapyAntibiotic therapy 8)Admission

MENINGITIS Pathophysiology:Pathophysiology: A.Mostly, as a complication of a primary bacteremi, e.g., alternation of BBB resulting in brain edema, IICP, and vascular thombosis. B.Less commonly, via the hematogenous rout from a distant primary focal infection, e.g., adjacent infection or skull base fx. C.Highest incidence between the age of birth and 2 years D.Host defense factors impairment as sepsis Host defense factors impairment as sepsisHost defense factors impairment as sepsis E.Pathogenic organisms as sepsis Pathogenic organisms as sepsisPathogenic organisms as sepsis F.Associated with vaccinations

MENINGITIS Clinical Features:Clinical Features: A.Insidious progression of a febrile illness in most cases. B.Less commonly, a fulminant progression to septic shock and meningitis --- N. meningitidis C.Fever associated with altered mental status D.Decreased responsiveness, poor feeding, vomiting, and irritability. E.Bulging frontanelle F.Headache, nausea/vomiting, and photophobia G.Stiff neck, Kerning sign, and Brudzinski sign. H.Seizure or other focal neurologic findings

MENINGITIS Diagnosis:Diagnosis: 1.Brain CT – should not antibiotic therapy 2.CSF studies 3.Bedside blood sugar level 4.CBC/DC 5.Electrolytes panel 6.Blood culture 7.Urine culture 8.D/D as in sepsis D/D as in sepsisD/D as in sepsis

CSF FINDINGS in MENINGITIS NormalBacterialViral AppearanceClear Clear to cloudy Clear Cell count (WBCs/mm 3 ) ＜ 10 ＞ ,000 ＞ Differential (% PMNs) 0 ＞ Glucose (mg/dL) ＜ Protein (mg/dL) Gram stain (bacterial) NegativePositiveNegative

MENINGITIS Treatment:Treatment: 1.Early resuscitation and stabilization. IV, O 2, Monitors, and ET+MV if indicated 2.Maintain rate of fluid to minimize cerebral edema 3.Treat seizure with BZDs or Phenytoin, or Phenobarbital 4.Hyperventilation and mannitol (1mg/kg) for IICP 5.Empiric antibiotics as soon as possible Empiric antibiotics as soon as possibleEmpiric antibiotics as soon as possible 6.Dexamethasone 0.15mg/kg IV either before or immediately after the initial antibiotic dose to children 1 month of age or older. --- especially for HIB meningitis 7.Prophylaxis Rifampin for contacts mg/kg daily in HIB for 4days, 10mg/kg BID in N. meningitidis for 2 days (maximum, 600mg) 8.Admit all patients suspected with meningitis.

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