Pediatric Infectious Disease - Sepsis, Meningitis, And Pneumonia

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Newborn (Premature, Term)

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Premature < 37 weeks gestation
Term 37 or greater weeks of gestation

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Neonate

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1 day - 1 month

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Infant

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1 month - 1 year

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Children

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1 -11 years

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Adolescent

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12-18 years

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Definition of Systemic Inflammatory Response Syndrome (SIRS)

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Temperature <36 C or >38.5
WBC elevated or depressed for age or > 10% immature neutrophils (low WBC - viral, high WBC - bacterial)
Bradycardia or tachycardia
Tachypnea

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Definition of Sepsis

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SIRS + Infection (suspected or proven)

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Definition of Severe Sepsis

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Sepsis + one of the following:
-Cardiovascular organ dysfunction
-ARDS
Two or more other organ dysfunctions

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Definition of Septic Shock

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Sepsis with refractory hypoperfusion

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Risk Factors for Neonatal Sepsis - Early Onset

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1. Preterm delivery
2. Prolonged rupture of membranes
3. Maternal Group B Streptococcus (GBS) colonization
4. Chorioamnionitis
5. Intrapartum maternal fever >38C within 24 hours of delivery
6. Intrauterine monitoring devices or the use of obsterical forceps
(Source of pathogen: Maternal genital tract

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Risk Factors for Neonatal Sepsis - Late onset

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1. Low birth weight
2. IV catheters or indwelling devices
3. Community acquired infections
(Source of pathogen: noscomial or maternal genital tract)

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Risk Factors for Pediatric Sepsis

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1. Indwelling catheters
2. Asplenic or sickle cell patients
3. Immunosuppressed patients (oncology, HIV positive, transplant pts)

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Causative Organisms of Neonatal Sepsis - Early Onset

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1. GBS
2. E.Coli
3. Listeria Monocytogenes

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Causative Organisms of Neonatal Sepsis - Late Onset

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1. Coagulase-negative Staphylococci (CoNS)
2. S. Aureus
3. Pseudomonas
4. Anaerobes
5. Candida

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Empiric Therpay of Neonatal Sepsis - Early Onset

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Ampicillin + AG or
Ampicillin + 3rd gen cephalosporin

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Empiric Therapy of Neonatal Sepsis - Late Onset

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Discharged: Same as early onset
Hospitalized: Vanco + AG

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Causative Organisms of Pediatric Sepsis - Healthy Children

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N. Meningitidis
H. Influenza B
S. Pneumoniae
S. Aureus
Salmonella

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Causative Organisms of Pediatric Sepsis - Immunodeficient or Chronically ill

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CoNS
Enterococcus
Viridian Streptococci
Enterobacteriaceae
P. Aeruginosa
Anaerobes
Candida
Viral

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Empiric treatment for Pediatric Sepsis - Healthy Children

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Vanco + 3rd gen cephalosporin

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Empiric treatment for Pediatric Sepsis - Immunocompromized or Chronically Ill

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Vanco + Antipseudomonal Agent

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Sepsis Adjunctive/Supportive Care

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1. Fluid and electrolytes
2. Inotropes
3. Blood products
4. Respiratory support
5. Nutrition
6. Glycemic Control
7. Steroids

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Sepsis - Duration of Therapy

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Rule out Sepsis:
Clinically asymptomatic --> 48 hours
Clinically septic --> 7-10 days

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Definition of Shock

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Circulatory system fails to supply oxygen and nutrients to meet cellular and metabolic demands

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Evaluation of Shock

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ABC's
Airway
Breathing
Circulation (HR, BP, perfusion)

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Early Signs of Shock - Compensated

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Sinus tachycardia
Delayed capillary refill
Fussy/irritable

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Late Signs of Shock - Uncompensated

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Bradycardia
Altered mental status
Hypotension

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Classification of Shock

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1. Hypovolemic or hemorrhagic
2. Cardiogenic
3. Distributive
4. Septic

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Hypovolemic or Hemorrhagic Shock - Cause

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Water loss and/or blood loss
Low preload leads to decreased stroke volume --> decreased cardiac output
Compensate by increasing HR and SVR

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Hypovolemic or hemorrhagic shock - Treatment

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1. Hypovolemic = Fluids (rapid restoration of intravascular volume)
2. Blood = PRBCs

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Cardiogenic Shock - Cause

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Result of primary cardiac dysfunction (low Co and high SVR)

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Cardiogenic Shock - Treatment

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1. Fluids (1st line)
2. If no improvement with fluids suspect cause if cardiac in origin
3. Inotrope support

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Distributive Shock - Cause

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Misdistribution of blood flow leads to in adequate tissue perfusion - most commom form is early septic shock
Causes: anaphylaxis, spinal cord and head injuries, drug intoxification and infection

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Distributive Shock - Treatment

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1. Maintain intravascular volume and minimize increases in interstitial fluid
2. Crystalloids
3. Inotropes agents - Dopamine
4. Underlying cause ie Antibiotics

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Septic Shock - Treatment

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1. Treat the underlying case
2. Begin antibiotics within 1 hour of presentation (treated as STAT)

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Restoration of Circulatory Volume

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1. Crystalloid: 10-20 mL/kg (60 ml/kg over 2 hour period)
2. Colloid: 10 mL/kg

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Inotropes - Dopamine

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2 -3 mcg/kg/min (Dopa effects) - increase renal blood flow
5-10 mcg/kg/min (Beta effects) - increased contractility
10-20 mcg/kg/min (Alpha effects) - increased BP from vasoconstriction

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Inotropes - Dobutamine

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Beta stimulation to increase cardiac output
Used in cardiogenic shock

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Inotropes - Norepinepherine

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"Warm shock" hypotensive and vasodilated
Alpha and beta 1 stimulation
Used in conjunction with dopamine

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Inotropes - Epinephrine

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"Cold shock" hypotensive and vasoconstricted
0.1- 0.2 mcg/kg/min (Beta effects)
0.3 mcg/kg/min (Alpha effects) increase BP

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Inotropes - Milrinone

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Decreased afterload and preload secondary to vasodilation

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Pediatric and Infant Meningitis - Definition

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Inflammation of the meninges cause by an infection

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Neonatal Meningitis - Signs and Symptoms

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Non-specific and subtle:
-Symptoms of sepsis including fever
-CNS instability
-Seizures
-Irritability
-Vomiting
-Not urinating well

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Pediatric Meningitis - Clinical Presentaion

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Very specific
-Fever
-Chills
-Photophobia
-Headache
-Seizures
-Mental status changes
-Nuchal rigidity (Brudzinskis and Kernig's signs)

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Pediatric Meningitis - Pathogens

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Meningococcemia
-Petechia and purpural eruptions
H. Influenzae
-Joint involvement

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Brudzinski's Sign

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Knee flexion with forward movement of leg

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Kernig's Sign

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Inability to straighten the leg when elevated

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Diagnosis of Meningitis

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Lumbar puncture for CSF analysis:
-Leukocyte count (high)
-Neutrophils (>90%)
-Protein (high)
-CSF/Blood glucose ratio (low)

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Most Common Pathogen Based on Age <1 month

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Strep Agalactiae
E. Coli
Listeria Monocytogenes
Klebsiella species

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Most Common Pathogen Based on Age 1 - 23 months

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Strep pneumo
Neisseria meningitidis
S. Agalactiae
Haemophilus Influenzae
E. Coli

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Most Common Pathogen Based on Age 2-50 years

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N. Meningitidis
S. Pneumo

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Empiric Anti-Microbial Treatment - Early Onset Neonatal Meningitis

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Ampicillin + AG +/- 3rd gen cephalosporin

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Empiric Anti-Microbial Treatment -Late Onset Neonatal Meningitis

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Vanco + AG +/- 3rd gen cephalosporin

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Empiric Anti-Microbial Treatment - Pediatric Meningitis

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Vanco + 3rd gen ceph

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Long-term Complications of Bacterial Meningitis

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1. Seizures
2. Hearing deficits (esp with strep pneumo)
3. Neurologic squelae (learning, neuromotor, behavioral problems)

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Prevention of Meningitis - Vaccinations

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HIb (2 months)
Pneumococcal (2-6 months)
Meningococcal (2 years)

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Meningitis - Prophylaxis

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Given to anyone within close contact within the past 7 days.
-Ceftriaxone
-Ciprofloxacin
-Rifampin

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Pediatric Pneumonia - Definition

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-Presence of fever
-Acute respiratory symptoms
-Evidence of parenchymal infiltrates on chest radiography

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Pediatric Pneumonia - Risk Factors

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-Immune deficiency
-Congenital heart disease
-Bronchopulomanry dysplasia
-Sickle cell disease
-CF
-Asthma
-GI disorders (reflux)
-Exposure to cigerette smoke

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Pediatric Pneumonia - Signs and symptoms

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-Fever
-Cyanosis
-Respiratory distress

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Pediatric Pneumonia - Diagnosis

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Largely based on patient's history and physical exam (CXR may be normal or abnormal depending on their fluid status - often lags behind clinical findings)

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Pediatric Pneumonia - Lab tests

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-CBC w diff (WBC > 15,000 = bacterial, WBC <15,000 = viral)
-C-reactive protein (CRP)
-Gram stain and culture
-Viral antigen testing (viral vs bacterial; RSV?)
-Serum electrolytes (assess hydration)
-

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Etiologic Pathogens of Pneumonia in Neonates

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E. Coli
GBS
Listeria Monocytogenes

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Etiologic Pathogens of Pneumonia in 1-3 months

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Bacterial
-Strep pneumo
-H. influenza
Viral
-Adenovirus
-Influenza virus
-Parainfluenza virus
-RSV

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Etiologic Pathogens of Pneumonia in 4 months - 5 months

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Bacterial
-Strep pneumo
-H. influenza
-Chlamydia pnemoniae
Viral
-Adenovirus
-Influenza virus
-Parainfluenza virus
-RSV
-Rhinovirus

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Etiologic Pathogens of Pneumonia in 5 years - adolescence

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Bacterial
-Strep pneumo
-Chlamydia pnemoniae
-Mycoplasma pneumonia
Atypicals are only seen in >5 year old, unless you have the risk factor of having a sibling in day care

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Pediatric Pneumonia Treatment - Well Appearing to Mildly Ill

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Hospital (<3 months):
-Fully immunized: Ampicillin IV or Amoxicillin PO
-Not fully immunized: 3rd gen ceph
Discharge (>3 months): C

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Pediatric Pneumonia Treatment - Mildly to Severely Ill Appearing

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Admit to the inpatient floor or PICU
Moderate:
-Fully immunized: Ampicillin IV
-Not fully immunized: 3rd gen ceph
-Consider adding a macrolide for atypical PNA
Secverely Ill
-Vancomycin + Ceftriaxone + Azithromycin IV

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Prevention of Pneumonia - Vaccinations

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-HIB
-Pnemococcoal conjugate (Prevnar)
-Influenza

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Therapeutic Drug Monitoring - (2) drugs

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Vancomycin
Aminoglycosides

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Vancomycin - MOA, Dosing and Monitoring

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MOA: inhibits bacterial cell wall synthesis, time dependent killing.
Ped dosing: 15 mg/kg Q6-24 hours - requires dosing adjustments in renal insufficiency
Monitor troughs:
-Meningitis - 15-20
-Bacteremia - 10-15

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Aminoglycosides - MOA, Dosing and Monitoring

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MOA: Concentration dependent killing
Ped dosing: 2.5 to 12 mg/kg Q8H - requires dosing adjustments for renal insufficiency
Monitor peaks:
-Most gram negative infections - 6 to 8
-Pseudomonal infections - 10 to 12

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Time Dependent Killing

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Longer time with drug concentration over MIC of target organism = higher rate of kill

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Concentration Dependent Killing

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Higher drug concentration = higher rate and extent of bacterial killing

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When do you want to get peaks and troughs?

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Wait 3-5 doses to reach SS
Peaks - drawn ~30 mins after the dose finished infusing
Troughs - immediately prior to when new dose starts infusing