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Pediatrics 2: Neonatology-Nephrology

Infections in the Newborn

Under Five Year Old Deaths, 2008


Neonatal 45%
o Prematurity 41%
o PN / Sepsis 16%
o Asphyxia 15%
o Congenital abnormality 14%
o Tetanus 2%
o Others 14%

Prematurity
Pneumonia 18%
NCD 9%
Diarrhea 7%
Injury 4%
Meningitis 3%
Pertussis 1%
Malaria 1%
HIV 0%
Measles 0%
Other infections 12%

Neonatal Sepsis clinical syndrome of bacteremia


characterized by systemic signs and symptoms of
infection in the first 4 weeks of life
(More than 1 organ system is involved, especially respiratory if earlyonset.)

Classification of Neonatal Sepsis

Time of Onset

Maternal
Obstetric
Complications
Transmission
/ Organism
Source
Clinical
Manifestation

Early Onset

Late Onset

Very Late
Onset
(Nosocomial)
>30 days

Birth to 7
days, usually
<72 hrs
Often present

7 days to 30
days
Usually
absent

Varies

Vertical:
Maternal
genital tract
Fulminant
course,
multisystem
involvement;
Pneumonia
common

Vertical
or
postnatal
environment
Insidious,
focal
infection;
Meningitis
common

Environment
/ community
Multisystem
or focal

Risk Factors for Sepsis


Early Onset
Prematurity
Low birth weight
Premature / prolonged
rupture of membranes

(high risk: >18 hrs)

Maternal fever
Chorioamnionitis
Maternal UTI
Functional deficiencies of
neonatal host defense
mechanisms

Late Onset
Prematurity
Prolonged hospitalization
Invasive
procedures:
umbilical
catheters,
endotracheal intubation
Parenteral alimentation
Prior use of antibiotics
Medications (H2-blockers)
(alter GI environment pH)

Functional deficiencies of
neonatal host defense
mechanisms

Poor handwashing technique may also cause late-onset sepsis.

The most important neonatal factor predisposing to


infection
Premature infants have a 3 to 10-fold higher incidence of
infection than full-term infants.
- Immature immune system, especially chemotactic
phagocytic activity
- susceptibility especially to capsulated organisms
- Usually require a longer stay in NICU ( exposure)

and

Chorioamnionitis
Elevated maternal temperature
Uterine tenderness
Maternal leukocytosis
Fetal tachycardia
Foul-smelling amniotic fluid
(Send placenta for histopathologic examination.)

Why are Newborns Prone to Develop Sepsis?


Immunology and Pathogenesis
Newborn specific immune mechanisms are anatomically
competent yet antigenically inexperienced and functionally
deficient.
Antibody responses to infection are poor.
Complement levels are low.
Decreased ability of the granulocytes and phagocytes to
kill bacteria
Deficient neutrophil chemotactic response

Transmission of Infection
1. Transplacental
CMV and Rubella
Listeria monocytogenes
Treponema pallidum (syphilis)
2. Vertical
Ascending route: following rupture of membranes
Passage through the birth canal by colonization
3. Postnatal
Direct contact with caregiver
Environmental / contaminated equipment

Predominant Pathogens for Sepsis


Early Onset
Escherichia coli
- Most common pathogen in
the Philippines
- Number 1 cause of earlyonset sepsis
- Also the common pathogen
if infant is born at home)

Group B streptococcus
(most common in developed
countries)

Listeria monocytogenes
Haemophilus influenzae

Late Onset
Coagulase negative
Staphylococcus
epidermidis (nosocomial
pathogen)

Staphylococcus aureus
Gram negative enteric
bacilli
Pseudomonas aeruginosa
Enterococcus spp.
Fungal (most common:
Candida albicans in babies
with prolonged stay in NICU)

Enterobacter aeruginosa
Klebsiella pneumoniae
Staphylococcus aureus

Clinical Signs of Sepsis


Respiratory distress
Tachypnea, retractions, grunting, nasal flaring, apnea
Abnormal skin color perfusion
Mottling, pale color, gray color, delayed capillary
refill time, jaundice (early jaundice especially common in E.
coli)

Temperature instability
Hypothermia and, rarely, hyperthermia
Feeding intolerance
Vomiting, abdominal distension, poor feeding
pattern
Abnormal heart rate and blood pressure
Tachycardia, bradycardia, hypotension (to measure
BP, use the flush method; normal: >50 mmHg)

Metabolic problems
Hypoglycemia, hyperglycemia, metabolic acidosis
Abnormal neurologic status
Lethargy, hypotonia, seizures

Evaluation of a Newborn for Sepsis


History (Specific risk factors)
o Maternal infection / Chorioamnionitis
o Maternal colonization with GBS
o Gestational age / Birthweight
o Duration of membrane rupture
o Complicated delivery
o Medical intervention (endotracheal intubation,
vascular access, surgery)
Laboratory Studies
1. Evidence of Infection
o Culture from a normally sterile site: blood, CSF,
urine
o Demonstration of a microorganism in tissue or fluid
o Molecular detection (blood, CSF, urine)
o Maternal or neonatal serology (syphilis)
2. Evidence of inflammation
o Leucocytosis, increased I/T ratio
o Acute phase reactants: CRP, ESR
o Cytokines: IL-6, TNF
o Pleocytosis: CSF or pleural fluid
o DIC: D-dimer, fibrin degradation products
3. Evidence of Multiorgan System Disease
o Metabolic acidosis: pH
o Renal function: BUN, creatinine
o Pulmonary function: pO2, pCO2
o Hepatic injury: PT, APTT, bilirubin
o Bone marrow function: thrombocytopenia, anemia,
neutropenia
4. Positive CBC screen:
o Total WBC 5,000
o I/T 0.2 (immature neutrophil (band) to total neutrophil
ratio)

o ANC 1,500
o Platelets <100,000

Blood is usually tested after 6-8 hours of life to remove the effect of
stress.
CRP:
- Not useful in the first 48 hrs d/t presence of inflammatory
changes leading to false (+) results
- (+) result: agglutination of latex beads using undiluted serum
- More useful for monitoring
Final Diagnosis:
- Sepsis in the newborn, unspecified if culture (-)
- Sepsis in the newborn, E. coli if culture (+)

Treatment of Sepsis
In any infant suspected of sepsis, antimicrobial therapy
should be initiated immediately after completion of
diagnostic evaluation.
The progression of the disease may be too rapid to await
confirmation from blood or other cultures.
The decision to initiate treatment for sepsis is based
upon clinical history, signs and symptoms, and laboratory
results.
A normal CBC or a negative culture does not rule out the
presence of sepsis.
EARLY ONSET: In the initial treatment of neonatal sepsis,
it is best to begin antimicrobial therapy with
ampicillin or penicillin in combination with an
aminoglycoside. (always with 2 drugs and given IV!)
LATE ONSET: The principles of management of late-onset
sepsis (nosocomial) are identical to those for the
treatment of early onset sepsis. It is best to initiate
therapy with broad spectrum coverage that will be
effective for most nosocomial pathogens.
Duration:
o The duration of parenteral antibiotic therapy should be
10-14 days.
Gram (+) : 10 days
Gram (-) : 14
o In the presence of meningitis, antibiotic treatment
should be given for 14-21 days.
Gram (+) : 14 days
Gram (-) : 21 days
Adjunctive Therapies:
o Intravenous immunoglobulin
o Granulocyte transfusion
o Exchange transfusion (to remove toxins in the circulation)
Supportive Therapy:
o Respiratory adequate oxygenation (mechanical
ventilator if needed)

o Cardiovascular support blood pressure and perfusion


(dopamine, dobutamine)

o Hematologic transfuse blood products in DIC (FFP,


platelets)

o Metabolic monitor and treat hypo- or hyperglycemia


and acidosis
o Nutrition provide optimal nutrition (parenteral
nutrition if cant feed yet)
- MRSA vancomycin + aminoglycoside
- If nosocomial, broader antibiotics are needed.
- Look for hospital data on common organisms grown in culture.
Choose antibiotics based on this.
- Dont give oral antibiotics. Neonates cant absorb these, thus
bioavailability is unpredictable.

Complications of Sepsis
Bacterial meningitis (sometimes already present upon
presentation)

Disseminated intravascular coagulopathy (infection liver


damage production of clotting factors)

Septic shock
Multiple organ failure

Other stuff not mentioned in the lecture:


Septic shock presence of sepsis with evidence of end organ
hypoperfusion with at least one of the following:
- Acute mental changes
- Hypoxemia
- Metabolic acidosis
- Oliguria

The last 3 are irreversible and can lead to death.


Focal sepsis due to swallowed or inhaled amniotic fluid

Prevention
What measures may be undertaken to prevent severe
sepsis?
The presence of maternal risk factors for newborn
sepsis warrant immediate diagnosis and treatment of the
infant following delivery.
To prevent nosocomial infections, the following
measures should be implemented:
o Meticulous handwashing by caregivers
o Proper staffing ratio and adequate space in between
babies
o Rational use of antimicrobials (meropenem and

Nosocomial sepsis
- Acquired in the hospital: delivery room, nursery, neonatal ICU
- Late or very late onset (more common in babies who stay
longer at the hospital)
- Relatively uncommon in the normal term infants but higher
incidence among low birth weight infants)
Deficient cellular and humoral immune response
- IgG transplacentally transferred; therefore, IgG levels of
infant is dependent on the mother
- WBC neutrophils lack capability to phagocytose bacteria

vancomycin shouldnt be used as first line, or else resistance


will develop)

o Rational use of invasive monitoring equipment


2012
FOR JP