Neonatal Sepsis

Sheryl Del Rosario-Famadico, MD

UP-PGH
Department of Pediatrics
Division of Newborn Medicine
 Objectives:
At the end of the session, the participant should be
able to:
☼ Define Newborn Infection in terms of definition,
age of onset, incidence and etiologies
☼Understand pathogenesis, manifestations and
different evaluations of neonatal sepsis
☼List the different approach to management and
preventive strategies on decreasing Neonatal Sepsis
 Newborn Infections:
Congenital ☼denotes infection acquired in utero
infection ☼caused by viral or other nonbacterial
organisms
☼often associated with injury to
developing organs
Perinatal ☼indicates acquisition around the time of
infection Delivery include both bacteria and
viruses
Early-onset ☼occurs in the 1st week of life
infection ☼generally the consequence of infection
caused by organisms acquired during
the perinatal period

Nelsons Textbook of Pediatrics 21th ed

 Newborn Infections:

Late-onset ☼occurs between 7 and 30 days of life

infection ☼include bacteria, viruses, or other
organisms that are typically
acquired in the postnatal period
Hospital-acquired ☼typically occur beyond the 1st wk of
infections life

Nelsons Textbook of Pediatrics 21th ed

 Why Neonatal Infections are Unique?
Ontogeny of skin, soluble, and cellular innate defense systems

SKIN

Mucous
Membrane

BLOOD

Nelsons Textbook of Pediatrics 21th ed

CAUSES OF DEATH CHILDREN
UNDER 5 YEARS, GHO, WHO 2015
 Neonatal Sepsis: Definition

☼clinical syndrome characterized by signs and

symptoms of infection with or without accompanying
bacteremia in the first month of life.
☼It encompasses various systemic infections of the
newborn such as septicemia, meningitis, pneumonia,
arthritis, osteomyelitis, and urinary tract infections.

CDC and WHO definition of sepsis 2020

Nelsons Textbook of Pediatrics 21th ed

 Infection according to age of onset:
Early Onset Neonatal Infections

☼defined as the onset of symptoms before 7 days of

age
☼some experts limit the definition to infections
occurring within the 1st 72 hr of life.

Nelsons Textbook of Pediatrics 21th ed

 Infection according to age of onset:
Late Onset Neonatal Infections

☼generally defined as the onset of symptoms at ≥7

days of age
☼variability in the definition, ranging from an onset
at >72 hr of life to ≥7 days of age

Nelsons Textbook of Pediatrics 21th ed

 Infection according to age of onset:
Early and Late Onset Neonatal Infections

☼Early Onset infections: acquired before or during

delivery (vertical mother to child transmisison)
☼Late Onset infections: develop after delivery from
organisms acquired in the hospital or the
community.
☼The age at onset depends on the timing of
exposure and virulence of the infecting
organisms.
Nelsons Textbook of Pediatrics 21th ed
 Infection according to age of onset:
Very Late Onset Neonatal Infections

☼(onset after age 1 mo) may also occur

☼particularly in very-low-birthweight (VLBW)
preterm infants or term infants requiring prolonged
neonatal intensive care

Nelsons Textbook of Pediatrics 21th ed

Incidence of Neonatal Bacterial Sepsis :
☼varies from 1-4 per 1,000 livebirths

Rates of early sepsis by weight:

Nelsons Textbook of Pediatrics 21th ed

 Epidemiology: GBS Sepsis
☼Improvement in prenatal and neonatal care,
intrapartum antibiotic prophylaxis -> reduction of
early onset GBS sepsis
☼Late-onset GBS infection rates have remained
relatively stable in the same interval 
 Pathogens associated with
Early Onset Sepsis and Early Onset
Meningitis :

Nelsons Textbook of Pediatrics 21th ed

Pathogens associated with
Late onset Sepsis:
 Pathogenesis:
Pathways of Ascending or Intrapartum infection

Nelsons Textbook of Pediatrics 21th ed

 CHORIOAMNIONITIS

☼ maternal fever
☼ With or without local or
systemic signs of
chorioamnionitis
☼ uterine tenderness,
☼ Foulsmelling vaginal
discharge/amniotic fluid
☼ maternal leukocytosis
☼ Maternal and/or fetal
tachycardia)

Nelsons Textbook of Pediatrics 21th ed

 Intrauterine Inflammation or Infection
Triple I

☼
fetal tachycardia
☼
maternal
leukocytosis(>15,000 cells in
the absence of
corticosteroids)
☼
purulent fluid from the
cervical os,
☼
biochemical or microbiologic
amniotic fluid changes
consistent with infection,
☼
fever (≥39.0°C/10.2°F)

Nelsons Textbook of Pediatrics 21th ed

 Rupture of Membranes

☼Prolonged Rupture of membranes: ruptured more than

24 hours
☼ microscopic evidence of inflammation of the membranes is
uniformly present when the duration of rupture exceeds 24 hr.
☼18 hours of membrane rupture:
☼ appropriate cutoff for increased risk of neonatal infection
☼ incidence of group B streptococcusEONS (GBS) increases
significantly;

Nelsons Textbook of Pediatrics 21th ed

 Factors influencing balance between
health and disease in neonates:

Nelsons Textbook of Pediatrics 21th ed

 Clinical Manifestations:
☼ Early signs of Neonatal sepsis are frequently nonspecific and
subtle and do not distinguish among organisms

General Fever Respiratory: Apnea

Temperature Dyspnea
instability Tachypnea
Poor feeding Retractions
Cyanosis

GIT Abdominal Renal System Oliguria

distention
Vomiting
Diarrhea

CVS Tachycardia CNS Irritability

Hypotension Lethargy
Bradycardia Seizures

Nelsons Textbook of Pediatrics 21th ed

 Evaluation of Sepsis:

Nelsons Textbook of Pediatrics 21th ed

 Evaluation:
☼ High Index of suspicion

☼Signs of sepsis are nonspecific and are observed

with other noninfectious conditions.
☼Bacteremia can occur in the absence of clinical
signs
☼Available diagnostic testing is not helpful in
deciding which neonate requires empirical
antimicrobial therapy but can assist with the
decision to discontinue treatment
Nelsons Textbook of Pediatrics 21th ed
 Laboratory Findings
Culture based diagnostics

 CATEGORY OPTIMAL TIMING, APPLICABILITY

PARAMETER VOLUME OF SPECIMEN, FOR
NEONATAL SEPSIS

 Blood  >1 mL of whole blood, from  Gold standard for

2 sites bacteremia

CSF  When clinically feasible Optimize

antimicrobial therapy

Nelsons Textbook of Pediatrics 21th ed

 Culture based diagnostics

 CATEGORY OPTIMAL APPLICABILITY

PARAMETER TIMING,VOLUME OF FOR
SPECIMEN, NEONATAL SEPSIS

Urine >72 hr of life Not useful for EOS;

potential
benefits for LOS
Tracheal Neonates with endotracheal  Usually reflects
aspirate tube in place and signs of colonization
progressive
respiratory distress
Nelsons Textbook of Pediatrics 21th ed
 NON Culture based diagnostics

 CATEGORY OPTIMAL TIMING, VOLUME APPLICABILITY FOR

PARAMETER OF NEONATAL SEPSIS
SPECIMEN,
ROUTINE/INVESTIGATIONAL

Neutrophil Neutropenia After 12 hr of life  Neutropenia better

Indices Absolute Consider GA, delivery predictor for
  neutrophil mode, sepsis than
count altitude, arterial versus leukocytosis
Absolute venous
immature sampling, time since birth
neutrophil
count
Platelet count Thrombocytopenia  Late findings; slow to  Thrombocytopeni
respond a associated with
thrombocytosis fungal infection
Nelsons Textbook of Pediatrics 21th ed
 NON Culture based diagnostics

 CATEGORY OPTIMAL TIMING, APPLICABILI

PARAMETER VOLUME OF TY FOR
SPECIMEN, NEONATAL
ROUTINE/ SEPSIS
INVESTIGATIONAL
Acute phase CRP  8–24 hr after infection Good NPV
reactants
Procalcit 2–12 hr after infection  Better
onin sensitivity but
less
specificity than
CRP

Nelsons Textbook of Pediatrics 21th ed

 NON Culture based diagnostics

 CATEGORY OPTIMAL TIMING, VOLUME OF APPLICABILITY

PARAMETER SPECIMEN, FOR
NEONATAL SEPSIS

CSF cell CSF  Uninfected neonates: mean 10 Does not predict

count WBC cells/mm3  ; range up to 20 culture-proven
cells/mm3 meningitis
 CSF CSF Term <100 mg/dL  Elevated in
chemistries protein fungal meningitis

CSF Preterm higher; 70–80% of  Low glucose

glucose serum specific for
glucose bacterial
meningitis
Nelsons Textbook of Pediatrics 21th ed
 Culture based and Non culture based
diagnostics- Investigational :
 CATEGORY OPTIMAL TIMING, APPLICABILITY
PARAMETER VOLUME OF FOR
SPECIMEN, NEONATAL SEPSIS

Immune MHC II  Both decreased in

function TNF-α chorioamnionitis
and sepsis

Neutrophil CD64 Elevated for 24 hr after Cut points between 2.38

markers infection and 3.62
Requires 50 μL blood optimal sensitivity,
Results within hours specificity, and
Investigational NPV for EOS

 Sepsis After 24 hr of life Most useful for NPV

panels/scores and
discontinuation of
antimicrobial
therapy

Nelsons Textbook of Pediatrics 21th ed

 General Approach to Management:
Challenges of Neonatal Sepsis:

☼ Identify neonates with a high likelihood of sepsis

promptly and initiating antimicrobial therapy
☼ Distinguishing “high risk” healthy-appearing
infants or infants with clinical signs who do not
require treatment
☼ Discontinuing antimicrobial therapy once sepsis
is deemed unlikely.

Nelsons Textbook of Pediatrics 21th ed

CONDITION THERAPY Additional
CONSIDERATIONS
Emperical Management
 Early-onset sepsis Ampicillin +  Consider a third-
aminoglycoside generation
10 days for bacteremia; cephalosporin
14 days for GBS (cefotaxime preferred)
and uncomplicated or carbapenem for
meningitis; extend to meningitis.
21-28 days for
complicated infections

Nelsons Textbook of Pediatrics 21th ed

CONDITION THERAPY Additional
CONSIDERATIONS
Emperical Management
 Late- onset sepsis Vancomycin +  Aminoglycoside-based
aminoglycoside regimen preferred to
cephalosporin given
reduced risk of resistance.
Consider cephalosporin if
meningitis
suspected.
Consider a carbapenem if third
generation
cephalosporin recently
received.

Nelsons Textbook of Pediatrics 21th ed

CONDITION THERAPY Additional
CONSIDERATIONS
Non Antimicrobial Treatment Strategies
Recombinant Enhance  Insufficient evidence
G-CSF neutrophil number
Recombinant and function
GM-CSF

IVIG Augments Insufficient evidence

antibody-
dependent
cytotoxicity and
improves
neutrophilic
function

Nelsons Textbook of Pediatrics 21th ed

 PREVENTION
STRATEGIES:
Primary Prevention ☼ Prenatal care
☼ Universal GBS screening
☼ Exclusive Breastfeeding
☼ Proper Infection control
Secondary Prevention ☼ Intrapartum antibiotics
prophylaxis

Tertiary Prevention ☼ Prompt Antibiotic Therapy

Nelsons Textbook of Pediatrics 21th ed

 Intrapartum Antibiotic Prophylaxis to
Prevent Early-Onset GBS Disease :

 IAP Administration
of penicillin or
ampicillin 4 hr
before
parturition

Nelsons Textbook of Pediatrics 21th ed

 INTRAPARTUM GBS INTRAPARTUM GBS
PROPHYLAXIS INDICATED PROPHYLAXIS NOT
INDICATED
☼ Positive GBS screening culture ☼ Cesarean delivery before onset of
during current pregnancy labor or amniotic membrane
☼ Unknown GBS status at the onset rupture, regardless of GBS
of labor colonization status or gestational
☼ Delivery at <37 weeks' gestation age
☼ Amniotic membrane rupture ≥18 ☼ Negative vaginal and rectal GBS
hr screening culture
☼ Intrapartum temperature ≥38.0°C
(100.4°F)

Nelsons Textbook of Pediatrics 21th ed

Breastfeeding for prevention
of Sepsis:

☼ Lactoferrin is a human milk

glycoprotein with a role in innate
immune response
Nelsons Textbook of Pediatrics 21th ed
Hand Hygyiene