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Neonatal sepsis
Maria Victoria B. Pertubal, M.D.
PGY1
I.
II.
III.
IV.
Definition of terms
Epidemiology
Etiology & Pathogenesis
Evaluation and Diagnosis
A.
B.
C.
D.
V.
Clinical Manifestations
Laboratory
Management Algorithm of NB sepsis
Treatment options
Preventive management
Definition of terms
• Neonatal period
– first month / 28 days of life
• Neonatal sepsis
–clinical syndrome in an infant 28 days
of life or younger, manifested by
systemic signs of infection and/or
isolation of a bacterial pathogen from
the blood stream
Definition of terms
• Early-onset vs. Late-onset sepsis
Onset of symptoms
72 hours or ≥7 days of age
Definition of terms
• Intrapartum period
• (NSVD) - from onset of labor / ROM
to delivery
• (CS) - between admission for labor
and cord clamping
How common is it
and
who are at risk?
EPIDEMIOLOGY / RISK FACTORS
• Overall incidence
– 1-5 cases per 1000 live births
• Preterm vs. Full term
• GBS sepsis blacks>whites
• asphyxia, meconium stained AF
• Disrupted skin & mucosal integrity
– (IV catheter)
• Environmental exposure / direct contact
Maternal RISK FACTORS
• Socioeconomic
– SE status, poor prenatal care, maternal substance
abuse
• Infectious :
– Chorioamnionitis, fever (>38° C/100.4° F),
venereal diseases, UTI/bacteriuria, GBS+
• Obstetrical:
– amniocentesis, amnioinfusion, prolonged labor,
PPROM, preterm labor
Incidence of early- and late-onset invasive group B streptococcal
(GBS) disease:
Active Bacterial Core surveillance areas, 1990-2008*, and activities for prevention of GBS disease
•
•
ACOG: American College of Obstetricians and Gynecologists; AAP: American Academy of Pediatrics. * Incidence rates for 2008 are preliminary because the live birth
denominator has not been finalized.
Reproduced from: Verani, JR, McGee, L, Schrag, SJ, et al. Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010. MMWR Recomm
Rep 2010; 59(RR-10):1.
Original data from:
Jordan, HT, Farley, MM, Craig, A, et al. Revisiting the need for vaccine prevention of late-onset neonatal group B streptococcal disease: a multistate, populationbased analysis. Pediatr Infect Dis J 2008; 27:1057.
How is neonatal
infection acquired?
Routes of Infection
Transplacental
Vertical
Horizontal
Bacterial
Viruses > Bacterial
Bacterial >Viral
(nosocomial/
Environmental)
TORCHES
GBS E. Coli
HIV Coxsackie Polio
Adenovirus
EchoEnterovirus
Varicella Parvovirus*
TB Gonorrhea
Listeria Anaerobes
Malaria Lyme
(maternal)
Enterococcus
Chlamydia Gonorrhea
Ureaplasma Mycoplasma
Syphilis
Herpes HIV Hepatitis HPV
Candida
Klebsiella
Staphylococcus –MRSA
Pseudomonas Proteus
Enterobacter
Serratia C dificile
Rotavirus Fungi
Group B Streptococcus aka.
Streptococcus agalactiae
• Serotype distribution — corresponds to the capsular
polysaccharide.
– 9 serotypes: Ia, Ib, and II through VIII; serotype IX has been proposed
• Serotypes Ia, Ib, II, III, and V account for more than 95 percent
of early-onset cases in the United States and more than 90
percent of late-onset cases
• Serotype III – meningitis; high proportion of late-onset
infections
• The distribution of serotypes and surface proteins among GBS
isolates has important implications for the development of
vaccines to prevent GBS disease.
Pathways of ascending or intrapartum infection.
(Figure 103-2 Nelson Pediatrics)
Early onset sepsis is most commonly
due to:
A) Vertical / ascending transmission
B) Horizontal transmission?
How do we RECOGNIZE
and DIAGNOSE sepsis?
INITIAL SIGNS AND SYMPTOMS OF INFECTION
IN NEWBORN INFANTS
GENERAL
Fever, temperature instability
“Not doing well” Poor feeding
Edema
RESPIRATORY SYSTEM
Apnea, dyspnea, Tachypnea,
retractions, Flaring, grunting,
Cyanosis
CARDIOVASCULAR SYSTEM
Pallor; mottling; cold, clammy skin
Tachycardia Hypotension
Bradycardia
RENAL SYSTEM
Oliguria
GASTROINTESTINAL SYSTEM
Abdominal distention
Vomiting,
Diarrhea, Hepatomegaly
HEMATOLOGIC SYSTEM
Jaundice, Splenomegaly, Pallor,
Petechiae, purpura, Bleeding
CENTRAL NERVOUS SYSTEM
Irritability, lethargy, Tremors,
seizures, Hyporeflexia, hypotonia,
Abnormal Moro reflex, Irregular
respirations, Full fontanel, Highpitched cry
Kliegman: Nelson Textbook of Pediatrics, 19th ed.
Copyright © 2011 Saunders, An Imprint of Elsevier
History
• Review of the pregnancy, labor, and delivery
– Duration
– Mode of delivery
– Newborn condition at delivery (APGAR & BW)
Maternal-Neonatal Risk factors for
sepsis
•
•
•
•
•
Intrapartum maternal temperature ≥38ºC (100.4ºF)
Delivery at <37 weeks gestation
Chorioamnionitis
Five minute Apgar score ≤6 Evidence of fetal distress
Membrane rupture ≥18 hours
– risk of proven sepsis increases 10 fold to 1 %
• Maternal GBS colonization
– Use of Intrapartum antibiotic prophylaxis (IAP)
differential diagnosis
•
•
•
•
other systemic bacterial infections,
neonatal hypoxia,
in-born errors of metabolism,
neonatal respiratory distress.
What LABORATORY exams
will you request?
Laboratory
BLOOD TESTS:
• Blood culture establishes a definitive diagnosis
• Other blood tests:
– CBC – within 24h
– Immature to total PMN ratio (I:T ratio)
• Inflammatory markers:
– CRP, cytokines, procalcitonin (released by parenchymal
cells in response to bacterial toxins
Laboratory
Urine :
• Culture – for all infants older than 3 days of age
– If done on younger infants, it may only reflect high grade
bacteremia rather than isolated UTI
Other ancillary
• Chest X-ray
– If with clinical signs of RDS
• Cultures from other potential foci of infection
– Secretions/pus
Laboratory
BLOOD TESTS:
• Blood culture establishes a definitive diagnosis
• Other blood tests:
– CBC – within 24h
– Immature to total PMN ratio (I:T ratio)
• Inflammatory markers:
– CRP, cytokines, procalcitonin (released by parenchymal
cells in response to bacterial toxins
Laboratory
CSF analysis:
• should be considered in all neonates; clinical signs of
meningitis can be lacking in young infants
• Send for :
– Culture
– gram stain,
– cell count
– protein
– glucose
Bacterial meningitis
CSF findings
Culture
Gram
stain
WBC
protein
glucose
Can be
negative
in 30-38%
of
20 percent of
neonates with
cultureconfirmed
bacterial
meningitis
have negative
>20 to 30
cells/
microL
preterm
>150
mg/dL
preterm
<20
mg/dL
Gram-stained
(1.1 mmol/L)
>1000
*greater
count in Gneg
meningitis
term
>100
mg/dL in
term
<30
mg/dL
(1.7 mmol/L)
What is our
Management GOAL?
Be HIGHLY suspicious of all
potential neonatal sepsis cases
Algorithm for secondary prevention of early-onset group B streptococcal
(GBS) disease among newborns
•Full diagnostic evaluation :
blood culture,
complete blood count (CBC) w/
differential and platelet counts,
chest radiograph (if respiratory
abnormalities are present),
lumbar puncture (if patient is stable
enough to tolerate procedure and
sepsis is suspected).
† Antibiotic therapy - directed toward
the most common causes of neonatal
sepsis,
intravenous ampicillin for GBS
and coverage for other
organisms (including Escherichia
coli and other gram-negative
pathogens) -must take into
account local antibiotic
resistance patterns.
§ Consultation with obstetric
providers is important to
determine the level of clinical
suspicion for chorioamnionitis.
Chorioamnionitis is diagnosed
clinically and some of the signs
are nonspecific.
¶ Limited evaluation
blood culture (at birth)
CBC with differential and
platelets (at birth and/or at 6–12
hours of life).
** See indications for
intrapartum GBS
prophylaxis.
†† If signs of sepsis develop:
Conduct full diagnostic
evaluation
 Initiate antibiotic therapy
§§ observation may occur at
home
If ≥37 weeks’ gestation, after
24 hours if other discharge
criteria have been met
 access to medical care is
readily available,
person who is able to comply
fully for home instruction will be
present.
If any of these conditions is
not met, the infant should be
observed in the hospital for at
least 48 hours and until
discharge criteria are achieved.
For LOW RISK
¶¶ Some experts
recommend a CBC with
differential and platelets at
age 6–12 hours.
¶ Limited evaluation
blood culture (at birth)
CBC with differential and
platelets (at birth and/or at
6–12 hours of life).
What is the value of
antenatal screening for GBS?
Year 2002
• Universal screening at 35--37 weeks'
gestation for maternal GBS colonization and
use of intrapartum antibiotic prophylaxis has
resulted in substantial reductions in the
burden of early-onset GBS disease among
newborns.
Incidence of early- and late-onset invasive group B streptococcal
(GBS) disease:
Active Bacterial Core surveillance areas, 1990-2008*, and activities for prevention of GBS disease
•
•
ACOG: American College of Obstetricians and Gynecologists; AAP: American Academy of Pediatrics. * Incidence rates for 2008 are preliminary because the live birth
denominator has not been finalized.
Reproduced from: Verani, JR, McGee, L, Schrag, SJ, et al. Prevention of perinatal group B streptococcal disease--revised guidelines from CDC, 2010. MMWR Recomm
Rep 2010; 59(RR-10):1.
Original data from:
Jordan, HT, Farley, MM, Craig, A, et al. Revisiting the need for vaccine prevention of late-onset neonatal group B streptococcal disease: a multistate, populationbased analysis. Pediatr Infect Dis J 2008; 27:1057.
Recommended regimens for intrapartum antibiotic prophylaxis for
prevention of early-onset group B streptococcal (GBS) disease*
Algorithm for screening for GBS colonization and use of
intrapartum prophylaxis for women with preterm* labor (PTL)
SUMMARY
• Neonatal sepsis is is classified by the infant's age into
early-onset sepsis (≤3 to 7 days) and late-onset
sepsis (>3 or 7 to 28 days).
• Group B Streptococcus (GBS) and Escherichia coli are
the most common bacteria causing neonatal sepsis
• Risk factors for neonatal sepsis in term and late
preterm infants include intrapartum maternal
temperature ≥38ºC (100.4ºF), chorioamnionitis, five
minute Apgar score ≤6, maternal GBS colonization,
and membrane rupture ≥18 hours.
SUMMARY
• Evaluation include a prenatal history, delivery, complete
physical examination, and a laboratory evaluation that
minimally includes a blood culture.
• overall incidence of early onset GBS disease in NB
substantially decreased over the last decade with universal
screening for maternal GBS and use of IAP
• Initial empirical antibiotic therapy for suspected GBS disease
should include broad coverage for the most likely pathogens
(Ampicillin/Vancomycin-Gentamicin/Cefotaxime)
any deviation from an infant's usual
pattern of activity or feeding should be
regarded as a possible indication of
systemic bacterial infection
Nizet, V, Klein, JO. Bacterial sepsis and meningitis. In: Infectious diseases of the Fetus and
Newborn Infant, 7th ed, Remington JS et al (Ed), Elsevier Saunders, Philadelphia 2010.
p.222.
SUMMARY
Routine hand hygiene by health care
professionals is the best way to prevent health
care-associated spread of GBS infection
Salamat po 