Neonatal

Sepsis
Prof. Dr. Saad S Al Ani
Senior Pediatric Consultant
Head of Pediatric Department
Khorfakkan Hospital
Sharjah ,UAE
anahbaghdad@gmail.com
 Neonatal
Sepsis

Neonatal sepsis is an invasive infection,

usually bacterial, occurring during the
neonatal period
Signs are multiple, nonspecific
Diagnosis is clinical and based on culture results

11/23/2019 Neonatal Sepsis Prof. Dr. Saad S Al Ani 2

 Neonatal
Sepsis

Neonatal sepsis occurs in 0.5 to 8.0/1000 births.

• The highest rates occur in
 Low-birth-weight (LBW) infants
 Infants with depressed function at birth as manifested
by a low Apgar score
 Infants with maternal perinatal risk factors
 Males
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 Neonatal
Sepsis

Categories of neonatal sepsis

• Neonatal sepsis may be categorized as:
 Early onset (day of life 0-3)
 Late onset (day of life 4 or later)

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 Neonatal
Sepsis

Early-onset neonatal sepsis

• Early-onset sepsis is associated with acquisition of
microorganisms from the mother.
• Infection can occur via hematogenous, transplacental
spread from an infected mother or, more commonly,
via ascending infection from the cervix.

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 Neonatal
Sepsis

• Early-onset sepsis is 10 to 20 times more

likely to occur in premature, very low
birthweight infants

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 Neonatal
Sepsis

The microorganisms most commonly associated

with early-onset infection include the following :
• Group B Streptococcus (GBS)
• Escherichia coli
• Coagulase-negative Staphylococcus
• Haemophilus influenzae
• Listeria monocytogenes

Klinger G, Levy I, Sirota L, et al, for the Israel Neonatal Network. Epidemiology and risk factors for early onset sepsis among very-low-birthweight
infants. Am J Obstet Gynecol. 2009 Jul. 201 (1):38.e1-6.

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 Neonatal
Sepsis

With early-onset sepsis

• 85% present within 24 hours (median age of onset
6 hours)
• 5% present at 24-48 hours
• Smaller percentage present within 48-72 hours.
Onset is most rapid in premature neonates.

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 Neonatal
Sepsis

Late-onset neonatal sepsis

• Late-onset sepsis occurs at 4-90 days of life and is
acquired from the environment.

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 Neonatal
Sepsis

Organisms that have been implicated in late-onset sepsis

include the following:
• Coagulase-negative
Staphylococcus
• Staphylococcus aureus
• E coli
• Klebsiella
• Pseudomonas • Serratia
• Enterobacter • Acinetobacter
• Candida • Anaerobes
• GBS • Many additional
less-common organisms

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 Neonatal
Sepsis

In early-onset sepsis:
Pneumonia is more common

In late-onset sepsis
Meningitis and Bacteremia are more common

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 Neonatal
Sepsis

Pathophysiology
• Currently, GBS and E coli continue to be the
most commonly identified microorganisms
associated with neonatal infection

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 Neonatal
Sepsis

In neonatal sepsis additional organisms that have

been identified include:
• Coagulase-negative Staphylococcus
epidermidis
• L monocytogenes,
• Chlamydia pneumoniae
• H influenzae
• Enterobacter aerogenes,
• species of Bacteroides and Clostridium

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 Neonatal
Sepsis

Early onset: Risk factors

• Maternal perinatal and obstetric factors that increase
risk :
 Premature rupture of membranes (PROM) occurring
≥ 18 h before birth
 Maternal chorioamnionitis
 Colonization with GBS
 Preterm delivery
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 Neonatal
Sepsis

• Hematogenous and transplacental

dissemination of maternal infection occurs in
the transmission of certain:
 viral (e.g., rubella, cytomegalovirus)
 protozoal (e.g., Toxoplasma gondii)
 treponemal (e.g., Treponema pallidum)
pathogens
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 Neonatal
Sepsis

Late onset : risk factors

• The most important risk factor in late-onset sepsis
is preterm delivery. Others include:
 Prolonged use of intravascular  Exposure to antibiotics
catheters (which selects resistant bacterial strains)
 Associated illnesses  Prolonged hospitalization
 Contaminated equipment or IV or enteral solutions

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 Neonatal
Sepsis

Symptoms and Signs

• Early signs of neonatal sepsis are frequently nonspecific
and subtle and do not distinguish among organisms
Common early signs include:
Diminished spontaneous activity Apnea
Less vigorous sucking Bradycardia
Anorexia Temperature instability (hypothermia or
hyperthermia)

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 Neonatal
Sepsis

• Fever is present in only 10 to 15% but, when

sustained (e.g. > 1 h), generally indicates infection
Other symptoms and signs include:
Respiratory distress Vomiting
Neurologic findings Diarrhea
(e.g., seizures, jitteriness)
Jaundice Abdominal distention
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 Neonatal
Sepsis

Diagnosis

•High index of suspicion

•Blood, CSF, and sometimes urine culture

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 Neonatal
Sepsis

Neonates with clinical signs of sepsis

Should have :
• CBC, Differential • Urine culture
with smear (not necessary for evaluation of early-onset
sepsis)
• Blood culture • lumbar puncture (LP), if clinically
feasible, As soon as possible.

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 Neonatal
Sepsis

Neonates with clinical signs of sepsis (Cont.)

• Neonates with respiratory symptoms require chest x-ray.
• Diagnosis is confirmed by isolation of a pathogen in
culture.
• Other tests may have abnormal results but are not
necessarily diagnostic.
• Infants should be given broad-spectrum empiric
antimicrobial therapy
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 Neonatal
Sepsis

Other tests for infection and inflammation

Acute-phase reactants
• Quantitative C-reactive protein.
-The sensitivity is higher if measured after 6 to 8 h of life.
-Two normal values obtained between 8 h and 24 h after birth and then
24 h later have a negative predictive value of 99.7%.
• Procalcitonin
- Appears more sensitive than C-reactive protein, it is less specific
Pontrelli G, De Crescenzo F, Buzzetti R, et al: Accuracy of serum procalcitonin for the diagnosis of sepsis in neonates and children with systemic
inflammatory syndrome: A meta-analysis. BMC Infect Dis 17(1):302, 2017.
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 Neonatal
Sepsis
Prognosis
The fatality rate is 2 to 4 times higher in LBW infants than in
full-term infants
The overall mortality rate of:
- Early-onset sepsis is 3 to 40%
(that of early-onset GBS infection is 2 to 10%)
- Late-onset sepsis is 2 to 20%
(that of late-onset GBS is about 2%)
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 Neonatal
Sepsis

Treatment
•Antibiotic therapy
•Supportive therapy

11/23/2019 Neonatal Sepsis Prof. Dr. Saad S Al Ani 24

 Neonatal
Sepsis

Treatment (Cont.)

Because sepsis may manifest with nonspecific

clinical signs and its effects may be devastating,
rapid empiric antibiotic therapy is recommended

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 Neonatal
Sepsis
Treatment (Cont.)
Drugs are later adjusted according to sensitivities and the
site of infection.

If no source of infection is identified clinically, the infant

appears well, and cultures are negative, antibiotics can be
stopped after 48 h (up to 72 h in small preterm infants).
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 Neonatal
Sepsis

Treatment (Cont.)
General supportive measures, including
respiratory and hemodynamic management,
are combined with antibiotic treatment.

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 Antimicrobials
• Early-onset sepsis, initial therapy should
include ampicillin plus an aminoglycoside
• Cefotaxime may be added to or substituted
for the aminoglycoside if meningitis
caused by a gram-negative organism is
suspected
• Antibiotics may be changed as soon as an
organism is identified.
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 Antimicrobials (Cont.)
• late-onset sepsis should also receive
therapy with ampicillin plus gentamicin
or ampicillin plus cefotaxime
• If gram-negative meningitis is suspected,
ampicillin, cefotaxime, and an
aminoglycoside may be used

11/23/2019 Neonatal Sepsis Prof. Dr. Saad S Al Ani 29

 Antimicrobials (Cont.)
In late-onset hospital-acquired sepsis:
 Initial therapy should include Vancomycin
(active against methicillin-resistant S. aureus)
plus an Aminoglycoside.
 If P. aeruginosa is prevalent in the nursery,
Ceftazidime, Cefepime, or Piperacillin/
Tazobactam may be used in addition to, or
instead of, an aminoglycoside depending on
local susceptibilities.
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 Antimicrobials (Cont.)
• For neonates previously treated with
a full 7- to 14-day aminoglycoside
course who need retreatment, a
different aminoglycoside or a 3rd-
generation cephalosporin should be
considered.

11/23/2019 Neonatal Sepsis Prof. Dr. Saad S Al Ani 31

 Antimicrobials (Cont.)
• If coagulase-negative staphylococci are
suspected (e.g., an indwelling catheter
has been in place for > 72 h) or are
isolated from blood or other normally
sterile fluid and considered a pathogen:
 Initial therapy for late-onset sepsis
should include vancomycin.
 If the organism is sensitive to nafcillin ,
cefazolin should replace vancomycin.
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 Other treatment ???
• Exchange transfusions
• Fresh frozen plasma
• Granulocyte transfusions
• Recombinant colony-stimulating
factors (granulocyte colony-stimulating
factor [G-CSF] and granulocyte-
macrophage colony-stimulating factor
[GM-CSF])
• IV immune globulin
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 Prevention
• Neonates who appear well may be at
risk of group B streptococcus infection
• If there is:
 Neither chorioamnionitis
 Nor indication for group B
streptococcus prophylaxis
NO testing OR treatment is indicated.
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 Prevention (Cont.)
• If chorioamnionitis is present or strongly
suspected:
- Preterm and term neonates should:
*have a blood culture at birth and
*begin empiric broad-spectrum
antibiotic therapy.

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 Prevention (Cont.)
-Testing should also include:
* WBC count and differential
* C-reactive protein at 6 to 12 h of life.
-Further management depends on the
clinical course and results of the
laboratory tests.

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 Prevention (Cont.)
• If maternal group B streptococcus
prophylaxis was indicated and given
appropriately (i.e., penicillin, ampicillin,
or cefazolin given IV for ≥ 4 h):
- Infants should be:
* Observed in the hospital for 48 h
* Testing and treatment are done only if
symptoms develop.

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 Prevention (Cont.)

• If adequate group B streptococcus prophylaxis

was not given:
- Infants are observed in the hospital for 48 h
without antimicrobial therapy.

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 Prevention (Cont.)
- If membranes ruptured ≥ 18 h before birth or
gestational age is < 37 wk.:
*blood culture, CBC with differential, and
perhaps a C- reactive protein level is
recommended at birth and/or at 6 to 12 h
of life.
-The clinical course and results of the laboratory
evaluation guide management.

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 Neonatal
Sepsis

Summary:

1.Neonatal sepsis can be early onset (≤ 3

days of birth) or late onset (after 3 days).

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 Neonatal
Sepsis

Summary:

2.Early-onset sepsis usually results from

organisms acquired intrapartum, and
symptoms appear within 6 h of birth.

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 Neonatal
Sepsis

Summary:

3.Late-onset sepsis is usually acquired from the

environment and is more likely in preterm
infants, particularly those with prolonged
hospitalization, use of IV catheters, or both.
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 Neonatal
Sepsis

Summary:

4.Early signs are frequently nonspecific

and subtle, and fever is present in only
10 to 15% of neonates.

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 Neonatal
Sepsis

Summary:

5.Do blood and CSF cultures and, for

late-onset sepsis, also do urine culture

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 Neonatal
Sepsis
Summary:
6.Treat early-onset sepsis initially with
ampicillin plus gentamicin (and/or
cefotaxime if gram-negative meningitis is
suspected ), narrowed to organism-specific
drugs as soon as possible.
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 References
• van den Hoogen A, Gerards LJ, Verboon-Maciolek MA, Fleer A, Krediet TG. Long-
term trends in the epidemiology of neonatal sepsis and antibiotic susceptibility of
causative agents. Neonatology. 2010. 97 (1):22-8
• Berardi A, Rossi C, Spada C, et al, for the GBS Prevention Working Group of
Emilia-Romagna. Strategies for preventing early-onset sepsis and for managing
neonates at-risk: wide variability across six Western countries. J Matern Fetal
Neonatal Med. 2019 Sep. 32 (18):3102-8
• https://www.msdmanuals.com/professional/pediatrics/infections-in-
neonates/neonatal-sepsis
• https://emedicine.medscape.com/article/978352
• Escobar GJ, Puopolo KM, Wi S, et al: Stratification of risk of early-onset sepsis in
newborns ≥ 34 weeks' gestation. Pediatrics 133(1):30–36, 2014.
• Pontrelli G, De Crescenzo F, Buzzetti R, et al: Accuracy of serum procalcitonin for
the diagnosis of sepsis in neonates and children with systemic inflammatory
syndrome: A meta-analysis. BMC Infect Dis 17(1):302, 2017

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 Good Job, Pal!

11/23/2019 Neonatal Sepsis Prof. Dr. Saad S Al Ani 47