NEONATAL

SEPSIS
DR. CRISBERT I. CUALTEROS
 Definition

Neonatal sepsis is a clinical syndrome

of systemic illness accompanied by
bacteremia occurring in the first month
of life.
 Incidence

 primary sepsis is 1 - 8 per 1000 live

births
 as high as 13-27 per 1000 for infants
weighing <1500 g
 mortality rate is high (13-25%)
 higher rates are seen in premature
infants and in those with early fulminant
disease
 Pathophysiology

3 Clinical Situations :

C. Early- Onset Disease

E. Late - Onset Disease

G. Nosocomial Sepsis
 Pathophysiology
A.Early-Onset Disease
 first 5 – 7 days of life
 is usually a multi-system fulminant illness
with prominent respiratory symptoms
 Typically, the infant has acquired the
organism during the intrapartum period from
the maternal genital tract…
 Pathophysiology
In this situation, the infant is colonized with the
pathogens in the perinatal period..
Several infectious agents….
 Treponemes
 Viruses
 Listeria
 Candida
 can be acquired transplacentally via
hematogenous routes
 Pathophysiology

 acquisition of other organisms is associated

with the birth process.
 with rupture of membranes, vaginal flora or
various bacterial pathogens may ascend to
reach the amniotic fluid and the fetus 
Chorioamnionitis develops, leading to fetal
colonization and infection.
 aspiration of infected amniotic fluid by the fetus
or neonate may play a role in resultant
respiratory symptoms.
 Pathophysiology
 presence of vernix or meconium impairs the
natural bacteriostatic properties of amniotic
fluid.

Finally, the infant may be exposed to vaginal

flora as it passes through the birth canal.

PRIMARY SITES of colonization :

n nasopharynx
n oropharynx
n conjuctiva
n umbilical cord
 Pathophysiology

Trauma to these mucosal surfaces  infection

Early-onset disease is characterized by a sudden

onset and fulminant course that can
progress rapidly to septic shock with a high
mortality rate.
 Pathophysiology

2.Late - Onset Disease

 as early as 5 days of age but common 1st
week of life
 although these infants may have a history of
obstetric complications  less frequent than
early-onset disease

 infants usually have an identifiable focus, most

often meningitis in addition to sepsis
 Pathophysiology

bacteria responsible for late-onset sepsis

and meningitis include those :
1. acquired after birth from the maternal
genital tract
2. acquired after birth from human contact
or from contaminated equipment
 Pathophysiology

 The reasons for delay in development in clinical

illness, the predilection for central nervous
system (CNS) disease, and the less severe
systemic and cardiorespiratory symptoms are
unclear.
 Pathophysiology

C. Nosocomial Sepsis
 occurs in high-risk newborn infants
They are related to :
n to the underlying illness and debilitation of the
infant
n the flora in the NICU environment
n invasive monitoring and other techniques used
in neonatal intensive care
 Pathophysiology

Breaks in the natural barrier function of the

skin and intestine allow this opportunistic
organism to overwhelm the neonate

Infants, especially premature infants, have an

increased susceptibility to infection 
underlying illnesses and immature defenses
that are less efficient at localizing and clearing
bacterial invasion.
 Causative Organisms

Agents associated with primary sepsis are usually

from the vaginal flora :
 group B streptococci (GBS)  most
common
 Gram-negative enteric organisms
especially E. coli
 Listeria monocytogenes
 Staphylococcus
 other streptococci (including the
enterococci)
 anaerobes
 Haemophilus influenzae
 Causative Organisms

The flora causing nosocomial sepsis vary in

each nursery…
The Agents are :
 Staphylococci (especially Staph.
epidermidis)
 gram-negative rods (including
Pseudomonas, Klebsiella, Serratia, and
Proteus and fungal organisms predominate
 Clinical Presentation

 initial diagnosis of sepsis is, by necessity, a

clinical one because it is imperative to begin
treatment before the results of culture are
available

 Clinical S/Sx of sepsis are nonspecific, and the

differential diagnosis is broad
 Clinical Presentation

 Temperature irregularity. Hypo- or

hyperthermia (greater heat output required by
the incubator or radiant warmer to maintain a
neutral thermal environment or frequent
adjustments of the infant servo control probe).
 Change in behavior. Lethargy, irritability, or
change in tone.
 Skin. Poor peripheral perfusion, cyanosis,
mottling, pallor, petechiae, rashes, sclerema,
or jaundice.
 Clinical Presentation

1. Feeding problems. Feeding intolerance,

vomiting, diarrhea (watery loose stool), or
abdominal distention with or without visible
bowel loops.
2. Cardiopulmonary. Tachypnea, respiratory
distress (grunting, flaring, and retractions),
apnea within the first 24 h of birth or of new
onset (especially after 1 week of age),
tachycardia, or hypotension, which tends to be
late sign.
3. Metabolic. Hypo- or hyperglycemia or
metabolic acidosis.
 Risk Factors :

 Prematurity and low birth weight

 Rupture of membranes. Premature or
prolonged (>18 h) rupture of membranes
 Maternal peripartum fever (≥38 ˚C/100.4
˚F) or infection. Chorioamnionitis, urinary
tract infection (UTI), vaginal colonization
with E..coli. and other obstetric
complications.
 Amniotic fluid problems. Meconium-
stained or foul-smelling, cloudy amniotic
fluid.
 Risk Factors :

1. Resuscitation at birth. Infants who had

fetal distress, were born by traumatic
delivery or were severely depressed at birth
and required intubation and resuscitation.
2. Multiple gestation.
3. Invasive procedures. Invasive monitoring
and respiratory or metabolic support.
4. Infants with galactosemia (predisposition
to E. coli sepsis), immune defects, or
asplenia.
 Risk factors
1. Iron therapy (iron added to serum in vitro
enhances the growth of many organisms).
2. Other factors.
 males are 4 times more affected than
females
 more common in black than in white
infants
 Variations in immune function may play a
role
 NICU staff and family members are often
vectors for the spread of microorganisms,
primarily as a result of improper hand
 Diagnosis

A . Laboratory Studies
1. Cultures
 Blood and other normally sterile body fluids
should be obtained for culture.. *Positive
bacterial cultures will confirm the diagnosis of
sepsis
Computer-assisted, automated blood culture
systems  shown to identify up to 94% of all
microorganisms by 48 hr of incubation
 Diagnosis
Cultures …
 Results may vary because of a number of
factors, including maternal antibiotics
administered before birth, organisms that are
difficult to grow and isolate (ie., anaerobes),
and sampling error with small sample
volumes (the optimal amount is 1-2
mL/sample).
 Therefore, in many clinical situations, infants
are treated for “presumed” sepsis despite
negative cultures, with apparent clinical
benefit.
 Diagnosis
2. Gram's stain of various fluids
 helpful for the study of CSF
 Gram-stained smears and cultures of
amniotic fluid or of material obtained by
gastric aspiration
Adjunctive laboratory tests
E. WBC count with differential
 Neutropenia may be a significant finding
with an ominous prognosis when
associated with sepsis
 Serial white blood cell counts several hours
apart may be helpful in establishing a trend.
 Diagnosis

A. Platelet count
 decreased platelet count is usually a
late*sign and is very nonspecific
C. Acute-phase reactants
 complex multifunctional group comprising
complement components, coagulation
proteins, protease inhibitors, C-reactive
protein (CRP), and others that rise in
concentration in the serum in response to
tissue injury.
 Diagnosis

 remain elevated with ongoing

inflammation, but with resolution they
decline rapidly due to a short half-life of 4
—7 h
 CRP demonstrates high sensitivity and
negative predictive value
III. The standard ESR
 may be elevated but usually not until
well into the illness
 Diagnosis

I. CRP
 increases the most in the presence of
inflammation caused by infection or tissue
injury
 highest concentrations in patients with
bacterial infections, whereas moderate
elevations chronic inflammatory conditions
 onset of inflammation, CRP synthesis
increases within 4—6 h, doubling every 8
h, and peaks at about 36—50 h
 Diagnosis

I. Cytokines IL-1ß, IL-6, IL-8, and TNF

 major mediators of the systemic response
to infection
 Studies have shown that combined use of
IL-8 and CRP as part of the workup for
bacterial infection reduces unnecessary
antibiotic treatment
IV. Surface neutrophil
 CD11 has been shown to be an
excellent marker of early infection that
correlates well with CRP but peaks earlier.
 Diagnosis

I. Miscellaneous tests.
 Abnormal values for bilirubin,
glucose, and sodium may, in the proper
clinical situation, provide supportive
evidence for sepsis.
 Diagnosis

Radiologic Studies
 Chest X-ray film in case with respiratory
symptoms
 Urinary Tract Imaging. Imaging with renal
ultrasound examination, renal scan, or
voiding cystourethrography - should be part
of the evaluation when UTI accompanies
sepsis. Sterile urine for culture must be
obtained by either a suprapubic or catheterized
specimen
 Diagnosis

1. Other studies. Examination of the

placenta and fetal membranes may
disclose evidence of chorioamnionitis
and thus an increased potential for
neonatal infection
 Differential Diagnosis

 Respiratory distress syndrome (RDS)

 Metabolic diseases
 Hematologic disease
 CNS disease
 Cardiac disease
 other infectious processes (ie. TORCH
infections)
 Management

 GBS prophylaxis
 major pathogen in the late 1960s and currently
remains the most common cause of early-
onset sepsis
 10 to 30% of pregnant women are colonized
with GBS in the vaginal or rectal area
 incidence of infection has been estimated at
0.8—5.5/1000 live births (unchanged for the
past three decades).
 Case fatality rate ranges from 5—15%
 Management
Consensus guidelines regarding
management of GBS were published by
CDC in 1996 and were supported by
American Association of Pediatrics and
American College of Obstetricians and
Gynecologists. The guidelines
recommended one of two approaches:
b) the prenatal screening approach
(screening all pregnant women for GBS
infection at 35—37 weeks gestation and
treatment of those women with positive
cultures)
 Management

a) identifying women who present with risk

factors treating them during labor
 To ensure appropriate treatment for neonates
born to mothers who receive antibiotics for
fever and presumed choriomanionitis, as well
as for those born to mothers who receive
intrapartum antibiotic prophylaxis (IAP)
because of GBS colonization, they are
clinically using an algorithm in their hospital
based on AAP guidelines, with some
alterations based on clinical experiences.
 Signs & Symptoms of
sepsis in infant
Maternal Maternal
no temp <102 temp
yes
F >102F
Full dx Gestational
eval. age S/sx of sepsis in
Emperic Tx infant

no yes
<37 wks >37
wks

Limited eval.
Limited eval No evaluation Observe 48H
Observe 48H No therapy If sepsis
If sepsis Observe min, 48 suspected, full Full eval. w/
suspected, full H eval & empiric empiric Rx
eval & empiric Rx
Rx
 Management

1. Standard precautions
 have been mandated by the U.S.
Occupational Safety and Health
Administration (OSHA) and apply to
blood, semen, vaginal secretions, wound
exudate and CSF and amniotic fluids
 caution to prevent injuries when using or
disposing of needles or other sharp
instruments
 Management

1. Initial therapy
 Treatment is most often begun before a
definite causative agent is identified.
 Penicillin, usually Ampicillin, plus an
Aminoglycoside such as Gentamicin.

 In nosocomial sepsis  flora of the NICU

must be considered: however, generally,
staphylococcal coverage with
 Vancomycin plus either an
Aminoglycoside or a 3rd Gen. ephalosporin
 Management

1. Continuing therapy is based on culture

and sensitivity results, clinical course,
and other serial lab studies (eg., CRP).

Monitoring for antibiotic toxicity is

important as well as monitoring levels of
aminoglycosides and vancomycin.
 Management

When GBS is documented as the

causative agent Penicillin is the DOC
Aminoglycoside is often given as well
because of documented synergism
 Complications and Supportive
Therapy
 RESPIRATORY
 Ensure adequate oxygenation with blood
gas monitoring and initiate O2 therapy or
ventilator support if needed
3. CARDIOVASCULAR
 Support BP and perfusion to prevent
shock. Use volume expanders, 10-20 mL/kg
(normal saline, albumin, and blood), and
monitor the intake of fluids and output of urine.
 Pressor agents such as dopamine or
dobutamine may be needed.
 Complications and Supportive
Therapy
1. Hematologic
b. DIC
  one may observe generalized bleeding at
puncture sites, the gastrointestinal tract, or
CNS sites. In the skin, large vessel
thrombosis  gangrene.

 Lab. parameters consistent with DIC include :

thrombocytopenia, inc. PT, and inc. Partial
Thromboplastin Time
Complications and Supportive
Therapy
Measures include treating the underlying
disease; fresh-frozen plasma, 10 mL/kg;
vitamin K; platelet infusion; and possible
exchange transfusion.
 Complications and Supportive
Therapy
a) Neutropenia
 Multiple factors contribute to the increased
susceptibility of neonates to infection, including
developmental quantitative and qualitative
neutrophil defects.
 Studies suggest  use of recombinant human
granulocyte colony-stimulating factor (rhG-
CSF) or recombinant human granulocyte-
macrophage colony-stimulating factor (rhGM-
CSF) can partially counterbalance these
defects and reduce morbidity and mortality.
 Complications and Supportive
Therapy
1. CNS
 Implement seizure control measures 
Phenobarbital, 20 mg/kg loading dose
 monitor for the syndrome of inappropriate
antidiuretic hormone (SIADH) :
iv. decreased urine output,
v. hyponatremia,
vi. decreased serum osmolarity, and
vii. increased urine specific gravity and osmolarity
 Complications and Supportive
Therapy
1. METABOLIC
 Monitor for and treat hypo- or
hyperglycemia.  Metabolic acidosis
may accompany sepsis and is treated
with bicarbonate and fluid replacement.
 Future Developments

 Immunotherapy progress continues in the

development of various hyperimmune
globulins, monoclonal antibodies to the specific
pathogens causing neonatal sepsis
 They may prove to be significant adjuvants to
the routine use of antibiotics for the treatment
of sepsis
 Research is also ongoing into blocking some
of the body's own inflammatory mediators that
result in significant tissue injury, including
endotoxin inhibitors, cytokine inhibitors, nitric
oxide synthetase inhibitors, and neutrophil
adhesion inhibitors.
………………………….Thank you