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NEONATAL INFECTION

Julniar M Tasli
Herman Bermawi

INFECTION
Objective :
- Student must be able to understand the important of
neonatal infection
- Student must be able to recognize risk factor which
predispose new born infant to infection
- Student must be able to diagnose neonatal infection
- Student must be able to implement infection control
to prevent infection

- Infection is an ever present problem in the


newborn
- Infection is not only common, but also
present in many different ways involving
almost any system in the body
- The Incidence f infections is approximattely
5 per 1000 live birth and more common in
premature infants

The Immature Imune System


The immature imune system develops from early in fetal life,
but is not functionally fully integrated until 1 year age.
Immunity :
- specific
- non specific

Specific Immunity :
- is mediate through lymphocytes
- B cells
- T cells
Neonatal lymphocytes owing to a reduced production of
cytokine
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stimulate
cells
plasma cells
produce Ig
- Ig M produce at 15 week gestation
- Ig G produce at 20 week gestation
- At birth : Ig minimal & very low
- Only Ig can cross the placenta
- Maternal Ig G birth
fall in months
T cells : - produced in fetal bone marrow
migrates to
the thymus
There are 3 function :
- Produce citokine
- Supplies the immune respon of other cells
- Kill target cells
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Non specific immunity


- Cellular : phagocytic white cells ( neutrophile and
monocytes) ingest bacteria
chemical chemotactic
(complement and leukotrienes)
site of inflamation
Humoral :

- complement
- interferon
- lactoferin
- lysozyme
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Susceptibility of the neonate to infection


I. Endogenous factors
1. Low levels of IgG : IgM & Ig A
2. Premature infant fail to receive IgG from
mother
3. Phagocytic action is less afective
4. Humoral activity is impaired ( complement are
low )
5. IUGR infant also appear to be more susceptible
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II. Endogenous Factors:


1. Baby is bacteriologically steril
little
competition existing bacterial flora
2. Breaches of the skin barrier
entry of
bacteria to the baby
3. Drugs may impair immune function
(corticosteroids)
4. Fat emulsion (intralipid impair the fagocytic
function of white cells)
5. Hiperbillirubinemia reduces immune function in
several differet ways
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Origins of infections :
1. In utero (congenitally)
2. Intrapartum
3. Postnatally

Congenitally (intrauterine)
I. Transplacentally
- First semester : TORCH (infection)
- Toxoplasmosis
- Others e.g coxsaches B virus, varicella, HIV
- Rubella
- CMV
- Herpes simplex type 2
- Second semester : syphilis
- Third semester :
1. Viral : Varicella, Hepatitis B, coxsachoe B, HIV,
echovirus.
2. Bacterial : - group B haemolyticus, streptococcus
- histeria monocytogenes, haemophilus influenza
pneumococcus
3. Protozoa : malaria
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II. Ascending infections : after rupture of membranes


Pathogens : Esch.coli, Klebsiella, pneumonas
proteus, Enterococcus fecalis, group B
streptococcus beta haemolyticus,
group A streptococcus,
staphylococcus.
Intrapartum
- PROM intrapartum infection
- Pathogens : - Herpes simples, neiserria GO,
Hepatitis B, Grup B streptococcus
- Chlamydia trachomatis
- Candida albicans, HIV
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Aquired
In the nursery (nasochomial) :
1. Bacteria : coagulate_negative staphylococcus,
staph aureus, group B streptococcus
coliform, salmonella, shigella,
anaerobic bacteria, pseudomonas.
2. Viruses : coxsachie, rotavirus, RSV, adenovirus,
echovirus
3. Fungal : candida albicans, candida parapsilosis.

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Risk Factor Intrapartum Infection


Mathernal factor :
1. Maternal factors of sepsis ( feber, WBC high, tender
uterus, purulent liquor )
2. Prolonged rupture of membrane
3. Duration of labour ( >12 hours )
4. Fregment vaginal examinations
5. The present of fertal distress or birth asphyxia

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Neonatal Sepsis

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Neonatal Sepsis: Learning Objectives

Define neonatal sepsis


Recognize the importance of neonatal sepsis as a major cause of infant
mortality and morbidity in Indonesia
Recognize infants who are at increased risk of developing sepsis
Obtain a neonates history in order to identify risk factors and symptoms
of sepsis
Perform a physical examination of a neonate to recognize signs of
sepsis.
Suspect the bacterial pathogens responsible for causing sepsis
Use laboratory tests appropriately to diagnose sepsis, including the use
of cultures to identify the suspected organism
Decide on the appropriate specific and supportive treatment.
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Definition of Neonatal Sepsis


Disease of infants who are younger than 1
month of age
are clinically ill and
have positive blood cultures (or positive
cultures from other normally sterile sites)

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Incidence of Neonatal Sepsis


Asia: 7.1 to 38 per 1000 live births
Africa: 6.5 - 23 per 1000 live births
South America: 3.5 to 8.9 per 1000 live births
United States: 6 - 9 per 1000 live births
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Direct Causes of Neonatal Deaths


World Health Organization.
State of the Worlds Newborns 2001

Infections 32%
Asphyxia 29%
Complications of prematurity 24%
Congenital anomalies 10%
Other 5%
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Case fatality due to


neonatal sepsis is
12 to 68%
in developing
countries
Why is the case
fatality so high?
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Neonatal sepsis- morbidity in survivors


Brain damage due to
meningitis, septic shock,
or hypoxemia
Other organ damage lung, liver, limbs, joints

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Neonatal Sepsis
Early Onset
< 72 hours of age
Acquired around birth
Vertical transmission
from mother to baby

Late Onset
> 72 hours of age
Acquired from the
environment
Nosocomial or
hospital acquired

Distinction between Early onset sepsis and Late onset sepsis


not clear in developing countries:
baby born at home and brought to the hospital at 3 days of age
baby referred from another hospital
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Early Onset Sepsis - risk factors


Prolonged rupture of membranes >18 h
Maternal chorioamnionitis
Foul smelling amniotic fluid
Handling by untrained midwife
Maternal urinary tract infection
Premature labor
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Chorioamnionitis
Maternal fever during labor 38C
uterine tenderness
leucocytosis
fetal tachycardia
High risk of neonatal sepsis

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Late Onset Sepsis risk factors


Prematurity/ LBW
In hospital
Invasive procedures- ventilator, IV lines, central lines,
urine catheter, chest tube
Contact with infectious disease - doctors, nurses,
babies with infections,
Not fed maternal breast milk
POOR HYGIENE in NICU

Module: Neonatal Sepsis-Session 1

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Bacterial Pathogens Responsible for Sepsis in


Developing Countries
Early onset sepsis
Gram negative bacilli
E.coli
Klebsiella

Enterococcus
Group B streptococcus

Late onset sepsis


Gram negative bacilli
Pseudomonas
Klebsiella

Staph aureus
Coagulase negative
staphylococci

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Organisms associated with sepsis in


developing countries (Stoll BJ Clin Perinatol 1997)
% Gram
negative

% Group B
Streptococcus

India / Pakistan/ SE Asia

46- 85 %

0- 5%

Sub - Saharan Africa

16 68 %

0- 30%

Americas / Caribbean

43- 71 %

2- 35%

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Neonatal Meningitis

Organisms: Gram negative in 1st week


Strep pneumoniae > 1 week
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Diagnosis of Neonatal Sepsis


Clinical signs and symptoms
Laboratory tests
culture of bacterial pathogen
other laboratory indicators

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Diagnosis of Neonatal Sepsis clinical signs and symptoms


Clinical Signs: early signs non- specific, may be subtle
Respiratory distress- 90%
Apnea
Temperature instability- temp more common
Decreased activity
Irritability
Poor feeding
Abdominal distension
Hypotension, shock, purpura, seizures- late signs
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Clinical Criteria for Severe Bacterial Infection


WHO Handbook Integrated Management of Childhood Illnesses, 2000

Respiratory rate > 60 breaths per minute


Severe chest indrawing
Nasal flaring
Grunting
Any of these signs:
Bulging fontanelle
Suspect Serious
Convulsions
Bacterial Infection
Pus draining from ear
Redness around umbilicus extending to the skin
Temperature > 37.7 C (or feels hot) or < 35.5C (or feels cold)
Lethargic or unconscious
Reduced movements
Not able to feed
Not attaching to the breast
No sucking at all

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Laboratory Tests
Cultures to identify bacterial pathogen
blood, csf, urine, other

Hematological tests
WBC count
Platelet count
Erythrocyte Sedimentation Rate (ESR)

Other tests
C- reactive protein
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Blood Culture

Gold standard for diagnosis of bacteremia


Add at least 0.5 -1.0 ml blood obtained by sterile
venipuncture to culture bottle
Most bacteria grow within 24 to 48 hours
Talk to your microbiology lab every day- do not
wait for the written report.
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Baby has risk factors and clinical signs of sepsis


but
blood culture is negative

Blood cultures are positive in only 2 to 25%


of babies with clinically suspected sepsis.
Mother may have received antibiotics in labor
Baby may have received antibiotics before blood
culture
Volume of blood taken for blood culture too small
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Lumbar Puncture

Possibility of meningitis 1-10%


Babies with meningitis may not have
specific symptoms
15% of babies with meningitis will have
negative blood cultures
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Normal CSF values in newborn


WBC count: 0 - 32 wbc / mm3
Glucose concentration : 24 - 119 mg / dl
Protein concentration: 20 - 170 mg / dl

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Urine culture
Useful in neonates
with late onset sepsis
Sterile specimen
obtained by sterile
catheterization or by
suprapubic bladder
aspiration.

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Other cultures
Surface cultures
Endotracheal cultures
Gastric aspirate cultures
Poor Sensitivity and Specificity

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Abnormal white blood cell count

Total WBC count < 5000 /L, > 25, 000/L


Absolute neutrophil count: <1500/L
Immature to total neutrophil ratio > 0.2
Immature to mature neutrophil ratio > 0.2
bandform

neutrophil

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There is No Substitute for Clinical Acumen


WBC counts may be normal in babies with sepsis
High WBC counts at birth not very specific- may be due
to stress, asphyxia
Better Predictors of Sepsis
Total WBC count < 5000 /L
Absolute neutrophil count: <1500/L
Abnormal IT ratio at 12 to 24 hours of age

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C- Reactive Protein
Acute phase reactant: synthesized in 6 to 12 hours
Normal: < 1.6 mg/ dl on day 1, then < 1.0 mg/ dl
Falsely elevated with asphyxia, meconium
aspiration, PROM
May not be positive early (only 60% sensitivity)
Repeated tests more useful (up to 84% sensitivity)
Negative Predictive value: 90%
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Micro-ESR
Measures ESR in vertically placed capillary tube in
1 hour
Normal values increase with age (due to increasing
fibrinogen and falling hematocrit)
Normal: day of life plus 3 mm/ hr, up to a maximum
of 14 mm/ hr
Poor sensitivity and specificity
False positive tests with hemolysis
False negative tests with DIC
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If WBC count, CRP, micro- ESR are not reliable,


why do we do these tests?

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Severe Clinical Symptoms


Blood culture
(CSF culture, if possible)

Start antibiotics immediately

Module: Neonatal Sepsis-Session 1

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Risk factors for sepsis present but


baby appears well
WBC count / CRP may be
useful in excluding sepsis
Baby still needs close
observation for at least 48
hours
If mother had
chorioamnionitis, perform
blood culture CSF testing
and start antibiotics.
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Treatment: antibiotics
Choice: tailored to organisms prevalent in region
USA:
Early onset sepsis: Group B strep / E.Coli
Ampicillin and Gentamicin
Indonesia?

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First line therapy in facility setting


(WHO 2003)

Ampicillin 50 mg/ kg
every 12 hours in 1st week of life
every 8 hours from 2- 4 weeks

PLUS
Gentamicin once daily.

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Suspected Staphylococcal Infection

Use Cloxacillin or flucloxacillin instead of


Ampicillin.
Plus gentamicin
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Baby not responding to first line antibiotics


or suspected hospital acquired infection
3rd generation cephalosporin
cefotaxime
ceftazidime

For nosocomial infection :


vancomycin plus gentamicin/ amikacin or
ceftazidime

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Duration of antibiotic treatment


Septicemia
Gram negative septicemia: 14 days
Group B Strep septicemia: 10-14 days
Repeat blood culture within 24 - 48 hours of
beginning treatment to document clearance
of organism.

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Duration of antibiotic treatment


Meningitis
Gram negative meningitis: 21 days
minimum
Group B Strep meningitis: 14 - 21 days
Document negative culture within 24 - 48
hours of beginning treatment
Consider neuroimaging studies
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Prevention of Nosocomial Infection

Hand washing
Early feeding
Maternal breast milk
Decrease use of broad spectrum antibiotics
Decreased use of invasive procedures
Proper sterilization procedures
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Localized Infections

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Localized Infections
-

An infections is a certain part of the babys body ( cord, skin, eye,


mouth )
Can spread quickly through the newborns small body and causes
sepsis
Quick & correct treatment of localized infections may prevent sepsis
and possible death

I. Umbilical cord infections


- infection around the umbilical cord in the umbilicus
- can easily pass through the cord sepsis is and death if treatment is
delayed or not given
- Treatment : - wash the cord and stump and apply gention violet
0,5 %
- amphisillin & gentamycin
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II. Skin Infection


- Skin pustules
- Localized or serious skin infection
- Th/ : Localized : - wash the skin and remove all dirty and pus
- apply gentian violet 0,5 %
Serious infections : - Cloxacillin 50mg/kg IM
III. Eye infection
- Etiologi : - Chemical : AgNO3 ( no treatment )
- Bacteria : - clamydia
- G.O
- Treatment : - Topical erytromycin for clamydia
- Ceftrixone 50 mg/kgBB ( max 125 mg/kg ) single
doze for G.O )

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IV. Oral Trush


- White patches on the mucous membrane or tongue
(candida albican)
- Treatment : - nystatin 100.000 U/ml : 1 2 ml into the
babys mouth 4 x / day
- Gentian violet 0,5 %

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TERIMAKASIH

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