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NEONATAL INFECTION

Julniar M Tasli
Herman Bermawi
Afifa Ramadanti

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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

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- 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

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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
Β 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

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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 β 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 11
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 neonate’s 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 World’s 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 Late Onset
• < 72 hours of age • > 72 hours of age
• Acquired around birth • Acquired from the
environment
• Vertical transmission • Nosocomial or
from mother to baby 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  38ºC


± 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 24
Bacterial Pathogens Responsible for Sepsis in
Developing Countries

• Early onset sepsis • Late onset sepsis


– Gram negative bacilli – Gram negative bacilli
• E.coli • Pseudomonas
• Klebsiella • Klebsiella
– Enterococcus – Staph aureus
– Group B streptococcus – Coagulase negative
staphylococci

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Organisms associated with sepsis in
developing countries (Stoll BJ Clin Perinatol 1997)

% Gram % Group B
negative 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, > 34, 000/L
• Absolute neutrophil count: <1500/L
• Immature to total neutrophil ratio > 0.2

bandform

neutrophil 38
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 43


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 baby’s body ( cord, skin, eye,
mouth )
- Can spread quickly through the newborn’s 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
baby’s mouth 4 x / day
- Gentian violet 0,5 %

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TERIMAKASIH

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