NEONATAL INFECTION

Julniar M Tasli Herman Bermawi

NEONATAL 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 approxmattely 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

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 11 - Candida albicans, HIV

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 24

Bacterial Pathogens Responsible for Sepsis in Developing Countries Early onset sepsis
Gram negative bacilli
E.coli Klebsiella

Late onset sepsis

Gram negative bacilli
Pseudomonas Klebsiella

Enterococcus Group B streptococcus

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 Sub - Saharan Africa Americas / Caribbean

46- 85 % 16 68 % 43- 71 %

0- 5% 0- 30% 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 Any of these signs: Grunting Suspect Serious Bulging fontanelle Bacterial Infection Convulsions 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 : - Ampicillin 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 600.000 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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