NEONATAL INFECTION

Julniar M TasliHerman Bermawi

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

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Module: Neonatal Sepsis-Session 1

Infection is an ever present problem in the newbornInfection is not only common, but also present in many different ways involving almost any system in the bodyThe 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 specificSpecific Immunity :- is mediate through lymphocytes- B cells- T cells Neonatal lymphocytes owing to a reduced production of cytokine*

stimulate cells plasma cells produce Ig Ig M produce at 15 week gestationIg G produce at 20 week gestationAt birth : Ig minimal & very lowOnly Ig can cross the placentaMaternal Ig G birth fall in monthsT cells : - produced in fetal bone marrow migrates to the thymusThere are 3 function :- Produce citokine- Supplies the immune respon of other cells- Kill target cells*

Non specific immunityCellular : phagocytic white cells ( neutrophile and monocytes) ingest bacteria chemical chemotactic (complement and leukotrienes)

site of inflamationHumoral : - complement - interferon - lactoferin - lysozyme

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Susceptibility of the neonate to infectionI. Endogenous factors1. Low levels of IgG : IgM & Ig A2. Premature infant fail to receive IgG from mother3. Phagocytic action is less afective4. 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 flora2. Breaches of the skin barrier entry of bacteria to the baby3. 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*

Origins of infections :In utero (congenitally)IntrapartumPostnatally

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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 haemolyticus, streptococcus - histeria monocytogenes, haemophilus influenza pneumococcus3. Protozoa : malaria *

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*

AquiredIn the nursery (nasochomial) :Bacteria : coagulate_negative staphylococcus, staph aureus, group B streptococcus coliform, salmonella, shigella, anaerobic bacteria, pseudomonas.2. Viruses : coxsachie, rotavirus, RSV, adenovirus, echovirus3. Fungal : candida albicans, candida parapsilosis.*

Risk Factor Intrapartum InfectionMathernal factor : 1. Maternal factors of sepsis ( feber, WBC high, tenderuterus, 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

*Neonatal Sepsis: Learning ObjectivesDefine neonatal sepsisRecognize the importance of neonatal sepsis as a major cause of infant mortality and morbidity in IndonesiaRecognize infants who are at increased risk of developing sepsisObtain a neonates history in order to identify risk factors and symptoms of sepsisPerform a physical examination of a neonate to recognize signs of sepsis.Suspect the bacterial pathogens responsible for causing sepsisUse laboratory tests appropriately to diagnose sepsis, including the use of cultures to identify the suspected organismDecide on the appropriate specific and supportive treatment.

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Definition of Neonatal SepsisDisease of infants who are younger than 1 month of ageare clinically ill and have positive blood cultures (or positive cultures from other normally sterile sites)

*Incidence of Neonatal SepsisAsia: 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 DeathsWorld Health Organization. State of the Worlds Newborns 2001 Infections 32% Asphyxia 29% Complications of prematurity 24% Congenital anomalies 10% Other 5%

* Case fatality due to neonatal sepsis is 12 to 68% in developing countries Why is the case fatality so high?

*Neonatal sepsis- morbidity in survivorsBrain damage due to meningitis, septic shock, or hypoxemiaOther organ damage - lung, liver, limbs, joints

*Neonatal SepsisEarly Onset < 72 hours of ageAcquired around birth

Vertical transmission from mother to baby

Late Onset> 72 hours of ageAcquired from the environmentNosocomial 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

*Early Onset Sepsis - risk factorsProlonged rupture of membranes >18 hMaternal chorioamnionitis Foul smelling amniotic fluidHandling by untrained midwifeMaternal urinary tract infectionPremature labor

*ChorioamnionitisMaternal fever during labor 38C uterine tenderness leucocytosis fetal tachycardia High risk of neonatal sepsis

Module: Neonatal Sepsis-Session 1*Late Onset Sepsis -risk factorsPrematurity/ LBWIn hospital Invasive procedures- ventilator, IV lines, central lines, urine catheter, chest tubeContact with infectious disease - doctors, nurses, babies with infections,Not fed maternal breast milkPOOR HYGIENE in NICU

Module: Neonatal Sepsis-Session 1

*Bacterial Pathogens Responsible for Sepsis in Developing Countries Early onset sepsisGram negative bacilliE.coli KlebsiellaEnterococcusGroup B streptococcus

Late onset sepsisGram negative bacilliPseudomonasKlebsiellaStaph aureusCoagulase negative staphylococci

*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%

*Neonatal Meningitis

Organisms: Gram negative in 1st week Strep pneumoniae > 1 week

*Diagnosis of Neonatal SepsisClinical signs and symptomsLaboratory testsculture of bacterial pathogenother laboratory indicators

*Diagnosis of Neonatal Sepsis - clinical signs and symptomsClinical Signs: early signs non- specific, may be subtleRespiratory distress- 90%Apnea Temperature instability- temp more common Decreased activity IrritabilityPoor feeding Abdominal distensionHypotension, shock, purpura, seizures- late signs

*Clinical Criteria for Severe Bacterial InfectionWHO Handbook Integrated Management of Childhood Illnesses, 2000Respiratory rate > 60 breaths per minuteSevere chest indrawingNasal flaringGruntingBulging fontanelleConvulsionsPus draining from earRedness around umbilicus extending to the skinTemperature > 37.7 C (or feels hot) or < 35.5C (or feels cold)Lethargic or unconsciousReduced movementsNot able to feedNot attaching to the breastNo sucking at all

Any of these signs:Suspect Serious Bacterial Infection

*Laboratory TestsCultures to identify bacterial pathogenblood, csf, urine, otherHematological testsWBC countPlatelet countErythrocyte Sedimentation Rate (ESR)Other testsC- reactive protein

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Blood Culture

Gold standard for diagnosis of bacteremiaAdd at least 0.5 -1.0 ml blood obtained by sterile venipuncture to culture bottleMost bacteria grow within 24 to 48 hoursTalk to your microbiology lab every day- do not wait for the written report.

*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 laborBaby may have received antibiotics before blood cultureVolume of blood taken for blood culture too small

*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

*Normal CSF values in newborn

WBC count: 0 - 32 wbc / mm3Glucose concentration : 24 - 119 mg / dlProtein concentration: 20 - 170 mg / dl

*Urine cultureUseful in neonates with late onset sepsisSterile specimen obtained by sterile catheterization or by suprapubic bladder aspiration.

*Other cultures

Surface culturesEndotracheal culturesGastric aspirate culturesPoor Sensitivity and Specificity

*Abnormal white blood cell count Total WBC count < 5000 /L, > 25, 000/LAbsolute neutrophil count: 0.2Immature to mature neutrophil ratio > 0.2bandformneutrophil

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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, asphyxiaBetter Predictors of SepsisTotal WBC count < 5000 /L Absolute neutrophil count:

*C- Reactive ProteinAcute phase reactant: synthesized in 6 to 12 hoursNormal: < 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%

*Micro-ESRMeasures ESR in vertically placed capillary tube in 1 hourNormal 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/ hrPoor sensitivity and specificityFalse positive tests with hemolysisFalse negative tests with DIC

*If WBC count, CRP, micro- ESR are not reliable, why do we do these tests?

Module: Neonatal Sepsis-Session 1*Severe Clinical Symptoms Blood culture (CSF culture, if possible)Start antibiotics immediately

Module: Neonatal Sepsis-Session 1

*Risk factors for sepsis present but baby appears wellWBC count / CRP may be useful in excluding sepsisBaby still needs close observation for at least 48 hoursIf mother had chorioamnionitis, perform blood culture CSF testing and start antibiotics.

*Treatment: antibiotics

Choice: tailored to organisms prevalent in region USA: Early onset sepsis: Group B strep / E.ColiAmpicillin and Gentamicin Indonesia?

*First line therapy in facility setting (WHO 2003)

Ampicillin 50 mg/ kg every 12 hours in 1st week of lifeevery 8 hours from 2- 4 weeksPLUSGentamicin once daily.

*Suspected Staphylococcal Infection

Use Cloxacillin or flucloxacillin instead of Ampicillin.Plus gentamicin

*Baby not responding to first line antibiotics or suspected hospital acquired infection3rd generation cephalosporincefotaximeceftazidime

For nosocomial infection : vancomycin plus gentamicin/ amikacin or ceftazidime

*Duration of antibiotic treatment Septicemia Gram negative septicemia: 14 daysGroup B Strep septicemia: 10-14 days

Repeat blood culture within 24 - 48 hours of beginning treatment to document clearance of organism.

*Duration of antibiotic treatmentMeningitisGram negative meningitis: 21 days minimum Group B Strep meningitis: 14 - 21 days

Document negative culture within 24 - 48 hours of beginning treatmentConsider neuroimaging studies

*Prevention of Nosocomial InfectionHand washingEarly feedingMaternal breast milkDecrease use of broad spectrum antibioticsDecreased use of invasive proceduresProper sterilization procedures

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Localized Infections

Module: Neonatal Sepsis-Session 1

*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 sepsisQuick & correct treatment of localized infections may prevent sepsis and possible death

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

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 )*

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 % *

*TERIMAKASIH

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