الرحيم الرحمن الله الرحيم بسم الرحمن الله بسمNeonatal SepsisNeonatal Sepsis

BKTH BKTH

Department of PediatricsDepartment of Pediatrics

Dr. magdah & Dr. Amal UniteDr. magdah & Dr. Amal Unite

April 2010April 2010

By:By:

Dr.Dr. Mohamed Eisam Elhag Mohamed Eisam Elhag MahmoudMahmoud

MBBS, Alneelain University MBBS, Alneelain University Faculty of MedicineFaculty of Medicine

Note: Dr. Mohammed Isam Al-Hajj does not have any financial relationships to disclose nor will he discuss any non-approved drug or device uses.

Babies and Babies and Bacteria...Bacteria...

What will I learn?

Pathology * Causes * Symptoms * Diagnosis * Treatments

DefinitionDefinition

Neonatal sepsisNeonatal sepsis is a clinical is a clinical syndrome of systemic illness syndrome of systemic illness accompanied by bacteremia accompanied by bacteremia occurring in the first month of life.occurring in the first month of life.

EpidemiologyEpidemiology IncidenceIncidence:: 1-8 cases per 1000 live 1-8 cases per 1000 live

birthsbirths Mortality:Mortality: 50% 50%

– 13-69% 13-69% world wideworld wide– 13-15% of all neonatal deaths (US) (813-15% of all neonatal deaths (US) (8thth

cause)cause) Morbidity:Morbidity: Meningitis occurs in one occurs in one

third of sepsis casesthird of sepsis cases SexSex: males more: males more

– Culture proven 2/1000 (3-8% of infants Culture proven 2/1000 (3-8% of infants evaluated for sepsis); 10-20/1000 VLBWevaluated for sepsis); 10-20/1000 VLBW

AgeAge : : premature infants premature infants (1000-2000 g : 8-9/1000(1000-2000 g : 8-9/1000 <1000 g : 26/1000)<1000 g : 26/1000)

PathophysiologyPathophysiology

Neonate immune deficiencyNeonate immune deficiency neutrophil, monocyte, macrophage, T cell, neutrophil, monocyte, macrophage, T cell,

immunoglobulin, complementimmunoglobulin, complement physical and chemical barriers physical and chemical barriers Because of the interdependence of the Because of the interdependence of the

immune response, these individual immune response, these individual deficiencies of the various components deficiencies of the various components of immune activityof immune activity in the neonate in the neonate cospire to cospire to create a hazardous situation create a hazardous situation for the neonate exposed to infectious for the neonate exposed to infectious threatsthreats!!!!

ClassificationClassification

Early onset sepsis (EOS):Early onset sepsis (EOS):– bacteria acquired before and during bacteria acquired before and during

deliverydelivery– 5-7/1000 live birth5-7/1000 live birth

Late onset sepsis (LOS):Late onset sepsis (LOS): – bacteria acquired after delivery bacteria acquired after delivery

(Nosocomial or community) (Nosocomial or community) – 20% of VLBW infants20% of VLBW infants

Early onset sepsisEarly onset sepsisLate onset sepsisLate onset sepsis

PathogensPathogensGroup B StreptococcusGroup B Streptococcus

E. coliE. coli

Haemophilus Haemophilus influenzaeinfluenzae

ListeriaListeria

Virus, STDVirus, STD

Coagulase negative Coagulase negative staphylococcusstaphylococcus

Staphy. aureusStaphy. aureus

E. coliE. coli

KlebsiellaKlebsiella

PseudomonasPseudomonas

EnterobacterEnterobacter

Baby in riskBaby in riskTerm, near-term babyTerm, near-term babyPreterm babyPreterm baby

Predisposing FactorsPredisposing FactorsGeneral Host FactorsGeneral Host Factors Prematurity (OR 25 if < 1,000 gms)Prematurity (OR 25 if < 1,000 gms) Race – GBS sepsis blacks>whites (x4)Race – GBS sepsis blacks>whites (x4) Sex – sepsis & meningitis more common Sex – sepsis & meningitis more common

in males, esp. gram negative infectionsin males, esp. gram negative infections Birth asphyxia, meconium staining, stressBirth asphyxia, meconium staining, stress Breaks in skin & mucous membrane Breaks in skin & mucous membrane

integrity integrity (e.g. omphalocoele, meningomyelocoele)(e.g. omphalocoele, meningomyelocoele)

Environmental exposureEnvironmental exposure Procedures Procedures (e.g. lines, ET-tubes)(e.g. lines, ET-tubes)

Predisposing FactorsPredisposing Factors Maternal/Obstetrical FactorsMaternal/Obstetrical Factors

GeneralGeneral – – socioeconomic status, poor prenatal socioeconomic status, poor prenatal care, vaginal flora, maternal substance abuse, care, vaginal flora, maternal substance abuse, known exposures, known exposures, prematurityprematurity, twins, twins

Maternal infectionsMaternal infections – –chorioamnionitis (1-10% of chorioamnionitis (1-10% of pregnancies), fever (>38° C/100.4° F), sustained pregnancies), fever (>38° C/100.4° F), sustained fetal tachycardia, venereal diseases, fetal tachycardia, venereal diseases, UTI/bacteriuria, foul smelling lochia, GBS+ (OR 204), UTI/bacteriuria, foul smelling lochia, GBS+ (OR 204), other infectionsother infections

Obstetrical manipulationObstetrical manipulation – – amniocentesis, amniocentesis, amnioinfusion, prolonged labor, fetal monitoring, amnioinfusion, prolonged labor, fetal monitoring, digital exams, previa/abruption?digital exams, previa/abruption?

Premature & Prolonged ROM, preterm laborPremature & Prolonged ROM, preterm labor

pathogens can enter a neonate’s pathogens can enter a neonate’s body in many ways !body in many ways !

PrenatalMaternal Substance Abuse

Premature Rupture of Membranes (>18 Hours)

Maternal Infection

PerinatalMicrobial Colonization at Birth

Maternal Infection

Vaginal Exam of Mother

PostnatalInvasive Catheters

Endotracheal Intubation

Exposure to Nosocomial Microorganisms

Predisposing FactorsPredisposing Factors

Overall sepsis rateOverall sepsis rate 2/10002/1000

Maternal FeverMaternal Fever 4/10004/1000

PROMPROM 10-13/100010-13/1000

Fever & PROMFever & PROM 87/100087/1000

Preterm Labor/PROMPreterm Labor/PROM

Prematurity Prematurity (~10%) 15-25% due to (~10%) 15-25% due to maternal infectionmaternal infection

>18-24h term; >12-18h preterm>18-24h term; >12-18h preterm Bacterial infectionBacterial infection

synthesis of PGsynthesis of PG– Macrophage TNF/IL stimulate PG Macrophage TNF/IL stimulate PG

synthesis, cytokine releasesynthesis, cytokine release****– Release of collagenase & elastase Release of collagenase & elastase

ROMROM + Amniotic fluid cultures 15% + Amniotic fluid cultures 15% (with (with

intact membranes)intact membranes)

SSEPSISEPSISORGANISMSORGANISMS (all babies) (all babies) Group B strep Group B strep (most common G+) (most common G+)

4141%%

Other strep Other strep 23%23%

Coliforms Coliforms (E. coli most common G-)(E. coli most common G-) 17%17%

Staph aureusStaph aureus 4% 4%

ListeriaListeria 2%2%

Nosocomial infectionsNosocomial infections CandidaCandida

Note: Note: 73% G+ and 27% G-73% G+ and 27% G-

SSEPSISEPSISORGANISMSORGANISMS (VLBW) (VLBW) Group B strep Group B strep (most common G+)(most common G+) 12%12%

Other strep Other strep 9% 9%

Coliforms Coliforms ((E. coli E. coli most common G-)most common G-) 41%41%

CONSCONS 15%15%

ListeriaListeria 2%2%

Nosocomial infectionsNosocomial infections CandidaCandida 2%2%

Note: 45% G+ and 53% G-Note: 45% G+ and 53% G-Source: Stoll et al Ped Inf Dis 2005, 24:635Source: Stoll et al Ped Inf Dis 2005, 24:635

Routes of InfectionRoutes of Infection

Transplacental/HematogenousTransplacental/Hematogenous Ascending/Birth CanalAscending/Birth Canal AspirationAspiration Device Associated InfectionDevice Associated Infection NosocomialNosocomial EpidemicEpidemic

Transplacental/Transplacental/HematogenousHematogenous Organisms (Not just “TORCHS”)Organisms (Not just “TORCHS”)

Toxoplasmosis Toxoplasmosis ParvovirusParvovirusRubella Rubella GonorrheaGonorrheaCytomegalovirus Cytomegalovirus MumpsMumpsHerpes* Herpes* TBTBSyphilis Syphilis VaricellaVaricellaAcute VirusesAcute Viruses HIVHIV

CoxsackieCoxsackie PolioPolioAdenovirusAdenovirus GBSGBSEchoEcho MalariaMalariaEnterovirusEnterovirus LymeLyme

Ascending/Birth CanalAscending/Birth Canal

Organisms - GI/GU flora, Organisms - GI/GU flora, Cervical/BloodCervical/Blood

E. Coli E. Coli HerpesHerpesGBSGBS CandidaCandida

ChlamydiaChlamydia HIVHIV

UreaplasmaUreaplasma MycoplasmaMycoplasma

ListeriaListeria HepatitisHepatitis

EnterococcusEnterococcus AnaerobesAnaerobes

GonorrheaGonorrhea SyphilisSyphilis

HPVHPV

NosocomialNosocomial Organisms – Organisms –

Skin Flora, Equipment/Environment Skin Flora, Equipment/Environment Staphylococcus – Coagulase neg & posStaphylococcus – Coagulase neg & posMRSAMRSAKlebsiellaKlebsiellaPseudomonasPseudomonasProteusProteusEnterobacterEnterobacterSerratiaSerratiaRotavirusRotavirusClostridium – C dificileClostridium – C dificileFungiFungi

Coagulase-Negative Coagulase-Negative StaphylococciStaphylococci commonest cause of commonest cause of

Nosocomial bacteremiaNosocomial bacteremia– ventriculoperitoneal shunt ventriculoperitoneal shunt

infection infection – Endocarditis with umbilical linesEndocarditis with umbilical lines

S. epidermidisS. epidermidis, , S. haemolyticusS. haemolyticus, , S. hominisS. hominis, , S. saprophyticusS. saprophyticus

InfectionInfection

TimingTiming

OnsetOnset– Early OnsetEarly Onset 1 1stst 24 hrs 24 hrs 85 %85 %

24-48 hrs24-48 hrs5%5%

– Late OnsetLate Onset 7-90 days 7-90 days

Clinical PresentationClinical Presentation

initial diagnosis of sepsis is, by initial diagnosis of sepsis is, by necessity, a clinical one because it is necessity, a clinical one because it is imperative imperative to begin treatment to begin treatment beforebefore the results of culture are available the results of culture are available

Clinical S/Sx of sepsis are Clinical S/Sx of sepsis are nonspecificnonspecific, ,

and the differential diagnosis is broad and the differential diagnosis is broad

Non-specific/CommonNon-specific/Common1.1. Temperature irregularityTemperature irregularity.. Hypo- or Hypo- or

hyperthermia (greater heat output hyperthermia (greater heat output required by the incubator or radiant required by the incubator or radiant warmer to maintain a neutral thermal warmer to maintain a neutral thermal environment or frequent adjustments of environment or frequent adjustments of the infant servo control probe).the infant servo control probe).

2.2. Change in behaviorChange in behavior.. Lethargy, Lethargy, irritability (23%), or change in tone.irritability (23%), or change in tone.

3.3. SkinSkin.. Poor peripheral perfusion, cyanosis, Poor peripheral perfusion, cyanosis, mottling, pallor, petechiae, rashes, mottling, pallor, petechiae, rashes, sclerema, or jaundice.sclerema, or jaundice.

4.4. SkinSkin.. Poor peripheral perfusion, Poor peripheral perfusion, cyanosis, mottling, pallor, petechiae, cyanosis, mottling, pallor, petechiae, rashes, sclerema, or jaundice.rashes, sclerema, or jaundice.

5.5. Feeding problemsFeeding problems. . Feeding Feeding intolerance, vomiting, diarrhea intolerance, vomiting, diarrhea (watery loose stool), or abdominal (watery loose stool), or abdominal distention with or without visible distention with or without visible bowel loops/ ileus,.bowel loops/ ileus,.

5 -Cardiopulmonary5 -Cardiopulmonary.. Tachypnea, Tachypnea, respiratory distress (90%)(grunting, respiratory distress (90%)(grunting, flaring, and retractions), apnea within flaring, and retractions), apnea within the first 24 h of birth or of new onset the first 24 h of birth or of new onset (especially after 1 week of age), (especially after 1 week of age), tachycardia, or hypotension (5%),, tachycardia, or hypotension (5%),, which tends to be late sign.which tends to be late sign.

6-6-MetabolicMetabolic.. Hypo- or hyperglycemia Hypo- or hyperglycemia or metabolic acidosis.or metabolic acidosis.

SymptomsSymptoms Less commonLess common

– SeizuresSeizures– DICDIC– PetechiaePetechiae– HepatosplenomegalyHepatosplenomegaly– ScleremaSclerema

Meningitis symptomsMeningitis symptoms– Irritability, lethargy, poorly responsiveIrritability, lethargy, poorly responsive– Changes in muscle tone, etc.Changes in muscle tone, etc.

EvaluationEvaluation Non-specific Non-specific

– CBC/diff, platelets – ANC, I/T ratioCBC/diff, platelets – ANC, I/T ratio– RadiographsRadiographs– CRPCRP– Fluid analysis – LP, Fluid analysis – LP, U/A U/A – Glucose, lytes, gasesGlucose, lytes, gases

Specific – Cultures, stainsSpecific – Cultures, stains Other – immunoassays, PCR, DNA Other – immunoassays, PCR, DNA

microarraymicroarray

Results “Trigger Results “Trigger Points” Points” CBCCBC

– WBC <5.0, abs neutro <WBC <5.0, abs neutro <1,7501,750, bands >2.0, bands >2.0– I/T ratio > I/T ratio > 0.2*0.2*– Platelets < 100,000Platelets < 100,000

CRP > 1.0 mg/dlCRP > 1.0 mg/dl CSF > 20 WBC’s with few or no RBC’s CSF > 20 WBC’s with few or no RBC’s Radiographs: infiltrates on CXR, ileus Radiographs: infiltrates on CXR, ileus

on KUB, periosteal elevation, etc.on KUB, periosteal elevation, etc.

Lumbar punctureLumbar puncture(CSF)(CSF)

Indications Indications -- Sepsis is considered primary diagnosis -- Sepsis is considered primary diagnosis -- Blood culture positive -- Blood culture positive -- Neurologic signs or symptoms-- Neurologic signs or symptoms Specific Tests Specific Tests -- CSF examination-- CSF examination-- CSF Culture -- CSF Culture --CSF antigens--CSF antigens

pneumonia pneumonia CXR CXR Meningitis Meningitis CT, head ultrasound CT, head ultrasound

Late onset sepsis:Late onset sepsis:

In addition to the above considerIn addition to the above consider

Blood culture taken through central line. Blood culture taken through central line. Urine by suprapubic aspirate by suprapubic aspirate

[preferable] or catheter. [preferable] or catheter.

False negative Blood False negative Blood CultureCulture

Maternal antibioticsMaternal antibiotics Small blood sampleSmall blood sample Bacteria load, timing of Bacteria load, timing of

sampling sampling

DDifferential ifferential DDiagnosis iagnosis

1.1. Respiratory distress syndrome Respiratory distress syndrome (RDS)(RDS)

2.2. Metabolic diseasesMetabolic diseases

3.3. Hematologic diseaseHematologic disease

4.4. CNS diseaseCNS disease

5.5. Cardiac diseaseCardiac disease

6.6. other infectious processes (ie. other infectious processes (ie. TORCH infections)TORCH infections)

TreatmentTreatmentFirst five days.First five days. After first five days.After first five days.

Start Start ampicillinampicillin and and gentamicingentamicin for for

1.all VLBW neonates 1.all VLBW neonates andand

2. any infant who2. any infant who

--Appears septic or is sicker than--Appears septic or is sicker than

would be usually anticipated.would be usually anticipated.

--Has any vascular catheter --Has any vascular catheter

Start Start amoxycillinamoxycillin and and

cefoxitincefoxitin in all other babies in all other babies

Start Start vancomycinvancomycin and and amikacinamikacin in all babies in all babies

(Almost all Coag negative Staph is (Almost all Coag negative Staph is sensitive to Amikacin but resistant sensitive to Amikacin but resistant to gentamicin. )to gentamicin. )

((FlucloxacillinFlucloxacillin being used at being used at present because of an increased present because of an increased number of Staph aureus isolates number of Staph aureus isolates within the unit )within the unit )

Add Add amoxycillinamoxycillin if specific if specific cover for Enterococci, Strep cover for Enterococci, Strep fecaelis [suspected NEC], Listeria fecaelis [suspected NEC], Listeria or Group B Strep is needed. or Group B Strep is needed.

TreatmentTreatment

Ampicillin and Amikacin for Ampicillin and Amikacin for empiric treatment of EONSempiric treatment of EONS

Oxacillin and amikacin for empiric Oxacillin and amikacin for empiric treatment of LONS reducetreatment of LONS reduce

TreatmentTreatment PreventionPrevention – vaccines, GBS prophylaxis, – vaccines, GBS prophylaxis,

HAND-WASHINGHAND-WASHING SupportiveSupportive – respiratory, metabolic, – respiratory, metabolic,

thermal,nutrition(Encourage breast milk thermal,nutrition(Encourage breast milk provide immunologic protectionprovide immunologic protection)), monitoring , monitoring drug levels/toxicitydrug levels/toxicity

SpecificSpecific – antimicrobials, immune – antimicrobials, immune globulinsglobulins

Non-specificNon-specific – IVIG, NO inhibitors & – IVIG, NO inhibitors & inflammatory mediatorsinflammatory mediators

Neonatal Sepsis:Neonatal Sepsis:the special case ofthe special case of

Group B Strep Group B Strep SepsisSepsis

RISK FACTORSRISK FACTORS Previous GBS-infected babyPrevious GBS-infected baby Gestational age <37 wksGestational age <37 wks Maternal disease (esp. GBS UTI)Maternal disease (esp. GBS UTI) Ruptured membranes > 18 hoursRuptured membranes > 18 hours Location of delivery (e.g., home)Location of delivery (e.g., home) Infant/Fetal symptommatologyInfant/Fetal symptommatology Clinical suspicionClinical suspicionNote: incidence has fallen 80% since CDC prevention guidelines Note: incidence has fallen 80% since CDC prevention guidelines

were published in 1996were published in 1996

GBS SGBS SEPSISEPSIS

Mothers in labor or Mothers in labor or with ROM with ROM should be should be treated treated if:if: ChorioamnionitisChorioamnionitis History of previous GBS+ baby History of previous GBS+ baby Mother GBS+ or GBS-UTI this preg.Mother GBS+ or GBS-UTI this preg. Mother’s GBS status unknown and:Mother’s GBS status unknown and:

– < 37 wks gestation< 37 wks gestation– ROM ROM ≥≥ 18 hrs 18 hrs– Maternal temp Maternal temp ≥≥ 38 38o o (100.4(100.4ooF)F)

INFANTS TO BE SCREENEDINFANTS TO BE SCREENED Maternal “chorioamnionitis”Maternal “chorioamnionitis” Maternal illness Maternal illness (i.e. UTI, pneumonia)(i.e. UTI, pneumonia) Maternal peripartum fever > 38Maternal peripartum fever > 38oo

(100.4(100.4ooF)F) Prolonged ROM Prolonged ROM ≥≥ 18 hrs ( 18 hrs (≥≥ 12 hrs 12 hrs

preterm)preterm) Mother GBS+ with inadequate Mother GBS+ with inadequate

treatment (treatment (< 4 hrs< 4 hrs))– No screening necessary if C-section delivery No screening necessary if C-section delivery

with intact membraneswith intact membranes

GBS SGBS SEPSISEPSIS

INFANTS TO BE SCREENEDINFANTS TO BE SCREENED Prolonged labor (> 20 hrs)Prolonged labor (> 20 hrs) Home or contaminated deliveryHome or contaminated delivery ““Chocolate-colored”/foul smelling Chocolate-colored”/foul smelling

amniotic fluidamniotic fluid Persistent fetal tachycardiaPersistent fetal tachycardia SYMPTOMATIC INFANTSYMPTOMATIC INFANT

– treat immediately (in DR if possible)treat immediately (in DR if possible)

GBS SGBS SEPSISEPSIS

SEPSIS SCREENSEPSIS SCREEN CBC with differentialCBC with differential Platelet countPlatelet count Blood culture x 1-2 (ideally 1 ml)Blood culture x 1-2 (ideally 1 ml) Chest X-ray &/or LP if Chest X-ray &/or LP if

symptommaticsymptommatic Close observation and frequent Close observation and frequent

clinical evaluationclinical evaluation Role of CRPRole of CRP

GBS SGBS SEPSISEPSIS

GBS prophylaxis GBS prophylaxis

The guidelines recommended one of two The guidelines recommended one of two approaches:approaches:

1- 1- the prenatal screening approach (screening the prenatal screening approach (screening all pregnant women for GBS infection at 35—all pregnant women for GBS infection at 35—37 weeks gestation and treatment of those 37 weeks gestation and treatment of those

women with positive cultureswomen with positive cultures) ) 2-2- identifying women who present with identifying women who present with

risk factors treating them during laborrisk factors treating them during labor

Diagnosis

SSEPSISEPSIS

SIGNS and SYMPTOMSSIGNS and SYMPTOMS temp instabilitytemp instability • lethargy • lethargy poor feeding/residualspoor feeding/residuals • resp distress • resp distress

>60 >60 glucose instabilityglucose instability • poor • poor

perfusionperfusion hypotensionhypotension • bloody stools • bloody stools abdominal distentionabdominal distention • bilious emesis • bilious emesis apneaapnea • tachycardia • tachycardia skin/joint findingsskin/joint findings

Clinical Signs according to WHO Integrated Management of

Childhood illness

Respiratory rate >60 breaths/minRespiratory rate >60 breaths/min Retraction, flaring, GruntingRetraction, flaring, Grunting CrepitationCrepitation CyanosisCyanosis Temperature >37.7°C (or feels hot) or <35.5°C (or feels Temperature >37.7°C (or feels hot) or <35.5°C (or feels

cold)cold) Convulsions ,Lethargic or unconscious Convulsions ,Lethargic or unconscious Reduced movements and activity)Reduced movements and activity) Not able to feed (sustain suck)Not able to feed (sustain suck) Bulging fontanels Bulging fontanels

LABORATORY EVALUATIONLABORATORY EVALUATION Provide added value when results are normalProvide added value when results are normal

– high negative predictive valuehigh negative predictive value– low positive predictive valuelow positive predictive value

abnl results could be due to other reasons and abnl results could be due to other reasons and not infectionnot infection

IT < 0.3, ANC > 1,500 (normal) do not start IT < 0.3, ANC > 1,500 (normal) do not start abx, or d/c abx if started, if pt remains abx, or d/c abx if started, if pt remains clinically stableclinically stable

IT IT >> 0.3, ANC < 1,500 consider initiation of 0.3, ANC < 1,500 consider initiation of abx pending bld cx in “at-risk” pt who was not abx pending bld cx in “at-risk” pt who was not already begun on antibiotics for other factorsalready begun on antibiotics for other factors

SSEPSISEPSIS

LABORATORY EVALUATIONLABORATORY EVALUATION Positive screenPositive screen

– total total WBCWBC << 5,000 5,000 – – I/T I/T >> 0.3 0.3– ANC ANC << 1,500 1,500 – platelets < 100,000– platelets < 100,000

Additional work-upAdditional work-up– CXRCXR, , urine cxurine cx, and , and LP LP as clinically indicatedas clinically indicated

CRPCRP– Best discriminatory value for predicting septicemia Best discriminatory value for predicting septicemia – no added value for diagnosis of early onset no added value for diagnosis of early onset

sepsissepsis– best for best for negativenegative predicativepredicative valuevalue or when or when

used serially used serially sensitivity 48 to 63%sensitivity 48 to 63%– notnot to be used to decide about rx, duration of to be used to decide about rx, duration of

rx or need for LPrx or need for LP– positive results for a single value obtained at positive results for a single value obtained at

24 hrs ranges > 4.0 - 10.0 mg/dL24 hrs ranges > 4.0 - 10.0 mg/dL

New Diagnostic New Diagnostic Methods Methods Interleukin 6,8Interleukin 6,8 IgMIgM Polymerase chain reaction (PCR)Polymerase chain reaction (PCR) DNA microarray technologyDNA microarray technology ImmunoassayImmunoassay

SSEPSISEPSISTREATMENTTREATMENT Review protocolReview protocol AntibioticsAntibiotics

– Ampicillin 100 mg/kg/dose IV q 12 hoursAmpicillin 100 mg/kg/dose IV q 12 hours– Gentamicin 4 mg/kg/dose IV q 24 hoursGentamicin 4 mg/kg/dose IV q 24 hours

IM route may be used in asymptomatic pt on IM route may be used in asymptomatic pt on whom abx are initiated for maternal risk factors whom abx are initiated for maternal risk factors or or to avoid delays to avoid delays when there is difficulty when there is difficulty obtaining IVobtaining IV

– For meningitis: Ampicillin 200-300 mg/kg/dFor meningitis: Ampicillin 200-300 mg/kg/d Symptomatic managementSymptomatic management

– respiratory, cardiovascular, fluid supportrespiratory, cardiovascular, fluid support

PrognosisPrognosis

Fatality rate 2-4 times higher in Fatality rate 2-4 times higher in LBW than in term neonatesLBW than in term neonates

Overall mortality rate 15-40%Overall mortality rate 15-40% Survival less likely if also Survival less likely if also

granulocytopenic (I:T > 0.80 granulocytopenic (I:T > 0.80 correlates with death and may correlates with death and may justify granulocyte transfusion).justify granulocyte transfusion).

Infection and ND Infection and ND OutcomeOutcome IUI and postnatal infection both IUI and postnatal infection both

appear to increase the risk for appear to increase the risk for adverse ND outcomeadverse ND outcome

Role of inflammatory mediators/SIRS Role of inflammatory mediators/SIRS in brain injury in the preterm infantin brain injury in the preterm infant– Pressure passive CNS circulationPressure passive CNS circulation– Direct cytotoxicity to the developing brainDirect cytotoxicity to the developing brain– Inherent vulnerability of the Inherent vulnerability of the

oligodendrocyte precursoroligodendrocyte precursor

Clinical Infection

Sepsis Alone

Sepsis+NEC

Sepsis+Meningitis

Late Onset InfectionLate Onset Infection Majority of ELBW infants will develop Majority of ELBW infants will develop

late onset sepsislate onset sepsis Significant associated morbidity and Significant associated morbidity and

mortalitymortality CONSCONS still the most common pathogen still the most common pathogen Gram-negative pathogens increasing Gram-negative pathogens increasing

in prevelance and are associated with in prevelance and are associated with higher mortality ratehigher mortality rate

Prevention of Nosocomial Prevention of Nosocomial InfectionsInfections

HANDWASHINGHANDWASHING HANDWASHINGHANDWASHING Universal precautionsUniversal precautions Limit use devices and cathetersLimit use devices and catheters Minimize catheter manipulationMinimize catheter manipulation Nursery designNursery design Meticulous skin careMeticulous skin care EducationEducation

Congenital Rubella Congenital Rubella SyndromeSyndrome

• • Microcephaly, IUGRMicrocephaly, IUGR • • Pulmonary stenosis, PDAPulmonary stenosis, PDA • • Cataracts, chorioretinitis, microphthalmiaCataracts, chorioretinitis, microphthalmia • • Sensorineural DeafnessSensorineural Deafness • • Long bone radiolucenciesLong bone radiolucencies • • Renal AnomaliesRenal Anomalies • • Anaemia, low platlets, Anaemia, low platlets,

HepatosplenomegalyHepatosplenomegaly

Chicken PoxChicken Pox

95% pregnant women have immunity- no risk95% pregnant women have immunity- no risk Mat. Varicella: onset 7days pre to 5d post partumMat. Varicella: onset 7days pre to 5d post partum - give ZIG asap to baby once born- give ZIG asap to baby once born - Acyclovir to Mum, to baby if ? infected- Acyclovir to Mum, to baby if ? infected - Isolate- Isolate Small risk of syndrome in 1st and 2nSmall risk of syndrome in 1st and 2nd trimesterd trimester - scarring, skin defects, optic atrophy- scarring, skin defects, optic atrophy ZIG to pregnant Mum if exposed and not ZIG to pregnant Mum if exposed and not

immuneimmune

When to suspect Cong. When to suspect Cong. InfectionInfection

• • IUGR - all parametersIUGR - all parameters • • Head Circ is <3rd or >97thileHead Circ is <3rd or >97thile • • Anaemia, ThrombocytopaeniaAnaemia, Thrombocytopaenia • • Hepatosplenomegaly, RashHepatosplenomegaly, Rash • • Cataract, blindness, deafness ( late Cataract, blindness, deafness ( late

pick-up)pick-up) • • Poor tone, poor suck, late milestonesPoor tone, poor suck, late milestones • • Stillbirth / FDIU / Neonatal deathStillbirth / FDIU / Neonatal death

How investigate Cong. How investigate Cong. InfectionInfection

• • Cord blood : total IgMCord blood : total IgM • • Cord /baby blood:TORCH screen IgM, IgGCord /baby blood:TORCH screen IgM, IgG • • CMV: Urine culture Throat/ saliva PCRCMV: Urine culture Throat/ saliva PCR • • FBE, LFTs, EUC, RPR, VDRL +/- LPFBE, LFTs, EUC, RPR, VDRL +/- LP • • Toxo culture by inoculate mice with bloodToxo culture by inoculate mice with blood • • Cranial US , Cardiac ECHO ( rubella)Cranial US , Cardiac ECHO ( rubella) • • Long Bone xrays ( rubella)Long Bone xrays ( rubella) • • Ophthalmological r/vHearing screenOphthalmological r/vHearing screen

How to treatHow to treat

• • Rubella - to lateRubella - to late • • Toxo - Pyrimethamine, Toxo - Pyrimethamine,

Sulphadiazine,Sulphadiazine, • • Folinic Ac + regular FBE, LFTsFolinic Ac + regular FBE, LFTs • • CMU - GanciclovirCMU - Ganciclovir • • Syphilis - Penicillin for 10-14 daysSyphilis - Penicillin for 10-14 days • • HSV - AciclovirHSV - Aciclovir

I hope you have enjoyed your I hope you have enjoyed your experience and have learned experience and have learned some new information about some new information about neonatal sepsis. neonatal sepsis.

Thank You!!Thank You!!