Neonatal SepsisNeonatal Sepsis

Steve Spencer, MDSteve Spencer, MD

ObjectivesObjectives

• Review of terminologies associated with Review of terminologies associated with neonatal infectionsneonatal infections

• Review risk factors for neonatal Review risk factors for neonatal infectionsinfections

• Review presentations of neonatal sepsisReview presentations of neonatal sepsis• Review most common organisms and Review most common organisms and

treatmentstreatments• We will concentrate on the child <3 We will concentrate on the child <3

months of agemonths of age

CasesCases

• You are on-call You are on-call tonight when the tonight when the ER calls with two ER calls with two kidskids

CasesCases

• Kid 1Kid 1• 9 week old, term 9 week old, term

babybaby• 100.6 temp100.6 temp• Looks wellLooks well• CBC WNLCBC WNL• UA cleanUA clean• Everyone at home Everyone at home

with coldswith colds

• Kid 2Kid 2• 12 day old, term 12 day old, term

babybaby• Fever to 101Fever to 101• JaundicedJaundiced• SeizuresSeizures• WBC of 3.2 KWBC of 3.2 K• PLT of 89PLT of 89

Do you treat these kids the same or different and why?

Your TextYour Text

TerminologiesTerminologies

• Rule out sepsisRule out sepsis• Neonate with feverNeonate with fever• Neonatal feverNeonatal fever• Neonatal sepsisNeonatal sepsis• Serious Bacterial Infection (SBI)Serious Bacterial Infection (SBI)• Occult BacteremiaOccult Bacteremia• Neonate- the first month 28days of lifeNeonate- the first month 28days of life• Infant- up to one yearInfant- up to one year

Back When I was an Back When I was an Intern…..Intern…..

• Any kid 3 months or less with fever Any kid 3 months or less with fever got admittedgot admitted

• Kids stayed longerKids stayed longer• If it sneezed, writhed, wiggled or If it sneezed, writhed, wiggled or

wheezed, it got an LPwheezed, it got an LP• Kids had to crawl seven miles Kids had to crawl seven miles

through the snow, up hill both through the snow, up hill both ways, to daycare…..ways, to daycare…..

Age GroupsAge Groups

• Currently ages 0-28 days Currently ages 0-28 days automatically admitted by most automatically admitted by most cliniciansclinicians

• 1-3 months is a grey zone guided 1-3 months is a grey zone guided by clinical opinionby clinical opinion

• Greater than three months Greater than three months generally not admittedgenerally not admitted

Why Have Why Have Recommendations Recommendations

Changed?Changed?• GBS prophylaxisGBS prophylaxis• ImmunizationsImmunizations

• HIB, PneumococcusHIB, Pneumococcus

• Better understanding of neonatal Better understanding of neonatal physiologyphysiology

• Better laboratory techniquesBetter laboratory techniques• Better understanding of the diseaseBetter understanding of the disease• Different antibioticsDifferent antibiotics

Definition of FeverDefinition of Fever

• ““Gold Standard” is generally thought of as Gold Standard” is generally thought of as 100.4 (38.0) rectally with a glass mercury 100.4 (38.0) rectally with a glass mercury thermometerthermometer

• Lots of ways to take a baby’s temperatureLots of ways to take a baby’s temperature• I recommend using a quality thermometerI recommend using a quality thermometer• When in doubt, let the pros sort it outWhen in doubt, let the pros sort it out• In Newborn Nursery, need to counsel parents In Newborn Nursery, need to counsel parents

about significance of fever in neonateabout significance of fever in neonate

Why the Worry?Why the Worry?

• Neonatal immune system immatureNeonatal immune system immature• Perinatal exposure to pathogens via birth Perinatal exposure to pathogens via birth

canalcanal• High rate of infection in kids less than 3 High rate of infection in kids less than 3

months with feversmonths with fevers• >4% age 0-28 days with bacteremia or >4% age 0-28 days with bacteremia or

meningitis (drops to 1% by 3 months)meningitis (drops to 1% by 3 months)• Almost 10% with UTIAlmost 10% with UTI• Rates increase with degree of feverRates increase with degree of fever

• 39C with >10% rate of bacteremia39C with >10% rate of bacteremia

• Well appearing infant may have an infectionWell appearing infant may have an infection

Why not admit Why not admit everybody?everybody?

• Not without risk of hospital Not without risk of hospital acquired infectionacquired infection

• CostCost• Lost time to parents at workLost time to parents at work• Family stressFamily stress• etcetc

What data supports our What data supports our practice?practice?

• Rochester criteriaRochester criteria• Philadelphia criteriaPhiladelphia criteria• Boston criteriaBoston criteria• EtcEtc

Risk FactorsRisk Factors

• Prematurity and low birth weightPrematurity and low birth weight• Maternal GBSMaternal GBS• Prolonged rupture of membranesProlonged rupture of membranes• Maternal chorioamnionitisMaternal chorioamnionitis• Sibling with sepsisSibling with sepsis• Meconium at deliveryMeconium at delivery• Need for resuscitationNeed for resuscitation• Male childMale child• Multiple gestationMultiple gestation

““Early” Pathogens Early” Pathogens (first week)(first week)

• Group B Strep (GBS)Group B Strep (GBS)• Incidence used to be 4-6/1000 live births (0.4%)Incidence used to be 4-6/1000 live births (0.4%)• Now <0.1% after prenatal screening guidelinesNow <0.1% after prenatal screening guidelines

• E. coliE. coli• Every few decades flips back and forth with GBS as Every few decades flips back and forth with GBS as

most common causemost common cause• Gram negative rods (esp. in urine)Gram negative rods (esp. in urine)

• Occasional Salmonella sepsisOccasional Salmonella sepsis• Listeria monocytogenesListeria monocytogenes• Herpes SimplexHerpes Simplex• EnterovirusEnterovirus

““Late” Pathogens (~1-2 Late” Pathogens (~1-2 weeks)weeks)

• GBS or group A strepGBS or group A strep• Enterics/Enterococcus in urineEnterics/Enterococcus in urine• HSVHSV• Enterovirus, RSV, FluEnterovirus, RSV, Flu

Community Acquired Community Acquired (after 4-6 weeks)(after 4-6 weeks)

• PneumococcusPneumococcus• MeningococcusMeningococcus• GABHSGABHS• Haemophilus influenzaeHaemophilus influenzae (HIB) not (HIB) not

really a problem anymorereally a problem anymore

Signs/SymptomsSigns/Symptoms

• Temperature Temperature irregularityirregularity• FeverFever• HypothermiaHypothermia

• Tone and BehaviorTone and Behavior• Poor tonePoor tone• Weak suckWeak suck• Shrill cryShrill cry• Weak cryWeak cry• IrritabilityIrritability

• SkinSkin• Poor perfusionPoor perfusion• CyanosisCyanosis• MottlingMottling• PallorPallor• PetechiaePetechiae• Unexplained Unexplained

jaundicejaundice

Most by themselves mean little, but three (or two) strikes and you are Out!

Signs/SymptomsSigns/Symptoms

• Feeding Feeding ProblemsProblems• VomitingVomiting• DiarrheaDiarrhea• Abdominal Abdominal

distensiondistension• Hypo or Hypo or

HyperglycemiaHyperglycemia

• CardiopulmonaryCardiopulmonary• TachypneaTachypnea• RetractionsRetractions• Tachycardia for Tachycardia for

ageage• Bradycardia in first Bradycardia in first

few days of lifefew days of life• Hypotension for Hypotension for

ageage• Low PO2Low PO2

Signs/Symptoms Signs/Symptoms

• Sunken fontanelleSunken fontanelle• Bulging or pulsating fontanelleBulging or pulsating fontanelle• Neck stiffness CAN NOT be usedNeck stiffness CAN NOT be used• Babies can be bacteremic but look Babies can be bacteremic but look

wellwell• Presence of a “cold” does not Presence of a “cold” does not

change anythingchange anything

PIDJ April 2005PIDJ April 2005

• Study in India Study in India found that any found that any two of these signs two of these signs had an almost had an almost 100% sensitivity 100% sensitivity for sepsis and for sepsis and over 90% over 90% mortalitymortality

• Reduced suckingReduced sucking• Weak cryWeak cry• Cool extremitiesCool extremities• VomitingVomiting• Poor tonePoor tone• RetractionsRetractions

LabsLabs

• Normal WBC (5-15K) is better than high Normal WBC (5-15K) is better than high WBC is better than very high WBC (over WBC is better than very high WBC (over 35K) which is better than very low WBC 35K) which is better than very low WBC (<5K)(<5K)

• Less than 28 days- blood, urine, CSF Less than 28 days- blood, urine, CSF cultures +/- stoolcultures +/- stool• Get urine culture, even if UA WNLGet urine culture, even if UA WNL

• >28 days see handout>28 days see handout• CXR if respiratory symptomsCXR if respiratory symptoms

Lab Dilemmas- Urine Lab Dilemmas- Urine collectioncollection

• Don’t use bag urines!Don’t use bag urines!• A negative culture on a bag urine is negativeA negative culture on a bag urine is negative• A positive means nothingA positive means nothing

• Cath or Suprapubic aspirate?Cath or Suprapubic aspirate?• SPA- any growth is considered a positiveSPA- any growth is considered a positive• CathCath

• Can have false positives, especially if uncirc’d maleCan have false positives, especially if uncirc’d male• New debates on what constitutes a positive cultureNew debates on what constitutes a positive culture• Most references use >10K CFU’s as positive, some Most references use >10K CFU’s as positive, some

use as little as 1K (equals one plaque)use as little as 1K (equals one plaque)• Microbiologists feel we should use 100K on all Microbiologists feel we should use 100K on all

samples regardless of sourcesamples regardless of source

Lab Dilemmas- The Bloody Lab Dilemmas- The Bloody TapTap

The Bloody TapThe Bloody Tap

• Don’t ask me, you should have Don’t ask me, you should have gotten it right the first timegotten it right the first time

The Bloody TapThe Bloody Tap

• No right answerNo right answer• Results can vary based on the Results can vary based on the

amount of blood in amount of CSF, amount of blood in amount of CSF, what is the HCT, what is the what is the HCT, what is the peripheral WBC count etc. Some use peripheral WBC count etc. Some use CBC to CSF ratios.CBC to CSF ratios.

• Sometimes seems like too many Sometimes seems like too many WBC’s or seems OKWBC’s or seems OK

• Sometimes just need to re-tap Sometimes just need to re-tap

TreatmentTreatment

• Age 0 to ~4-6 weeksAge 0 to ~4-6 weeks• Ampicillin/AminoglycosideAmpicillin/Aminoglycoside• Ampicillin/CefotaximeAmpicillin/Cefotaxime

• Amp kills GBS and ListeriaAmp kills GBS and Listeria• Gent and Cefotaxime for GNR’sGent and Cefotaxime for GNR’s

• Ceftriaxone not used- causes Ceftriaxone not used- causes neonatal hepatitis and biliary sludgingneonatal hepatitis and biliary sludging

AminoglycosidesAminoglycosides

• DisadvantagesDisadvantages• OtotoxicityOtotoxicity• NephrotoxicityNephrotoxicity• Need for levelsNeed for levels

• AdvantagesAdvantages• Little resistanceLittle resistance• Cheap (30 cents Cheap (30 cents

or so a dose)or so a dose)• Highly Highly

concentrated in concentrated in urineurine

• No need for levels No need for levels if QD dosing in a if QD dosing in a 48 hour admission48 hour admission

TreatmentTreatment

• After 4-6 weeks, ampicillin and a After 4-6 weeks, ampicillin and a 33rdrd generation cephalosporin generation cephalosporin• Offers better coverage for community Offers better coverage for community

acquired organismsacquired organisms• At 4-8 weeks, switch to cephalosporin At 4-8 weeks, switch to cephalosporin

alone.alone.

What About Herpes?What About Herpes?

• Some clinicians begin acyclovir on all Some clinicians begin acyclovir on all neonatal admissions for feverneonatal admissions for fever

• We use the guideline of “Fever Plus”We use the guideline of “Fever Plus”• HSV is rare & tends to present in certain HSV is rare & tends to present in certain

waysways• Fever in addition toFever in addition to

• Hepatitis/jaundiceHepatitis/jaundice• MeningitisMeningitis• SeizuresSeizures• ThrombocytopeniaThrombocytopenia• Vesicles Vesicles • Rash/purperaRash/purpera

HSV Risk FactorsHSV Risk Factors

• Maternal history- only present in Maternal history- only present in • Maternal primary infection- as many as Maternal primary infection- as many as

50% of babies infected50% of babies infected• Active lesionsActive lesions• ROM > 4-6 hoursROM > 4-6 hours• Fetal scalp electrodeFetal scalp electrode• PrematurityPrematurity• Caregiver with cold sore/fever blisterCaregiver with cold sore/fever blister

HSV in NeonateHSV in Neonate

• Three typesThree types• SEM (Skin, Eye, Mucous membranes)- SEM (Skin, Eye, Mucous membranes)-

15%15%• Isolated CNS- 35%Isolated CNS- 35%• Disseminated (+/- CNS)- 50%Disseminated (+/- CNS)- 50%

• 75% HSV-2 25% HSV-175% HSV-2 25% HSV-1• Incidence 1:1K-5K birthsIncidence 1:1K-5K births

HSV timingHSV timing

• SEM (Skin, Eye, Mucous SEM (Skin, Eye, Mucous membranes)- can be earlymembranes)- can be early

• Isolated CNS- 2-3 weeksIsolated CNS- 2-3 weeks• Disseminated (+/- CNS, +/-SEM)- Disseminated (+/- CNS, +/-SEM)-

~1 week~1 week

HSV Labs- three pointsHSV Labs- three points

• CSF PCR alone CSF PCR alone DOES NOTDOES NOT rule rule out HSVout HSV

• CSF PCR alone CSF PCR alone DOES NOTDOES NOT rule rule out HSVout HSV

• CSF PCR alone CSF PCR alone DOES NOTDOES NOT rule rule out HSVout HSV

HSV Labs- if do it, do it HSV Labs- if do it, do it rightright

• CSF for PCR (>98% sensitive, >95% CSF for PCR (>98% sensitive, >95% specific) and/or culture (30-50%)specific) and/or culture (30-50%)

• CSF tends to be “bloody”– 100-200 CSF tends to be “bloody”– 100-200 RBC with elevated WBCRBC with elevated WBC

• Mucous membrane culturesMucous membrane cultures• Eyes, ears, anus, mouth, nose, vesicles if Eyes, ears, anus, mouth, nose, vesicles if

present, some add urinepresent, some add urine• In nursery, wait 24 hours after birth to In nursery, wait 24 hours after birth to

culture (indicates active infection) culture (indicates active infection)

HSV Labs cont.HSV Labs cont.

• LFT’sLFT’s• I now get for any R/O SBI kid that I am I now get for any R/O SBI kid that I am

worried enough about to get a BMPworried enough about to get a BMP• Serial CBC’sSerial CBC’s

• ThrombocytopeniaThrombocytopenia• LeukopeniaLeukopenia

• Tzank smear of lesions(~40% sensitive, Tzank smear of lesions(~40% sensitive, not specific)not specific)

• DFA or EIA of lesions (80% sensitive)DFA or EIA of lesions (80% sensitive)• Serology NOT usefulSerology NOT useful

ImagingImaging

• Classic CT/MRI - Classic CT/MRI - temporal lobe temporal lobe lesion but may lesion but may have many have many presentations to presentations to include include hydrocephalushydrocephalus

HSV treatmentHSV treatment

• Acyclovir 20mg/kg/dose Q8 hrsAcyclovir 20mg/kg/dose Q8 hrs• SEM only- 14 daysSEM only- 14 days• Disseminated (no CNS)- 21 daysDisseminated (no CNS)- 21 days• CNS- at least 21 days (PCR must CNS- at least 21 days (PCR must

clear)clear)

CasesCases

• Kid 1Kid 1• 9 week old, term 9 week old, term

babybaby• 100.6 temp100.6 temp• Looks wellLooks well• CBC WNLCBC WNL• UA cleanUA clean• Everyone at home Everyone at home

with coldswith colds

• Kid 2Kid 2• 12 day old, term 12 day old, term

babybaby• Fever to 101Fever to 101• JaundicedJaundiced• SeizuresSeizures• WBC of 3.2 KWBC of 3.2 K• PLT of 89PLT of 89