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Neonatal Sepsis. Steve Spencer, MD. Objectives. Review of terminologies associated with neonatal infections Review risk factors for neonatal infections Review presentations of neonatal sepsis Review most common organisms and treatments We will concentrate on the child <3 months of age.

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neonatal sepsis

Neonatal Sepsis

Steve Spencer, MD

objectives
Objectives
  • Review of terminologies associated with neonatal infections
  • Review risk factors for neonatal infections
  • Review presentations of neonatal sepsis
  • Review most common organisms and treatments
  • We will concentrate on the child <3 months of age
cases
Cases
  • You are on-call tonight when the ER calls with two kids
cases4
Kid 1

9 week old, term baby

100.6 temp

Looks well

CBC WNL

UA clean

Everyone at home with colds

Kid 2

12 day old, term baby

Fever to 101

Jaundiced

Seizures

WBC of 3.2 K

PLT of 89

Cases

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

terminologies
Terminologies
  • Rule out sepsis
  • Neonate with fever
  • Neonatal fever
  • Neonatal sepsis
  • Serious Bacterial Infection (SBI)
  • Occult Bacteremia
  • Neonate- the first month 28days of life
  • Infant- up to one year
back when i was an intern
Back When I was an Intern…..
  • Any kid 3 months or less with fever got admitted
  • Kids stayed longer
  • If it sneezed, writhed, wiggled or wheezed, it got an LP
  • Kids had to crawl seven miles through the snow, up hill both ways, to daycare…..
age groups
Age Groups
  • Currently ages 0-28 days automatically admitted by most clinicians
  • 1-3 months is a grey zone guided by clinical opinion
  • Greater than three months generally not admitted
why have recommendations changed
Why Have Recommendations Changed?
  • GBS prophylaxis
  • Immunizations
    • HIB, Pneumococcus
  • Better understanding of neonatal physiology
  • Better laboratory techniques
  • Better understanding of the disease
  • Different antibiotics
definition of fever
Definition of Fever
  • “Gold Standard” is generally thought of as 100.4 (38.0) rectally with a glass mercury thermometer
  • Lots of ways to take a baby’s temperature
    • I recommend using a quality thermometer
    • When in doubt, let the pros sort it out
    • In Newborn Nursery, need to counsel parents about significance of fever in neonate
why the worry
Why the Worry?
  • Neonatal immune system immature
  • Perinatal exposure to pathogens via birth canal
  • High rate of infection in kids less than 3 months with fevers
    • >4% age 0-28 days with bacteremia or meningitis (drops to 1% by 3 months)
    • Almost 10% with UTI
    • Rates increase with degree of fever
      • 39C with >10% rate of bacteremia
  • Well appearing infant may have an infection
why not admit everybody
Why not admit everybody?
  • Not without risk of hospital acquired infection
  • Cost
  • Lost time to parents at work
  • Family stress
  • etc
what data supports our practice
What data supports our practice?
  • Rochester criteria
  • Philadelphia criteria
  • Boston criteria
  • Etc
risk factors
Risk Factors
  • Prematurity and low birth weight
  • Maternal GBS
  • Prolonged rupture of membranes
  • Maternal chorioamnionitis
  • Sibling with sepsis
  • Meconium at delivery
  • Need for resuscitation
  • Male child
  • Multiple gestation
early pathogens first week
“Early” Pathogens (first week)
  • Group B Strep (GBS)
    • Incidence used to be 4-6/1000 live births (0.4%)
    • Now <0.1% after prenatal screening guidelines
  • E. coli
    • Every few decades flips back and forth with GBS as most common cause
  • Gram negative rods (esp. in urine)
    • Occasional Salmonella sepsis
  • Listeria monocytogenes
  • Herpes Simplex
  • Enterovirus
late pathogens 1 2 weeks
“Late” Pathogens (~1-2 weeks)
  • GBS or group A strep
  • Enterics/Enterococcus in urine
  • HSV
  • Enterovirus, RSV, Flu
community acquired after 4 6 weeks
Community Acquired (after 4-6 weeks)
  • Pneumococcus
  • Meningococcus
  • GABHS
  • Haemophilus influenzae (HIB) not really a problem anymore
signs symptoms
Temperature irregularity

Fever

Hypothermia

Tone and Behavior

Poor tone

Weak suck

Shrill cry

Weak cry

Irritability

Skin

Poor perfusion

Cyanosis

Mottling

Pallor

Petechiae

Unexplained jaundice

Signs/Symptoms

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

signs symptoms19
Feeding Problems

Vomiting

Diarrhea

Abdominal distension

Hypo or Hyperglycemia

Cardiopulmonary

Tachypnea

Retractions

Tachycardia for age

Bradycardia in first few days of life

Hypotension for age

Low PO2

Signs/Symptoms
signs symptoms20
Signs/Symptoms
  • Sunken fontanelle
  • Bulging or pulsating fontanelle
  • Neck stiffness CAN NOT be used
  • Babies can be bacteremic but look well
  • Presence of a “cold” does not change anything
pidj april 2005
Study in India found that any two of these signs had an almost 100% sensitivity for sepsis and over 90% mortality

Reduced sucking

Weak cry

Cool extremities

Vomiting

Poor tone

Retractions

PIDJ April 2005
slide22
Labs
  • Normal WBC (5-15K) is better than high WBC is better than very high WBC (over 35K) which is better than very low WBC (<5K)
  • Less than 28 days- blood, urine, CSF cultures +/- stool
    • Get urine culture, even if UA WNL
  • >28 days see handout
  • CXR if respiratory symptoms
lab dilemmas urine collection
Lab Dilemmas- Urine collection
  • Don’t use bag urines!
    • A negative culture on a bag urine is negative
    • A positive means nothing
  • Cath or Suprapubic aspirate?
    • SPA- any growth is considered a positive
    • Cath
      • Can have false positives, especially if uncirc’d male
      • New debates on what constitutes a positive culture
      • Most references use >10K CFU’s as positive, some use as little as 1K (equals one plaque)
      • Microbiologists feel we should use 100K on all samples regardless of source
the bloody tap
The Bloody Tap
  • Don’t ask me, you should have gotten it right the first time
the bloody tap26
The Bloody Tap
  • No right answer
  • Results can vary based on the amount of blood in amount of CSF, what is the HCT, what is the peripheral WBC count etc. Some use CBC to CSF ratios.
  • Sometimes seems like too many WBC’s or seems OK
  • Sometimes just need to re-tap
treatment
Treatment
  • Age 0 to ~4-6 weeks
    • Ampicillin/Aminoglycoside
    • Ampicillin/Cefotaxime
  • Amp kills GBS and Listeria
  • Gent and Cefotaxime for GNR’s
    • Ceftriaxone not used- causes neonatal hepatitis and biliary sludging
aminoglycosides
Disadvantages

Ototoxicity

Nephrotoxicity

Need for levels

Advantages

Little resistance

Cheap (30 cents or so a dose)

Highly concentrated in urine

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

Aminoglycosides
treatment29
Treatment
  • After 4-6 weeks, ampicillin and a 3rd generation cephalosporin
    • Offers better coverage for community acquired organisms
    • At 4-8 weeks, switch to cephalosporin alone.
what about herpes
What About Herpes?
  • Some clinicians begin acyclovir on all neonatal admissions for fever
  • We use the guideline of “Fever Plus”
    • HSV is rare & tends to present in certain ways
    • Fever in addition to
      • Hepatitis/jaundice
      • Meningitis
      • Seizures
      • Thrombocytopenia
      • Vesicles
      • Rash/purpera
hsv risk factors
HSV Risk Factors
  • Maternal history- only present in
    • Maternal primary infection- as many as 50% of babies infected
  • Active lesions
  • ROM > 4-6 hours
  • Fetal scalp electrode
  • Prematurity
  • Caregiver with cold sore/fever blister
hsv in neonate
HSV in Neonate
  • Three types
    • SEM (Skin, Eye, Mucous membranes)- 15%
    • Isolated CNS- 35%
    • Disseminated (+/- CNS)- 50%
    • 75% HSV-2 25% HSV-1
    • Incidence 1:1K-5K births
hsv timing
HSV timing
  • SEM (Skin, Eye, Mucous membranes)- can be early
  • Isolated CNS- 2-3 weeks
  • Disseminated (+/- CNS, +/-SEM)- ~1 week
hsv labs three points
HSV Labs- three points
  • CSF PCR alone DOES NOT rule out HSV
  • CSF PCR alone DOES NOT rule out HSV
  • CSF PCR alone DOES NOT rule out HSV
hsv labs if do it do it right
HSV Labs- if do it, do it right
  • CSF for PCR (>98% sensitive, >95% specific) and/or culture (30-50%)
  • CSF tends to be “bloody”– 100-200 RBC with elevated WBC
  • Mucous membrane cultures
    • Eyes, ears, anus, mouth, nose, vesicles if present, some add urine
    • In nursery, wait 24 hours after birth to culture (indicates active infection)
hsv labs cont
HSV Labs cont.
  • LFT’s
    • I now get for any R/O SBI kid that I am worried enough about to get a BMP
  • Serial CBC’s
    • Thrombocytopenia
    • Leukopenia
  • Tzank smear of lesions(~40% sensitive, not specific)
  • DFA or EIA of lesions (80% sensitive)
  • Serology NOT useful
imaging
Imaging
  • Classic CT/MRI - temporal lobe lesion but may have many presentations to include hydrocephalus
hsv treatment
HSV treatment
  • Acyclovir 20mg/kg/dose Q8 hrs
    • SEM only- 14 days
    • Disseminated (no CNS)- 21 days
    • CNS- at least 21 days (PCR must clear)
cases40
Kid 1

9 week old, term baby

100.6 temp

Looks well

CBC WNL

UA clean

Everyone at home with colds

Kid 2

12 day old, term baby

Fever to 101

Jaundiced

Seizures

WBC of 3.2 K

PLT of 89

Cases