1. Management of Neonatal Sepsis
Niki Kosmetatos, MD
Anthony Piazza, MD
J. Devn Cornish, MD
Emory University
Department of Pediatrics

2. Incidence Mortality Meningitis Sepsis 13-69% world wide
13-15% of all neonatal deaths (US)
Meningitis
/1000 live births (US /1000)
Mortality 13-59%; US 4% of all neonatal deaths
Sepsis
1-21/1000 world wide; US1-8/1000 live births
Culture proven 2/1000 (3-8% of infants evaluated for sepsis)
Prematures <1000 g 26/ g /1000

3. Predisposing Factors General Host Factors Prematurity
Race – GBS sepsis blacks>whites
Sex – sepsis & meningitis more common in males, esp. gram negative infections
Birth asphyxia, meconium staining, stress
Breaks in skin & mucous membrane integrity (e.g. omphalocoele, meningomyelocoele)
Environmental exposure
Procedures (e.g. lines, ET-tubes)

4. Predisposing Factors Maternal/Obstetrical Factors
General – socioeconomic status, poor prenatal care, vaginal flora, maternal substance abuse, known exposures, prematurity, twins
Maternal infections –chorioamnionitis (1-10% of pregnancies), fever (>38° C/100.4° F), sustained fetal tachycardia, venereal diseases, UTI/bacteriuria, foul smelling lochia, GBS+, other infections
Obstetrical manipulation – amniocentesis, amnioinfusion, prolonged labor, fetal monitoring, digital exams, previa/abruption?
Premature & Prolonged ROM, preterm labor

5. Predisposing Factors Overall sepsis rate 8/1000 Maternal Fever 4/1000
PROM /1000
Fever & PROM 87/1000

6. Preterm Labor/PROM Prematurity (~10%) 15-25% due to maternal infection
>18-24h term; >12-18h preterm
Bacterial infection
 synthesis of PG
Macrophage TNF/IL stimulate PG synthesis, cytokine release**
Release of collagenase & elastase  ROM
+ Amniotic fluid cultures 15% (with intact membranes)

7. SEPSIS ORGANISMS Note: 50% G+ and 50% G-
Group B strep (most common G+)
Coliforms (E. coli most common G-)
Listeria
Nosocomial infections
Staph epidermidis
Candida
Note: 50% G+ and 50% G-

8. Routes of Infection Transplacental/Hematogenous Ascending/Birth Canal
Nosocomial

9. Transplacental/Hematogenous
Organisms (Not just “TORCHS”)
Syphilis Herpes*
Toxoplasmosis Gonorrhea
Rubella Mumps
Cytomegalovirus TB
Acute Viruses HIV
Coxsackie Polio
Adenovirus GBS
Echo Malaria
Enterovirus Lyme
Varicella
Parvovirus*

10. Ascending/Birth Canal
Organisms - GI/GU flora, Cervical/Blood
E. Coli Herpes
GBS Candida
Chlamydia HIV
Ureaplasma Mycoplasma
Listeria Hepatitis
Enterococcus Anaerobes
Gonorrhea Syphilis
HPV

11. Nosocomial Organisms – Skin Flora, Equipment/Environment MRSA
Staphylococcus – Coagulase neg & pos
MRSA
Klebsiella
Pseudomonas/Proteus
Enterobacter
Serratia
Rotavirus
Clostridia – C dificile
Fungi

12. Infection Timing Onset Early Onset 1st 24 hrs 85 % 24-48 hrs 5%
Late Onset days

13. Symptoms Non-specific/Common
Respiratory distress (90%) - RR, apnea (55%), hypoxia/vent need (36%), flaring/grunting
Temperature instability, feeding problems
Lethargy-irritability (23%)
Gastrointestinal – poor feeding, vomiting, abdominal distention, ileus, diarrhea
Color—Jaundice, pallor, mottling
Hypo- or hyperglycemia
Cardiovascular – Hypotension (5%), hypoperfusion, tachycardia
Metabolic acidosis NICHD data

14. Symptoms Less common Meningitis symptoms Seizures DIC Petechiae
Hepatosplenomegaly
Sclerema
Meningitis symptoms
Irritability, lethargy, poorly responsive
Changes in muscle tone, etc.

15. Evaluation Non-specific Specific – Cultures, stains
CBC/diff, platelets – ANC, I/T ratio
Radiographs
CRP
Fluid analysis – LP, U/A
Glucose, lytes, gases
Specific – Cultures, stains
Other – immunoassays, PCR, DNA microarray

16. Results “Trigger Points”
CBC
WBC <5.0, abs neutro <1,750, bands >2.0
I/T ratio > 0.2*
Platelets < 100,000
CRP > 1.0 mg/dl
CSF > 20 WBC’s with few or no RBC’s
Radiographs: infiltrates on CXR, ileus on KUB, periosteal elevation, etc.

17. Treatment Prevention – vaccines, GBS prophylaxis, HAND-WASHING
Supportive – respiratory, metabolic, thermal, nutrition, monitoring drug levels/toxicity
Specific – antimicrobials, immune globulins
Non-specific – IVIG, NO inhibitors & inflammatory mediators

18. Neonatal Sepsis: the special case of Group B Strep Sepsis

19. GBS SEPSIS RISK FACTORS Gestational age Maternal well-being
Ruptured membranes > 18 hours
Location of delivery
Infant/Fetal symptomatology
Clinical suspicion

20. Mothers in labor or with ROM should be treated if:
Chorioamnionitis
History of previous GBS+ baby
Mother GBS+ or GBS-UTI this preg.
Mother’s GBS status unknown and:
< 37 wks gestation
ROM ≥ 18 hrs
Maternal temp ≥ 38o (100.4oF)

21. GBS SEPSIS INFANTS TO BE SCREENED Maternal “chorioamnionitis”
Maternal illness (i.e. UTI, pneumonia)
Maternal peripartum fever > 38o (100.4oF)
Prolonged ROM ≥ 18 hrs (≥ 12 hrs preterm)
Mother GBS+ with inadequate treatment (< 4 hrs)
No screening necessary if C-section delivery with intact membranes

22. GBS SEPSIS INFANTS TO BE SCREENED Prolonged labor (> 20 hrs)
Home or contaminated delivery
“Chocolate-colored”/foul smelling amniotic fluid
Persistent fetal tachycardia
SYMPTOMATIC INFANT
treat immediately (in DR if possible)

23. GBS SEPSIS SEPSIS SCREEN CBC with differential Platelet count
Blood culture x 1 (ideally 1 ml)
Chest X-ray &/or LP if symptomatic
Close observation and frequent clinical evaluation
Role of CRP

24. Algorithm for Neonate whose Mother Received Intrapartum Antibiotics
Maternal antibiotics
for suspected
chorioamnionitis?
Duration of IAP
before delivery
< 4 hours #
Full diagnostic evaluation *
Empiric therapy++
Limited evaluation$ &
Observe ≥ 48 hours
If sepsis is suspected, full
diagnostic evaluation and
empiric therapy ++
Gestational age
<35 weeks?
No evaluation
No therapy
Observe ≥ 48 hours**
Maternal Rx for GBS?
Signs of neonatal sepsis?
YES
YES
YES NO NO NO
* CBC, blood cx, & CXR if resp sx. If ill consider LP.
++ Duration of therapy may be 48 hrs if no sx.
$ CBC with differential and blood culture
# Applies only to penicillin, Ampicillin, or cefazolin.
** If healthy & ≥ 38 wks & mother got ≥ 4 hours IAP, may D/C at 24 hrs.

25. Immediate Antibiotics Blood Culture Positive
Careful Observation
&
Immediate Antibiotics
Careful Observation pending review of screen
Symptomatic INFANT
Maternal intrapartum fever > 38.6o
“Chocolate” or foul smelling fluid
Ill mother
Fetal tachycardia
Home delivery
Maternal fever < 38.6o
PROM
Mat GBS with < 2 dose abx
(-) Screen (+) Screen (-) Screen (+) Screen
d/c abx; careful obs and monit bld cx until d/c
Cont abx until bld cx neg for 48o if asympt. Use clini-cal judgement for cessation of abx if pt is/was sympt
Careful obs and monit bld cx until d/c
Initiate abx & cont until bl cx (-) for 48o. Clinical judgement for cessation of abx if pt sympt
Blood Culture Positive
Initiate, resume or continue abx therapy and treat for 7-10 days for gram pos organism or longer if gram neg organism cultured. LP may be performed at the discretion of attending, especially in seriously symptomatic pt

26. SEPSIS SIGNS and SYMPTOMS temp instability • lethargy
poor feeding/residuals • resp distress
glucose instability • poor perfusion
hypotension • bloody stools
abdominal distention • bilious emesis
apnea • tachycardia
skin/joint findings

27. LABORATORY EVALUATION
SEPSIS
LABORATORY EVALUATION
Provide added value when results are normal
high negative predictive value
low positive predictive value
abnl results could be due to other reasons and not infection
IT < 0.3, ANC > 1,500 (normal) do not start abx, or d/c abx if started, if pt remains clinically stable
IT > 0.3, ANC < 1,500 consider initiation of abx pending bld cx in “at-risk” pt who was not already begun on antibiotics for other factors

28. LABORATORY EVALUATION
SEPSIS
LABORATORY EVALUATION
Positive screen
total WBC < 5,000 – I/T > 0.3
ANC < 1,500 – platelets < 100,000
Additional work-up
CXR, urine cx, and LP as clinically indicated
CRP
no added value for diagnosis of early onset sepsis
best for negative predicative value or when used serially
not to be used to decide about rx, duration of rx or need for LP
positive results for a single value obtained at 24 hrs ranges > mg/dL

29. SEPSIS TREATMENT Review protocol Antibiotics Symptomatic management
Ampicillin 100 mg/kg/dose IV q 12 hours
Gentamicin 3.5 mg/kg/dose IV q 24 hours
IM route may be used in asymptomatic pt on whom abx are initiated for maternal risk factors or to avoid delays when there is difficulty obtaining IV
For meningitis: Ampicillin mg/kg/d
Symptomatic management
respiratory, cardiovascular, fluid support

30. Prognosis Fatality rate 2-4 times higher in LBW than in term neonates
Overall mortality rate 15-40%
Survival less likely if also granulocytopenic (I:T > 0.80 correlates with death and may justify granulocyte transfusion).