Management of Neonatal Sepsis: Niki Kosmetatos, MD Anthony Piazza, MD J. Devn Cornish, MD

Management of
Neonatal Sepsis
Niki Kosmetatos, MD
Anthony Piazza, MD
J. Devn Cornish, MD
Emory University
Department of Pediatrics
Incidence
 Mortality
– 13-69% world wide
– 13-15% of all neonatal deaths (US)
 Meningitis
– 0.4-2.8/1000 live births (US 0.2-0.4/1000)
– 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 26/1000
1000 - 2000 g 8-9/1000
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)

 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
Overall sepsis rate 8/1000
Maternal Fever 4/1000
PROM 10-13/1000
Fever & PROM 87/1000

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)
SEPSIS
ORGANISMS
 Group B strep (most common G+)
 Coliforms (E. coli most common G-)
 Listeria
 Nosocomial infections
 Staph epidermidis
 Candida
 Note: 50% G+ and 50% G-
Routes of Infection
 Transplacental/Hematogenous
 Ascending/Birth Canal
 Nosocomial
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*
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
Nosocomial
 Organisms –
Skin Flora, Equipment/Environment
Staphylococcus – Coagulase neg & pos
MRSA
Klebsiella
Pseudomonas/Proteus
Enterobacter
Serratia
Rotavirus
Clostridia – C dificile
Fungi
Infection
Timing
 Onset
– Early Onset 1st 24 hrs 85 %
24-48 hrs 5%
– Late Onset 7-90 days
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
Symptoms
 Less common
– Seizures
– DIC
– Petechiae
– Hepatosplenomegaly
– Sclerema
 Meningitis symptoms
– Irritability, lethargy, poorly responsive
– Changes in muscle tone, etc.
Evaluation
 Non-specific
– 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
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.
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
Neonatal Sepsis:
the special case of
Group B Strep Sepsis
GBS SEPSIS
RISK FACTORS
 Gestational age
 Maternal well-being
 Ruptured membranes > 18 hours
 Location of delivery
 Infant/Fetal symptomatology
 Clinical suspicion
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)
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
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)
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
Algorithm for Neonate whose Mother Received Intrapartum Antibiotics
Maternal
Rx for
GBS?
Maternal antibiotics
for suspected
chorioamnionitis?
Signs of
neonatal sepsis? Full diagnostic
evaluation *
Empiric therapy++
Gestational age
<35 weeks? Limited evaluation$ &
Observe ≥ 48 hours
If sepsis is suspected, full
diagnostic evaluation and
Duration of IAP
empiric therapy ++
before delivery
< 4 hours #
* CBC, blood cx, & CXR if resp sx. If ill consider LP.
++ Duration of therapy may be 48 hrs if no sx.
No evaluation $ CBC with differential and blood culture
No therapy # Applies only to penicillin, Ampicillin, or cefazolin.
Observe ≥ 48 hours** ** If healthy & ≥ 38 wks & mother got ≥ 4 hours IAP, may D/C at 24 hrs.
Careful Observation Careful Observation
& pending review of
Immediate Antibiotics screen
• Fetal tachycardia
• Symptomatic INFANT
• Home delivery
• Maternal intrapartum fever > 38.6o
• Maternal fever < 38.6o
• “Chocolate” or foul smelling fluid
• PROM
• Ill mother
• Mat GBS with < 2 dose abx
(-) Screen (+) Screen (-) Screen (+) Screen

d/c abx; careful Cont abx until bld Careful obs Initiate abx &
obs and monit cx neg for 48o if and monit cont until bl cx (-)
bld cx until d/c asympt. Use clini- bld cx until for 48o. Clinical
cal judgement for d/c judgement for
cessation of abx if cessation of abx
pt is/was sympt 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
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
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
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 > 4.0 - 10.0 mg/dL
SEPSIS
TREATMENT
 Review protocol
 Antibiotics
– 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 200-300 mg/kg/d
 Symptomatic management
– respiratory, cardiovascular, fluid support
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).

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Management of Neonatal Sepsis: Niki Kosmetatos, MD Anthony Piazza, MD J. Devn Cornish, MD

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Management of

 Race – GBS sepsis blacks>whites

 Sex – sepsis & meningitis more common in

 Breaks in skin & mucous membrane

 Procedures (e.g. lines, ET-tubes)

Overall sepsis rate 8/1000

Maternal Fever 4/1000

Fever & PROM 87/1000

– Temperature instability, feeding problems

(-) Screen (+) Screen (-) Screen (+) Screen

Blood Culture Positive

 Fatality rate 2-4 times higher in LBW

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