Transcript Management of Neonatal Sepsis - Emory University Department of

Management of
Neonatal Sepsis
Niki Kosmetatos, MD
Anthony Piazza, MD
Ira Adams-Chapman, MD
J. Devn Cornish, MD
Emory University
Department of Pediatrics
Note: Dr. Cornish does not have any financial
relationships to disclose nor will he discuss any
non-approved drug or device uses.
Babies and Bacteria…
Gram positive bacteria
(anthrax)
Gram negative bacteria
(pseudomonas)
…Don’t mix!
Incidence

Mortality
–
–

Meningitis
–
–

13-69% world wide
13-15% of all neonatal deaths (US) (8th cause)
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; US,1-2/1000 live births
Culture proven 2/1000 (3-8% of infants
evaluated for sepsis); 10-20/1000 VLBW
Prematures <1000 g
26/1000
1000 - 2000 g
8-9/1000
Predisposing Factors
General Host Factors
 Prematurity (OR 25 if < 1,000 gms)
 Race – GBS sepsis blacks>whites (x4)
 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)
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+ (OR 204), other infections
Obstetrical manipulation – amniocentesis,
amnioinfusion, prolonged labor, fetal monitoring, digital
exams, previa/abruption?
Premature & Prolonged ROM, preterm labor
Predisposing Factors
Overall sepsis rate
2/1000
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 (all babies)

Group B strep (most common G+)
Other strep
Coliforms (E. coli most common G-)
Staph aureus
Listeria
Nosocomial infections
Candida
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Note: 73% G+ and 27% G-
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

41%
23%
17%
4%
2%
SEPSIS
ORGANISMS (VLBW)

Group B strep (most common G+)
Other strep
Coliforms (E. coli most common G-)
CONS
Listeria
Nosocomial infections
Candida
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Note: 45% G+ and 53% G-
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




Source: Stoll et al Ped Inf Dis 2005, 24:635
12%
9%
41%
15%
2%
2%
Routes of Infection
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Transplacental/Hematogenous
Ascending/Birth Canal
Aspiration
Device Associated Infection
Nosocomial
Epidemic
Transplacental/Hematogenous

Organisms (Not just “TORCHS”)
Toxoplasmosis
Rubella
Cytomegalovirus
Herpes*
Syphilis
Acute Viruses
Coxsackie
Adenovirus
Echo
Enterovirus
Parvovirus
Gonorrhea
Mumps
TB
Varicella
HIV
Polio
GBS
Malaria
Lyme
Ascending/Birth Canal

Organisms - GI/GU flora, Cervical/Blood
E. Coli
GBS
Chlamydia
Ureaplasma
Listeria
Enterococcus
Gonorrhea
HPV
Herpes
Candida
HIV
Mycoplasma
Hepatitis
Anaerobes
Syphilis
Nosocomial

Organisms –
Skin Flora, Equipment/Environment
Staphylococcus – Coagulase neg & pos
MRSA
Klebsiella
Pseudomonas
Proteus
Enterobacter
Serratia
Rotavirus
Clostridium – C dificile
Fungi
Infection
Timing

Onset
– Early Onset
– Late Onset
1st 24 hrs
24-48 hrs
7-90 days
85 %
5%
Symptoms

Non-specific/Common
– Respiratory distress
hypoxia/vent need
(90%) - RR, apnea (55%),
(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
Mother to Infant Transmission
GBS colonized mother (20-30% in US)
50%
50%
Non-colonized
newborn
Colonized
newborn
98%
Asymptomatic
2%
Early-onset sepsis,
pneumonia, meningitis
GBS SEPSIS
RISK FACTORS




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

Previous GBS-infected baby
Gestational age <37 wks
Maternal disease (esp. GBS UTI)
Ruptured membranes > 18 hours
Location of delivery (e.g., home)
Infant/Fetal symptommatology
Clinical suspicion
Note: incidence has fallen 80% since CDC prevention guidelines were
published in 1996
Mothers in labor or with
ROM should be treated if:



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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)
Cases per 1000 live births
Rate of Early- and Late-onset GBS
Disease in the 1990s, U.S.
2.5
2
Group B
Strep
Association
formed
1st ACOG & AAP
statements
CDC draft
guidelines published
Consensus
guidelines
1.5
1
0.5
0
1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
Year
Early-onset
Schrag, New Engl J Med 2000 342: 1520
Late-onset
GBS SEPSIS
INFANTS TO BE SCREENED


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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
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
CBC with differential
Platelet count
Blood culture x 1-2 (ideally 1 ml)
Chest X-ray &/or LP if symptommatic
Close observation and frequent clinical
evaluation
Role of CRP
Algorithm for Neonate whose Mother Received Intrapartum Antibiotics
Maternal
Rx for
GBS?
Signs of
neonatal sepsis?
Gestational age
<35 weeks?
Duration of IAP
before delivery
< 4 hours #
No evaluation
No therapy
Observe ≥ 48 hours**
Maternal antibiotics
for suspected
chorioamnionitis?
Full diagnostic
evaluation *
Empiric therapy++
Limited evaluation$ &
Observe ≥ 48 hours
If sepsis is suspected, full
diagnostic evaluation and
empiric therapy ++
* 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.
Careful Observation
&
Immediate Antibiotics
• Symptomatic INFANT
• Maternal intrapartum fever > 38.6o
• “Chocolate” or foul smelling fluid
• Ill mother
(-) Screen
d/c abx; careful
obs and monit
bld cx until d/c
(+) Screen
Cont abx until bld
cx neg for 48o if
asympt. Use clinical judgement for
cessation of abx if
pt is/was sympt
Careful Observation
pending review of
screen
• Fetal tachycardia
• Home delivery
• Maternal fever < 38.6o
• PROM
• Mat GBS with < 2 dose abx
(-) Screen
Careful obs
and monit
bld cx until
d/c
(+) Screen
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
SEPSIS
SIGNS and SYMPTOMS
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temp instability
poor feeding/residuals
glucose instability
hypotension
abdominal distention
apnea
skin/joint findings
•
•
•
•
•
•
lethargy
resp distress
poor perfusion
bloody stools
bilious emesis
tachycardia
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
– ANC < 1,500

– I/T > 0.3
– 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 4 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).
Infection and Outcome

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Leviton, et al, Ped Res 1999
1078 infants <1500 grams and/or <32
wks
Infants with IUI were more likely to
have PVL
Chorioamnionitis was associated with a
4-fold increased risk of CP (17% vs.
3%)
Nelson, et al reported increased
cytokine response in population based
study of term but not preterm infants
Infection and ND
Outcome


IUI and postnatal infection both
appear to increase the risk for adverse
ND outcome
Role of inflammatory mediators/SIRS
in brain injury in the preterm infant
– Pressure passive CNS circulation
– Direct cytotoxicity to the developing brain
– Inherent vulnerability of the
oligodendrocyte precursor
Postnatal Infection and ND Outcome: PDI < 70
Infection Groups Compared to Uninfected by Logistic
Regression
Clinical Infection (N=1415)
Sepsis Alone (N=1740)
Sepsis+NEC (N=252)
Sepsis+Meningitis (N=152)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Adjusted Odds Ratios and 95%
CIs
Postnatal Infection and ND Outcome: Cerebral Palsy
Infection Groups Compared to Uninfected by Logistic
Regression
Clinical Infection (N=1415)
Sepsis Alone (N=1740)
Sepsis+NEC (N=252)
Sepsis+Meningitis (N=152)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
Adjusted Odds Ratios and 95% CIs
Stoll, JAMA 2004
Late Onset Infection
Majority of ELBW infants will develop
late onset sepsis
 Significant associated morbidity and
mortality
 CONS still the most common pathogen
 Gram-negative pathogens increasing
in prevelance and are associated with
higher mortality rate

Neonatal Infection and
Outcome




Increased risk of adverse ND outcome
in ELBW infants with LOS
Increased risk of poor growth at 18
months AA in ELBW with LOS
Poor outcome associated with NEC
?Role of cytokines and inflammatory
mediators in CNS
Prevention of Nosocomial
Infections








HANDWASHING
HANDWASHING
Universal precautions
Limit use devices and catheters
Minimize catheter manipulation
Nursery design
Meticulous skin care
Education
Thank You!!