Transcript Neonatal Sepsis - Colorado Perinatal Care Council

• Differentiate between the evaluation of a
symptomatic newborn and the assessment of
risk factors in an asymptomatic infant at risk
for sepsis
• Review obstetric risk factors for neonatal
sepsis in an asymptomatic newborn
• Review diagnostic tools for evaluation of
sepsis in an asymptomatic newborn
• Symptomatic infants require prompt
diagnostic testing and institution of antibiotic
therapy given the rapidity of deterioration and
the high likelihood of successful treatment in
infants with true bacteremia.
• The need for clinical judgment in this
decision-making process precludes the use of
an algorithm or protocol.
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Respiratory distress/grunting
Lethargy
Irritability
Hypothermia
Hypoglycemia
Hypotonia
Acidosis
Apnea
Cyanotic spells
Poor perfusion
• CBC with manual differential-WBC corrected for NRBCs
• Blood culture
• A significant number of infants with meningitis will have a
negative blood culture. A lumbar puncture may be
considered if:
– the infant has specific symptoms of meningitis
– symptoms more suggestive of sepsis than MAS or RDS
– the blood culture is positive
• Urine culture is not indicated
• Tracheal aspirate/gastric cultures may be useful in the
first 12 hours of life. A positive culture may be found in
44% of infants with clinical pneumonia and a negative
blood culture.
 Gram positive, beta hemolytic bacteria
 Common colonizer of human gastrointestinal and
genitourinary tracts
 Recognized as causing disease in humans in the
1930s
 Causes serious disease in young infants, pregnant
women and older adults
 Emerged as most common cause of sepsis and
meningitis in infants <3 months in the 1970s
Percent of cases
Early-onset: 0-6 days of life
90
80
70
60
50
40
30
20
10
0
Late onset: 7-89 days of life
< 1 1-3
wk wk
1
2
3
4
5
6
Age (months)
A Schuchat. Clin Micro Rev 1998;11:497-513.
7
8
9
10
11
GBS colonized mother
50%
50%
Non-colonized
newborn
Colonized
newborn
98%
Asymptomatic
2%
Early-onset sepsis,
pneumonia, meningitis
Early-onset GBS
Late-onset GBS
Before national prevention policy Transition
Universal screening
Source: Active Bacterial Core surveillance / Emerging Infections Program
• Penicillin the first-line agent for IAP
• Dosage: 5 million IU IV then 2.5-3.0 million IU IV
every 4 hours
• Revised dose (2.5-3.0 million IU) consistent with
available penicillin formulations
• Ampicillin an acceptable alternative
Antibiotics for IAP in Women Allergic to Penicillin
• Cefazolin best option for a woman allergic to
penicillin but not at high risk for anaphylaxis
• Drugs with less evidence for effectiveness (e.g.
clindamycin, vancomycin) only for women at high
risk of anaphylaxis
– High risk for anaphylaxis defined as history of
anaphylaxis, angioedema, respiratory distress or
urticaria following penicillin
• Erythromycin no longer included as option
• On the basis of signs and symptoms:
– fever (which might be low-grade)
– uterine tenderness
– fetal tachycardia
– maternal tachycardia
– foul-smelling or purulent amniotic fluid
• Fever alone in labor may be used as a
sign of chorioamnionitis and hence
indication for antibiotic treatment
• In Manroe’s 1977 study all 45 infants
had clinical signs of sepsis by 14 hours
• Time to onset of symptoms is not
delayed by maternal antibiotics: CDC
surveillance (GBS)
– 208 no abx 60 min prior to delivery; median
illness 2 hours of life range 0-144 hours
– 33 got abx > 60 min prior to delivery;
median illness 0 hours of life range 0-19
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PROM >18 hours
1%
Maternal + GBS (preprophylaxis era)
0.5-1%
Maternal + GBS (in prophylaxis era)
0.2-0.4%
Maternal + GBS + PROM, fever or preterm 4-7%
Chorioamnionitis
3-8%*
+GBS and chorioamnionitis
6-20%
PROM + preterm
4-6%
PROM + low Apgar score
3-4%
Prematurity. The risk of sepsis from any cause starts and
continues to rise at any gestation < 36 weeks.
*Escobar, Pediatrics, 2000
• N=12
• 25% would start antibiotics for
asymptomatic chorioamnionitis without
other evidence
• 75% wanted screening tests first
Adjunctive test
Sensitivity (%)
PPV (%)
NPV (%)
ANC <= 1750
38-96
20-77
96-99
I/T >= 0.2
90-100
11-51
99-100
I/T >= 0.25
45
6
98
I/T >= 0.3
35
7
98
CRP > 1.0 mg/dL
70-93
7-43
97-99.5
*WBC <= 5000
I/T >= 0.2
CRP > 1.0 mg/dL
* 2/3 tests positive
100
27
100
• Two CRP levels <1 mg/dL obtained 24 hours
apart, 8 to 48 hours after presentation,
indicate that bacterial infection is unlikely.
• The sensitivity of a normal CRP at the initial
evaluation is not sufficient to justify
withholding antibiotic therapy.
• CRP elevation begins 4-6 hours after the
onset of sepsis (or other stimulus) and peaks
at 24-48 hours.
• The positive predictive value of elevated CRP
levels is low.
• Fastidious organisms, maternal
antibiotic treatment and small volumes
(<1ml) decrease sensitivity
• Contamination with skin organisms
• Molecular methods may eventually
improve detection in less time
• Purpose was to differentiate “wet lung”
from GBS pneumonia
• No sensitivities or predictive values
were calculated
• Upper limits of normal for I:T ratios were
“designated”
• Combine sensitivity and specificity
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(probability that person with disease has positive test) sensitivity
(probability that person without disease has positive test) 1-specificity
• A person with disease A is “___” more
times likely to have a positive test than
someone without the disease
• “Pre-test probability” is estimated based
on personal experience, prevalence
data, published reports, etc.
• The test is used to modify pre-test
probability to “post-test probability”
• Post-test odds= pre-test odds x LR
• 34 weeks and up, 350 cases (cultureconfirmed bacterial sepsis at <72 hours)
from 608,014 births
• Combining cutoff methods (ROM>x,
T>x, GA<x) flags 17% of population at
risk but only identifies 47% of sepsis
cases
VARIABLE
OR
VARIABLE
OR
37-40wk
ref
GBS -
REF
34-36wk
2.56
GBS +
1.14
41wk-
1.62
GBS -/UNK
REF
ROM < 12hr
ref
GBS +
1.38
12-17.9 hr
3.65
No intrapartum abx
Ref
18-23.9 hr
2.81
Any antibiotic
1.91
24 hr-
14.8
GBS IAP
1.77
<100.5
ref
Broad spectrum abx
6.25
100.5-101.4
4.53
Abx < 4 hr prior to del
ref
101.5-102.4
20.08
Abx > 4 hr prior to del
.34
102.5-
103.37
• 67,623 34 week and up infants, 245
positive blood cultures
• GBS 56%(decreasing over time)
• Ecoli 22%
• Enterococcus 4%
• Other 18%
Test
<1 hour
1-3.99 hours
4+ hours
WBC x 103/ul
LR
LR
LR
0.4.99
n/a
27.6
80.5
5-9.99
1.4
2.4
6.4
10-14.99
1.1
0.65
1.0
15-19.99
0.73
0.64
0.41
20-
1.2
0.77
0.16
ANC x 103/ul
LR
LR
LR
0-0.99
7.5
33.5
115
1-1.99
2.3
9.3
51.7
2-4.99
1
1.1
6.9
5-9.99
0.89
0.92
0.64
10-
0.93
0.55
0.31
I/T
LR
LR
LR
0-0.14
0.45
0.46
0.25
0.15-0.29
1.3
1.2
1.2
0.3-0.449
1.4
2.9
3.1
0.45-0.599
4.8
3.3
8.8
0.6-
6.1
8.4
10.7
• 38 week infant, asymptomatic, mother
diagnosed with chorioamnionitis
• Temp 101.5, GBS+ antibiotics >4 hours
prior, ampicillin. ROM 28 hours
• What is pretest risk based on
experience?
• Based on Escobar’s paper? (0.23%)
• CBC WBC count 22.5K (LR1.2, .77, .06)
• I/T ratio of 0.3 (LR 1.4, 2.9, 3.1)
• ANC 6000 (LR .89, .82, .64)
• 38 week infant, asymptomatic, mother
diagnosed with chorioamnionitis
• Temp 103, GBS+ antibiotics >4 hours
prior, ampicillin. ROM 24 hours
• What is pretest risk based on
experience?
• Based on Escobar’s paper? (2.21%)
• CBC WBC count 4K (N/A, 27, 80)
• I/T ratio of .6 (LR 6, 8.4, 10.7)
• ANC 750 (LR 7.5, 33.5, 115)
• 40 week infant, asymptomatic, mother
diagnosed with chorioamnionitis (no
question)
• No prenatal information
• What is pretest risk based on
experience? (5%?)
• CBC WBC count 4K (N/A, 27, 80)
• I/T ratio of .6 (LR 6, 8.4, 10.7)
• ANC 750 (LR 7.5, 33.5, 115)
I/T ratio .3
I/T ratio .6
ANC < 1000
I/T ratio .3
I/T ratio .6
ANC < 1000