• 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.

• 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

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 wk
1-3 wk
1 2 3 4 5 6 7 8 9 10 11
Age (months)
A Schuchat. Clin Micro Rev 1998;11:497-513.

50%
Non-colonized newborn
GBS colonized mother
50%
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

• PROM >18 hours 1%
• Maternal + GBS (preprophylaxis era)
• Maternal + GBS (in prophylaxis era)
• +GBS and chorioamnionitis
0.5-1%
0.2-0.4%
• Maternal + GBS + PROM, fever or preterm 4-7%
• Chorioamnionitis 3-8%*
6-20%
• PROM + preterm
• PROM + low Apgar score
4-6%
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
ANC <= 1750
I/T >= 0.2
I/T >= 0.25
I/T >= 0.3
Sensitivity (%)
38-96
90-100
45
35
CRP > 1.0 mg/dL 70-93
*WBC <= 5000
I/T >= 0.2
CRP > 1.0 mg/dL
* 2/3 tests positive
100
PPV (%)
20-77
11-51
6
7
7-43
27
NPV (%)
96-99
99-100
98
98
97-99.5
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
•
(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
37-40wk
34-36wk
41wk-
ROM < 12hr
12-17.9 hr
18-23.9 hr
24 hr-
<100.5
100.5-101.4
101.5-102.4
102.5-
OR ref
2.56
1.62
ref
3.65
VARIABLE
GBS -
GBS +
GBS -/UNK
GBS +
No intrapartum abx
2.81
14.8
ref
4.53
Any antibiotic
GBS IAP
Broad spectrum abx
Abx < 4 hr prior to del
1.91
1.77
6.25
ref
20.08
Abx > 4 hr prior to del .34
103.
37
OR
REF
1.14
REF
1.38
Ref

• 67,623 34 week and up infants, 245 positive blood cultures
• GBS 56%(decreasing over time)
• Ecoli 22%
• Enterococcus 4%
• Other 18%

Test
WBC x 10 3 /ul
0.4.99
5-9.99
10-14.99
15-19.99
20-
ANC x 10 3 /ul
0-0.99
1-1.99
2-4.99
5-9.99
10-
I/T
0-0.14
0.15-0.29
0.3-0.449
0.45-0.599
0.6-
1.3
1.4
4.8
6.1
1.2
LR
7.5
2.3
1
0.89
0.93
LR
0.45
<1 hour
LR n/a
1.4
1.1
0.73
1.2
2.9
3.3
8.4
0.77
LR
33.5
9.3
1.1
0.92
0.55
LR
0.46
1-3.99 hours
LR
27.6
2.4
0.65
0.64
0.16
LR
115
51.7
6.9
0.64
0.31
LR
0.25
4+ hours
LR
80.5
6.4
1.0
0.41
1.2
3.1
8.8
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