approach to early onset sepsis jochen profit, md,...
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Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
ADDRESSING DISPARITIES IN NICU CARE
Antibiotic Stewardship – Approach to Early Onset Sepsis
Jochen Profit, MD, MPH
Associate Professor of Pediatrics, Stanford University
Chief Quality Officer, California Perinatal Quality Care Collaborative
Objectives
Discuss rationale for abx use and stewardship efforts
Discuss stewardship tools
- Traditional risk-factor approach
- KP calculator
- Enhanced observation
Collaborative stewardship results
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Why abx stewardship
• Neonatal sepsis is uncommon (0.3-0.8/1,000 live births)
• In well appearing term and late preterms the incidence
of early onset sepsis (EOS) is as low as 1/25,000
• Prior CDC guidelines for abx therapy based on time prior
to OB GBS prophylaxis
• Sepsis incidence 5-10x lower
• 5%-20% of term and late preterms being evaluated for
sepsis, with 5% to 8% receiving empirical antibiotics
• Prolonged abx therapy associated with disruption of
maternal bonding, cost, dysbiosis, obesity,? atopic illness
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Early-Onset Sepsis Screening
What Was Wrong With The Old Way?
Kaiser Permanente Northern California Experience
Escobar 2000, Kuzniewicz 2017
Epoch 1995-96 2010-13
Population ≥ 2000 g ≥ 35 weeks
n 18,299 95,543
Babies Evaluated 2785 13,797
Babies Treated 855 5226
EOS Cases 22 24
Evaluations/EOS Case 127 575
Babies Treated/EOS Case 39 218
EOS Rate (/1000 births) 1.20 0.25
Slide courtesy of Bill Benitz, MD
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
40 – fold variation in abx use
Schulman 2015
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
https://neonatalsepsiscalculator.kaiserpermanente.org
• Models combining risk factors, intrapartum abx and
newborn condition to estimate individual infant risk of
EOS
• Allows for evolution of clinical condition
• Recommends clinical actions at specific levels of risk • Requires structures for repeated risk calculation
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Prospective evidence of effectiveness
Kuzniewicz 2017
12 infants with EOS, 6 clinically sick at birth 5 initially well, got sick during birth hospitalization culture, abx, clinically well 1 would have met CDC criteria, low calculator risk (0.15) tachypnea, cx, well, dc, cx + E. coli, readmit, repeat cx neg 1 would have met CDC criteria, always well, calc risk (2.3), cx pos
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Benefits of the Kaiser Calculator
• Uses continuous data rather than arbitrary cut-offs
• Doesn’t rely on blood testing
• Doesn’t rely on diagnosis of chorioamnionitis (which is flawed)
• Provides you with estimate of starting risk with a chance
to reassess if clinical picture changes
• Doesn’t require intense monitoring in nursery
• Allows for data-driven approach rather than expert
opinion
• Need to recognize that some uncertainty is unavoidable
Puopolo, Escobar 2019
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Enhanced Observation EOS Screening
Examination-Based EOS Ascertainment: Northeastern Italy
Cantoni 2013
Epoch 2004-05 2005-06
Population ≥ 37 weeks
n 7628 7611
Blood Cultures 527 44
Babies Treated 89 36
EOS Cases 3* 2
Evaluations/EOS Case 176 22
Babies Treated/EOS Case 30 18
EOS Rate (/1000 births) 0.39 0.26
* excluding 10 cases of coagulase-negative Staphylococcus
Management of
Infants at Risk
Epoch 1: 2002 CDC protocol
Epoch 2: simplified exams
(skin appearance,
respiratory rate,
retractions) at 1, 2, 4, 8,
12, 16, 20, 24, 30, 36, 42,
and 48 hrs of age
Slide courtesy of Bill Benitz, MD
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Enhanced Observation EOS Screening
Examination-Based EOS Ascertainment: Northern Italy
Berardi 2015
Epoch 2009-11
Population ≥ 35 weeks
n 10,104
Babies Evaluated 465
Babies Treated 36
EOS Cases 8
Evaluations/EOS Case 58
Babies Treated/EOS Case 4.5
EOS Rate (/1000 births) 0.79
No missed cases or severe cases with
onset of signs after 6 hours of age.
Slide courtesy of Bill Benitz, MD
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Enhanced Observation Lucile Packard Children’s Hospital Stanford
• ~4500 deliveries annually –High and Low risk
• Prior EOS approach based on 2010 CDC/2012 AAP guidelines
• High antibiotic utilization rate – 12.3% in late preterm and
term
Exposing >300 infants to antibiotics
for every one ‘true’ infection!
Slide courtesy of Adam Frymoyer, MD
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
L&D
• Hospitalist at Delivery
• Level II Nurse remains
with infant
Level II NICU • NO Antibiotics / Labs
• Nurse assessment
& Vital signs q4 h
• CR Monitoring
Newborn
Nursery • Routine Couplet Care
• VS q8 h until D/C
Admit Transfer
After
24 hrs
Clinical Signs Sepsis • Laboratory and/or antibiotics initiated
• No formal criteria - discretion of treating physician
Started March 2015
Chorioamnionitis Exposed Infants: Well Appearing
Clinical Exam Based Approach - Phase 1: Admit to Level II NICU -
Slide courtesy of Adam Frymoyer, MD
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
L&D
• Hospitalist at Delivery
• Level II Nurse remains
with infant
Level II NICU • NO Antibiotics / Labs
• Nurse assessment & Vital signs q4 h
• CR Monitoring
Newborn
Nursery • Routine Couplet Care
• VS q8 h until D/C
Admit Transfer
After
24 hrs
Chorioamnionitis Exposed Infants: Well Appearing
Clinical Exam Based Approach - Phase 2: Admit to Newborn Nursery -
Direct Admit to Newborn Nursery
Ensure Adequate Resources
Nursing staffing Ratio 1:3
In-house Neonatal Hospitalist 24/7
Started August 2016
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Concurrent Change in Newborn Nursery
• No routine use of sepsis screening labs –Regardless of risk
factors
• Vitals signs q4 h x 24 hours –All infants!
Well Appearing Infants: Regardless of Risk Factors
Clinical Signs Sepsis• Laboratory and/or antibiotics initiated
• No formal criteria - discretion of treating physician
Newborn Nursery
• NO Sepsis Screening Labs
• Vital Signs q4 h x 24 h with Nurse assessment
Started 2015
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Joshi N, et al. Hosp Pediatr. 2019;9:227-233.
Impact of Clinical Exam Based Approach Well-Appearing Chorioamnionitis-Exposed Infants
Reduction
in Antibiotic Use
Reduction
in Sepsis Lab Testing
Remain with Mother
in Couplet Care
95% (n = 304/319)
93% (n = 296/319)
92% (n = 295/319)
One positive blood culture (GBS)
No readmissions for sepsis within 30 days after discharge
Slide courtesy of Adam Frymoyer, MD
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
One GBS Case – Clinical Exam was Key!
• New-onset tachypnea at 24 h – Identified by postpartum nurse
• Kaiser Calculator Risk – 0.38 per 1000 at birth (low
risk)
• Repeated clinical assessments essential to identifying infant
EOS Case Details
• GA 40 wks
• ROM 0.4 h
• GBS+ (no IAP)
• Maternal fever 38.3oC
• Well-appearing at birth
Joshi N, et al. Hosp Pediatr. 2019;9:227-233.
Slide courtesy of Adam Frymoyer, MD
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Antibiotics
LPCH QI**
An
tib
ioti
cs
Ka
ise
r C
alc
ula
tor*
No Yes
No 90.3% 0.8%
Yes 4.2% 4.7%
What if We Had Used the Kaiser Calculator?
* Risk >3 per 1000 after incorporating clinical exam
** Antibiotics started within first 24 hol
• 95% Agreement
– Kaiser Calculator recommended
antibiotic use
– LPCH QI actual antibiotic use
• Clinical exam strongest driver
• Large weight of exam in model
– Well-appearing: LR -> 0.41
– Equivocal: LR -> 5
– Clinical Illness: LR -> 21.1
LPCH Chorio-Exposed Infants
N=596
Joshi N, Pediatrics. 2018 Apr;141(4). pii: e20172056 Joshi N, Hosp Pediatr. 2019;9:227-233
Kuzniewicz MW. Jt Comm J Qual Patient Saf. 2016;42:232-9
Slide courtesy of Adam Frymoyer, MD
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
0%
5%
10%
15%
20%
May-
14
Sep-14
Jan-1
5
May-
15
Sep-15
Jan-1
6
May-
16
Sep-16
Jan-1
7
May-
17
Sep-17
Jan-1
8
May-
18
Sep-18
% I
nfa
nts
Re
ceiv
ed
Am
pic
illi
n
Phase I - Clinical Monitoring Level II NICU
Mean = 12.3%
Mean = 5.0%
UCL
LCL
Phase II - Clinical MonitoringNewborn Nursery
>60%
antibiotic
reduction
Impact: Antibiotic Exposure in All Infants
Estimated
savings over 4
years
1200+ antibiotic
exposures
1,800+ sepsis
laboratory tests
2000+ NICU
admission days
N=17,255 births
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
EOS Cases at LPCH All Infants GA ≥ 34 wk (2015-18)
• 3 ‘symptomatic’ at birth
• 3 ‘well appearing’ at birth
– Developed signs illness at 6, 24, and 36 hours of life
– If used Kaiser calculator…. • All were low risk at birth (<0.5 per 1000)
• Clinical Exam was key to identifying!
Cases of Sepsis*
n = 6
Well Appearing at Birth
n = 3
Symptomatic
at Birth
n = 3
Became Symptomatic
n = 3
N=17,242 births EOS risk 0.41 per 1000
Slide courtesy of Adam Frymoyer, MD
*Excludes one case of sepsis at 65 hol in
setting of UVC placed for hypoglycemia. Sepsis screen at birth negative.
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Enhanced Observation EOS Screening
Examination-Based EOS Ascertainment: Stanford
Joshi 2018, Joshi 2019, Frymoyer 2019
Epoch 2015-2018
Population ≥ 34 weeks
n 17,242
Babies Treated 833
EOS Cases 7
Babies Treated/EOS Case 119
EOS Rate (/1000 births) 0.42 No missed cases or severe cases with onset of
signs after 6 hours of age.
Four infants were not clinically ill at birth.
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Options in EOS Screening: AAP Clinical Reports
Puopolo 2018, Puopolo 2019
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Vermont Oxford Network Collaborative
The median AU rate decreased from 16.7% to 12.1%
(P=0.0013), a 34% relative risk reduction.
Dukhovny 2019
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
CPQCC collaboratives
The 28 NICUs in the Antibiotic
Stewardship Collaborative
eliminated roughly 11,700
“antibiotic days” across California and safely decreased the antibiotic
utilization rate by 13.8%.
11, 700 fewer
“antibiotic days”
01
23
45
6kdensity (
%)
0 10 20 30 40 50 60 70 80 90 100AUR (%)
Regional NICUs Community NICUs
Intermediate NICUs Non-CCS NICUs
2013
01
23
45
6kdensity (%
)
0 10 20 30 40 50 60 70 80 90 100AUR (%)
Regional NICUs Community NICUs
Intermediate NICUs Non-CCS NICUs
2014
2015 2016
01
23
45
6kdensity (
%)
0 10 20 30 40 50 60 70 80 90 100AUR (%)
Regional NICUs Community NICUs
Intermediate NICUs Non-CCS NICUs
2015
01
23
45
6kdensity (
%)
0 10 20 30 40 50 60 70 80 90 100AUR (%)
Regional NICUs Community NICUs
Intermediate NICUs Non-CCS NICUs
2016
Profit Lab c a l i f o r n i a p e r i na t a l q ua l i t y c a r e c o l l a b o r a t i ve
Summary
Evidence-Based Approach to EOS
No matter which strategy is adopted for primary ascertainment
of early-onset neonatal sepsis, it will initially fail to identify a
substantial proportion of affected infants.
All infants, without regard to presence or absence of risk
factors, must be closely observed for developing signs of sepsis,
and promptly evaluated when that occurs.
If serial examination of all infants is not feasible, risk
stratification on the basis of maternal risk factors is essential.