Approach to Early Onset Sepsis Jochen Profit, MD, MPHkfafhconferences.com/neonate/images/2-Antibiotic stewardship 2.18… · Allows for data-driven approach rather than expert opinion

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


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


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


40 – fold variation in abx use

Schulman 2015


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


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


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


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




Examination-Based EOS Ascertainment: Northern Italy

Berardi 2015

Epoch 2009-11


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.



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


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 -



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


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


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



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.



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



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


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


*Excludes one case of sepsis at 65 hol in

setting of UVC placed for hypoglycemia. Sepsis screen at birth negative.



Examination-Based EOS Ascertainment: Stanford

Joshi 2018, Joshi 2019, Frymoyer 2019

Epoch 2015-2018


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.


Options in EOS Screening: AAP Clinical Reports

Puopolo 2018, Puopolo 2019


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


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 (%)



2014

2015 2016

01

23

45

6kdensity (

%)

0 10 20 30 40 50 60 70 80 90 100AUR (%)



2015

01

23

45

6kdensity (

%)

0 10 20 30 40 50 60 70 80 90 100AUR (%)



2016


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.

Documents

Approach to Early Onset Sepsis Jochen Profit, MD, MPHkfafhconferences.com/neonate/images/2-Antibiotic stewardship 2.18… · Allows for data-driven approach rather than expert opinion