Why Does Antibiotic Stewardship

Matter?

Jonathan Swanson MD, MSc Associate Professor of Pediatrics

Chief Quality Officer for Children’s Services University of Virginia Children’s Hospital

Objectives

Define what antibiotic stewardship means as it applies to the NICU

Examine the impact antibiotics have on the NICU and neonatal populations

Define who may comprise a NICU antibiotic stewardship team

Disclosures

I have no financial issues to disclose or conflicts to resolve.

Disclosures

I have no financial issues to disclose or conflicts to resolve.

NICU Environment

Antibiotic Stewardship

~ 50% of all antimicrobial is inappropriate

Challenges in the NICU environment Non-specific signs/symptoms of sepsis NEC Culture-negative clinical sepsis Limited pharmacokinetic data and/or clinical

studies Contamination/colonization vs infection Ventilator-associated pneumonia vs RDS/CLD

CDC, 2013 Report

Unique Risks in the NICU

Risk for Infection

Low Birth

Weight

Central Line Days

Prolonged Length of

Stay

Opportunities

Relatively few antimicrobials used in the NICU Ampicillin / Nafcillin / Gentamicin /

Vancomycin Handful of indications Empiric treatment of EOS / LOS Perioperative prophylaxis Blood/urine infections

Large proportion of patients treated

Antibiotic Use in the NICU

Maternal IAP significantly decreases risk of sepsis

Duration of therapy not correlated with EOS risk or CRIB scores

Clark RH et al. Pediatrics 2006

Wide Variability

NICHD – 19 centers

4039 ELBW infants

Survival >5 days Negative initial

blood cultures

Cotten et al. Pediatrics, 2009

Wide Variability

CPQC Abx use

varied 40-fold

Independent of: Sepsis NEC Surgery Mortality

Schulman J et al. Pediatrics, 2015

Does it Matter?

Widely Used

Wide Variability ???

Antibiotics & Feeding Tolerance

Adult mice exposed to antimicrobials Decreased intestinal motor function through

increased bone morphogenetic protein 2 (BMP-2)

Brazilian Collaborative <35 weeks and <1500 g Excluded:

Maternal fever Maternal abx treatment ROM > 1 hr Clinical sepsis Positive blood cultures Use of vasoactive drugs SNAPPE score >20

901 infants 2006 - 2013 Martinez FE et al. JPGN 2017

Antibiotics & Feeding Tolerance

Antibiotics & NEC

Yale Case-Control 124 cases of NEC

Antibiotic exposure

(in absence of sepsis) increases probability of NEC by 20% daily

Alexander VN et al. J Pediatr 2011

Bacterial Diversity

74 infants <32 wks Cx (-) Amp/Gent

Greenwood C et al. J Pediatr 2014

Antibiotics & BPD

BPD is closely linked to perinatal inflammation

Microbiome can modulate inflammation within neonatal gut

Lung microbiome impacts adult lung disease Asthma, CF, COPD

VLBW infants from 2000 – 2015 Excluded death, culture proven sepsis & NEC

within first 14 days 1140 infants (571 with BPD/death)

Cantey JB et al. J Pediatr 2016

Antibiotics & BPD

All Infants Infants < 29 wks Infants > 29 wks Death or BPD 1.13 (1.09 – 1.16 1.13 (1.09 – 1.18) 1.11 (1.06 – 1.17)

Mild BPD 1.02 (0.96 – 1.11 1.08 (0.99 – 1.22) 1.00 (0.87 – 1.16)

Moderate BPD 1.14 (0.86 – 1.68) 1.14 (0.62 – 1.81) 1.1 (0.58 – 2.10)

Severe BPD 1.16 (1.04 – 1.33) 1.15 (1.08 – 1.27) 1.19 (1.03 – 1.54)

*Adjusted for CRIB-II score and Sepsis

• Novitsky et al (Columbia) • > 48 hours of empiric antibiotic therapy in first week • BPD - OR 2.2 (95% CI 1.4 – 3.5)

Antibiotics & Morbidity

Canadian Neonatal Network – 2010 – 2014 Antibiotic Utilization Rate # of days exposed to antibiotic / total length of

stay Excluded infants with EOS, LOS, & NEC

8824 infants AUR decreased from 0.29 (2010) to 0.25

(2014) LOS decreased from 19% (2010) to 13.8%

(2014)

Ting JY et al. JAMA Peds 2016

Antibiotics & Resistance

Cephalosporins & Adverse NICU Outcomes

Cantey JB et al. Inf Dis Clin N Am 2014

Three Paths Forwards

• Ignore

QI • ASP • Guidelines

Research • Prospective studies

Antibiotic Stewardship Program

Essential Participants Neonatologist Infectious Disease physician Infection preventionists Neonatal or ID-trained pharmacist Bioinformatician Neonatal nurse

Antibiotic Stewardship Program

Essential Participants Neonatologist

Influencer of other clinicians Help determine what metrics are useful Help determine which interventions are preferred Present data to colleagues/division

Infectious Disease physician Infection preventionists Neonatal or ID-trained pharmacist Bioinformatician Neonatal nurse

Antibiotic Stewardship Program

Essential Participants Neonatologist Infectious Disease physician Infection preventionists

Specialized ID training / experience Local knowledge of resistance patterns

Neonatal or ID-trained pharmacist Bioinformatician Neonatal nurse

Antibiotic Stewardship Program

Essential Participants Neonatologist Infectious Disease physician Infection preventionists Neonatal or ID-trained pharmacist

Understanding of pharmacokinetics Knowledge of pharmacy practices

Bioinformatician Neonatal nurse

Antibiotic Stewardship Program

Essential Participants Neonatologist Infectious Disease physician Infection preventionists Neonatal or ID-trained pharmacist Bioinformatician

CPOE tools Data mining

Neonatal nurse Frontline for diagnosis and diagnostic

procedures

AS Programs in the NICU

Cantey JB et al. Inf Dis Clin N Am 2014

Stewardship Suggestions

Cantey JB et al. Inf Dis Clin N Am 2014

SCOUT Study

Observational study at Parkland (Dallas, TX)

Baseline Period (2012) Collected & Analyzed antimicrobial use

Intervention Period (2013 – 2014) Targeted Interventions

Pneumonia / culture-negative sepsis limited to 5 days Empiric treatment timed out at 48 hrs

Followed Antibiotic Days of Therapy Composite safety measures

SCOUT

Cantey JB et al. Lancet Infect Dis 2016

SCOUT

SCOUT

UVA Experience with AS

Antibiotic Stewardship Team within Children’s Hospital

Antibiotic Timeliness Initiative Sepsis Panel Order Set

Fellow M&M Fall 2016 Pneumonia treatment “guidelines” Antibiotic treatment “time-out” after 48 hours

UVA NICU Antibiotic Days

Order Panel

M&M

UVA NICU Antibiotic Days

Order Panel

M&M

??

Next Steps

Evaluate your own data

Develop an Antibiotic Stewardship Team

Consider early discontinuation of empiric antibiotics with negative cultures (24 hours vs. 48 hours)

Summary

Antibiotics in the NICU are common and will remain the top medications used

Summary

Antibiotics in the NICU are common and will remain the top medications used

There is wide variability in duration of therapy (with little evidence to guide us)

Summary

Antibiotics in the NICU are common and will remain the top medications used

There is wide variability in duration of therapy (with little evidence to guide us)

Prolonged antibiotics place our patients at risk for major morbidities and even mortality

Summary

Antibiotics in the NICU are common and will remain the top medications used

There is wide variability in duration of therapy (with little evidence to guide us)

Prolonged antibiotics place our patients at risk for major morbidities and even mortality

NICU Antibiotic Stewardship is warranted and will lead to improved patient care, population health and lower costs