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
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
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 & 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
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)
Antibiotics & Resistance
Cephalosporins & Adverse NICU Outcomes
Cantey JB et al. Inf Dis Clin N Am 2014
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
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
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
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
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