PQCNC

Antibiotic Stewardship
Neonatal Sepsis (ASNS)
Making North Carolina the best place to give
birth and be born!

Martin J McCaffrey, MD, CAPT USN (Ret)

Director Perinatal Quality Collaborative of North Carolina (PQCNC)
For the Perinatal Quality Collaborative of North Carolina
martin_mccaffrey@med.unc.edu
984 974-7852
 Impact of ASNS in NC

30 Hospitals Participating

60,000 North Carolina 3600-6000

Newborns Infants Currently Being Exposed

720-1200
Infants per year protected from
unnecessary exposure to antibiotics
 Its Been Six Months? Where is ASNS?
46 Hospitals
58 Teams
Newborn Infants Impacted: 28,433
NICU Infants Impacted: 7,160
Total Babies Impacted by ASNS: 35,593 (70,000)
In NBN 298 babies have avoided acute antibiotic exposure
In NICU 232 babies have avoided acute antibiotic exposure
In NICU 227 MORE babies had antibiotics stopped at 48 hours with
negative cultures (assume 7 day antibiotic course)
So.
 Its Been Six Months? Where is ASNS?
NBN298 x 2 days = 596
NICU..232 x 2 days = 464
227 NICU babies with 480 courses227 x 5 days = 1135
757 infants avoided antibiotics!
(1500 infants avoided antibiotic
courses)
But of NICU 232, 74 with 7 Day courses...74 x 5 days = +371
2566
2566 Antibiotic Days Avoided!!!!!
Empty Every Bed in NICU
in the State for Three
Days!!!
 ASNS in the Newborn Nursery
A Web-based survey was sent to each Better Outcomes through Research for
Newborns network nursery site representative
Responses were received from 81 (83%) of 97 nurseries located in 33 states.
For maternal chorioamnionitis, 51 of 79 sites used AAP/CDC guidelines to
inform clinical care; 11 used a published sepsis risk calculator; and 2 used
clinical observation alone.
Complete blood cell count (94.8%) and C-reactive protein (36.4%) were the
most common laboratory tests obtained and influenced duration of empirical
antibiotics at 13% of the sites.
Some degree of motherinfant separation was required for EOS evaluation at
95% of centers, and separation for the entire duration of antibiotic therapy was
required in 40% of the sites.

Mukhopadhyay S et al. Variation in Sepsis Evaluation Across a National Network of Nurseries. Pediatrics. 2017 Mar;139(3).
 ASNS in the Newborn Nursery
N(%)

Mukhopadhyay S et al. Variation in Sepsis Evaluation Across a National Network of Nurseries. Pediatrics. 2017 Mar;139(3).
 Impact of EOS Evaluations on Breastfeeding
Initiation

Mukhopadhyay S et al. Effect of early-onset sepsis evaluations on in-hospital breastfeeding practices among asymptomatic term
neonates. Hosp Pediatr. 2015 Apr;5(4):203-10.
 Antibiotic Use in the NICU

Included 127
NICUs, 52061
infants, and
746051
patient-days

AUR variation is detailed in Fig 1 and Table 1. Overall, AUR varied 40-fold, from 2.4% of patient-days to 97.1% of patient-
days (median = 24.5%; quartile 1 17.5%, quartile 4 33.5%). Regional NICU AUR varied almost sevenfold; community NICU
AUR varied 12-fold; intermediate NICU AUR varied almost 31-fold; non-CCS NICU AUR varied almost fivefold.

Schulman J. et al. Neonatal intensive care unit antibiotic use. Pediatrics. 2015;135(5):826-33.
 Antibiotic Risks in the NICU
Retrospective cohort analysis used prospectively collected data for all VLBW infants born at 32
weeks' gestation
Antibiotic therapy was recorded for 1140 infants from birth up to and including day 14 of life
Primary outcome was a composite of death before 36 weeks postmenstrual age or BPD
After controlling for CRIB-II score, each additional antibiotic day associated with increased risk for
the combined outcome of death or BPD (OR, 1.13; 95% CI, 1.09-1.16)

Cantey JB et al. Antibiotic Exposure and Risk for Death or Bronchopulmonary Dysplasia in Very Low Birth Weight Infants. J Pediatr. 2017 Feb;181:289-293.
 Empirical Antibiotics (Negative Cultures) and
Death or NEC in ELBWs
Retrospective cohort analysis of extremely low birth weight
infants admitted to tertiary centers in 19982001.
5693 ELBWs admitted to 19 centers, 4039 (71%) survived >5
days, received initial empirical antibiotic treatment, and had
sterile initial culture results through the first 3 postnatal days.
Median therapy duration was 5 days (range: 136 days); 2147
infants (53%) received prolonged empirical therapy (center
range: 27%85%)
Longer durations of initial empirical antibiotic treatment (>5
days) were more likely to be associated with NEC or death
and NEC alone

Cotten CM et al. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of
necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics. 2009 Jan;123(1):58-66.
 Empirical Antibiotics (Negative Cultures) and
Death or NEC in ELBWs
The NNTH (the number of infants
who would need to be treated with
prolonged initial empirical antibiotic
treatment before 1 infant developed
NEC or died who would not have
otherwise) was 22 infants. For death
alone, the number needed to harm
was 21 infants; for NEC, the value
was 54 infants.
 NICU Opportunities in ASNS:
Empirical Antibiotics in VLBW Infants

1999 to 2012, 2851 VLBW infants were admitted to the NICU.

109 nine EOS cases (20.5/1000 VLBW births
Preterm labor, preterm rupture of membranes and/or the obstetrical diagnosis of chorioamnionitis were
present in 106/109 cases (97
Time to culture positivity was 36 hours for 88% and 48 hours for 98% of cases.
From 1999 to 2013, 97% of VLBW infants were evaluated for EOS and 90% administered empiric
antibiotics;
22% of these infants were born by cesarean section to mothers with preeclampsia and without preterm
labor or chorioamnionitis and had a 12-fold lower incidence of EOS compared with the remaining infants.

Mukhopadhyay S, Puopolo KM. Clinical and Microbiologic Characteristics of Early-onset Sepsis Among Very Low Birth Weight Infants: Opportunities for Antibiotic
Stewardship. Pediatr Infect Dis J. 2017 May;36(5):477-481.
 NICU Opportunities in ASNS: Empirical
Antibiotics in VLBW Infants 1
#1 Consider birth indication as well as birth weight and gestation.
Preterm deliveries for maternal indications account for ~30% of preterm births
Absence of labor has in ~25% of the extremely low birth weight population
#2 The technical approach to blood culture.
If antibiotic decisions are to be guided by blood culture results, such cultures must be reliable.
At least 1 cc per bottle
Consider 2 cultures allowed for the determination of contaminant species in 15% of cultures with
microbial growth in this study
#3 Reflect on the concern that intrapartum antibiotics interfere with neonatal blood culture,
resulting in false-negative blood cultures, necessitating longer treatment.
Over 30% of women laboring at term now receive IAP
In this study1 68% of EOS case infants were born to women who received antibiotics before delivery.
Cannot make definitive conclusions regarding false-negative blood culture, did not find any difference
in TTP between infants born to women who did or did receive intrapartum antibiotics.1
Similar data in term newborns2 (TTP 19.6 hrs IAP, IQR 16-28 hrs vs. 19.5 hrs no IAP, IQR 17.2-21.6 hrs, p =
0.7489).
1.Mukhopadhyay S, Puopolo KM. Clinical and Microbiologic Characteristics of Early-onset Sepsis Among Very Low Birth Weight Infants: Opportunities for Antibiotic Stewardship. Pediatr Infect
Dis J. 2017 May;36(5):477-481.
2. Sarakar SS et al. Does maternal intrapartum antibiotic treatment prolong the incubation time required for blood cultures to become positive for infants with early-onset sepsis? Am J
Perinatol. 2015 Mar;32(4):357-62.