Antibiotic Stewardship in Assessing Risk of Early-onset Sepsis

Antibiotic stewardship programs aim to optimize antimicrobial use to prevent the emergence of resistance species and protect patients from the side effects of unnecessary medication. Antibiotic stewardship is not about giving fewer antibiotics; it’s about giving the right antibiotics, to the right babies, at the right time, and for the right reasons.

The high incidence of systemic instability and the morbidity and mortality from infections among newborns leads providers to frequently initiate antibiotic therapy, meaning empiric antibiotic courses are one of the main contributors to antibiotic use in neonatal units. Antibiotic use for culture-confirmed infection is a small contributor to overall NICU antibiotic utilization. Research suggests that early neonatal antibiotic exposure in particular may have negative consequences for both term and preterm infants.

Yet early-onset sepsis (EOS) is a serious and potentially fatal illness, particularly among preterm infants of the lowest gestational ages. Assessing newborn infants for risk of EOS is one of the most common clinical tasks conducted by neonatal providers. Traditional algorithms for management of neonatal EOS result in medical intervention for large numbers of uninfected infants. Our research has been focused on finding a better way to evaluate infants for infection, specifically EOS, in order to provide opportunities for stewardship practice and to optimize antibiotic initiation for the risk of EOS. We have come up with promising but different strategies for term and preterm infants.

Sepsis risk calculator

Working with collaborators at Kaiser-Permanente Northern California, we developed an accurate multivariate method for predicting risk of EOS among late preterm and term infants that combines maternal risk factors with objective measures of a newborn’s clinical examination. The sepsis risk calculator (SRC) includes the following steps:

Step 1: Begin with the population risk (eg, all you know is that it is a term baby born at 34 weeks or above).

• Prior probability of EOS

Step 2: Add the information you get before you even look at the baby (eg, maternal fever, duration of rupture of membranes, group B strep status) and modify the population risk.

• Modified prior probability of EOS

Step 3: Add the baby’s clinical status (eg, now you examine the baby). 

• Final posterior probability of EOS

Step 4: Make your decision to evaluate +/- empirically treat the baby for EOS.

Our local multidisciplinary teams of obstetric, neonatal, and information technology staff have collaborated to implement use of the SRC at our birth hospitals. Our obstetric electronic medical record was modified to provide a link to the SRC (available at neonatalsepsiscalculator.kaiserpermanente.org). Labor and delivery nurses calculate the sepsis risk at birth and alert neonatal clinicians to risk estimates. Subsequent interventions are based on the risk estimate and newborn clinical examination.

We have published our prospective validation and implementation work using this approach in everyday clinical care and demonstrated that using the SRC as the primary means of evaluating term infants for risk of EOS is a safe way to administer empiric antibiotics to a smaller proportion of newborns compared to use of previously recommended approaches. We have also done research using both single-center and multicenter longitudinal data to identify preterm infants at lowest risk of EOS. We have demonstrated that risk categorization using delivery characteristics can identify preterm infants at lowest risk of EOS. We are currently performing implementation work at Pennsylvania Hospital, part of the CHOP Newborn Care Network, to assess the safety and efficacy of preterm EOS evaluation based on this approach.

Our current funded research addressing the impact of intrapartum and neonatal antibiotic exposures includes:

Intrapartum Antibiotics Study

Funding: CDC grant 200-2017-96221 (Puopolo, PI; Mukhopadhyay, co-investigator) Title: “Perinatal Antibiotics and Weight Gain in Childhood” The purpose of this study is to determine the impact of perinatal antibiotic exposure on the rate of weight gain in the first 5 years of life. We are studying a cohort of ~14,000 children born in the University of Pennsylvania Health System and receiving pediatric care in the CHOP system.

Atopic Outcomes Study

Funding: NICHD 5K23HD088753-02 (Mukhopadhyay, PI; Puopolo, Mentor)

Title: “Incidence of Atopy and Childhood Infections in Uninfected Term Newborns with Perinatal Antibiotic Exposure”

One-third of American babies are exposed to antibiotics around the time of birth. We will assess the relationship of these antibiotic exposures to the development of early childhood allergy and infections. The results of this study may alter the perceived safety of prophylactic antibiotics and profoundly affect newborn clinical practice.

MAGIC Study

Funding: NIAID R01 AI121383 (Gerber, PI; Puopolo, co-investigator; Mukhopadhyay, co-investigator)

Title: “Early Life Antibiotics, Gut Microbiome Development, and Risk of Childhood Obesity”

The objective of this study is to assemble and follow longitudinally a large, diverse birth cohort to determine the relationship between (1) antibiotic exposure and gut microbiome development; (2) antibiotic exposure and weight gain/adiposity; and (3) microbiome development and weight gain/adiposity. We have recruited 420 of the anticipated 500 newborns and their families that have agreed to participate through 2 years of age.