Empiric Antibiotics in Extremely Low Birthweight Neonates: Do they Do More Harm than Good?

The NICU Antibiotics and Outcomes Trial (NANO) seeks to answer this important clinical question.

For infants born with extremely low birthweight, clinical use of empirically administered antibiotics has been common as a prophylactic measure against early-onset sepsis from exposure to intraamniotic pathogens.

While the incidence of early-onset sepsis is low in this patient population, it can be challenging to determine who is most at risk. Therefore, empirically administered broad-spectrum antibiotics have been commonly used while clinicians assess and wait for pathology and microbiology results to guide continuation/discontinuation of the agents.

However, recent studies suggest that this practice and the use of empirically administered antibiotics may set up some of these infants to develop necrotizing enterocolitis, late on-set sepsis, and an overall increased risk for mortality.

To uncover if these morbidities are associated with empirically administered antibiotics in this patient population, a new multicenter trial, the NICU Antibiotics and Outcomes Trial (NANO), developed and led by the Division of Pediatric Surgery at UPMC Children’s and the UPMC Newborn Medicine program, is in progress and recruiting participants at 13 sites around the U.S.

Leading the study is principal investigator Michael Morowitz, MD, FACS, Professor of Surgery in the Department of General and Thoracic Surgery at UPMC Children’s, and Toby Yanowitz, MD, Associate Professor of Pediatrics and Director of Clinical Research in the UPMC Newborn Medicine Program.

“While empirically administered antibiotics is a long-standing practice, there’s little hard evidence on its utility and risks,” says Dr. Morowitz. “With some of the recent studies coming out related to NEC, sepsis, and mortality, it is important to answer the question as to whether to practice should continue, and if so, in which patients.”

Study Highlights and Details

The NANO study will enroll 802 participants to randomly receive ampicillin, gentamicin, or a placebo in order to test the hypothesis that, “the incidence of adverse outcomes is higher in babies receiving empiric antibiotics (EA) in the first week of life compared to babies receiving placebo.”

“We’re specifically interested in those infants with extremely low birthweight, less than 1000 grams, for whom its most difficult to determine if antibiotics should be administered,” says Dr. Yanowitz. “Infants who are clinically stable and did not have a known exposure to intraamniotic infection and were not born preterm for maternal indications is where the challenge and controversy lies.

Given the extremely grave nature of NEC and its downstream consequences, sepsis, and other potential long-term complications, the NANO trial will provide urgently needed data to help shape clinical practice and potentially avoid or lessen the risk of iatrogenic injury from the practice.

Full details of the study protocol and more information on the NICU Antibiotics and Outcomes (NANO) trial protocol can be found at ClinicalTrials.gov (NCT03997266).

Learn more about Dr. Morowitz and Pediatric Surgery at UPMC Children’s.

Learn more about Dr. Yanowitz and UPMC Newborn Medicine Program.

Further Reading

Morowitz MJ, Katheria AC, Polin RA, Pace E, Huang DT, Chang C-C H, Yabes JG. The NICU Antibiotics and Outcomes (NANO) trial: A Randomized Multicenter Clinical Trial Assessing Empiric Antibiotics and Clinical Outcomes in Newborn Preterm Infants. Trials. 2022 May 23; 23(1): 428.