Shorter Antibiotic Courses Appear Safe for Uncomplicated Gram-Negative Bloodstream Infections in the NICU

Neonatology and pediatric pharmacy partner to advance antibiotic stewardship.

For years, Pablo J. Sánchez, MD, principal investigator in the Center for Perinatal Research in the Abigail Wexner Research Institute at Nationwide Children’s Hospital, observed that approximately 7 days of antibiotic therapy appeared sufficient for selected neonates with uncomplicated gram-negative bloodstream infections that does not involve the central nervous system. This practice contrasts with traditional recommendations favoring longer treatment durations.

Pablo J. Sánchez, MD

“Prolonged antibiotic treatment is routine in many centers,” Dr. Sánchez explains. “However, in our experience, shorter courses are often adequate for uncomplicated infections. We wanted to formally evaluate the safety of this approach.”

That clinical observation, combined with ongoing neonatal antimicrobial stewardship discussions, led to a multicenter retrospective study published in The Journal of Pediatrics.

The research team compared short-duration therapy (8 days or fewer) with long-duration therapy (9 days or more) in infants treated for uncomplicated gram-negative bloodstream infections across 7 neonatal intensive care units within two health systems in Columbus, OH and San Antonio, TX.

Colleen Djordjevich, PharmD, BCPPS, a neonatal intensive care unit patient care pharmacist at Nationwide Children’s, led data collection as a pediatric pharmacy resident under Dr. Sánchez’s mentorship. Jacqueline K. Magers, PharmD and Pavel Prusokiv, PharmD at Nationwide Children’s contributed to the study, while Joseph B Cantey, MD was the lead author for the San Antonio site.

Colleen Djordjevich, PharmD

“Our goal was to determine whether we could safely implement shorter therapy in this specific population,” Dr. Djordjevich says. “Given the known risks of prolonged antibiotic exposure, duration matters.”

The study included 76 infants, 39 in the short-duration group and 37 in the long-duration group. Infants with polymicrobial infections, meningitis, osteomyelitis, endocarditis or death prior to completion of therapy were excluded. The primary outcome was the recurrence of bloodstream infection with the same organism within 14 days of antibiotic discontinuation. Secondary outcomes included the development of later multidrug-resistant gram-negative infections and mortality.

The median duration of therapy in the short and long duration groups was 7 and 14 days, respectively. Escherichia coli was the most common pathogen in both groups. Two recurrences occurred, both in the long-duration group. All five subsequent multidrug-resistant infections occurred in infants who received 9 or more days of therapy. Mortality did not differ between groups.

This evidence suggests that extending therapy beyond 7 days does not reduce recurrence and may increase exposure to downstream risks.

The investigators also examined antibiotic selection. Once clinicians determined susceptibilities, one targeted agent usually proved effective. Broad-spectrum antibiotics, such as third- or fourth-cephalosporins, failed to improve outcomes.

“Our approach emphasizes narrowing to an appropriate single agent whenever possible,” Dr.Djordjevich says. “We did not observe increased injury or adverse outcomes with this strategy.”

The American Academy of Pediatrics Red Book recommends a minimum of 10 days of therapy for neonatal bacteremia.[2] However, practice variation remains substantial across institutions.

This research grew out of discussions with members of the Nationwide Children’s Neonatal Antimicrobial Stewardship Program aimed at safely shortening treatment to reduce unnecessary antibiotic exposure and associated risks such as microbiome disruption, invasive fungal infections and multidrug-resistant organisms.

“Reducing unnecessary days of antibiotic treatment aligns with our current stewardship priorities,” Dr. Sánchez explains.

“This collaboration between neonatology and pediatric pharmacy allows us to evaluate treatment approaches more rigorously,” Dr. Djordjevich adds. “Integrating pharmacy expertise into the neonatal intensive care unit is essential to optimizing care for critically ill infants.”

Both investigators stress that these findings apply only to uncomplicated, monomicrobial gram-negative bloodstream infections without signs of focal or metastatic infection. Infants with persistent bacteremia, ongoing instability or disseminated infection need individualized treatment.

“Our ultimate goal is to inform prospective trials that can guide future updates to neonatal treatment recommendations,” Dr. Sánchez says. “Optimizing antibiotic duration is essential to balancing effective treatment with minimizing unintended harm in this vulnerable population.”

References:

1. Djordjevich CJ, Magers J, Cantey JB, Prusakov P, Sánchez PJ. Duration of Antibiotic Therapy for Gram-Negative Bloodstream Infections in the Neonatal Intensive Care Unit. Journal of Pediatrics. 2026 Jan 17:292:114993
2. Pediatrics AAP. Serious Neonatal Bacterial Infections Caused by Enterobacterales (Including Septicemia and Meningitis). In: Kimberlin DW BR, Barnett ED, Lynfield R, Sawyer MH, editor. Red Book: 2024-2027 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics; 2024. p. 365-368.

Image credit: iStock (header); Nationwide Children’s (portraits)