In a groundbreaking retrospective analysis spanning a decade, researchers from a single neonatal center have unveiled compelling insights into the pervasive use of antibiotics in preterm infants who show no clinical or laboratory evidence of infection. This comprehensive study, published in Pediatric Research, sheds light on a critical issue in neonatal medicine: the administration of antibiotics to culture-negative preterm neonates and its implications for both individual patient outcomes and broader antimicrobial stewardship practices.
The investigation meticulously reviewed medical records of preterm infants admitted over ten years, focusing specifically on those who received antibiotic treatment despite negative culture results for bacterial infection. This cohort represents a significant clinical challenge, as physicians must balance the imperative to preemptively combat potentially life-threatening infections against the risks associated with unnecessary antibiotic exposure. The study’s findings highlight not only the frequency and duration of antibiotic use in this vulnerable population but also underline the complexity of neonatal immune system evaluation in the absence of definitive microbial confirmation.
Antibiotics have long been a cornerstone of neonatal intensive care, particularly in preterm infants who are uniquely susceptible to sepsis due to their immature immune defenses and invasive medical interventions. However, indiscriminate antibiotic administration can lead to adverse outcomes, including disruption of the developing microbiome, increased risks of antibiotic resistance, and potential long-term impacts on neurodevelopment. This study provides critical data that underscore the urgent need for refined diagnostic criteria and judicious antibiotic stewardship in neonatal units worldwide.
One of the pivotal findings reported is the high prevalence of antibiotic exposure in culture-negative preterm infants. Over the study period, a substantial proportion of these neonates received antibiotics, often for extended courses, despite negative culture results. This trend reflects a prevailing clinical caution driven by the devastating consequences of missed infections but also points to inherent limitations in current diagnostic protocols, which may lack sensitivity or timeliness in confirming neonatal sepsis.
The study delves into the diagnostic methodologies employed for detecting infections, noting the reliance on blood cultures as the gold standard. However, blood cultures can be hampered by low sensitivity in neonates, sometimes yielding false-negative results due to low bacterial loads or prior maternal antibiotic exposure. In such contexts, clinicians may err on the side of caution, initiating or continuing empirical antibiotic therapies to mitigate perceived risks. The data further reveal that protracted antibiotic courses are often administered until clinical improvement or alternative diagnoses are made, prolonging infant exposure to these potent medications.
Another critical aspect explored is the impact of prolonged antibiotic exposure on the developing gut microbiota. Emerging evidence implicates early-life microbiome perturbations in predisposition to a host of conditions ranging from necrotizing enterocolitis to allergic and metabolic diseases. This study aligns with growing concerns that indiscriminate antibiotic use in culture-negative preterm infants might inadvertently contribute to these sequelae, reinforcing calls for targeted, evidence-based antibiotic prescribing practices that balance infection control with microbiome preservation.
The authors also examined temporal trends in antibiotic administration, observing fluctuations in prescribing patterns over the decade studied. These shifts may reflect evolving clinical guidelines, enhanced awareness of antimicrobial stewardship principles, and advancements in diagnostic technologies. However, despite such improvements, the persistence of high antibiotic exposure rates in culture-negative infants underscores ongoing challenges in decision-making processes within neonatal intensive care units.
Highlighting the complexity of neonatal sepsis evaluation, the study draws attention to emerging biomarkers and molecular diagnostic tools that promise greater sensitivity and specificity than traditional cultures. These advancements, including polymerase chain reaction assays and host-response biomarkers, offer potential avenues to more accurately discriminate infected from non-infected preterm infants, enabling clinicians to limit unnecessary antibiotic use without compromising patient safety.
The research also discusses the multifactorial factors influencing antibiotic prescribing practices, including clinical presentation heterogeneity, variability in institutional protocols, and differing interpretations of risk thresholds among practitioners. This heterogeneity calls for standardized algorithms incorporating clinical, laboratory, and emerging diagnostic data to guide antibiotic initiation and discontinuation decisions more consistently across neonatal care settings.
Moreover, the study underscores the importance of interdisciplinary collaboration among neonatologists, microbiologists, and pharmacists to optimize antimicrobial stewardship. Implementing stewardship programs tailored to the neonatal population could help mitigate unnecessary antibiotic exposure by promoting evidence-based guidelines, ongoing education, and systematic audit and feedback mechanisms.
From a public health perspective, the findings resonate with global efforts to combat antimicrobial resistance, emphasizing that neonatal intensive care units represent critical frontlines. Every dose of unnecessary antibiotic use in preterm infants potentially fuels resistance development, posing risks not only to individual patients but also to broader community health dynamics. Therefore, optimizing antibiotic use in neonatal care is paramount for sustaining the efficacy of current antimicrobial agents.
The study also calls attention to the ethical dimensions of antibiotic use in neonates, highlighting the tension between the imperative to do no harm and the drive to prevent catastrophic infections. This ethical landscape necessitates transparent communication with families about the rationale for antibiotic use, potential risks, and ongoing monitoring strategies, ensuring informed consent and shared decision-making where feasible.
Future research directions proposed by the authors include prospective studies incorporating advanced diagnostics and biomarker panels to refine risk stratification for infection in preterm infants. Additionally, interventional trials comparing antibiotic stewardship approaches could provide high-quality evidence to inform clinical guidelines, ultimately improving care quality and patient outcomes.
In conclusion, this seminal ten-year analysis provides an unprecedented window into antibiotic prescribing patterns in culture-negative preterm infants, revealing extensive exposure that challenges current neonatal care paradigms. By highlighting diagnostic limitations, potential adverse consequences, and stewardship opportunities, this study serves as a clarion call for innovation, collaboration, and vigilance in safeguarding both the immediate and long-term health of our most vulnerable patients.
As neonatal care continues to evolve with technological and scientific advancements, translating these findings into practice will be critical. Balancing the dual imperatives of protecting preterm infants from infection while minimizing the unintended harms of antibiotic overuse represents one of the defining challenges of modern neonatal medicine. This study lays the groundwork for such progress and marks an important milestone in our understanding of antibiotic administration in this sensitive population.
Subject of Research: Antibiotic exposure and usage patterns in culture-negative preterm infants within neonatal intensive care
Article Title: Antibiotic exposure in culture-negative preterm infants: a 10-year single-centre study
Article References:
Mackay, C.A., Nathan, E.A., Porter, M.C. et al. Antibiotic exposure in culture-negative preterm infants: a 10-year single-centre study.
Pediatr Res (2026). https://doi.org/10.1038/s41390-025-04707-5
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