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Quantifying the Silent Selection Pressure: Antimicrobial Stewardship and Gut Microbiome Integrity in the NICU and

Fauna Herawati1,2, Faathimah Az'zahra1, Maria Anggeraini1

  • 1Department of Clinical Pharmacy, Faculty of Pharmacy, University of Surabaya, Surabaya 60293, Indonesia.

Biomedicines
|May 27, 2026
PubMed

Insights

Antimicrobial stewardship in NICU and PICU settings requires better metrics than DDD. Appropriate antibiotic use significantly reduces length of stay, highlighting the need for precise measures like DOT to combat resistance.

Area of Science:

  • Pediatric Infectious Diseases
  • Antimicrobial Stewardship
  • Health Services Research

Background:

  • Neonatal (NICU) and Pediatric Intensive Care Units (PICUs) face unique antimicrobial stewardship challenges due to physiological immaturity and vulnerable gut microbiomes.
  • Traditional metrics like Defined Daily Dose (DDD) inadequately represent antibiotic utilization density in these critical care settings.
  • This study investigates antimicrobial consumption patterns and their impact on patient outcomes in Indonesian NICUs and PICUs.

Purpose of the Study:

  • To evaluate antimicrobial consumption patterns and adherence to the WHO AWaRe framework in two Indonesian hospitals.
  • To assess the impact of antimicrobial use on patient length of stay in NICU and PICU settings.
  • To identify limitations of current antimicrobial utilization metrics in pediatric intensive care.

Main Methods:

  • A retrospective multicenter study was conducted in two Indonesian hospitals (Haji Hospital and HU Hospital) from 2024-2025.
  • Included 315 NICU and 12 PICU patients, quantifying consumption using DDD/100 bed-days.
  • Qualitative assessment utilized the WHO AWaRe classification, with generalized linear modeling for outcome analysis.

Main Results:

  • Appropriate antibiotic therapy correlated with a significant 17% reduction in hospital length of stay (p=0.035).
  • HU Hospital's PICU showed substantially higher antimicrobial density (37.56 DDD/100) than its NICU (5.22 DDD/100).
  • Weight-normalized simulations revealed that low absolute DDD in neonates can mask intense selection pressure on the gut microbiome due to immature renal clearance; HU Hospital's PICU heavily relied on "Watch" agents (71.27%), contributing to resistance.

Conclusions:

  • Low absolute antibiotic dosing in neonates does not imply low therapeutic density or reduced environmental pressure.
  • High utilization of broad-spectrum antibiotics in PICUs is a primary driver of microbiome disruption and antimicrobial resistance.
  • Transitioning to precise metrics like Days of Therapy (DOT) and prioritizing "Access" antibiotics is crucial for effective stewardship and preserving microbiome integrity in pediatric intensive care settings.

Keywords:
anti-bacterial agentsantimicrobial stewardshipbacterialdrug resistancedrug utilization reviewintensive care unitsneonatalpediatric

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