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

Herawati, Fauna and Az’zahra, Faathimah and Anggeraini, Maria and Setiawan, Eko and Kantono, Kevin and Yulia, Rika (2026) Quantifying the Silent Selection Pressure: Antimicrobial Stewardship and Gut Microbiome Integrity in the NICU and PICU. Biomedicines, 14 (05). p. 1080. ISSN 2227-9059

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Abstract

Background: Antimicrobial stewardship in Neonatal (NICU) and Pediatric Intensive Care Units (PICUs) is complicated by rapid physiological maturation and the high vulnerability of the developing gut microbiome. Traditional metrics fails to capture the true utilization density of antibiotics in these settings. This study evaluated antimicrobial consumption patterns and alignment with the WHO AWaRe framework in two Indonesian hospitals and its impact towards patients’ length of stay. Methods: A retrospective multicenter study was conducted at a public hospital (Haji Hospital) and a private university hospital (HU Hospital) across 2024–2025. The study population includes all admitted patients (n = 315 in NICU and n = 12 in PICU) to calculate utilization density. Consumption was quantified using Defined Daily Dose (DDD)/100 bed-days, and qualitative assessment was performed using the WHO AWaRe classification. Results: Generalized linear modeling revealed that appropriate antibiotic therapy was significantly associated with a 17% reduction in hospital length of stay (β = −0.187, p = 0.002). At HU Hospital, PICU exhibited a seven-fold higher antimicrobial density (37.56 DDD/100) compared to NICU (5.22 DDD/100). At Haji Hospital, NICU density was 4.95 DDD/100 bed-days. Weight-normalized simulations revealed weight-based dosing disparity with low absolute DDD values in neonates mask a significant biological burden and intense selection pressure on the gut resistome due to immature renal clearance. While Haji Hospital maintained high “Access” category adher- ence (99.58%), HU Hospital’s PICU showed a high reliance on “Watch” agents (71.27%), specifically Ceftriaxone and Meropenem, which are known drivers of multidrug resistance. Conclusions: Low absolute dosing in neonates does not equate to low therapeutic density or reduced environmental pressure. The heavy use of broad-spectrum agents in the PICU acts as a primary driver for microbiome disruption. To mitigate the emergence of multidrug- resistant organisms, stewardship must transition from adult-indexed metrics (DDD) to more precise measures like Days of Therapy (DOT) and prioritize “Access” protocols to preserve microbiome integrity.

Item Type:	Article
Uncontrolled Keywords:	antimicrobial stewardship; anti-bacterial agents; drug utilization review; intensive care units; neonatal; intensive care units; pediatric; drug resistance; bacterial
Subjects:	R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Pharmacy > Department of Pharmacy
Depositing User:	BAMBANG SEPTIAWAN
Date Deposited:	11 May 2026 04:42
Last Modified:	11 May 2026 04:42
URI:	http://repository.ubaya.ac.id/id/eprint/50709

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