Antimicrobial-associated adverse events in neonates: an integrated literature review and FAERS pharmacovigilance analysis.

Antimicrobials are among the most frequently used drug classes in neonates, yet their safety profile remains incompletely characterized because neonatal pharmacokinetics, organ immaturity, off-label prescribing, and under-reporting complicate adverse event (AE) detection. This review aimed to synthesize published evidence on antimicrobial-associated AEs in neonates and to contextualize these findings using pharmacovigilance signals from the FDA Adverse Event Reporting System (FAERS). A structured literature review was conducted in PubMed, Embase, and the Cochrane Library to identify studies reporting AEs associated with antimicrobial exposure in neonates and preterm infants. In parallel, FAERS reports from Q1 2004 to Q2 2024 were retrieved through OpenVigil 2.1 for 12 commonly used antimicrobial agents: gentamicin, vancomycin, fluconazole, ampicillin, amphotericin B, metronidazole, piperacillin, meropenem, amikacin, amoxicillin, voriconazole, and cefotaxime. Reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network analyses were used to identify disproportionality signals. AEs were classified using MedDRA Preferred Terms(PTs) and System Organ Classes (SOCs). Published evidence grouped neonatal antimicrobial-associated AEs into three clinically relevant categories: secondary or resistant infections, immediate organ toxicity, and longer-term developmental or metabolic sequelae. The FAERS analysis identified 639 eligible neonatal reports and 97 disproportionality signals across 20 SOCs. The most frequently represented categories were infections and infestations, gastrointestinal disorders, and hepatobiliary disorders. Prominent PTs included systemic Candida infection, necrotizing enterocolitis neonatal, sepsis, respiratory disorder, multiple organ dysfunction syndrome, liver abscess, intestinal obstruction, hepatotoxicity, and tubulointerstitial nephritis. Notably, intestinal obstruction was associated with fluconazole (ROR: 75.95) and ampicillin (ROR: 59.51); capillary leak syndrome was detected for amphotericin B (ROR: 312.26) and fluconazole (ROR: 296.66); and multiple organ dysfunction syndrome was observed with voriconazole (ROR: 65.13) and fluconazole (ROR: 52.86). These signals are insufficiently characterized in the neonatal antimicrobial safety literature and warrant further investigation. This review provides a comprehensive synthesis of literature and pharmacovigilance data to support cautious and individualized antimicrobial use in neonates. Given the multifactorial nature of neonatal outcomes, these findings should be interpreted as associations rather than definitive causal relationships. Clinically, our results support conservative antimicrobial stewardship, individualized dosing, and organ-specific monitoring in routine neonatal intensive care unit (NICU) care. Future research should prioritize gestational age-stratified analyses and prospective registries linking antimicrobial exposure to long-term outcomes to define drug-specific safety profiles.