Oral Antibiotic Pharmacokinetics in Young Infants

Characterizing Absorption Kinetics of Oral Antibiotics in Young Infants to Enhance Precision Dosing

This observational study will characterize the pharmacokinetics of linezolid in young infants. Participants will receive linezolid either as part of routine clinical care or as a single, one-time study dose. Blood samples collected following linezolid administration will be used to measure drug concentrations and describe how linezolid is absorbed, distributed, metabolized, and eliminated in this population. Clinical information, including demographic characteristics, laboratory values, and treatment details, will also be collected. The results will be used to develop pharmacokinetic models to improve linezolid dosing recommendations and support precision dosing in young infants.

Young infants are at increased risk for serious bacterial infections, yet limited pharmacokinetic data are available to guide evidence-based dosing of oral linezolid in this population. Developmental changes in drug absorption, distribution, metabolism, and elimination during early infancy contribute to variability in drug exposure, making it difficult to optimize dosing using existing recommendations.

This prospective pharmacokinetic study will enroll young infants who receive linezolid either as part of routine clinical care or as a single, one-time study dose. Blood samples will be collected to measure plasma linezolid concentrations, and demographic, clinical, laboratory, and medication data will be collected from the medical record. These data will be used to develop pharmacokinetic models and evaluate sources of variability in linezolid exposure, including developmental and clinical factors.

The results of this study are expected to improve the understanding of oral linezolid pharmacokinetics in young infants and support the development of model-informed dosing strategies to optimize antibiotic exposure, maximize treatment effectiveness, and minimize toxicity in this vulnerable population.

Inclusion Criteria:

• Hospitalized neonate or young infant ≤90 days postnatal age at screening
• Weight ≥2 kg
• Receiving systemic antibiotic therapy
• Tolerating enteral medication(s) and/or enteral feeds
• Group 1: Receiving oral linezolid as part of routine clinical care.
• Group 2: Receiving systemic antibiotic therapy but not prescribed linezolid clinically and eligible to receive a single oral study dose.

Exclusion Criteria:

• Known hypersensitivity or allergy to linezolid
• Renal dysfunction (defined by age-appropriate serum creatinine and/or urine output)
• Hepatic dysfunction (AST or ALT ≥3x age-specific upper limit of normal or clinically significant hepatic failure)
• Gastrointestinal disorders expected to significantly impair drug absorption (e.g., short bowel syndrome, severe malabsorption)
• Severe anemia or other condition that precludes study-required blood sampling
• Extracorporeal support or other devices expected to substantially alter drug pharmacokinetics (e.g., extracorporeal membrane oxygenation [ECMO]).
• Therapeutic hypothermia
• Ongoing clinical instability that, in the opinion of the treating team or principal investigator (PI), would make study participation unsafe (e.g., escalating vasoactive support or rapidly worsening organ dysfunction).