TDM-Guided Dalbavancin Treatment for Complex Staphylococcus aureus Osteoarticular Infections in Children

Background/Objectives: Dalbavancin is approved for pediatric acute bacterial skin and skin structure infections (ABSSSIs), yet real-world practice frequently necessitates off-label use for deep-seated infections requiring prolonged suppression. While adult data support therapeutic drug monitoring (TDM)-guided maintenance, the pediatric evidence for repeated-dose pharmacokinetics (PK) is limited. We evaluated the efficacy, safety, multi-dose PK, and pharmacoeconomic impact of dalbavancin in a complex pediatric cohort. Methods: A retrospective study (2023-2025) of enrolled patients < 18 years treated with dalbavancin. A subgroup receiving ≥3 doses underwent PK analysis to assess concentration decay against conservative efficacy targets (4 and 8 mg/L). A pharmacoeconomic analysis compared resource utilization against the standard of care. Results: Sixteen patients (median age 12) were included, primarily treated for Staphylococcus aureus (S. aureus) osteoarticular infections (75%), and frequently device-associated (66.7%). Clinical success was 93.8% (15/16) with no adverse events. A PK analysis (n = 9; 78 samples) ruled out dangerous accumulation but revealed a significant concentration drop at week 4 (mean 6.06 mg/L; p = 0.005). Logistic regression identified the time since the previous dose as the sole predictor of sub-therapeutic levels, with >50% of the patients dropping below 8 mg/L by the fourth week. An analysis showed median net savings of EUR 3215.84 per patient (p = 0.004). Conclusions: Dalbavancin is effective and cost-saving for complex pediatric infections. However, due to distinct pediatric PK, dosing regimens extrapolated from adults may result in sub-therapeutic concentrations by week 4. We recommend TDM around week 3 to tailor dosing or limiting maintenance intervals to a maximum of 4 weeks.