Offer, Martina

Abstract Background Dalbavancin is increasingly used off-label for chronic Gram-positive bone and joint infections (BJIs) requiring prolonged antimicrobial therapy, but optimal dosing strategies and the role of therapeutic drug monitoring (TDM) remain unclear. We evaluated the real-world implementation of a proactive TDM-guided dalbavancin workflow within an outpatient parenteral antimicrobial therapy (OPAT) programme. Methods Single-centre prospective observational implementation study including adult patients with BJIs consecutively treated with dalbavancin in OPAT service between July 2022 and August 2025. A multidisciplinary team developed a workflow incorporating TDM-guided pharmacokinetic modelling to individualize dosing intervals after fixed initial administrations (Days 1, 8 and 43). Target Cmin concentrations were ≥8 mg/L, later increased to ≥15 mg/L after European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint revision. Primary outcomes included implementation metrics (feasibility, fidelity and appropriateness). Secondary outcomes were clinical effectiveness, safety and overall workflow success. Results The workflow was applied to 101 patients accounting for 418 TDM-guided dalbavancin administrations (feasibility). Three patient-driven treatment discontinuations were observed (3/101, 3.0%), and scheduled administrations occurred within the predefined time window in 335/418 (83.5%) of cases (fidelity). Pharmacological target attainment was achieved in 285/342 (89.6%) of administrations without dosing delays (appropriateness). Clinical effectiveness was achieved in 55/73 (75.3%) patients completing therapy, with 28/101 (28%) still on treatment. Adverse events–related discontinuation occurred in 3/101 (3%) patients. Overall workflow success was observed in 74/101 (73.2%) patients. Conclusions A multidisciplinary TDM-guided dalbavancin workflow within an OPAT programme was feasible and safe, achieving high target attainment and favourable clinical outcomes. This approach supports individualized long-acting dalbavancin therapy for complex chronic BJIs.

Background Bacterial infections remain a major global health burden, causing significant morbidity and mortality. Despite ongoing advances, prompt diagnosis is still hampered by nonspecific host biomarkers and the inherently slow turnaround of traditional microbiological cultures. These limitations often delay the initiation of appropriate treatments. In recent years, affinity-based proteomic approaches have been explored to address this gap. Among them, the Proximity Extension Assay (PEA) has emerged as a promising multiplexed protein quantification tool, capable of simultaneously measuring hundreds of immune and inflammatory proteins with high sensitivity from minimal sample volumes. Such technologies hold the potential to identify novel biomarkers, thereby improving both diagnosis and patient management in bacterial infections. Main body In this systematic scoping review, we examined studies applying PEA-based proteomics to adult bacterial infections. Out of the records screened, ten studies met inclusion criteria. Most were conducted in Europe and North America, relied primarily on plasma samples, and employed commercially available panels enriched for immune and inflammatory mediators. Study quality varied, with some evidence of variability and potential risk of bias. Across the 379 proteins investigated, a subset of proteins were consistently associated with bacterial infections across multiple clinical contexts, whereas others showed limited or no associations. Conclusions Current applications of PEA-based proteomics in adult bacterial infections is limited and largely exploratory. Rather than supporting immediate clinical translation, the available evidence suggests the value of PEA-based approaches for informing biomarker discovery. Future research should prioritize well-designed, longitudinal, and pathogen-stratified studies in clinically relevant settings to strengthen evidence robustness and support the rational development of proteomics-informed diagnostic and translational strategies.