Dalbavancin 500mg powder for solution for infusion vials

INTRODUCTION dalbavancin is approved for acute bacterial skin and soft tissue infections, but its off-label use in complex chronic infections has become increasingly common. Currently, no established dosing regimen exists for such infections. Given the need for prolonged treatments, a dose adjustment strategy based on therapeutic drug monitoring may optimize its use and allow for individualized regimens. This systematic review analyzes dalbavancin dosing in complex infections and TDM-based strategies to optimize treatment. MATERIALS AND METHODS A search was conducted in PubMed, Embase, Scopus, and the Cochrane Library (2014-2024) using the keywords: "dalbavancin", "pharmacokinetics", "pharmacodynamics", "therapeutic drug monitoring", and "TDM". Three independent reviewers selected and evaluated the studies. Clinical studies related to the pharmacokinetics of dalbavancin and the use of TDM in complex infections requiring prolonged regimens were included. Due to heterogeneity among studies, a qualitative analysis of the data was performed. RESULTS A total of 241 articles were identified. After removing duplicates and applying inclusion and exclusion criteria, 10 studies were included. These studies exhibited heterogeneity in design (6 retrospective and 4 prospective) and sample size, encompassing 457 patients and 1.298 samples. Most studies focused on osteoarticular infections treated with dalbavancin using an initial two-dose regimen of 1,500 mg administered one week apart, followed by dose adjustments based on plasma level monitoring. The most commonly targeted pharmacokinetic/pharmacodynamic parameters were a trough concentration above 8 μg/ml and an area under the curve/minimum inhibitory concentration ratio greater than 111.1. Therapeutic Drug Monitoring-Guided strategies were found to optimize dosing and maintain adequate plasma levels. Significant interindividual variability in plasma concentrations was observed, influenced by factors such as renal function and body surface area. DISCUSSION The use of Therapeutic Drug Monitoring in dalbavancin dosing optimizes the treatment of complex chronic infections by adjusting dosing intervals and maintaining adequate therapeutic levels over extended periods. However, further validation and definition of specific pharmacokinetic/pharmacodynamic targets are needed.

Abstract licence: CC BY-NC-ND

INTRODUCTION dalbavancin is approved for treating acute bacterial skin and soft tissue infections, but its off-label use for treating complex chronic infections has become increasingly common. Currently, there is no established dosing regimen for such infections. Given the need for prolonged treatments, a dosing adjustment strategy based on therapeutic drug monitoring may optimize its use and allow for individualized regimens. This systematic review analyzes dalbavancin dosing in complex infections and TDM-based strategies to optimize treatment. MATERIALS AND METHODS A search was conducted in PubMed, Embase, Scopus, and the Cochrane Library (2014-2024) using the following keywords: "dalbavancin", "pharmacokinetics", "pharmacodynamics", "therapeutic drug monitoring", and "TDM". Three independent reviewers selected and evaluated the studies. Clinical studies related to the pharmacokinetics of dalbavancin and the use of TDM in complex infections requiring prolonged regimens were included. Due to the heterogeneity among the studies, a qualitative analysis of the data was performed. RESULTS A total of 241 articles were identified. After removing duplicates and applying the inclusion and exclusion criteria, 10 studies were included. These studies exhibited heterogeneity in design (6 retrospective and 4 prospective) and sample size, encompassing 457 patients and 1.298 samples. Most studies focused on osteoarticular infections treated with dalbavancin using an initial two-dose regimen of 1,500 mg administered one week apart, followed by dose adjustments based on plasma level monitoring. The most commonly targeted pharmacokinetic/pharmacodynamic parameters were a trough concentration above 8 μg/ml and an area under the curve/minimum inhibitory concentration ratio greater than 111.1. Therapeutic Drug Monitoring-Guided strategies were found to optimize dosing and maintain adequate plasma levels. Significant interindividual variability in plasma concentrations was observed, influenced by factors such as renal function and body surface area. DISCUSSION The use of Therapeutic Drug Monitoring in dalbavancin dosing optimizes the treatment of complex chronic infections by adjusting dosing intervals and maintaining adequate therapeutic levels over extended periods. However, further validation and definition of specific pharmacokinetic/pharmacodynamic targets is required.

Abstract licence: CC BY-NC-ND

Purpose Infective endocarditis (IE) requires prolonged intravenous antibiotic therapy, leading to extended hospitalization and increased morbidity. Dalbavancin, a long-acting antibiotic with excellent tissue penetration and a favorable safety profile, can be a promising alternative. This systematic review aimed to investigate the current literature regarding the use of dalbavancin for infective endocarditis. Methods A systematic search of PubMed and Scopus was conducted according to PRISMA guidelines. Eligible studies included adult patients (≥ 18 years) with IE diagnosed by the modified Duke criteria, treated with dalbavancin as monotherapy or sequential/consolidation therapy. Data extraction included demographics, type of IE, causative pathogen, dosing regimen, surgical intervention, adverse events, and outcomes. Descriptive analyses were performed. Results Thirty-eight studies including 565 patients were analyzed. The overall cure rate was 88.0%, with a similar success rate across native valve (90.1%), prosthetic valve (90.0%), and cardiac device-related IE (86.0%). Staphylococcus aureus, Coagulase-negative staphylococci (CNS), Streptococcus spp., and Enterococcus faecalis were the most common pathogens. Cure rates were comparable among most pathogens, though a lower cure rate was evident in infections due to Enterococcus faecalis compared to Streptococcus spp. (80.7% vs. 96.6%, p = 0.008). An effective antimicrobial exposure of 2 weeks had similar success rate compared to a longer period of effective antimicrobial exposure (p = 0.31). Adverse events were rare (2.9%), with mild rash being the most common. Conclusions Dalbavancin demonstrates high cure rates and excellent tolerability in IE, and could offer an attractive alternative to conventional prolonged intravenous therapy. Further randomized controlled trials are warranted to define standardized protocols. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-026-05434-3.

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Background: Dalbavancin and oritavancin are long-acting lipoglycopeptides increasingly used off-label for a variety of Gram-positive infections. While their efficacy has been described in osteomyelitis, bacteremia, and infective endocarditis, evidence specifically addressing cardiovascular prosthetic infections such as prosthetic valve endocarditis (PVE), cardiac implantable electronic device (CIED) infections, left ventricular assist device infections (LVAD), and prosthetic vascular graft infections (PVGI) remains limited. These conditions are particularly challenging due to biofilm formation, difficulties in achieving surgical source control, and the frequent need for prolonged or suppressive therapy. Objectives: This systematic review aimed to summarize the available literature on the use of dalbavancin and oritavancin in cardiovascular prosthetic infections, with a focus on therapeutic strategies, clinical outcomes, and safety. Methods: We performed a systematic search of PubMed, Embase, Scopus, and Cochrane Library up to 24 June 2025 in accordance with PRISMA guidelines. Eligible studies included adults treated with dalbavancin or oritavancin for cardiovascular prosthetic infections. Data on study characteristics, population demographics, causative pathogens, and microbiological profiles, antibiotic regimens, treatment duration, use of therapeutic drug monitoring (TDM), indication or non-indication for chronic suppressive therapy, adverse events, clinical outcomes, and clinical efficacy were extracted. Results: Twenty studies comprising 113 patients were identified, of whom 111 received dalbavancin and 2 oritavancin. The main infections were PVE, CIED, LVAD, and PVGI. Dalbavancin was most effective as consolidation therapy after surgery or device removal, with high cure rates. Prolonged regimens were used as bridging or in partially treated cases, sometimes supported by TDM or PET/CT. Chronic suppressive therapy, mainly for LVAD and PVGI infections, achieved variable outcomes with relapses in about one fifth of patients. Adverse events were infrequent and generally mild. Conclusions: The included studies were highly diverse, conducted in various settings and with different objectives. Eight of the twenty included studies were single case reports on dalbavancin and oritavancin, highlighting the predominance of individual case descriptions in the available literature. Long-acting lipoglycopeptides may represent a valuable option for cardiovascular prosthetic infections. Their role appears most favorable as consolidation after adequate source control, while chronic suppressive use showed heterogeneous outcomes. This systematic review was registered on Open Science Framework. This work was supported by grants from the Italian Ministry of Health through Ricerca Corrente, Linea 3, Progetto 3.

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