Search Results (80)

Dalbavancin is a long-acting lipoglycopeptide antibiotic increasingly off-label used for the management of complex and chronic Gram-positive infections, including osteoarticular, prosthetic, and cardiovascular device-related infections. While its prolonged half-life enables infrequent dosing, marked inter-individual pharmacokinetic variability has been documented during extended treatment courses, potentially resulting in suboptimal exposure. This narrative review explores the role of proactive therapeutic drug monitoring (TDM) as a strategy to individualize dalbavancin dosing in patients requiring long-term therapy. We summarized current evidence on pharmacokinetic determinants of dalbavancin exposure, including renal function, body weight, and hypoalbuminemia, and discussed proposed pharmacokinetic/pharmacodynamic targets to support TDM implementation. Available analytical methods for dalbavancin quantification and clinical experiences with TDM-guided dosing are reviewed, highlighting their impact on optimizing injection timing and maintaining adequate drug concentrations over prolonged periods. In addition, emerging model-informed precision dosing approaches, such as Bayesian forecasting and machine learning-based tools, are discussed as promising strategies to further refine exposure prediction and re-dosing decisions. Overall, proactive TDM represents a valuable tool for optimizing dalbavancin therapy in chronic infections, although prospective multicenter studies are needed to validate target thresholds and standardized implementation strategies. Full article

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. Full article

Introduction: Suppressive antibiotic therapy (SAT) is a therapeutic alternative for complex infections where a cure is considered unlikely or impossible. SAT involves the prolonged, often indefinite, administration of antibiotics, typically given orally, to control symptoms. However, the increasing incidence of multidrug-resistant microorganisms limits the availability of oral options. Dalbavancin is a parenteral antibiotic with broad coverage against Gram-positive bacteria that offers the advantage of an extended dosing interval. The aim of this study was to describe the characteristics and clinical outcomes of patients with implant-associated osteoarticular infections receiving dalbavancin as SAT. A secondary objective was to identify factors associated with SAT failure with dalbavancin. Materials and Methods: We conducted a multicentre, observational study with retrospective recruitment of patients treated with dalbavancin as (SAT) for complex implant-associated osteoarticular infections, in which curative surgery was either not feasible or insufficient. Cohort characteristics were described, and variables associated with SAT failure under dalbavancin treatment were analysed. Results: A total of 43 patients received dalbavancin as SAT. The most frequent indication was prosthetic joint infection (38 [88.4%]). A total of 28 patients (65.1%) had chronic infections; the remaining cases were acute infections that had failed conservative management. Nine different dosing regimens of dalbavancin were used. Dalbavancin provided adequate symptomatic control in 32 patients (74.4%) over a follow-up period of 836.5 days (IQR 402–1288.5). The antibiotic was well tolerated; only one adverse effect was reported in a patient. Three patients developed resistance during treatment, which accounted for SAT failure. Conclusions: Dalbavancin is shown to be a safe and convenient alternative for SAT for orthopaedic implant infection. Although the development of resistance was infrequent, it can occur and should be monitored. Full article

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. Full article

Background: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as a genetically distinct lineage from healthcare-associated MRSA (HA-MRSA), often producing Panton-Valentine leukocidin (PVL) and causing severe skin and soft tissue infections (SSTIs) in otherwise healthy individuals. Methods: We describe five cases of PVL-positive CA-MRSA SSTIs admitted to the Infectious Diseases Unit of the University Hospital “Paolo Giaccone,” Palermo, Italy, between 2024 and 2025. Case inclusion followed the CDC criteria for CA-MRSA. Microbiological identification was performed using MALDI-TOF mass spectrometry, and antimicrobial susceptibility testing followed EUCAST standards. PVL gene presence was confirmed by polymerase chain reaction. Results: Clinical management included surgical drainage, systemic antibiotic therapy, and decolonization of both patients and close contacts. Long-acting lipoglycopeptides (oritavancin or dalbavancin) were evaluated as therapeutic options to achieve clinical resolution. Conclusions: PVL-positive CA-MRSA infections are characterized by recurrence, intrafamilial clustering, and frequent therapeutic failure with standard oral agents. Effective management requires an integrated approach combining prompt surgical drainage; systemic therapy, preferably including long-acting lipoglycopeptides; and comprehensive decolonization of all close contacts. Full article

Bone and joint infections remain therapeutic challenges, usually requiring prolonged intravenous therapy and hospitalization. Dalbavancin, a long-acting lipoglycopeptide, offers a simplified alternative. We retrospectively analysed 83 patients treated with dalbavancin for osteomyelitis, spondylodiscitis, septic arthritis, or prosthetic joint infection in two tertiary Greek hospitals (2022–2024). Mean age was 69 ± 16 years; 56.6% were male; Charlson Comorbidity Index averaged 4 ± 2.25. Common comorbidities included diabetes (28.9%) and coronary artery disease (18.1%). Infections were vertebral osteomyelitis/spondylodiscitis (48.2%), non-vertebral osteomyelitis (38.5%), prosthetic joint infection (10.8%), and septic arthritis (8.4%). Microbiological diagnosis was established in 62.6%; predominant pathogens were Staphylococcus aureus (38.4%: 30.7% MSSA, 7.7% MRSA) and enterococci (25%, including 5.7% VRE). Dalbavancin was administered as monotherapy (32.4%) or combined with other antibiotics (67.6%), mainly fluoroquinolones (63.6%) and minocycline (23.6%). Mean dosing was 2 ± 2.36 administrations (4 ± 4.38 g total). Surgical debridement was performed in 36.1% of patients. Clinically significant adverse events occurred in 4 patients (4.8%): acute kidney injury (n = 2), angioedema (n = 1), and Clostridioides difficile colitis (n = 1). Clinical cure was achieved in 90.4% at day 90 and 92.8% at day 180. Clinical cure rates were comparable between dalbavancin monotherapy and combination therapy, suggesting that the efficacy observed was primarily attributable to dalbavancin itself. Relapse at one year occurred in 10.8%, mainly due to inadequate source control. Dalbavancin demonstrated high efficacy, favourable safety, and treatment simplification in complex bone and joint infections. Its long half-life and reduced need for prolonged IV access support its role in minimizing hospitalization and catheter-related complications, particularly in regions with limited outpatient parenteral therapy infrastructure. Full article

Background and Clinical Significance: Corynebacterium striatum is an emerging multidrug-resistant pathogen increasingly implicated in infections among immunocompromised patients and patients with indwelling medical devices. Case Presentation: We report the probable first case of pseudomembranous inflammation associated with C. striatum infection in a 53-year-old male with an implanted left ventricular assist device (LVAD) awaiting heart transplantation. The patient experienced recurrent episodes of C. striatum bacteremia despite multiple courses of targeted antibiotic therapy, including vancomycin, linezolid, tedizolid, teicoplanin, and dalbavancin. During urgent heart transplantation, pseudomembranous tissue surrounding the LVAD driveline was observed, and cultures confirmed C. striatum device infection. Histopathological analysis revealed necrotic elements and Gram-positive organisms consistent with pseudomembranous inflammation. Conclusions: The case describes the diagnosis and treatment of this rare infection, highlighting the pathogenic potential of C. striatum, its role in device-related infections, and the histopathological evidence of pseudomembrane formation. Full article

Background: Data on antibiotic treatment for diabetic foot osteomyelitis are limited. This study aims to describe the real-world effectiveness and safety of dalbavancin in treating deep diabetic foot infections. Methods: A retrospective, observational, multicenter study was conducted in nine Spanish hospitals and one Irish hospital. Patients with diabetic foot osteomyelitis treated with dalbavancin were included. Data on demographics, clinical characteristics, microbiology, antibiotic regimens, adverse events, and clinical outcomes were analyzed. Results: Among 136 patients, 76% were male, with a mean age of 69 ± 12 years. Renal insufficiency was observed in 32%, and 6% required renal replacement therapy. Based on the McCabe scale, 70% of patients had a rapidly or ultimately fatal disease. Polypharmacy was noted in 83%, and 60% of infections were moderate. Dalbavancin was primarily used as second-line therapy (92%). The cure rate was 80.9% (95% CI: 73.5–86.6%), achieved after a median of two doses. Patients receiving dalbavancin as first-line therapy had a cure rate of 86%, comparable to 80% in second-line therapy, with no significant differences. Surgical interventions were required in 72% of cases, with minor amputations performed in 40% of patients. Polymicrobial infections were common (55%), and methicillin-resistant Staphylococcus aureus was identified in 26% of cases. Adverse events occurred in 5% of patients. Chronic kidney disease was the sole independent risk factor for therapeutic failure (IRR 0.80, 95% CI: 0.64–1.00, p = 0.045). Conclusions: Dalbavancin is effective and safe for treating diabetic foot osteomyelitis, including in complex patients with resistant microorganisms. Full article

Background: Skin and soft tissue infections (SSTIs) are a major cause of emergency room (ER) visits and hospitalizations. Long-acting lipoglycopeptides (LALs), such as dalbavancin and oritavancin, offer potential for early discharge and outpatient management, especially in patients at risk for methicillin-resistant Staphylococcus aureus (MRSA) or with comorbidities. Methods: We conducted a retrospective observational cohort study from March to December 2024 in an Italian tertiary-care hospital. Adult patients treated in the ER with a single dose of dalbavancin (1500 mg) or oritavancin (1200 mg) for SSTIs were included. Demographic, clinical, and laboratory data were collected. Follow-up evaluations were performed at 14 and 30 days post-treatment to assess outcomes. Results: Nineteen patients were enrolled (median age 59 years; 53% female). Most had lower limb involvement and elevated inflammatory markers. Three patients (16%) were septic. Fourteen patients (74%) were discharged without hospital admission; hospitalization in the remaining cases was due to comorbidities rather than SSTI severity. No adverse drug reactions were observed. At 14 days, 84% of patients had clinical resolution; only 10% had recurrence by day 30, with no mortality nor readmission reported. Conclusions: LALs appear effective and well-tolerated in the ER setting, supporting early discharge and reducing healthcare burden. Broader use may require structured care pathways and multidisciplinary coordination. Full article

Vancomycin, a cornerstone antibiotic against severe Gram-positive infections, is increasingly challenged by resistance in Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin Enterococcus spp. (VRE), necessitating the development of novel therapeutic strategies. This review examines how structural modifications to vancomycin can enhance its antibacterial activity and explores the critical role of computational approaches in designing the next generation of analogs. By analyzing the existing literature, we highlight how strategic alterations, such as the introduction of lipophilic side chains, substitutions on the sugar moieties, and modifications to the aglycone core, have yielded derivatives with improved antibacterial potency. Notably, certain analogs (e.g., Vanc-83, Dipi-Van-Zn) have demonstrated expanded activity against Gram-negative bacteria and exhibited enhanced pharmacokinetic profiles, including prolonged half-lives and improved tissue penetration, crucial for effective treatment. Semisynthetic glycopeptides like telavancin, dalbavancin, and oritavancin exemplify successful translation of structural modifications, offering sustained plasma concentrations and simplified dosing regimens that improve patient compliance. Complementing these experimental efforts, computational methods, including molecular docking and molecular dynamics simulations, provide valuable insights into drug–target interactions, guiding the rational design of more effective analogs. Furthermore, physiologically based pharmacokinetic modeling aids in predicting the in vivo behavior and optimizing the pharmacokinetic properties of these novel compounds. This review highlights a critical path forward in the fight against multidrug-resistant infections. By meticulously examining the previously carried out structural refinement of vancomycin, guided by computational predictions and validated through rigorous experimental testing, we underscore its immense potential. Full article

This study investigates the use of Neural Ordinary Differential Equations (NODEs) as an alternative to traditional compartmental models and Nonlinear Mixed-Effects (NLME) models for drug concentration prediction in pharmacokinetics. Unlike standard models that rely on strong assumptions and often struggle with high-dimensional covariate relationships, NODEs offer a data-driven approach, learning differential equations directly from data while integrating covariates. To evaluate their performance, NODEs were applied to a real-world Dalbavancin pharmacokinetic dataset comprising 218 patients and compared against a two-compartment model and an NLME within a cross-validation framework, which ensures an evaluation of robustness. Given the challenge of limited data availability, a data augmentation strategy was employed to pre-train NODEs. Their predictive performance was assessed both with and without covariates, while model explainability was analyzed using Shapley additive explanations (SHAP) values. Results show that, in the absence of covariates, NODEs performed comparably to state-of-the-art NLME models. However, when covariates were incorporated, NODEs demonstrated superior predictive accuracy. SHAP analyses further revealed how NODEs leverage covariates in their predictions. These results establish NODEs as a promising alternative for pharmacokinetic modeling, particularly in capturing complex covariate interactions, even when dealing with sparse and small datasets, thus paving the way for improved drug concentration predictions and personalized treatment strategies in precision medicine. Full article

Background: In Staphylococcus aureus, antimicrobial resistance (AMR) imposes significant fitness costs (FCs), including reduced growth rate, interbacterial competitiveness, and virulence. However, the FC molecular basis remains poorly understood. This study investigated the FC omic basis and compensatory adaptations in high-risk HA-, LA-, and CA-MRSA, acquiring mono- or cross-resistance to second-line daptomycin (DAP) and dalbavancin (DAL), as well as reduced susceptibility (RS) to first-line glycopeptides, i.e., vancomycin and teicoplanin (GLYs, i.e., VAN, TEC), related to the specific mechanism of action (MOA)-related AMR-mechanisms and genomic backgrounds, paying increasing FCs. Methods: The FC omic basis associated with mono- or cross- DAP-/DAL-R and GLY-RS were investigated by integrated omics. This study focused on core-genome essential (EG) and accessory virulence gene (VG) SNPomics and transcriptomics by Illumina MiSeq whole-genome sequencing, RNA-seq, and bioinformatic analysis. Results: Moderate impact nsSNPs were identified in EGs related to vital cellular functions and VGs. Comparative EG transcriptomics revealed differential expressions and key dysregulations—via asRNAs—prevalently affecting the protein synthesis and cell-envelope EG clusters, as well as the VG cluster. Conclusions: Our data, firstly, underlined the EG and VG mutation- and transcription-driven omic-based FC burden and the compensatory adaptations associated with the emergence of mono-DAP-R, cross-DAP-R/hGISA, and DAP-R/DAL-R/GISA, linked to specific MOA-related AMR-mechanisms and genomic backgrounds in high-risk HA-, LA-, and CA-MRSA. Full article

Introduction: Dalbavancin (DAL) is a long-acting lipoglycopeptide active against Gram-positive bacteria, including multidrug-resistant isolates. A growing body of evidence supports its efficacy in various difficult-to-treat infections. DAL shows time-dependent bactericidal activity in vitro at free drug concentrations equal to 4×MIC values. However, the optimal dosing scheme for achieving the PK/PD target in multidose treatment has not been fully established. Methods: Pharmacokinetic analysis was based on a nonlinear mixed effects modelling approach performed in NONMEM v7.5/Pirana, while R was used for data management and graphical summaries. Final model parameters were used to simulate the plasma disposition of DAL by Monte Carlo simulations to determine the multidose DAL regimen associated with a 90% target attainment of 100% fT > 4×MIC. Results: A two-compartmental model with first-order elimination and allometric-scaled bodyweight best described DAL disposition in patients with CLcr > 30 mL/min. Monte Carlo simulations showed that two 1500 mg DAL doses 7 days apart granted an optimal PTA > 90% of 100% fT > 4×MIC up to 5, 4, and 3 weeks in patients weighting from 40–80 kg, 80–120 kg and 120–200 kg, respectively. An additional third 1500 mg dose at the above time points by weight bands may extend the optimal PTA up to 9, 7, and 6 weeks of total treatment. Conclusions: Two 1500 mg DAL doses administered 7 days apart could be a valuable starting strategy for patients of all weight classes with CLcr > 30 mL/min. In patients requiring long-term DAL treatment, the optimal timing of additional administrations should be guided by routine TDM or empirically through patients’ total body weight when TDM is unavailable. Full article

Objectives: The aim of this work was to perform a systematic review assessing the pharmacokinetic/pharmacodynamic (PK/PD) properties of dalbavancin and the clinical use for in-label and off-label indications in pediatric patients. Methods: Two authors independently searched the PubMed-MEDLINE and Scopus databases and clinicaltrials.gov up to 20 November 2024, to retrieve randomized controlled trials (RCTs), observational studies, PK studies, and case series/reports assessing dalbavancin PK/PD properties or the clinical use for both in-label and off-label indications in pediatric patients. Data were independently extracted by the two authors, and the quality of the included studies was independently assessed by means of specific tools according to study design. Clinical success was selected as the primary outcome. Descriptive statistics were used for summarizing the retrieved data. Subgroup analysis according to PK/PD data, as well as in-label and off-label indications, was performed. Results: After screening 206 articles, nine studies were included in the systematic review (one RCT, three PK studies, and five case series/reports; n = 267). Dalbavancin exposure was 30% lower in pediatric patients compared to adults. In acute bacterial skin and skin structure infections (ABSSSIs), the overall clinical success of dalbavancin was 96.1-97.3% and 92.9% in RCT and case series, respectively. Bone and joint infections (60.7%) and central-line-associated bloodstream infections (14.3%) represented the most common dalbavancin off-label indications in pediatric patients. Overall, the clinical success for off-label indications was 92.9%. The rate of adverse events ranged from 7.1% to 10.7%. Conclusions: Our systematic review summarized evidence concerning the PK/PD properties of dalbavancin and its use for in-label or off-label indications in pediatric patients. The available findings suggest that dalbavancin may be a valuable alternative for the management of ABSSSIs and/or off-label indications in pediatric patients according to efficacy and safety data, allowing for a potential minimized duration of hospital stay. Full article