Proactive therapeutic monitoring of dalbavancin concentrations in the long-term management of chronic osteoarticular/periprosthetic joint infections.

Here, we describe the use of proactive therapeutic drug monitoring (TDM) to individualize the optimal timing of drug injections in 16 adult patients with chronic osteoarticular infections receiving a median of 7 injections of dalbavancin (up to 12 injections in 15 months). Dalbavancin injections were repeated at medians of 39-47 days, with infusion intervals ranging from 26 to 69 days. TDM can facilitates a precise, targeted use of dalbavancin for infections requiring prolonged treatments.

Recurrent bacteremia and endocarditis due to Staphylococcus capitis in a patient with Bowen's disease: a case report.

This case report details the management of a 79-year-old male with recurrent methicillin-resistant Staphylococcus capitis bacteremia and endocarditis. The patient's clinical journey encompassed multiple hospital admissions, with challenges in managing endocarditis, pacemaker replacements, and potential cutaneous sources of infection. The treatment regimen included intravenous antibiotic therapy during hospitalization and suppressive antibiotic treatment upon discharge, alongside a decolonization strategy for his scalp lesions.

Dalbavancin as suppressive therapy for implant-related infections: a case series with therapeutic drug monitoring and review of the literature.

Implant-related infections may need suppressive antibiotic therapy (SAT). We describe a SAT strategy using dalbavancin with therapeutic drug monitoring (TDM). This is a retrospective bicentric study of patients with implant-related infection who received dalbavancin SAT between January 2021 and September 2023. Fifteen patients were included. Median number of injections was 4 (IQR: 2-7). Median time between two reinjections was 57 days (IQR 28-82). Dalbavancin plasma concentrations were above 4 mg/L for 97.9% of dosages (93/95) and above 8 mg/L for 85% (81/95). These results support the use of dalbavancin SAT for implant-related infections.

In-label, off-label prescription, efficacy and tolerability of dalbavancin: report from a National Registry.

PURPOSE: Although dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration. METHODS: We conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments. RESULTS: During the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15-96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%). CONCLUSION: In conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections.

Experience with dalbavancin use in various gram-positive infections within Aberdeen Royal Infirmary OPAT service.

PURPOSE: Dalbavancin, approved in 2014 for Gram-positive acute bacterial skin and skin structure infections (ABSSSI), has pharmacokinetics enabling treatment with one or two doses. Dalbavancin might be useful in outpatient parenteral antibiotic therapy (OPAT) of deep-seated infections, otherwise requiring inpatient admission. We documented our experience with pragmatic dalbavancin use to assess its effectiveness for varied indications, on- and off-label, as primary or sequential consolidation therapy. METHODS: Patients prescribed dalbavancin between 1 December 2021 and 1 October 2022 were screened for demographics of age, sex, Charlson comorbidity index (CCI), allergies, pathogens, doses of dalbavancin, other antibiotics administered and surgery. Where available, infection markers were recorded. The primary outcome was a cure at the end of treatment. Secondary outcomes included any adverse events and for those with treatment failures, response to salvage antibiotics. RESULTS: Sixty-seven per cent of patients were cured. Cure rates by indication were 93% for ABSSSI, 100% for bacteraemia, 90% for acute osteomyelitis, 0% for chronic osteomyelitis, 75% for native joint septic arthritis and 33% for prosthetic joint infection. Most bone and joint infections that were not cured did not have source control, and the goal of treatment was suppressive. Successful suppression rates were greater at 48% for chronic osteomyelitis and 66% for prosthetic joint infections. Adverse events occurred in 14 of 102 patients. CONCLUSION: This report adds to clinical experience with dalbavancin for off-label indications whilst further validating its role in ABSSSI. Dalbavancin as primary therapy in deep-seated infections merits investigation in formal clinical trials.

When surgical option is not provided: a successful multidisciplinary approach to a refractory case of sternal osteomyelitis following coronary surgery.

PURPOSE: Sternal osteomyelitis is a major complication of cardiac operations performed through median sternotomy. The surgical treatment, which involves the debridement and removal of whole infected and necrotic tissue is the standard of care, although it is sometimes unachievable. This may occur, for instance, when the infectious-inflammatory process invades the anterior mediastinum and tenaciously incorporates one or more of vital anatomical structures. METHODS AND RESULTS: An inoperable case of postoperative sternal osteomyelitis that involved the right ventricle and the right coronary artery, and that was successfully treated using a nonsurgical multidisciplinary approach, is reported here. CONCLUSION: For highly selected patients with sternal osteomyelitis for whom surgery is a too risky option, an approach including the contribution of various specialists might be a viable way out.

A systematic review of dalbavancin efficacy as a sequential therapy for infective endocarditis.

INTRODUCTION: Dalbavancin is an antibiotic characterized by an extended half-life and efficacy against methicillin-resistant Staphylococci. Currently, there are only narrative reviews summarizing the evidence about the use of dalbavancin for infective endocarditis (IE), many of which are focused primarily on its use as consolidation therapy. For this reason, we conducted a systematic review to describe the clinical efficacy and the safety of dalbavancin in IE treatment. METHODS: We searched for available evidence using the MEDLINE (PubMed), Embase, Scopus, Cochrane Library and Web of Science libraries, with no restrictions regarding the publication year. The risk of bias was performed using the Cochrane ROBINS-I tool for the comparative studies and the Newcastle-Ottawa Scale for descriptive studies. RESULTS: Nine studies were included. All of them were observational. Native valve endocarditis was the most common kind of IE found in the studies' populations (128/263, 48.7%), followed by prosthetic valve endocarditis, and cardiovascular implantable electronic device-related endocarditis. Coagulase-negative Staphylococci were the most common pathogens isolated (83/269, 30.1%), followed by S. aureus, Enterococci spp and Streptococci spp. Five out of nine studies documented a clinical failure rate of less than 10%. Dalbavancin showed a favourable safety profile. Dalbavancin appears to be a promising option for the consolidation therapy of IE. However, further studies comparing dalbavancin with standard of care are needed. PROSPERO REGISTRATION NUMBER: CRD42023430032.

Unraveling novel mutation patterns and morphological variations in two dalbavancin-resistant MRSA strains in Austria using whole genome sequencing and transmission electron microscopy.

BACKGROUND: The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains resistant to non-beta-lactam antimicrobials poses a significant challenge in treating severe MRSA bloodstream infections. This study explores resistance development and mechanisms in MRSA isolates, especially after the first dalbavancin-resistant MRSA strain in our hospital in 2016. METHODS: This study investigated 55 MRSA bloodstream isolates (02/2015-02/2021) from the University Hospital of the Medical University of Vienna, Austria. The MICs of dalbavancin, linezolid, and daptomycin were assessed. Two isolates (16-33 and 19-362) resistant to dalbavancin were analyzed via whole-genome sequencing, with morphology evaluated using transmission electron microscopy (TEM). RESULTS: S.aureus BSI strain 19-362 had two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene. Isolate 16-33 had a 534 bp deletion in the DHH domain of GdpP and a SNV in pbp2 (p.G146R). Both strains had mutations in the rpoB gene, but at different positions. TEM revealed significantly thicker cell walls in 16-33 (p < 0.05) compared to 19-362 and dalbavancin-susceptible strains. None of the MRSA isolates showed resistance to linezolid or daptomycin. CONCLUSION: In light of increasing vancomycin resistance reports, continuous surveillance is essential to comprehend the molecular mechanisms of resistance in alternative MRSA treatment options. In this work, two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene were newly identified as possible causes of dalbavancin resistance.

A comprehensive study on the identification and characterization of degradation products of lipoglycopeptide Dalbavancin using LC and LC-HRMS/MS.

Dalbavancin is the second-generation approved semisynthetic lipoglycopeptide by the United States Food and Drug Administration (USFDA) for the treatment of acute bacterial skin and skin-structure infections. Unlike other lipoglycopeptides, the stability behavior of Dalbavancin was least explored, which is a prerequisite. The current study endeavors to elucidate the oxidative and hydrolytic stability behavior of Dalbavancin by exposing the drug to oxidative, acidic, and basic stress conditions. A simple liquid chromatography (LC) method was developed, where significant resolution between Dalbavancin, its homologs, and the generated degradation products was achieved. Seven degradation products were identified under acidic, basic, and oxidative stress conditions. Using liquid chromatography and high-resolution mass spectrometry (LC-HRMS), MS/MS studies, the generated degradation products were identified and characterized. Formation of isomeric degradation products was identified especially upon exposure to basic stress conditions. The mechanistic fragmentation pathway for the seven degradation products was established, and the chemical structure for the identified degradation products was elucidated. The results strongly suggest that Dalbavancin is highly susceptible to degradation under oxidative and hydrolytic stress conditions. This study provides insights into the hydrolytic and oxidative stability of Dalbavancin, which can be employed during drug development and discovery in synthesizing relatively stable analogs.

Dalbavancin for the treatment of bone and joint infections: A meta-analysis.

BACKGROUND: Bone and joint infections are challenging infectious diseases to treat and require prolonged antimicrobial treatment. Dalbavancin demonstrated promising pharmacokinetic/pharmacodynamic properties for the treatment of these infections. The objective of this meta-analysis is to compare the effectiveness of dalbavancin to standard of care (SOC) for the treatment of bone and joint infections. METHODS: Two independent authors performed a comprehensive search through the major databases up to September 2023. Interventional and observational studies that compared the clinical success of dalbavancin to SOC for the treatment of osteoarticular infections (OAI) were included. RESULTS: A total of 6 studies and 581 patients were included, 282 in dalbavancin group and 299 in SOC group. Only one study was randomized clinical trial. When the data from the 6 studies were pooled in a meta-analysis, clinical success did not differ in those who received dalbavancin versus SOC (OR = 1.55, 95 % CI = 0.95-2.55, I-squared = 15.89 %) for the treatment of OAI infections. Four studies compared the two groups in terms of hospital length of stay and demonstrated a significant shorter length of stay in dalbavancin group compared to SOC group. Treatment-emergent adverse effects were reported in up to 21.4 % of patients in the dalbavancin group and up to 36.7 % of patients in the SOC group. CONCLUSION: This meta-analysis showed that dalbavancin is as effective as SOC for the treatment of patients with OAI infections. More data are needed to validate these findings.