Dalbavancin is a novel antimicrobial against Gram-positive pathogens: clinical experience beyond labelled indications

Abstract

Very limited labelled indications have been approved for the newer antimicrobials. Data on the clinical uses, efficacy and safety of dalbavancin are scarce, thus here we sought to describe our clinical experience. 16-month observational prospective study was performed. 19 (86%) were used under off-label indications. 10 (46%) for osteoarticular infections, 5 (23%) bloodstream infections and 3 (14%) endocarditis. To highlight, one patient received dalbavancin as long-term suppressive therapy. Most frequent use reasons were promptly hospital discharge, 11 (65%), and the presence of resistant organisms involving limited treatment options, 5 (23%). Successful outcome was observed in >95% of the patients and only 1 (4.5%) adverse event was reported. Further evidence beyond labelled indications is urgently needed. Despite the limitations, dalbavancin appears to be a safe and efficient option for adult patients who have tried and/or failed other therapies due to multidrug-resistant Gram-positive organisms.

Real-World Use of Dalbavancin in the Era of Empowerment of Outpatient Antimicrobial Treatment: A Careful Appraisal Beyond Approved Indications Focusing on Unmet Clinical Needs

“…In a case of prosthetic graft infection due to Enterococcus faecium , dalbavancin was successfully administered as long-term suppressive therapy for a total of 62 weeks. 40 Overall, relapse was reported in 3.5% of cases. The development of resistance to dalbavancin has emerged in only one case.…”

“… 5 Streptococcus spp. 4 P. acnes 21 Others 90 days after the last dose of dalbavancin Overall clinical success: 89% (66.7% CR-BSI) 90-day mortality rate: 5% (33.3% CR-BSI) Overall clinical failure: 5% NA 3% (overall) Nunez-Nunez et al, 2018 40 Prospective observational 1 (19 overall patients included in the study) 1 Long-term suppressive therapy in prosthetic graft infection 100% Dalbavancin 750 mg (LD) + 375 mg weekly for a total of 62 doses (IHD) 1 E. faecium 90 days Clinical success: 100.0% Relapse: 0.0% None Hitzenbichler et al, 2020 46 Case series 4 4 Long-term suppressive therapy for BSI due to intravascular source 2 LVAD 1 Transfemoral aortic valve implantation 1 Prosthetic aortic valve 100% Dalbavancin 1000 mg (LD) + 375/500 mg/weekly or 1500 mg (LD) + 1000 mg biweekly 2 E. faecalis 1 E. faecium + CoNS 1 MSRA NA Overall clinical success: 50% Overall mortality rate: 75% Relapse: 25% 50% ( C. difficile infection – Rash) Jones et al, 2018 47 Case report 1 CR-BSI with associated empyema OPAT Vancomycin + Piperacillin-Tazobactam + Levofloxacin Dalbavancin 1500 mg single dose E. faecalis NA Clinical success: 100.0% Relapse: 0.0% None Cho et al, 2015 48 Case report …”

“… Range median MIC 0.032–0.064 mg/L NA Clinical cure: 100.0% (BSI) Relapse: 4% (overall) 6.7% (not serious) Bouza et al, 2018 37 Retrospective cohort study, multicentric 10 8 CR-BSI 2 other endovascular infections OPAT 73.9% 97.1% (median 18 days) Dalbavancin 1500 mg single dose or 1000 mg (LD) + 500 mg 4 MRSA 3 CoNS 2 MSSA 2 Enterococcus spp. NA Clinical success: 80.0% Mortality rate: 10.0% Relapse: 0.0% 13.0% (2.9% serious) Bork et al, 2019 41 Retrospective cohort study, multicentric 10 (28 overall patients included in the study) 6 Endovascular 4 BSI OPAT 100% 100.0% (median 13.5 days) NA 8 MRSA 6 MSSA 4 CoNS 8 Other 5 NA 30–90 days Overall clinical success: 71% (BSI 60% at 30-day) NA 10.7% (overall) Nunez-Nunez et al, 2018 40 Prospective observational 5 (19 overall patients included in the study) OPAT 65% 100% Dalbavancin 1500 mg single dose or 1500 mg + 1500 mg or 1000 mg + 500 mg 7 MRSA 6 CoNS 5 MSSA 1 E. faecalis 1 E. faecium 90 days Clinical success: 100.0% Relapse: 0.0% 4.5% (not serious; overall) Bai et al, 2020 38 Retrospective cohort study, multicentric …”

“…Eleven observational studies [31][32][33][34][35][36][37][38][39][40][41] and five case reports 8,[42][43][44][45] assessed the efficacy and safety of dalbavancin for the treatment of infective endocarditis (IE; Table 2). Overall, 148 patients affected by infective endocarditis were treated with dalbavancin, resulting in a clinical success rate of 81.1%.…”

“…Ten observational studies, one case series, and six case reports 31,[33][34][35][36][37][38][39][40][41][46][47][48][49][50][51][52] assessed the efficacy and safety of dalbavancin for the treatment of bloodstream infections (BSIs) and vascular infections (Table 3). Overall, 144 patients affected by BSIs or vascular infections were treated with dalbavancin, resulting in a clinical success of 81.3%.…”