Dalbavancin in the Treatment of Bacteremia and Endocarditis in People with Barriers to Standard Care

Abstract

Introduction: Dalbavancin is an antibiotic administered by intravenous infusion weekly or bi-weekly and is currently FDA-approved only for treatment of skin and soft-tissue infections. It has shown promise, but is not considered the standard of care, for bacteremia and infective endocarditis (IE), which typically require outpatient parenteral antibiotic therapy (OPAT) for prolonged durations. People who inject drugs (PWID) with bacteremia or IE are often perceived as having barriers to OPAT and standard daily-administered antibiotics, prompting off-label use of dalbavancin in this population. Methods: A retrospective review of adult patients receiving at least one dose of dalbavancin for bacteremia or IE was conducted between 1 November 2017 and 31 October 2019. Outcomes and reasons for use of dalbavancin were recorded, including specific barriers to standard therapy. Results: Stated reasons for dalbavancin use in the 18 patients identified included active injection drug use (50%), inability to arrange standard OPAT due to patient adherence or inability to place in skilled nursing facility (SNF) (22%), risk for additional infections or other morbidity with OPAT (22%), and patient preference (6%). In 11 patients (61%) SNF placement was not attempted due to behavioral issues or patient declination. There were five patients who did not complete their intended course of treatment (28%). At 90 days, eight patients (44%) achieved a clinical or biologic cure, six (33%) failed treatment, and four (22%) were lost to follow-up. Conclusion: Dalbavancin may have a role as salvage therapy in the treatment of IE and bacteremia in PWID who have significant barriers to standard treatment.

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

“…of Patients Clinical Features Prior Antibiotic and Duration Antibiotic and Dosing Isolates Duration of Follow-Up Outcome Relapse Rate – Resistance Development Safety (Overall Proportion of AEs) Hidalgo-Tenorio et al, 2019 31 Retrospective cohort study 49 69.4% complicated BSI OPAT 93.8% 93.9% (median 8 days) 44.9% daptomycin 22.4% vancomycin 20.4% ceftriaxone 18.4% linezolid Dalbavancin 1000–1500 mg single-dose or 1000 mg (LD) + 500 mg 17 CoNS 15 MSSA 9 MRSA 2 Streptococcus spp. 2 E. faecium 1 E. faecalis 1 Other 90 days Clinical success: 100.0% Microbiological eradication: 97.2% Mortality rate: 0.0% Relapse: 0.0% 4.8% (not serious) Ajaka et al, 2020 39 Retrospective cohort study 14 Active injection drug user: 57.1% 100% (range 2–30 days) Dalbavancin 1500 mg single dose or 1000 mg (LD) + 500 mg or 1500 mg + 1000/1500 mg 8 MRSA 3 MSSA 2 GAS 2 CoNS 1 S. lugdunensis 1 E. faecalis 90 days Clinical success: 50.0% Microbiological eradication: 50.0% Mortality rate: 21.4% Relapse: 14.3% NA Vazquez Deida et al, 2020 36 Retrospective observational case series 13 9 complicated (2 with pneumonia) 4 uncomplicated 100.0% (range 6–27 days) 1500 mg single dose 10 MSSA 3 MRSA 1 GAS 1 S. anginosus 90 days …”

“…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%.…”

Review: A Safety Profile of Dalbavancin for On- and Off-Label Utilization

“…As regards off-label use of the drug, studies have been conducted in clinical practice [34][35][36][37][38][39][40][41][42][43][44][45] in patients with osteomyelitis, spondylodiscitis, gram-positive endocarditis, prosthetic infections, septic arthritis, and more generally in all those infections characterized by the presence of an important biofilm, confirming the effectiveness and safety of the drug. In a retrospective study 46 by Morata et al on 64 patients suffering from osteoarticular infections with S. aureus and S. epidermidis, only 7 cases of AEs were observed, including 1 self-limited rash, 3 gastrointestinal problems, 1 asthenia, 1 phlebitis, and 1 case with serum creatinine increase of 0.5 mg/dl.…”

New-Generation Antibiotics for Treatment of Gram-Positive Infections: A Review with Focus on Endocarditis and Osteomyelitis

“…For catheter-related BSI, in a phase 2 study with 75 patients, dalbavancin therapy showed a significantly higher success rate than vancomycin (87% vs. 50%) [80]. Further-more, dalbavancin seems to be a promising option for outpatient parenteral antibiotic therapy [81] or long-term suppression therapy [82].…”