Substance use disorder-associated infections' treatment with dalbavancin enabling outpatient transition (SUDDEN OUT) - an investigator-initiated single-arm unblinded prospective cohort study

Abstract

Background: Severe gram-positive infections are frequent in people who inject drugs, and successful completion of treatment presents unique challenges in this population.

Objectives: We aimed to evaluate the feasibility of a long-acting antibiotic, dalbavancin, as an alternative to standard-of-care antibiotics for severe infections due to vancomycin-susceptible pathogens requiring ⩾2 weeks of therapy.

Design: We designed an investigator-initiated single-arm unblinded prospective cohort study to evaluate the safety and efficacy of an early switch to dalbavancin in two doses administered 1 week apart.

Methods: We screened patients admitted with bloodstream infection, osteomyelitis, septic arthritis, infective endocarditis or deep abscesses, and comorbid substance use disorder (SUD) for eligibility. Consenting patients were switched to dalbavancin within 7 days from their index culture. They were monitored in the hospital for efficacy and safety of the treatment until the second dose of dalbavancin 7 days later and then discharged if stable. Study participants were evaluated with a decision support engine for a hypothetical appropriate level of care regarding their SUD after discharge. Their follow-up was planned for 12 months from the index culture, either in-person or via telehealth/telephone.

Results: The enrollment was terminated early due to significant loss-to-follow-up. In all, 11 patients were enrolled, 4 completed 12 months of follow-up, 2 completed 8 months of follow-up, and 1 was seen once after discharge. The remaining five patients were lost to follow-up immediately after discharge. All 11 patients continued to improve after switching to dalbavancin between the first and second doses. There were two per-protocol failures of treatment. Dalbavancin was well tolerated, though some adverse events were reported.

Conclusion: Dalbavancin may be a safe and effective alternative for an early switch in treating severe gram-positive infections.

Trial registration: The trial was registered as NCT04847921 with clinicaltrials.gov.

Keywords: Staphylococcus; Streptococcus; bacteremia; bloodstream infection; dalbavancin; gram-positive bacteria; infective endocarditis; long-acting lipoglycopeptide; osteomyelitis; septic arthritis; substance use disorder.

Figure 1.

Follow-up timeline. No evidence of treatment failure. Treatment failure. Treatment failure due to loss-to-follow-up alone. 1 → 2, 7 days from first to second dose of dalbavancin; LTF, loss-to-follow up; lightning bolts represent AEs and are color coded to match respective patients; M with numbers, consecutive month of follow up; OPAT, period similar to standard of care OPAT (weeks 3–6); SOC, up to 7 days standard of care (green bolt 1, wound infection; green bolt 2, gram-negative rod catheter-associated bloodstream infection; green bolt 3, methicillin-susceptible Staphylococcus aureus bacteremia and spine infection; red bolt 1, allergic rash; red bolt 2, headache; black bolt, nausea/vomiting; blue bolt, splenic abscess/necrosis).