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

Abstract

Severe gram-positive infections are frequent in people who inject drugs, and successful completion of treatment presents unique challenges in this population. 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. 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. 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. 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. Dalbavancin may be a safe and effective alternative for an early switch in treating severe gram-positive infections. The trial was registered as NCT04847921 with clinicaltrials.gov.