Head-to-head comparison of multi-dose oritavancin and dalbavancin for complicated infections: A propensity score-matched analysis.

BACKGROUND: Oritavancin and dalbavancin are long-acting lipoglycopeptide antibiotics approved for the treatment of skin and skin structure infections. Recently, they have been used for outpatient antimicrobial therapy for complicated infections. No head-to-head studies exist for this purpose. OBJECTIVE: To compare outcomes of patients treated with multiple doses of oritavancin or dalbavancin for complicated infections. PATIENTS AND METHODS: This was a single-centre, retrospective cohort study evaluating adult patients who received two or more doses of lipoglycopeptides for complicated infections from February 2019 through December 2022. Patients receiving oritavancin were compared to dalbavancin after propensity score-matching. The primary endpoint was clinical success at 90 days. Other endpoints included: 30-day re-admission, 30-day mortality, adverse drug reactions (ADRs), and changes in white blood cell count and inflammatory markers after the first dose. RESULTS: After exclusions and propensity score-matching, 131 matched pairs (N = 262) were included in the analysis. Most patients were receiving lipoglycopeptide therapy for osteomyelitis. There was no significant difference in clinical success at 90 days in patients who received oritavancin compared to those who received dalbavancin (99 [76%] vs. 103 [79%], respectively; P = 0.556). There was no significant difference in secondary endpoints, however, there was a trend towards higher incidence of ADRs oritavancin compared to dalbavancin (9 [7%] vs. 2 [2%], respectively; P = 0.060) which led to more treatment discontinuation. CONCLUSION: There was no significant difference in efficacy between multi-dose oritavancin and dalbavancin for the treatment of complicated infections. Both agents were generally well tolerated; however, dalbavancin may be better tolerated when long-term treatment is warranted.

Denosumab treatment lapses, discontinuation, and off-treatment fracture risk: A retrospective study of patients with osteoporosis in a real-world clinical setting.

INTRODUCTION: The purpose of this study was to retrospectively examine predictors of fracture risk when adult patients experienced a denosumab treatment lapse or discontinuation in a real-world clinic setting. MATERIALS AND METHODS: Eligible patients were adults who had received ≥2 doses of denosumab at an academic health center in the United States. Demographics, treatment doses, reasons for missed doses, and fractures, were collected retrospectively from electronic health records, from an 8-year period (2010-2018). The number of times each patient incurred a treatment lapse, defined as ≥240 days between two doses (excluding lapse due to discontinuation, death, or transfer of care) was computed. The occurrence of denosumab discontinuation (excluding discontinuation due to death or transfer of care), whether the patient initiated alternative therapy, and the reason for each lapse and discontinuation were collected. Cox proportional hazards models assessed characteristics associated with risk of fracture and treatment discontinuation. A logistic regression model was used to determine if cumulative amount of time off medication (i.e., cumulative lapse time) was associated with a higher likelihood of incurring a fracture. RESULTS: We included 534 patients: 95 % White, 86 % women, 33 % tobacco users, 13 % diagnosed with diabetes, median age 69 years (Interquartile Range (IQR): 62-77), and median Body Mass Index (BMI) 25 kg/m2 (IQR: 22-28). Thirty-six percent of patients incurred 250 lapses; 10 % discontinued therapy. Dental problems/procedures and logistical barriers were the most common reasons for lapses and discontinuations. Nineteen percent (n = 103) incurred a total of 190 fractures; of these, 121 were osteoporotic, 50 were vertebral. Risk of any, osteoporotic, and vertebral fractures were associated with off-treatment status (hazard ratio [HR] = 1.7, p = 0.043; HR = 2.0, p = 0.026; and HR = 4.2, p = 0.001, respectively) and older age (HR = 1.3, p = 0.015; HR = 1.5, p = 0.001; and HR = 1.8, p = 0.005, respectively). Older age was associated with higher risk of discontinuation (HR = 1.4, p = 0.022). There was a non-significant trend of a nonlinear association between incurring a fracture and cumulative lapse time (p = 0.087). CONCLUSION: Denosumab treatment lapses are common, and off-treatment status may be associated with a higher risk of fractures. Clinical teams should proactively identify and address adverse effects and potential logistical barriers to reduce the risk of treatment lapses.