The CHROME Study, a Real-world Experience of Single- and Multiple-Dose Oritavancin for Treatment of Gram-Positive Infections

Abstract

Background Oritavancin (ORI) is a long-acting lipoglycopeptide indicated for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSIs) caused or suspected to be caused by susceptible Gram-positive (GP) pathogens. Methods Data collected from a retrospective observational program (2014–2017), Clinical and Historic Registry and Orbactiv Medical Evaluation (CHROME), describe the utilization, outcomes, and adverse events (AEs) associated with ORI in 440 patients treated at 26 US sites for ABSSSI and other GP infections. Results Clinical success in evaluable patients receiving at least 1 dose of oritavancin was 88.1% (386/438). In a subgroup of patients who received ORI for skin and soft tissue infections (n = 401) and bacteremia (n = 7), clinical success was achieved in 89.0% and 100%, respectively. A cohort of 32 patients received 2–10 ORI doses separated by no more than 14 days for complicated GP infections. Clinical success was observed in 30 of 32 patients (93.8%), including 10 of 11 (90.9%) patients with bone and joint infections and 7 of 8 (87.5%) patients with osteomyelitis. In the safety evaluable population, the overall rate of AEs was 6.6%. Conclusions We describe results from a real-world program that includes the largest multicenter, retrospective, observational study in patients who received at least 1 dose of ORI for the treatment of GP infections. This study confirms that ORI is an effective, well-tolerated antibiotic used in single and multiple doses for the treatment of ABSSSIs and complicated GP infections.

Advantages of Outpatient Treatment with Long‐Acting Lipoglycopeptides for Serious Gram‐Positive Infections: A Review

“…The reported results are encouraging, as success rates are comparable or exceed those observed with other commonly used agents 32–34 . A recent study reported oritavancin use in 440 patients for treatment of a variety of gram‐positive infections including bacteremia (n=7), OM (n=4), SA (n=3), and prosthetic joint infections (n=3) 35 . In many of these cases, oritavancin was used as salvage therapy after clinical failure with other agents.…”

“…A phase II, randomized, controlled trial of 75 adult patients with catheter‐related BSIs showed higher success rates (combined clinical and microbiologic response) with two doses of dalbavancin than daily vancomycin (87.0% vs 50.0%) 28 . Similar success rates for bacteremia have been documented for oritavancin 61 Due to low cerebrospinal fluid penetration, central nervous system involvement in the infectious process should preclude the use of either laLGP agent (Daniel Read, PhD (Medical Science Liaison), written communication, Allergan [dalbavancin manufacturer], 3/29/2019) 62 …”

Successful treatment of a prosthetic hip infection due to Enterococcus faecalis with sequential dosing of oritavancin and prosthesis preservation without prosthetic joint surgical manipulation

“…Oritavancin is a long-acting lipoglycopeptide antibiotic initially approved for the treatment of acute bacterial skin and skin structure infection (ABSSSI) and supported by the phase 3 SOLO program [ [8] , [9] , [10] , [11] ]. Its terminal half-life is 245 h. Dosage adjustments are unnecessary for patients with mild to severe renal or mild to moderate hepatic impairments [ [8] , [9] , [10] , [11] , [12] ]. Given its protein binding of 85 %, with a single dose of 1200 mg, the predicted free drug concentrations at seven days would exceed the breakpoints for labeled pathogens [ 12 ].…”

“…Oritavancin exerts bactericidal activity against gram-positive bacteria, including E. faecalis and E. faecium , regardless of vancomycin susceptibility [ 14 ]. Phase 3 SOLO studies and real-world experience demonstrated the safety and tolerability of oritavancin [ [8] , [9] , [10] , [11] , 15 ].…”

Continued Dosing of Oritavancin for Complicated Gram-Positive Infections

“…To date, no randomized controlled trials have been conducted to assess oritavancin' s efficacy in off-label indications or continued dosing, but several case reports and retrospective cohort analyses show promising outcomes. [8][9][10][11][12][13][14][15][16] In an analysis of data from the Clinical and Historic Registry and Orbactiv Medical Evaluation (CHROME) patient registry, 32 patients received multiple doses of oritavancin for complicated Gram-positive infections with a 93.8% overall clinical success rate, including success rates of 90.9% (10/11) for general bone and joint infections and 87.5% (7/8) for patients diagnosed specifically with osteomyelitis. 8 Patients received between 2 and 10 doses of 1,200 mg IV given every 6 to 14 days.…”