Oritavancin is a lipoglycopeptide antibiotic. The US Food and Drug Administration (FDA) approved oritavancin in 2014 for adults with acute bacterial skin and skin structure infections (ABSSSI). 1 The antibiotic is currently FDA approved for infections caused by Gram-positive organisms, including methicillin-resistant and methicillinsusceptible Staphylococcus aureus (MRSA, MSSA), a variety of Streptococcus species, and vancomycin-susceptible Enterococcus faecalis (VSE). Oritavancin demonstrates concentrationdependent bactericidal activity and has a half-life of 245 hours. This half-life allows for treatment of ABSSSI with a single 1,200 mg IV dose, which has been shown to be noninferior to vancomycin dosed twice daily for 7 to 10 days. 1-3
Proposal for Expanded Uses
Although the approved indication for oritavancin is narrow, in vitro studies have shown that oritavancin also has activity against vancomycin-resistant enterococci (VRE), and rabbit studies have demonstrated its excellent bone penetration. 4,5 These findings have raised the question of whether oritavancin can be safely and effectively used for infections such as endocarditis, osteomyelitis, and bacteremia, which are often caused by invasive Grampositive organisms. These types of invasive infections, particularly when MRSA is implicated, generally require IV antibiotic therapy for several weeks, often with vancomycin. 6
To avoid long hospital stays solely for antibiotic administration, health care practitioners will often use outpatient parenteral antimicrobial therapy (OPAT). However, using OPAT presents many challenges due to the need for frequent dosing, the risk of peripheral or central-line infections, and therapeutic drug monitoring when using vancomycin; additionally, administration and line care oftentimes require caregiver support, which may not be present for all patients. 7 Concerns also have been raised regarding the use of OPAT in patients with a history of IV drug use due to the potential increased risk of line infections or line abuse. Few studies have explored OPAT in this population, and the Infectious Diseases Society of America OPAT guidelines recommend that the decision to use OPAT should be made on a case-by-case basis. 7 Thus, patients who are deemed inappropriate for OPAT oftentimes remain hospitalized or reside briefly in nursing facilities solely for antibiotic administration
Oritavancin’s long half-life and potent activity against Gram-positive organisms has led to increased interest in off-label use of infrequent dosing intervals, such as weekly, to treat complicated and invasive infections. Weekly rather than daily dosing would allow for less burdensome antibiotic administration regimens and shorter hospital stays especially for patients who are not candidates for OPAT.
Efficacy of Continued Dosing
This proposed weekly dosing pattern, referred to as continued dosing or a multiple-dose regimen, has gained traction in the literature. 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. 8-16 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