Can Oritavancin Be Used for Treatment and/or Suppressive Antimicrobial Therapy of Bone and Joint Infections Caused by Vancomycin-resistant Enterococcus faecium?

Background: Vancomycin-resistant enterococcus (VRE) infections pose substantial challenges for the treatment and suppression of bone and joint infections. Oritavancin, a long-acting lipoglycopeptide antibiotic, has shown promising in vitro activity against VRE. Limited data are available on using oritavancin for bone and joint infections caused by VRE, both for treatment (therapy to eliminate active infection) and suppressive antimicrobial therapy (long-term antibiotic administration to prevent infection recurrence in patients at high risk for that complication).

Questions/purposes: (1) What proportion of patients in a small case series achieve freedom from infectious symptoms with use of oritavancin for treatment of VRE bone and joint infections? (2) What proportion of patients achieve freedom from infection recurrence with use of oritavancin when used for suppressive antimicrobial therapy of VRE bone and joint infections? (3) What proportion of patients develop adverse drug events associated with oritavancin use in VRE bone and joint infections?

Methods: We describe a retrospective, multicenter, observational case series of patients who received oritavancin for treatment and/or suppressive antimicrobial therapy of VRE bone and joint infection, including osteomyelitis, native septic arthritis, myositis, and prosthetic joint infection, between December 2014 and April 2024. The minimum surveillance period was 1 year, unless infection recurrence or an adverse drug event was documented before 1 year. Patients were excluded if they had a life expectancy of less than 7 days, dual use of VRE antibiotics, or brain or spinal cord abscesses related to VRE, although no patients met these exclusion criteria in our study group. Clinical signs and symptoms of infection, corresponding microbiological cultures, and adverse drug events were assessed throughout follow-up. Eleven patients (6 treatment, 5 suppressive antimicrobial therapy) with VRE (all Enterococcus faecium) bone and joint infection in which at least one dose of oritavancin was used were included. No patients were excluded because of insufficient follow-up time. In the treatment group, the median (range) age was 60 years (48 to 66), 4 of 6 patients were male, and patients had received prior therapy for VRE with either linezolid or daptomycin. Infections were hardware-associated osteomyelitis in 2 of 6 patients, osteomyelitis in 3 of 6, and prosthetic joint infection in 1 of 6. In the suppressive antimicrobial therapy group, the median (range) age was 61 years (25 to 68), and 3 of 5 patients were female. Four of 5 patients had hardware-associated infections, including 3 of 5 with hardware-associated osteomyelitis and 1 of 5 with prosthetic joint infection of the hip.

Results: In the treatment group, 2 of 6 patients remained symptom free at a minimum follow-up of 3 years (range 3.0 to 3.25), and 2 patients developed recurrent infection-one with worsening knee stiffness and growth of VRE and one with radiologic signs of osteomyelitis and growth of methicillin-susceptible Staphylococcus aureus and Candida glabrata. One of 6 patients in the treatment group was lost to follow-up, and one pursued end-of-life care after 28 days. All 5 patients who underwent suppressive antimicrobial therapy remained free from recurrent symptoms with a minimum duration of therapy of 21 months (range 21 to 48). After 48 months of oritavancin as suppressive antimicrobial therapy, one patient in the cohort developed an infusion reaction-shortness of breath, cough, and hypotension-resulting in drug discontinuation.

Conclusion: In this small, retrospective cohort of patients with multiple comorbidities, oritavancin showed possible promise as suppressive antimicrobial therapy for VRE bone and joint infection, with all patients receiving suppressive antimicrobial therapy lacking recurrence of infectious symptoms. However, the role of oritavancin as treatment-in salvage situations after multiple therapies failed-appeared more limited in preventing infection recurrence. Larger studies are needed to further define the role of oritavancin in the treatment of VRE bone and joint infections.

Level of evidence: Level IV, therapeutic study.