Oritavancin as a Therapeutic Regimen for Cardiac Implantable Electronic Device Infections with Multidrug-Resistant Gram-Positive Cocci: Clinical Case Reports from the ORI-4-CIEDi Study

Background: Cardiac implantable electronic device (CIED) infections require transvenous lead extraction, followed by 2–6 weeks of antimicrobial treatment. Case presentation: This series describes CIED infection cases treated with the long-acting lipoglycopeptide antibiotic oritavancin, based on preliminary data from the ORI-4-CIEDi study (ClinicalTrials.gov ID: NCT07013552). Eleven patients (2 women), with a median age of 67.0 years (range 28.0–78.0), received oritavancin administered as a single dose or as multiple doses at 7-day intervals. The etiological factors included: (1) methicillin-sensitive (MS) or methicillin-resistant (MR) coagulase-negative staphylococci (CoNS) in three cases; (2) MS Staphylococcus aureus and MS-CoNS; (3) MR-CoNS and vancomycin-resistant (VRE) Enterococcus faecium; (4) vancomycin-intermediate S. aureus and VRE E. faecium; (5) MR-CoNS, Corynebacterium spp., Peanibacillus humicus, and Acinetobacter baumannii; and (6) Gram-positive rod Bacillus cereus. In two cases, oritavancin therapy was continued empirically. In one case, only Gram-negative bacillus Pseudomonas stutzeri was cultured, leading to discontinuation of oritavancin. Nine participants (81.8%) underwent transvenous lead extraction (TLE), one (9.1%) received pocket debridement and relocation, and one (9.1%) was managed conservatively. Definitive treatment success, defined as a clinical response without recurrence of infection during the 3-month follow-up, was achieved in five participants (62.5%) with infections involving Gram-positive cocci and in two participants (100.0%) with infection of unknown etiology, including one managed conservatively. In two cases infected with Gram-positive cocci, follow-up after TLE was discontinued prematurely due to death from cardiogenic shock, and only complete healing of the surgical wound was observed. In the patient who had undergone non-radical surgery, long-term suppressive therapy against CoNS proved ineffective. Discussion: Weekly administration of long-acting oritavancin in CIED infections with Gram-positive cocci has the potential to enhance patient comfort and support outpatient parenteral antimicrobial therapy. Conclusions: These preliminary findings are encouraging; however, outcomes should be interpreted within the context of the overall treatment strategy, including source-control procedures and combined antimicrobial therapy, rather than attributing results solely to oritavancin.