Oritavancin for CIED Infections With MDR Gram-positive Cocci

Summary

The study aimed to conduct a randomized, non-inferiority controlled trial to compare the short- and medium-term efficacy and safety of two antibiotic dosage regimens in cardiac implantable electronic devices (CIED) infections with multidrug-resistant Gram-positive cocci: 1) single-dose therapy with a long-half-life antibiotic (oritavancin) vs. standard 7-14 days of therapy with a short-half-life antibiotic (vancomycin) for CIED surgical incision site or pocket infection; and 2) fractionated therapy with a long-half-life antibiotic (oritavancin) at seven-day intervals compared to standard therapy with a short-half-life antibiotic (vancomycin) fractionated in 2-3 daily doses in cases of lead-related infectious endocarditis.

Timeline

Start

2025-06

Primary completion

2026-07

Completion

2026-10

Publications

• Background Gladysz-Wanha S, Joniec M, Wanha W, Pilat E, Drzewiecka A, Gardas R, Biernat J, Weglarzy A, Golba KS. Transvenous lead extraction safety and efficacy in infected and noninfected patients using mechanical-only tools: Prospective registry from a high-volume center. Heart Rhythm. 2024 Apr;21(4):427-435. doi: 10.1016/j.hrthm.2023.12.015. Epub 2023 Dec 28.
• Background Olsen T, Jorgensen OD, Nielsen JC, Thogersen AM, Philbert BT, Johansen JB. Incidence of device-related infection in 97 750 patients: clinical data from the complete Danish device-cohort (1982-2018). Eur Heart J. 2019 Jun 14;40(23):1862-1869. doi: 10.1093/eurheartj/ehz316.
• Background Stewart CL, Turner MS, Frens JJ, Snider CB, Smith JR. Real-World Experience with Oritavancin Therapy in Invasive Gram-Positive Infections. Infect Dis Ther. 2017 Jun;6(2):277-289. doi: 10.1007/s40121-017-0156-z. Epub 2017 Apr 6.
• Background Morrisette T, Miller MA, Montague BT, Barber GR, McQueen RB, Krsak M. On- and off-label utilization of dalbavancin and oritavancin for Gram-positive infections. J Antimicrob Chemother. 2019 Aug 1;74(8):2405-2416. doi: 10.1093/jac/dkz162.
• Background Rubino CM, Bhavnani SM, Moeck G, Bellibas SE, Ambrose PG. Population pharmacokinetic analysis for a single 1,200-milligram dose of oritavancin using data from two pivotal phase 3 clinical trials. Antimicrob Agents Chemother. 2015;59(6):3365-72. doi: 10.1128/AAC.00176-15. Epub 2015 Mar 30.
• Background Carvalhaes CG, Sader HS, Streit JM, Castanheira M, Mendes RE. Activity of Oritavancin against Gram-Positive Pathogens Causing Bloodstream Infections in the United States over 10 Years: Focus on Drug-Resistant Enterococcal Subsets (2010-2019). Antimicrob Agents Chemother. 2022 Feb 15;66(2):e0166721. doi: 10.1128/AAC.01667-21. Epub 2021 Nov 22.
• Background Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N; WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018 Mar;18(3):318-327. doi: 10.1016/S1473-3099(17)30753-3. Epub 2017 Dec 21.
• Background Lupia T, De Benedetto I, Bosio R, Shbaklo N, De Rosa FG, Corcione S. Role of Oritavancin in the Treatment of Infective Endocarditis, Catheter- or Device-Related Infections, Bloodstream Infections, and Bone and Prosthetic Joint Infections in Humans: Narrative Review and Possible Developments. Life (Basel). 2023 Apr 6;13(4):959. doi: 10.3390/life13040959.
• Background Thomas G, Henao-Martinez AF, Franco-Paredes C, Chastain DB. Treatment of osteoarticular, cardiovascular, intravascular-catheter-related and other complicated infections with dalbavancin and oritavancin: A systematic review. Int J Antimicrob Agents. 2020 Sep;56(3):106069. doi: 10.1016/j.ijantimicag.2020.106069. Epub 2020 Jun 27.
• Background Esposito S, Blasi F, Curtis N, Kaplan S, Lazzarotto T, Meschiari M, Mussini C, Peghin M, Rodrigo C, Vena A, Principi N, Bassetti M. New Antibiotics for Staphylococcus aureus Infection: An Update from the World Association of Infectious Diseases and Immunological Disorders (WAidid) and the Italian Society of Anti-Infective Therapy (SITA). Antibiotics (Basel). 2023 Apr 12;12(4):742. doi: 10.3390/antibiotics12040742.
• Background Corey GR, Arhin FF, Wikler MA, Sahm DF, Kreiswirth BN, Mediavilla JR, Good S, Fiset C, Jiang H, Moeck G, Kabler H, Green S, O'Riordan W; SOLO I, SOLO II Investigators. Pooled analysis of single-dose oritavancin in the treatment of acute bacterial skin and skin-structure infections caused by Gram-positive pathogens, including a large patient subset with methicillin-resistant Staphylococcus aureus. Int J Antimicrob Agents. 2016 Nov;48(5):528-534. doi: 10.1016/j.ijantimicag.2016.07.019. Epub 2016 Sep 13.
• Background Giske CG, Turnidge J, Canton R, Kahlmeter G; EUCAST Steering Committee. Update from the European Committee on Antimicrobial Susceptibility Testing (EUCAST). J Clin Microbiol. 2022 Mar 16;60(3):e0027621. doi: 10.1128/JCM.00276-21. Epub 2021 Aug 4.
• Background Delgado V, Ajmone Marsan N, de Waha S, Bonaros N, Brida M, Burri H, Caselli S, Doenst T, Ederhy S, Erba PA, Foldager D, Fosbol EL, Kovac J, Mestres CA, Miller OI, Miro JM, Pazdernik M, Pizzi MN, Quintana E, Rasmussen TB, Ristic AD, Rodes-Cabau J, Sionis A, Zuhlke LJ, Borger MA; ESC Scientific Document Group. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J. 2023 Oct 14;44(39):3948-4042. doi: 10.1093/eurheartj/ehad193. No abstract available.
• Background Milman A, Wieder-Finesod A, Zahavi G, Meitus A, Kariv S, Shafir Y, Beinart R, Rahav G, Nof E. Complicated Pocket Infection in Patients Undergoing Lead Extraction: Characteristics and Outcomes. J Clin Med. 2023 Jun 29;12(13):4397. doi: 10.3390/jcm12134397.
• Background Kusumoto FM, Schoenfeld MH, Wilkoff BL, Berul CI, Birgersdotter-Green UM, Carrillo R, Cha YM, Clancy J, Deharo JC, Ellenbogen KA, Exner D, Hussein AA, Kennergren C, Krahn A, Lee R, Love CJ, Madden RA, Mazzetti HA, Moore JC, Parsonnet J, Patton KK, Rozner MA, Selzman KA, Shoda M, Srivathsan K, Strathmore NF, Swerdlow CD, Tompkins C, Wazni O. 2017 HRS expert consensus statement on cardiovascular implantable electronic device lead management and extraction. Heart Rhythm. 2017 Dec;14(12):e503-e551. doi: 10.1016/j.hrthm.2017.09.001. Epub 2017 Sep 15. No abstract available.
• Background Blomstrom-Lundqvist C, Traykov V, Erba PA, Burri H, Nielsen JC, Bongiorni MG, Poole J, Boriani G, Costa R, Deharo JC, Epstein LM, Saghy L, Snygg-Martin U, Starck C, Tascini C, Strathmore N; ESC Scientific Document Group. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Europace. 2020 Apr 1;22(4):515-549. doi: 10.1093/europace/euz246.
• Background Polewczyk A, Jachec W, Polewczyk M, Nowosielecka D, Brzozowski W, Kutarski A. Outcomes in patients with definite and possible infective endocarditis related to a cardiac implantable electronic device. Pol Arch Intern Med. 2024 Aug 8;134(7-8):16775. doi: 10.20452/pamw.16775. Epub 2024 Jun 17.
• Background Bongiorni MG, Kennergren C, Butter C, Deharo JC, Kutarski A, Rinaldi CA, Romano SL, Maggioni AP, Andarala M, Auricchio A, Kuck KH, Blomstrom-Lundqvist C; ELECTRa Investigators. The European Lead Extraction ConTRolled (ELECTRa) study: a European Heart Rhythm Association (EHRA) Registry of Transvenous Lead Extraction Outcomes. Eur Heart J. 2017 Oct 21;38(40):2995-3005. doi: 10.1093/eurheartj/ehx080.
• Background Chmielarczyk A, Pomorska-Wesolowska M, Romaniszyn D, Wojkowska-Mach J. Healthcare-Associated Laboratory-Confirmed Bloodstream Infections-Species Diversity and Resistance Mechanisms, a Four-Year Retrospective Laboratory-Based Study in the South of Poland. Int J Environ Res Public Health. 2021 Mar 9;18(5):2785. doi: 10.3390/ijerph18052785.
• Background Joshi S, Shallal A, Zervos M. Vancomycin-Resistant Enterococci: Epidemiology, Infection Prevention, and Control. Infect Dis Clin North Am. 2021 Dec;35(4):953-968. doi: 10.1016/j.idc.2021.07.002.
• Background Cerini P, Meduri FR, Tomassetti F, Polidori I, Brugneti M, Nicolai E, Bernardini S, Pieri M, Broccolo F. Trends in Antibiotic Resistance of Nosocomial and Community-Acquired Infections in Italy. Antibiotics (Basel). 2023 Mar 24;12(4):651. doi: 10.3390/antibiotics12040651.

Drugs

Indications