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. 2025 Dec 29;32(6):695–703. doi: 10.5603/cj.107098

ORItavancin as a therapeutic regimen for Cardiac Implantable Electronic Devices infections with multidrug-resistant Gram-positive cocci (ORI-4-CIEDi) pilot study: rationale and design

Danuta Łoboda 1,2,✉, Denis Swolana 3, Michał Joniec 2,4, Sylwia Gładysz-Wańha 2,4, Michał Gibiński 1,2, Karolina Simionescu 1,2, Eugeniusz Piłat 2, Krzysztof S Gołba 1,2, Robert D Wojtyczka 3, Sławomir Wilczyński 5, Beata Sarecka-Hujar 5
PMCID: PMC12782539  PMID: 41084871

Background

The risk of cardiac implantable electronic device (CIED)-related infection in long-term follow-up (F/U) ranges from 1.19% to 3.35%, depending on the type of procedure, the number of implanted electrodes, and patient-related risk factors [1–4]. Cardiac implantable electronic device-related infections lead to increased patient morbidity and mortality and treatment costs due to long-term in-hospital antibiotic therapy and surgical procedures [2–4]. Superficial acute bacterial skin and skin structure infection (ABSSSI), such as surgical incision site infection, typically requires 7 to 10 days of targeted antibiotic therapy. Surgical tissue debridement may also be necessary. Deeper infection of the generator pocket (PI) requires the removal of the CIED generator, transvenous lead extraction (TLE), and subsequent treatment with antibiotics for 10 to 14 days post-surgery. Lead-related infectious endocarditis (LRIE), which can occur as a complication of a PI or a bloodstream infection, requires the surgical removal of the device and leads, either percutaneously or through open-heart surgery followed by an extensive course of antibiotic therapy lasting from 2 to 6 weeks [5–7].

Gram-positive cocci are etiological agents of the vast majority of serious CIED infections. In large registries conducted in Polish reference centers, the etiological factors of LRIE were staphylococci in 58%, streptococci in 6.7%, and enterococci in 8.2% [8]. Staphylococcus aureus (S. aureus) was the most common pathogen found in 28.8% of patients undergoing the TLE procedure [9]. The presence of this pathogen was the risk factor for the spread of local PI to the endocardium, as seen in LRIE (75.23% of PI cases) [3]. Then, coagulase-negative staphylococci (CoNS) were the most common etiological factor of isolated PI (approximately 25%) [3]. Therefore, the increase in antibiotic resistance among Gram-positive cocci is a relevant problem, limiting the effectiveness of perioperative prophylaxis and pharmacotherapy for healthcare-associated infections.

The antibiotic of choice for CIED infections caused by multidrug-resistant (MDR) Gram-positive cocci is vancomycin, a first-generation bactericidal glycopeptide antibiotic administered every 8–12 hours under the control of serum concentration [7, 10]. An alternative to vancomycin is the second-generation semisynthetic lipoglycopeptides, including oritavancin [11, 12]. Oritavancin acts more effectively and faster against Gram-positive cocci than vancomycin due to the complex mechanism of action: 1) inhibition of two stages of cell wall biosynthesis — transglycosylation (polymerization) and transpeptidation (cross-link formation) and 2) disruption of bacterial cell membrane integrity, which leads to depolarization, increased membrane permeability and rapid cell death within 15 minutes to 2 hours [13]. In a similar situation, glycopeptides, which have been shown to inhibit mainly newly synthesized cell walls in replicating bacteria, exert bactericidal activity after 24 hours [13]. Moreover, oritavancin has better tissue and intracellular penetration than vancomycin (with an intracellular-to-extracellular concentration ratio of 78.2 for oritavancin compared to 3.9 for vancomycin) and an excellent potency for eradicating intracellular staphylococcal reservoirs (i.e., within liver-resident Kupffer cells) [14]. The 10- to 17-day half-life of oritavancin ensures the maintenance of antibiotic concentrations in the serum and deep tissues above the minimum inhibitory concentration for many Gram-positive cocci for several weeks [15] and provides the opportunity for administration as a single-dose therapy in ABSSSI and fractionated doses every few days in prolonged therapy for complicated infections. A meta-analysis of studies comparing lipoglycopeptides with vancomycin showed that oritavancin had significantly fewer adverse events (AE) than vancomycin [12].

Based on the results of randomized control trials (RCTs) [16,17], the European Medicines Agency registered oritavancin (Orbactiv, Tenkasi) as a single-dose therapy for ABSSSI in adults and children over three months of age [18]. However, only a single report describes the use of so dosed oritavancin in several patients with CIED and uncomplicated ABSSSI/PI [19, 20]. Moreover, this antibiotic is not registered for the treatment of infections requiring multiple-dose therapy. Although the 2023 World Society of Infectious Diseases and Immune Disorders recommendations include the possibility of prolonged therapy for staphylococcal infections with oritavancin fractionated every seven days [11], no RCT has been conducted to assess the efficacy of such a treatment regimen, including in LRIE.

The study aimed to compare the efficacy and safety of two antibiotic dosing regimens in the treatment of CIED-related infections caused by MDR Gram-positive cocci, using a long-half-life lipoglycopeptide antibiotic (oritavancin) and a short-half-life glycopeptide antibiotic (vancomycin).

Methods

Study group

The study group will consist of patients aged 18 years or older (Caucasian, both sexes) with a diagnosis of CIED-related surgical incision site infection or generator pocket infection/pocket erosion, complicated or not complicated by LRIE. Lead-related infectious endocarditis will be defined as a systemic infection meeting the modified Duke’s criteria for a definite or probable diagnosis of right-sided endocarditis [5, 7]. Patients will be recruited from those hospitalized in the reference cardiology center, which has experience in treating CIED infections, including TLE procedures. The etiological factor will be MDR Gram-positive cocci, specifically Staphylococcus spp., Streptococcus spp., or Enterococcus spp., as confirmed by microbiological cultures. Strains that are resistant to three or more classes of antimicrobial drugs, including beta-lactam antibiotics, will be classified as MDR. The trial will also follow patients with clinical symptoms of CIED-related infection who are at high risk of contagion with MDR Gram-positive cocci, even in the case of negative microbial cultures, as well as patients who are given vancomycin or oritavancin instead of a beta-lactam antibiotic due to a history of type I anaphylaxis to penicillin. The planned group size is 100. The inclusion and exclusion criteria are presented in Table 1.

Table 1.

Inclusion and exclusion criteria of the ORI-4-CIEDi pilot study

Inclusion Criteria

  1. Completed 18 years of age

  2. Presence of transvenous implanted CIED, i.e., pacemaker, cardioverter defibrillator, or cardiac resynchronization therapy pacemaker/defibrillator

  3. Presence of at least one of the signs and symptoms of CIED-related ABSSSI or PI as follows:

    1. redness, warmth, swelling or pain

    2. separation of the edges of the surgical incision with signs of inflammation or the need for repeated surgical debridement of the wound

    3. the presence of decubitus of the skin and subcutaneous tissue in an area of the generator or skin abscess/erosion of the device pocket, with purulent discharge from the wound or discharge giving a positive microbial culture

  4. Probable (one major criterion and one minor criterion, or three minor criteria) or definite (two major criteria, or one major and three minor criteria, or five minor criteria) diagnosis of right-sided LRIE according to the modified Duke’s criteria [5, 7] (optional criterion)

  5. Suspected or confirmed healthcare-associated infection or infection with drug-resistant Gram-positive cocci, i.e., Staphylococcus spp. (Staphylococcus aureus or coagulase-negative staphylococci), Streptococcus spp. or Enterococcus spp. sensitive to vancomycin or oritavancin

  6. Suspected or confirmed infection with Gram-positive cocci, i.e., Staphylococcus spp., Streptococcus spp., Enterococcus spp., sensitive to vancomycin or oritavancin and beta-lactam antibiotics in patients with a history of type I anaphylaxis to penicillin

Exclusion Criteria

  1. Suspected or confirmed infection with Gram-positive or Gram-negative bacilli or anaerobic bacteria

  2. Suspected or confirmed community-acquired infection or infection with Gram-positive cocci sensitive to beta-lactam antibiotics, including penicillin, ampicillin, or methicillin, based on empirical data or cultures (does not apply to patients with a history of type I anaphylaxis to penicillin)

  3. Confirmed resistance of Gram-positive cocci, which are the etiological factor of the infection, to vancomycin and oritavanci.

  4. History of hypersensitivity to oritavancin or another lipoglycopeptide antibiotic (applies to the experimental group only)

  5. History of hypersensitivity to vancomycin or another glycopeptide antibiotics (applies to the control group only)

  6. No possibility of temporarily interrupting or initiating alternative therapy to intravenous infusion of unfractionated heparin

  7. Pregnancy or breastfeeding

  8. Lack of informed written consent of the patient to participate in the study
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ABSSSI — superficial acute bacterial skin and skin structure infection; CIED — cardiac implantable electronic device; LRIE — lead-related infectious endocarditis; ORI-4-CIEDi — oritavancin as a therapeutic regimen for cardiac implantable electronic devices infections with multidrug-resistant Gram-positive cocci pilot study; PI — pocket infection/pocket erosion

Study design

The “ORItavancin as a therapeutic regimen for Cardiac Implantable Electronic Devices infections with multidrug-resistant Gram-positive cocci (ORI-4-CIEDi)” pilot study (Clinical Trial Registration ID: NCT07013552) is planned as a single-center, randomized, non-inferiority-controlled trial. The intervention under investigation (experimental) will involve the administration of a long-half-life lipoglycopeptide antibiotic, oritavancin, as a single dose or as a multiple-dose therapy repeated at 7-day intervals, depending on clinical indications. The standard intervention (active comparator) will be the administration of a short half-life glycopeptide antibiotic, vancomycin, repeated daily in 8- to 12-hour intervals for a period of one to six weeks.

This study utilizes a parallel assignment interventional model. Patients who have given written informed consent to participate will be randomly assigned to either the experimental or control group to achieve a 1:1 group size ratio. Patients with vancomycin-intermediate S. aureus, vancomycin-resistant S. aureus, or vancomycin-resistant Enterococcus spp. infection or colonization within the preceding 6 months will be included in the study group without randomization. Patients who initiated targeted antibiotic therapy with vancomycin for more than 72 hours before recruitment will be included in the control group without randomization.

The planned recruitment period will last 15 months, followed by a 3-month observation period. The study will be blinded only at the randomization stage (open label). Figure 1 presents the flowchart of the ORI-4-CIEDi trial.

Figure 1.

Figure 1

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Flowchart of the ORI-4-CIEDi pilot study. ABSSSI — superficial acute bacterial skin and skin structure infection; CIED — cardiac implantable electronic device; F/U — follow-up; LRIE — lead-related infectious endocarditis; PI — pocket infection/pocket erosion; TLE — transvenous lead extraction

Intervention

The diagnostic and surgical approach, as well as the duration of antibiotic treatment, will be determined based on clinical indications and current guidelines from the European Heart Rhythm Association [5, 6] and the European Society of Cardiology [7]. The identification of MDR G (+) cocci causing CIED infections and monitoring their antibiotic resistance is consistent with the National Antibiotic Protection Program implemented under the National Health Program for 2021–2025 — “Counteracting the development of antibiotic resistance in microorganisms” [21].

Oritavancin dosage in the experimental group (according to [11]):

  1. Single-dose therapy of 1,200 mg (3 vials) administered as a 3-hour intravenous infusion in a 5% glucose solution (infusion volume: 1,000 mL) in ABSSSI and isolated PI.

  2. Multiple-dose therapy: first dose of 1,200 mg (3 vials) administered as a 3-hour intravenous infusion in a 5% glucose solution (infusion volume: 1,000 mL), subsequent doses of 800 mg (2 vials) administered as a 2–3 hour intravenous infusion at 7-day intervals, to achieve the required therapy duration of 2–6 weeks (counted from the day of the TLE procedure) in LRIE.

Vancomycin dosage in the control group (according to [10]):

  1. Repeated doses of 15–20 mg/kg body weight every 8–12 hours (maximum 3,000 mg/day for patients with normal renal function) administered as an hourly intravenous infusion in a 0.9% sodium chloride solution (infusion volume: 500–1,000 mL) under monitoring of the serum drug concentration for 7–10 days in superficial ABSSSI (not less than 7 days from surgical tissue debridement, if required) or for 10–14 days in isolated PI (counted from the day of the generator pocket surgical debridement or TLE.)

  2. Repeated doses of 15–20 mg/kg body weight every 8–12 hours (maximum 3,000 mg/day for patients with normal renal function) administered as an hourly intravenous infusion in a 0.9% sodium chloride solution (infusion volume: 500–1,000 mL), under monitoring the drug serum concentration, to achieve the required pharmacotherapy duration of 2–6 weeks in LRIE (counted from the TLE procedure).

Standard surgical procedures, especially the Transvenous lead extraction procedure, used in the documented center have been described in detail elsewhere [9].

Clinical follow-up

Observation will include:

  1. Physical examination with the assessment of the surgical incision site and generator pocket.

  2. Routine laboratory tests, including blood count, C-reactive protein (mg/L), and plasma creatinine (mg/dL).

  3. Transthoracic and transesophageal echocardiogram with the assessment of bacterial vegetations, with particular emphasis on the tricuspid valve and CIED leads.

  4. Positron emission tomography/computed tomography with fludeoxyglucose F18 or single-photon emission computed tomography using radioisotope-labeled leukocytes (depending on clinical indications).

Primary and secondary outcomes

  1. The co-primary efficacy endpoint will be the treatment success rate, defined as obtaining a clinical response and no recurrence of infection at the exact location (i.e., the pocket of removed CIED or the right ventricular endocardium) or at any site of CIED reimplantation within the 3-month F/U.

  2. The co-primary safety endpoint will be no treatment-related serious adverse events (SAEs) during the 3-month F/U. Serious adverse events will be defined as any AE classified as grade 3–5 according to the Health Technology Assessment report developed by the Agency for Health Technology Assessment and Tariff System (Poland) [22] and related to using the investigational product (scores of 3–5).

The following items will be classified as secondary outcome measures:

  1. Clinical response rate:

    1. in the case of ABSSSI, early clinical response (ECR) will be defined as a reduction in the size of the inflammatory lesion by at least 20% compared to the baseline after 48–72 hours of antibiotic therapy (in the case of conservative treatment) or the resolution of ABSSSI/complete healing of the surgical wound assessed after 7–10 days;

    2. in the case of isolated PI, ECR will be defined as the resolution of fever and a reduction in inflammatory parameters by ≥ 50% after 72–120 hours of antibiotic therapy, along with complete healing of the surgical wound, as assessed 10–14 days post-treatmen;

    3. in the case of PI complicated by LRIE, ECR will be defined as a reduction of inflammatory parameters by ≥ 50% after 72–120 hours, negative control blood cultures after 72 hours, and resolution of fever by the seventh day of antibiotic therapy, complete healing of the surgical wound after 10–14 days, and resolution/absence of new echocardiographic signs of infection after the end of antibiotic therapy.

  2. Median time to ECR, defined as in point 1 and given in hours or days (as required).

  3. Recurrent infection rate, defined as CIED-related infection occurring within 3 months of the completion of previous treatment, caused by the persistence of bacteria with the same phenotype in the skin, subcutaneous tissue, the device pocket, intracardiac leads, the right-sided endocardium/tricuspid valve.

  4. Rehospitalization rate due to recurrent CIED-related infection, defined as a hospital stay resulting from the need for repeated antibiotic administration or surgical intervention due to recurrent infection.

  5. Proportion of cases in which infection worsened from superficial or local (i.e., ABSSSI or PI) to systemic (i.e., LRIE) despite optimal medical therapy.

  6. Proportion of cases in which alternative “rescue” antibiotic therapy was used due to treatment failure.

Safety plan and study termination

The risk of complications associated with the administration of glycopeptide or lipoglycopeptide antibiotics is estimated at approximately 5%. In most cases, these will include AEs, such as nausea, headache, or reactions related to excessively rapid intravenous infusion. Serious adverse events include, among others, anaphylactic reactions such as urticaria, Quincke’s edema, and anaphylactic shock, as well as the consequences of ineffective infection treatment, including the development of septic shock and death.

Any medical event that causes AEs in a participant who has received a medicinal product will be documented in the study protocol, regardless of its cause-and-effect relationship with a specific treatment. The severity of AEs will be graded [22]. Grade 1 (mild) — no or mild symptoms, clinical or diagnostic observation required, intervention not recommended; grade 2 (moderate) — minimal, local, or noninvasive intervention indicated; grade 3 (severe or medically significant, disabling but not life-threatening) — the hospitalization or extension of existing hospitalization recommended; grade 4 (life-threatening) — urgent intervention indicated; grade 5 — death caused by an AE. Any AE classified as grade 3–5 will be considered a SAE.

Adverse events and SAEs will be classified according to the likelihood of being related to treatment on a 5-point scale: treatment-related (5), probably treatment-related (4), possibly treatment-related (3), unlikely treatment-related (2), not treatment-related (1). If the investigator, based on his/her clinical knowledge and patient records, determines that an AE or SAE is related to the use of the investigational product (score 3–5), then it will be classified as an adverse drug reaction. The Data Safety Monitoring Board will review all potential adverse drug reactions. The principal investigator has the authority to halt the study at any time if there are reasonable concerns regarding its safety.

Statistical analysis and sample size estimates

To determine the estimated sample size, data from the SOLO I trial was used [16]. Based on the primary outcome of ECR between the oritavancin and vancomycin groups, a 3% difference between groups was assumed. The sample size estimate was performed using an online calculator for an RCT (Parallel) noninferiority trial [23]. An assumed sample size of 50 participants per group was calculated to be sufficient to have an 80% probability of demonstrating a difference of more than 3% between groups, assuming a 10% dropout rate.

The possible stratifying factors in the statistical analysis will be: 1) the infection severity; 2) the etiological factor; 3) the antibiotic therapy used; 4) method of treatment (conservative vs. sparing surgery vs. TLE); 5) effectiveness of TLE; 6) the need for temporary pacing during antibiotic therapy; 7) site and method of device reimplantation (in the subclavian area on the opposite side vs. leadless or subcutaneous CIED).

Discussion

Prolonged parenteral antimicrobial therapy with vancomycin requires daily dosing and therapeutic drug monitoring to prevent nephrotoxicity [10]. In turn, the long half-life of oritavancin, ranging from 245 to 393 hours, allows for the administration of a single-dose therapy, providing up to a month of bactericidal effect in patients with ABSSSI [15]. The global Phase 3 noninferiority studies SOLO I and SOLO II confirmed the non-inferior effectiveness of oritavancin administered in this manner compared to fractionated twice-daily vancomycin in ABSSSI caused by methicillin-sensitive (MSSA) and methicillin-resistant (MRSA) S. aureus, with an efficacy response rate of approximately 80% for both antibiotics [16, 17]. Oritavancin was related to significantly less AEs than vancomycin (odds ratio 0.72; 95% confidence interval 0.59–0.89; p < 0.01). These results are supported by a recent multicenter, retrospective, observational study [24] and a systematic review of 9213 patients [25] with ABSSSI treated with oritavancin or standard-of-care antibiotics (most commonly vancomycin) in both outpatient and inpatient settings. In the studies, oritavancin was an effective and well-tolerated antibiotic that reduced the risk of emergency department visits and hospital readmissions during a 30-day F/U in patients with ABSSSI caused by S. aureus (the most common cases) or of unknown origin (receiving empirical therapy). Unfortunately, extensive studies conducted to date have not included participants with CIEDs. Furthermore, they did not provide sufficient data on the efficacy of oritavancin against Gram-positive cocci other than S. aureus. The ORI-4-CIEDi study may be the first RCT to deploy oritavancin in CIED-related infections caused by various types of Gram-positive cocci conducted in a broader group of patients.

Also, in the case of LRIE, the introduction of antibiotic therapy with effective and long-acting lipoglycopeptides might be an innovative treatment solution. There are some case reports and clinical case series documenting the efficacy and safety of off-label use of oritavancin administered every 7–14 days in conditions requiring prolonged antibiotic therapy, such as osteomyelitis, septic arthritis, prosthetic joint infections, infective endocarditis, infections related to vascular access, and bloodstream infections [20, 26]. In a recent meta-analysis of multiple-dose oritavancin treatment [26], the antibiotic was shown to be effective against MRSA, MSSA, CoNS, E. faecalis, and E. faecium, with a clinical cure achieved in 85% of participants and improvement noted in 8% of them. However, treatment failure was more commonly observed in wound infections (33.3%), bacteremia (25%), and osteomyelitis (8.1%). The treatment regimen, consisting of an initial dose of oritavancin 1,200 mg and subsequent doses of 800 mg, repeated 3 to 5 times every 7 days, had the highest clinical success rate, regardless of the site of infection or etiologic agent [26] and is currently accepted for use [11]. Multiple-dose treatment was well tolerated, with benign infusion-related reactions and hypoglycemia observed as the most frequent AEs [26]. In a study, comparing oritavancin to the standard-of-care (i.e., vancomycin, daptomycin, ceftaroline, ampicillin, ampicillin-sulbactam, nafcillin, oxacillin, or cefazolin) for the treatment of Gram-positive bloodstream infections, clinical failure occurred equally often in the oritavancin group compared to the control group (7.4% vs. 17.4%, p = 0.34), but acute renal failure did occur less frequently (3.7% vs. 27.5%, p = 0.01) [27]. Other data from the U.S. Cerner Real World Data platform [28] comparing the efficacy of long-acting lipoglycopeptides (oritavancin and dalbavancin) with standard-of-care antibiotics (most commonly vancomycin, cefazolin, cephalexin, and trimethoprim-sulfamethoxazole) for serious Gram-positive infections (i.e., bacteremia, endocarditis, osteomyelitis, and septic arthritis), showed similar treatment outcomes at 90 days for both treatment strategies. However, the ORI-4-CIEDi study might be the first RCT to investigate prolonged therapy in LRIE.

Study limitations

The ORI-4-CIEDi pilot study is expected to enroll a limited group of up to 100 patients. A continuation of the study with a larger group of participants may be necessary to obtain sufficient statistical power for all intended endpoints.

The ORI-4-CIEDi study compared oritavancin with short-acting vancomycin (the standard-of-care), not with long-acting dalbavancin. However, there are some data from RCTs, matched cohort studies, or meta-analyses for single-dose [29] and multiple-dose therapy [30, 31] with dalbavancin. None of these studies have included patients with CIED-related infections.

Conclusions

The deployment of a single-dose therapy with long-acting oritavancin in CIED-related ABSSSI/PI or multiple-dose therapy administered weekly in LRIE may shorten hospitalization stays, reduce costs, and enhance treatment comfort while maintaining a high treatment success rate and a low risk of complications associated with long-term vascular access and renal failure.

Footnotes

Funding: The research was funded by the Medical University of Silesia and the Medical Research Agency, Poland (Grant No KPOD.07.07-IW.07-0004/24).

Author contributions: DŁ, DS, MJ, SG-W, MG, KS, EP, KSG, RDW, SW, and BS-H developed the study concept; DŁ, DS, MJ, SG-W, EP, KSG, and RDW prepared the study protocol; DŁ and BS-H wrote the manuscript; KSG, RDW, and SW conducted a substantive assessment; DS, MJ, SG-W, MG, KS, EP, KSG, RDW, and SW critically reviewed the manuscript. All authors approved the final version to be published.

Conflict of interest: None.

Ethics statement: The Bioethics Committee of the Medical University of Silesia in Katowice, Poland, approved the medical experiment (Resolution No. BNW/NWN/0052/KB1/83/23 of September 12, 2023). Informed consent will be obtained from all subjects involved in this study.

References

  • 1.Olsen T, Jørgensen OD, Nielsen JC, et al. Incidence of device-related infection in 97 750 patients: clinical data from the complete Danish device-cohort (1982–2018) Eur Heart J. 2019;40(23):1862–1869. doi: 10.1093/eurheartj/ehz316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Polewczyk A, Jacheć W, Polewczyk M, et al. Outcomes in patients with definite and possible infective endocarditis related to a cardiac implantable electronic device. Pol Arch Intern Med. 2024;134(7–8):16775. doi: 10.20452/pamw.16775. [DOI] [PubMed] [Google Scholar]
  • 3.Jacheć W, Polewczyk A, Nowosielecka D, et al. Clinical profile and outcomes among patients with cardiac implantable electronic device presenting as isolated pocket infection, pocket-related infective endocarditis, or lead-related infective endocarditis. Europace. 2025;27(4):euaf053. doi: 10.1093/europace/euaf053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Jędrzejczyk-Patej E, Mazurek M, Kowalski O, et al. Device-related infective endocarditis in cardiac resynchronization therapy recipients - Single center registry with over 2500 person-years follow up. Int J Cardiol. 2017;227:18–24. doi: 10.1016/j.ijcard.2016.11.029. [DOI] [PubMed] [Google Scholar]
  • 5.Blomström-Lundqvist C, Traykov V, Erba PA, et al. 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) Eur Heart J. 2020;41(21):2012–2032. doi: 10.1093/eurheartj/ehaa010. [DOI] [PubMed] [Google Scholar]
  • 6.Bongiorni MG, Burri H, Deharo JC, et al. ESC Scientific Document Group. 2018 EHRA expert consensus statement on lead extraction: recommendations on definitions, endpoints, research trial design, and data collection requirements for clinical scientific studies and registries: endorsed by APHRS/HRS/LAHRS. Europace. 2018;20(7):1217. doi: 10.1093/europace/euy050. [DOI] [PubMed] [Google Scholar]
  • 7.Delgado V, Ajmone Marsan N, de Waha S, et al. ESC Scientific Document Group. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J. 2023;44(39):3948–4042. doi: 10.1093/eurheartj/ehad193. [DOI] [PubMed] [Google Scholar]
  • 8.Płońska-Gościniak E, Olędzki S, Kukulski T, et al. Pol-CDRIE registry — 1-year observational data on patients hospitalized due to cardiac device-related infective endocarditis in Polish referential cardiology centres. Kardiol Pol. 2019;77(5):561–567. doi: 10.33963/KP.14811. [DOI] [PubMed] [Google Scholar]
  • 9.Gładysz-Wańha S, Joniec M, Wańha W, et al. 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;21(4):427–435. doi: 10.1016/j.hrthm.2023.12.015. [DOI] [PubMed] [Google Scholar]
  • 10.Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. American Journal of Health-System Pharmacy. 2020;77(11):835–864. doi: 10.1093/ajhp/zxaa036. [DOI] [PubMed] [Google Scholar]
  • 11.Esposito S, Blasi F, Curtis N, et al. New antibiotics for 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;12(4) doi: 10.3390/antibiotics12040742. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Jame W, Basgut B, Abdi A. Efficacy and safety of novel glycopeptides versus vancomycin for the treatment of gram-positive bacterial infections including methicillin resistant Staphylococcus aureus: A systematic review and meta-analysis. PLoS One. 2021;16(11):e0260539. doi: 10.1371/journal.pone.0260539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Belley A, McKay GA, Arhin FF, et al. Oritavancin disrupts membrane integrity of Staphylococcus aureus and vancomycin-resistant enterococci to effect rapid bacterial killing. Antimicrob Agents Chemother. 2010;54(12):5369–5371. doi: 10.1128/AAC.00760-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Beadell B, Yamauchi J, Wong-Beringer A. Comparative in vitro efficacy of antibiotics against the intracellular reservoir of Staphylococcus aureus. J Antimicrob Chemother. 2024;79(10):2471–2478. doi: 10.1093/jac/dkae241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Rubino CM, Van Wart SA, Bhavnani SM, et al. Oritavancin population pharmacokinetics in healthy subjects and patients with complicated skin and skin structure infections or bacteremia. Antimicrob Agents Chemother. 2009;53(10):4422–4428. doi: 10.1128/AAC.00231-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Corey GR, Kabler H, Mehra P, et al. Single-dose oritavancin in the treatment of acute bacterial skin infections. N Engl J Med. 2014;370(23):2180–2190. doi: 10.1056/NEJMoa1310422. [DOI] [PubMed] [Google Scholar]
  • 17.Corey GR, Good S, Jiang H, et al. Single-dose oritavancin versus 7–10 days of vancomycin in the treatment of gram-positive acute bacterial skin and skin structure infections: the SOLO II noninferiority study. Clin Infect Dis. 2015;60(2):254–262. doi: 10.1093/cid/ciu778. [DOI] [PubMed] [Google Scholar]
  • 18.European Medicines Agency. Orbactiv. [accessed on May 8, 2025]. https://www.ema.europa.eu/en/medicines/human/EPAR/orbactiv .
  • 19.Co D, Roebuck L, VanLandingham J. Evaluation of Oritavancin Use at a Community Hospital. Hosp Pharm. 2018;53(4):272–276. doi: 10.1177/0018578717746415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Lupia T, De Benedetto I, Bosio R, et al. 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;13(4):959. doi: 10.3390/life13040959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Council of Ministers, Poland. Poland’s National Health Program for 2021–2025. Information on the tasks of the National Health Program assigned upon request in 2021–2025. 2021. https://www.gov.pl/web/zdrowie/npz-2021-2025 .
  • 22.Orzeł K, Żebrowska O, Wołowiec K. Drug safety assessment in the context of health technology assessment. Agency for health technology assessment and tariff system; Poland. Warsaw: 2019. [accessed on May 8, 2025]. https://power.aotm.gov.pl/static/Materialy/7.%20Ocena%20bezpieczeństwa%20leku%20w%20kontekście%20oceny%20technologii%20medycznych.pdf . [Google Scholar]
  • 23.Sample size estimation in clinical research: from randomized controlled trials to observational studies. Cleveland Clinic online calculator. [accessed on May 8, 2025]. https://riskcalc.org/samplesize/ [DOI] [PubMed]
  • 24.Redell M, Sierra-Hoffman M, Assi M, et al. The CHROME study, a real-world experience of single- and multiple-dose oritavancin for treatment of gram-positive infections. Open Forum Infect Dis. 2019;6(11):ofz479. doi: 10.1093/ofid/ofz479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Zhang H, Zhou W, Wang J, et al. Efficacy and safety of oritavancin for the treatment of acute bacterial skin and skin-structure infections: a systematic review and meta-analysis. J Glob Antimicrob Resist. 2021;25:380–389. doi: 10.1016/j.jgar.2021.04.013. [DOI] [PubMed] [Google Scholar]
  • 26.Baiardi G, Cameran Caviglia M, Piras F, et al. The clinical efficacy of multidose oritavancin: a systematic review. Antibiotics (Basel) 2023;12(10):1498. doi: 10.3390/antibiotics12101498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Moenster RP, Wallace-Lacey A, Western H, et al. Oritavancin vs standard of care for treatment of nonendovascular gram-positive bloodstream infections. Open Forum Infect Dis. 2023;10(11):ofad411. doi: 10.1093/ofid/ofad411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Goodman-Meza D, Weiss RE, Poimboeuf ML, et al. Comparative effectiveness of long-acting lipoglycopeptides vs standard-of-care antibiotics in serious bacterial infections. JAMA Netw Open. 2025;8(5):e2511641. doi: 10.1001/jamanetworkopen.2025.11641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Agarwal R, Bartsch SM, Kelly BJ, et al. Newer glycopeptide antibiotics for treatment of complicated skin and soft tissue infections: systematic review, network meta-analysis and cost analysis. Clin Microbiol Infect. 2018;24(4):361–368. doi: 10.1016/j.cmi.2017.08.028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Rappo U, Puttagunta S, Shevchenko V, et al. Dalbavancin for the treatment of osteomyelitis in adult patients: a randomized clinical trial of efficacy and safety. Open Forum Infect Dis. 2018;6(1):ofy331. doi: 10.1093/ofid/ofy331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Almangour TA, Perry GK, Alhifany AA. Dalbavancin versus standard of care for the treatment of osteomyelitis in adults: A retrospective matched cohort study. Saudi Pharm J. 2020;28(4):460–464. doi: 10.1016/j.jsps.2020.02.007. [DOI] [PMC free article] [PubMed] [Google Scholar]

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