The 2014 Infectious Diseases Society of America (IDSA) states that dalbavancin is effective in the treatment of skin and soft tissue infections (SSTI), including those caused by methicillin-resistant Staphylococcus aureus (MRSA), but at the time this guideline was written, dalbavancin or oritavancin had not yet been FDA approved. As such, the guidelines do not incorporate specific recommendations for use of either agent. [1]
A 2021 systematic review and meta-analysis evaluated the efficacy and safety of oritavancin compared to other antibiotics for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs). The analysis incorporated data from 9213 patients across two randomized clinical trials (RCTs) and four cohort studies. The meta-analysis demonstrated that oritavancin was statistically non-inferior to comparator agents across all efficacy and safety outcomes. Specifically, there was no difference between oritavancin and vancomycin for the primary efficacy outcome (a composite of cessation of spreading or reduction in lesion size, absence of fever and no need for administration of a rescue antibiotic) at early clinical evaluation 48 to 72 hours after administration. There was also no difference between oritavancin and control agents for the outcome of investigator-assessed clinical cure at post-therapy evaluation. Further, no differences were observed for the outcomes of additional post-treatment oral or intravenous antibiotics and 30-day emergency room visits. However, oritavancin significantly reduced the 30-day readmission rate (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.26 to 0.67; p= 0.0004) and the occurrence of drug-related adverse events (RR 0.78; 95% CI 0.67 to 0.91; p= 0.002) when compared to controls and vancomycin, respectively. It should be noted that there were no differences between groups when mortality was assessed. [2]
Economic data summarized from multiple referenced studies suggest that oritavancin is associated with significantly lower total healthcare costs compared to comparators (mean costs of $10,096 vs. $12,779 in one analysis) and a reduction in hospital length stay (3.5 vs. 6.5 days). The authors concluded that oritavancin is noninferior to comparator drugs for treating ABSSSIs and demonstrated superior outcomes in reducing readmission rates and drug-related adverse events. Notably, both included RCTs were sponsored by the Medicines Company, the manufacturer of branded oritavancin, which may have introduced publication bias to the results. [2]
A 2015 systematic review and network meta-analysis (NMA) evaluated the comparative efficacy of antibiotics used to treat acute bacterial skin and skin structure infections (ABSSSI), focusing on oritavancin. Fifty-two trials were included, with vancomycin and linezolid being the most frequently studied agents, appearing in 26 and 18 trials respectively. The analysis compared multiple regimens, including linezolid, vancomycin, daptomycin, ceftaroline, and various oritavancin dosing strategies. The odds ratios (ORs) for test-of-cure (TOC) relative to vancomycin were 1.55 (95% credible interval [CrI] 0.91 to 2.57) for linezolid, 2.18 (95% CrI 0.90 to 5.42) for daptomycin, and 1.06 (95% CrI 0.80 to 1.43) for oritavancin 1200 mg. The OR for early clinical response (ECR) with oritavancin 1200 mg was 1.02 (95% CrI 0.23 to 4.33). In the MRSA subgroup, TOC ORs were 1.55 (95% CrI 0.96 to 2.46) for linezolid, 0.74 (95% CrI 0.13 to 3.66) for daptomycin, and 0.94 (95% CrI 0.44 to 2.02) for oritavancin. For the MSSA subgroup, ORs were 1.36 (95% CrI 0.15 to 13.34) for linezolid and 0.82 (95% CrI 0.08 to 7.83) for oritavancin. The study found oritavancin 1200 mg to be equivalent to vancomycin at TOC and suggested equivalence to linezolid and daptomycin, though no significant differences were observed. [3]
A 2022 systematic review and meta-analysis evaluated the in vitro antibacterial activity of recently approved antibiotics against MRSA strains. A total of 38 studies that evaluated the effectiveness of telavancin, dalbavancin, oritavancin, and tedizolid were included. The selection criteria required studies to include detailed minimum inhibitory concentration (MIC) data for these antibiotics against MRSA. The combined results revealed that telavancin, dalbavancin, oritavancin, and tedizolid exhibited strong in vitro activity against MRSA isolates, demonstrating low MIC values and high susceptibility rates. Across 420 MRSA isolates, oritavancin demonstrated an MIC50 of 0.045 µg/mL and an MIC90 of 0.120 µg/mL, while tedizolid exhibited MIC50 and MIC90 values of 0.250 µg/mL and 0.500 µg/mL, respectively, across 12,204 isolates. Dalbavancin showed MIC50 and MIC90 values of 0.060 µg/mL and 0.120 µg/mL, respectively, across 28,539 isolates. There were no significant differences between agents in the pooled prevalence of susceptibilites against MRSA isolates from 2010-2015 and 2016-2020. Overall, the findings suggest that these antibiotics, with a pooled susceptibility rate of 100%, offer promising alternatives for treating MRSA infections, demonstrating more favorable MICs compared to historical data for vancomycin. [4]
A 2016 decision analytic, cost-minimization model compared the economic impact of different management strategies in patients with acute bacterial skin and skin structure infections (ABSSSI). The model specifically compared the costs between inpatient treatment with vancomycin and outpatient treatment with oritavancin for ABSSSI patients exhibiting few or no comorbidities. The cost analysis gathered retrospective data and modeled costs associated with hospitalization, drug acquisition, and intravenous (IV) administration. Patient criteria was limited to those with few or no comorbidities, specified as a Charlson Comorbidity Index Score (CCI) ≤1, having received IV vancomycin on day 1 or 2 of hospital admission, and had no life-threatening conditions. The findings demonstrated that costs associated with use of oritavancin in the outpatient setting ($3,409.46) and observation unit ($4,220.27) were estimated to be substantially lower than costs associated with inpatient vancomycin treatment ($5,972.73 to $9,885.33). Additionally, switching any individual patient from inpatient vancomycin treatment to outpatient oritavancin treatment was associated with an estimated savings of approximately $1752.46 to $6475.87, depending on CCI score, presence of systemic symptoms, and use of observation. Notably, the analysis estimated that up to approximately 38.12% of patients treated with outpatient oritavancin could be subsequently admitted to the hospital while still preserving budget neutrality. Overall, the study concluded that outpatient oritavancin may offer significant cost savings, though limitations include reliance on retrospective data. [5]
Multiple reviews discussed the individual role of oritavancin and dalbavancin in ABSSSIs and other off-label indications. Both categorized as lipoglycopeptides, oritavancin and dalbavancin exhibit long elimination half-life, which enables a single-dose regimen, increasing dose convenience and treatment compliance, especially in the treatment of infections that require long-term antibiotic coverage (i.e., infective endocarditis and osteomyelitis) and for outpatient therapy and early discharge in patients with ABSSSI. While in-vitro and clinical data reported nearly identical activity between oritavancin and dalbavancin against the following aerobic and facultative gram-positive bacteria (Staphylococcus aureus [including MRSA], Streptococcus pyogenes, Streptococcus agalactiae, Staphylococcus dysgalactiae, Staphylococcus anginosus group [including Staphylococcus anginosus, Staphylococcus intermedius, Staphylococcus constellatus], and Enterococcus faecalis), oritavancin provides additional coverage for vancomycin-resistant Enterococci (VRE; vanA and vanB). Unlike oritavancin, whose pharmacokinetics have not been evaluated in patients with severe renal impairment, dalbavancin can be given in individuals with a creatinine clearance of <30 mL/min, including hemodialysis. Moreover, dalbavancin is indicated for the treatment of ABSSSI in both adult and pediatric patients aged from birth to <18 years, whereas the use of oritavancin is limited to adults. The most common treatment-related adverse events for dalbavancin were nausea, diarrhea, and pruritus, whereas nausea, headache, and vomiting for oritavancin. Emerging data primarily from retrospective studies have observed the efficacy of both agents for bacteremia, osteomyelitis, endocarditis, and prosthetic joint infections; however, most available data are pertained to each agent separately with minimal head-to-head comparisons, making it challenging to conclude on interchangeability between the two agents. [6], [7], [8]
A 2017 systematic review, network meta-analysis, and cost analysis compared newer glycopeptides, including telavancin, dalbavancin, and oritavancin. A total of 7 randomized, double-blind studies were ultimately included, encompassing 6,398 patients with complicated skin and soft tissue infections (cSSTI) caused by a suspected or confirmed gram-positive organism and defined by the presence of a major abscess, infected burn, extensive cellulitis, wound infection or ulcer, along with systemic and local signs of infection. All studies were designed to compare one active treatment (IV telavancin [n= 3 studies], IV dalbavancin administered as 1 g on day 1, followed by 500 mg on day 8 [n= 2 studies], and IV oritavancin given as a single 1,200 mg dose [n= 2 studies]) versus the standard of care (a regimen consisting of vancomycin or its traditional alternatives including linezolid, tedizolid, daptomycin, clindamycin, trimethoprim-sulfamethoxazole, doxycycline, oxacillin, cefazolin, ceftaroline, and tigecycline). [9]
Telavancin, dalbavancin, and oritavancin demonstrated a comparable clinical response to the standard of care in both pairwise and network meta-analyses. Additionally, a similar clinical response was noted among telavancin, dalbavancin, and oritavancin via indirect head-to-head comparisons in the network meta-analysis. For the primary outcome of clinical response 1 to 2 weeks after the end of therapy (i.e., improvement in signs and symptoms associated with cSSTI), the odds ratio (OR) for oritavancin vs. dalbavancin was 1.36 (95% CI 0.85 to 2.18). The OR of clinical response in patients infected with methicillin-resistant Staphylococcus aureus was 1.29 (95% CI 0.11 to 15.48), and the OR of early clinical response at 48 to 72 hours among patients with ABSSSI was 1.02 (95% CI 0.72 to 1.46). [9]
No difference in the rate of overall or serious adverse events was observed between oritavancin and dalbavancin, but both oritavancin (OR 0.71; 95% CI 0.55 to 0.92) and dalbavancin (OR 0.58; 95% CI 0.45 to 0.76) were found to have fewer overall adverse events compared to telavancin. Dalbavancin was found to have fewer overall adverse events when compared to the standard of care (OR 0.77; 95% CI 0.64 to 0.93) in pairwise and network meta-analyses but with similar odds of serious adverse events. A cost analysis revealed that the use of dalbavancin could save third-party payers $1,442 to $4,803 per cSSTI patient treated, while the use of oritavancin could save $3,571 to $6,932 per cSSTI patient treated. Similarly, when compared to standard of care, dalbavancin could save between 6.5-10.0 and oritavancin between 7.5-11.0 days of treatment. The authors concluded that treatment with these agents, which can be administered in an outpatient setting in 1 to 2 doses, ultimately correlates with greater cost savings over the standard of care while providing similar efficacy and safety outcomes in patients with suspected or confirmed gram-positive cSSTI infections. Overall, the use of dalbavancin or oritavancin was deemed to be less costly compared with vancomycin-based regimens. [9]
Another 2021 meta-analysis compared novel glycopeptides against vancomycin for the treatment of gram-positive bacterial infections. Eleven trials comprising 7,289 participants were included for analysis. Overall, clinical response was similar between dalbavancin and vancomycin (OR 4.64; 95% CI 0.37 to 57.93); however, data was only available from one trial that provided relevant data on modified intention-to-treat patients. Clinical response was also similar between dalbavancin and vancomycin for clinically evaluable patients (OR 3.25; 95% CI 0.51 to 20.95) as well as in patients with SSTIs (OR 1.00; 95% CI 0.56 to 1.77), osteomyelitis (OR 4.64; 95% CI 0.37 to 57.93). Dalbavancin, however, was associated with significant efficacy in bacteremia patients (OR 15.89; 95% CI 1.73 to 145.79; p= 0.01). Similar to dalbavancin, two trials comparing oritavancin and vancomycin for treatment of SSTIs found no difference among patient in the modified intention-to-treat population (OR 1.08; 95% CI 0.86 to 1.35) or in the clinically evaluable population (OR 1.01; 95% CI 0.71 to 1.45). While dalbavancin resulted in significantly lower mortality compared to vancomycin (OR 0.18; 95% CI 0.03 to 0.98), oritavancin did not (OR 0.67; 95% CI 0.11 to 4.03). Dalbavancin and oritavancin were similar to vancomycin for rates of serious adverse events and discontinuation due to adverse events. Both dalbavancin (OR 0.73; 95% CI 0.57 to 0.94; p= 0.01) and oritavancin (OR 0.72; 95% CI 0.59 to 0.89; p<0.01) were associated with significantly less adverse events compared to vancomycin. Again, head-to-head comparisons between dalbavancin and oritavancin were not conducted. [10]