Single-Dose Oritavancin Compared to Standard of Care IV Antibiotics for Acute Bacterial Skin and Skin Structure Infection in the Outpatient Setting: A Retrospective Real-World Study

Total US healthcare spending now exceeds $3 trillion annually, or approximately $9523 per person, and 32% of that cost is spent on hospital care [1]. Acute bacterial skin and skin structure infections (ABSSSI) represent the tenth leading cause for non-maternal/non-neonatal hospital admissions, comprising a total of 569,259 admissions in 2013 and representing $14 billion in healthcare spending for hospital care alone [2]. Despite being a top-ten reason for admission, the mortality rate for these infections is only 0.08% [3].

The high utilization of the hospital inpatient setting for a low acuity condition is due in part to the increasing incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA), which comprises up to 60% of all ABSSSI cases [4‐6]. Treatment of MRSA frequently requires intravenous (IV) antibiotics, and because of the time it takes to identify the pathogen, patients are often admitted and treated empirically with IV MRSA-active antibiotics when MRSA is suspected.

Infectious Disease Society of America (IDSA) guidelines indicate that treatment for severe ABSSSI should include antibiotic treatment with IV antibiotics including vancomycin, daptomycin, linezolid, telavancin, or ceftaroline, all of which require multiple doses over several days [7]. Further, vancomycin requires regular serum monitoring for toxicity, another reason for potential hospital admission. A 2015 study funded by the US Centers for Disease Control and Prevention found that emergency room (ER) physicians cited the need for multi-dose intravenous (IV) antibiotics as a reason for admission for 85% of ABSSSI admissions, with IV antibiotics the sole reason for admission in 41.5% of cases [8]. Similarly, a 2015 study determined that 67% of patients hospitalized for ABSSSI had no life-threatening conditions and one or no comorbidities, indicating that a substantial portion of hospitalized ABSSSI patients have no clinical rationale for admission [3].

The cost-saving potential of treating ABSSSI patients in the outpatient instead of inpatient setting may be substantial. Non-drug medical costs for ABSSSI care has been estimated to range from $9813 to $18,014 in the inpatient setting compared with $4039 to $4924 for outpatient management [5]. Clinical studies indicate that outcomes may be equally good in the outpatient setting [3, 8], although delivery of successful outpatient care may be difficult for both provider and patient when multiple days of IV therapy are required.

Orbactiv^® (oritavancin for injection, The Medicines Company, Parsippany, NJ), a novel semisynthetic lipoglycopeptide antibiotic, is approved to treat ABSSSI caused by gram-positive pathogens, including MRSA. Oritavancin is administered as a one-time, single-dose infusion, making it a strong candidate for outpatient treatment of ABSSSI. The introduction of newer antibiotics like oritavancin, with one-time dosing and fewer intensive monitoring requirements, may be a good solution to the current pressure to manage healthcare costs through reduction of hospital utilization while maintaining quality of care [9‐11]. However, little is known about the outcomes and costs of ABSSSI treatment in a real-world outpatient setting. The objective of this analysis was to compare and evaluate clinical outcomes, healthcare costs, and resource utilization associated with single-dose oritavancin vs. multi-dose standard of care (SoC) antibiotics for the treatment of ABSSSI in a real-world outpatient setting.

In the current healthcare environment, there is substantial pressure to reduce costs and resource use while maintaining or improving quality of care. This study analyzed the effectiveness of ABSSSI treatment in an outpatient infusion center with single-dose oritavancin compared to SoC antibiotics and found that oritavancin was clinically comparable to SoC antibiotics, but less costly and resource intensive.

For overall effectiveness (cured or improved), oritavancin showed similar rates (90.2% cured or improved) to SoC antibiotics (77.4%). Notably, the clinical cure rate was statistically higher for the oritavancin cohort (73.2 vs. 48.4%; P = 0.0315). The effectiveness rates in this real-world study were comparable to rates seen in clinical trials. The phase 3 SOLO1 trial compared single-dose oritavancin to 7–10 days of twice daily vancomycin. Oritavancin demonstrated comparable effectiveness for the primary composite endpoint (cessation of spreading or reduction in lesion size) at early clinical evaluation (ECE) at 48–72 h (82.3% for oritavancin, 78.9% for vancomycin, 95% CI −1.6, 8.4); investigator-assessed clinical cure at post-therapy evaluation (79.6% for oritavancin, 80.0% for vancomycin, 95% CI −5.5, 4.7); and lesion size reduction ≥20% at ECE (86.9% for oritavancin, 82.9% for vancomycin, 95% CI −0.5, 8.6). [13] Similar results were seen in the phase 3 SOLO2 trial of single-dose oritavancin compared to twice daily vancomycin for 7–10 days. Oritavancin demonstrated comparable effectiveness for the primary composite endpoint at ECE (80.1 vs. 82.9%), investigator-assessed clinical cure at post-treatment evaluation (82.7 vs. 80.5%), and ≥20% lesion size reduction at ECE (85.9 vs. 85.3%). Clinical response rates were similar across sub-groups, including BMI, age, MRSA, gender, and race [13].

This analysis also found that oritavancin demonstrated consistent clinical effectiveness across subgroup populations with various clinical characteristics, including MRSA. This consistency is supported by a recent analysis of pooled SOLO study results that used a modified Eron severity classification system for skin and soft tissue infections to evaluate oritavancin compared with vancomycin in patients with varying degrees of morbidity and disease severity. The study concluded that single-dose oritavancin was an effective alternative to multi-dose IV vancomycin for the treatment of ABSSSI patients within modified Eron Classes I–III and that management in the inpatient or outpatient setting had comparable efficacy [14].

Based on these study results, the clinical effectiveness of oritavancin and SoC IV antibiotics in the real-world outpatient setting is comparable to that seen in clinical trials. This study further found that while outcomes are comparable, outpatient treatment with oritavancin was less expensive and less resource intensive than outpatient treatment with SoC IV antibiotics, with a mean cost savings of $2319 per patient. Cost savings were derived from both lower medication costs and fewer healthcare resources needed to deliver treatment. Importantly, this study also found that the cost of outpatient treatment with oritavancin was substantially lower than reported costs for inpatient management of ABSSSI. Ektare et al. estimated total costs to the payer of $9813 to $18,014 for inpatient treatment of ABSSSI [5]. A 2015 analysis by Lodise et al. based on a retrospective analysis of hospital discharge data from the Premier Research Database found that hospital costs for inpatient care ranged from $5851 to $12,457 for patients without life-threatening infections [3]. The Lodise analysis also determined that 94% of all hospitalized ABSSSI patients did not have a life-threatening infection, indicating that up to 535,100 hospital admissions in the US could be avoided with greater use of the outpatient setting [2, 3]. Further, in this study the majority of patients had no prior hospitalization (81.3% of oritavancin and 74.6% of SoC), and there was a low rate of ER visits and hospitalization following outpatient treatment (0% oritavancin vs. 3.4% SoC, NS; 0% oritavancin vs. 5.1% SoC, NS). This indicates that effective treatment can be provided entirely in the outpatient setting for most patients.

These findings and other recent investigations [8‐11] provide a clear implication of the potential for cost savings in moving ABSSSI treatment from the inpatient to outpatient setting. When this is coupled with the cost savings obtained from using single-dose over SoC antibiotics, outpatient treatment of ABSSSI with oritavancin may provide much-needed cost savings. These cost savings accrue not only to the health care system, but also to patients, as many patients are responsible for a co-insurance of ~20% on the cost of outpatient services. Further, oritavancin patients visited the infusion center only once for drug administration, compared to a mean of 7 visits for SoC patients. Given no difference in clinical outcomes, both the cost to the patient and overall treatment burden on patients should be considered when making appropriate treatment decisions.

This study, conducted in an outpatient infusion center, demonstrates that real-world treatment of ABSSSI with single-dose oritavancin provides equivalent outcomes compared with SoC antibiotics with 6 fewer days of treatment and a cost savings of greater than $2000. It also provides evidence of lower costs relative to hospital inpatient care, an important consideration when hospital costs comprise one-third of total healthcare spending. In an era of continued pressure to reduce costs without compromising outcomes, outpatient treatment with single-dose oritavancin may present a solution to the management of ABSSSI patients.