Potential savings through single-dose intravenous Dalbavancin in long-term MRSA infection treatment - a health economic analysis using German DRG data.
ABSTRACT: Complicated infections such as osteomyelitis, skin and soft tissue infections or endocarditis often require antibiotic therapies that can last up to several weeks. The prolonged hospital length of stay (LOS) leads to a dramatic increase in costs. Single-dose intravenous Dalbavancin is a novel antimicrobial agent for the treatment of acute bacterial skin, skin structure and soft tissue infections (ABSSSI) that allows an earlier discharge of patients, resulting in potential savings. Joint, bone and prostheses infections (JBPI) are also related with long LOS. The aim of this study is to determine the economic effects of single-dose intravenous Dalbavancin in suitable patients with Methicillin-resistant Staphylococcus aureus infections in Germany. For this purpose, an analysis with real-world patient treatment data was performed, which was subsequently validated in a large German hospital. In total, ABSSSI patients with MRSA infections could stay 6.45 days shorter and 2,865 € could be saved while JBPI patients could be discharged eventually 10.6 days earlier and 3,909 € could be saved. Single-dose intravenous Dalbavancin is thus an option for patients with ABSSSI and JBPI who are eligible for discharge.
Project description:INTRODUCTION:Admissions for acute bacterial skin and skin structure infections (ABSSSI) are often prolonged because of intravenous (IV) antibiotics. Use of a long-acting IV antibiotic may reduce length of stay (LOS) on a hospitalist service. The ENHANCE ABSSSI trial sought to determine the impact on LOS and work productivity in patients treated with a long-acting IV antibiotic, dalbavancin, vs. usual care at an urban tertiary-care center. METHODS:A single-center, pre- vs. post-period pragmatic trial at Weill-Cornell Medical Center assessed usual care for consecutively enrolled admitted ABSSSI patients during an observational period (pre-period). Identification and treatment of eligible admitted ABSSSI patients with dalbavancin were implemented in the post-period. Those with life-threatening infections, requiring multiple antibiotics/intensive care, or with unstable comorbidities were excluded. Outcomes were assessed over a 44-day follow-up period. RESULTS:Of 48 and 43 patients enrolled, respectively, in the pre- and post-periods, mean infection-related LOS was reduced in the post-period (3.2 days vs. 4.8 days; P?=?0.003). Similar results were found in an adjusted LOS analysis. Work productivity and activity impairment outcomes significantly improved in the post-period (P???0.01). Complete response rates were similar: 50% (pre-period) and 57% (post-period). Among AEs identified, 17% (n?=?7) were found to have possible causal relation to dalbavancin in the post-period. Few AEs were serious (n?=?3; 7% post-period versus n?=?1; 2% pre-period). CONCLUSION:After implementing the ENHANCE ABSSSI pathway, LOS was significantly reduced by almost 2 days, with potential improvements in work productivity and ability to complete daily activities. TRIAL REGISTRATION:ClinicalTrials.gov identifier, NCT03233438. FUNDING:Allergan plc.
Project description:Abstract Background Prolonged admissions for acute bacterial skin and skin structure infections (ABSSSI) present an opportunity to improve efficiency and quality of care. A primary reason for admission for ABSSSI is to receive intravenous (IV) antibiotics, where multiple guidelines support shifting care to outpatient settings for appropriate patients. A hospital pathway for ABSSSI that leverages long-acting IV antibiotic therapy, such as dalbavancin, may reduce the length of stay (LOS). The ENHANCE ABSSSI trial (NCT03233438) sought to quantify LOS vs. that of usual care after implementing a new ABSSSI pathway. Methods A single-center, pre- vs. post-period pragmatic trial at Weill-Cornell Medical Center assessed usual care for consecutively enrolled ABSSSI patients during an observational period (pre-period). A new ABSSSI pathway was implemented in the post-period, which included (1) identification of eligible admitted ABSSSI patients and (2) treatment with dalbavancin. Those with life-threatening infections, requiring multiple antibiotics/intensive care, or with unstable comorbidities were excluded. Outcomes were assessed over a 44-day follow-up period. Results Of 48 and 43 patients enrolled in pre- and post-periods (Figure 1), mean infection-related LOS was reduced in the post-period (3.2 days vs. 4.8 days; P = 0.003; Figure 2 and 3). Similar results were found in an adjusted LOS analysis. Work productivity and activity impairment outcomes significantly improved in the post-period, apart from absenteeism, while quality of life was similar between periods (Figure 4). Complete response to treatment was similar between periods: 50% (pre-period) and 57% (post-period). A greater proportion of total adverse events (AEs) occurred in the post-period (n = 20; 48%) vs. pre-period (n = 3; 6%) with most AEs being mild in severity and not related to antibiotic use; few AEs were serious (7% [n = 3] post-period vs. 2% [n = 1] pre-period). The most common AEs were unrelated infection in the pre-period and fever in the post-period. Conclusion After implementing the ENHANCE ABSSSI pathway among eligible patients, LOS was significantly reduced by almost 2 days, with potential improvements in work productivity and the ability to complete daily activities. Disclosures All authors: No reported disclosures.
Project description:Background:Persons who inject drugs (PWID) are at increased risk of acute bacterial skin and skin structure infections (ABSSSIs), a growing healthcare concern. Multiple medical, social, and economic issues, including adherence and comorbidities, complicate the medical care of the PWID population, adversely affecting patient outcomes. Methods:We assessed demographics and outcomes for the PWID population in a double-blind trial of 698 patients randomized to dalbavancin 1500 mg as a single intravenous (IV) infusion or as a 2-dose regimen (1000 mg IV on day 1; 500 mg IV on day 8) for ABSSSI. The primary endpoint was ?20% reduction in erythema at 48-72 hours in the intent-to-treat population; clinical status was also assessed at days 14 and 28. Results:There were 212/698 (30.4%) patients with a history of injection drug use in this clinical trial. Dalbavancin efficacy was similar between the single- and 2-dose therapy groups in the PWID and non-PWID populations at all timepoints. Dalbavancin was well tolerated in the PWID population, with similar rates of adverse events as the non-PWID population. Conclusion:Dalbavancin as a single-dose or 2-dose regimen had similar efficacy for the treatment of ABSSSI at all timepoints in the PWID and non-PWID populations. A single 30-minute IV infusion would eliminate the need for indwelling IV access. The convenience of a single dose supervised in a health setting may also optimize treatment adherence in the PWID population.
Project description:Dalbavancin is a lipoglycopeptide antibiotic recently approved by the United States Food and Drug Administration (FDA) for acute bacterial skin and skin structure infections (ABSSSIs). It is active against gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), and minimum inhibitory concentrations (MICs) are consistently <0.125 µg/ml, much lower than most other anti-MRSA agents. Dalbavancin possesses an extended half-life of over 1 week, allowing an initial dose of 1000 mg followed by 500 mg 1 week later to complete a course of therapy for ABSSSI. It is approximately 95% protein bound and is widely distributed throughout the body, achieving concentrations similar to plasma levels in numerous tissues. Against MRSA, dalbavancin is 4-8 times more potent than vancomycin in vitro, and limited data suggest it possesses activity against MRSA with reduced susceptibility to vancomycin such as hVISA and VISA. Dalbavancin also possesses in vitro activity against streptococci and enterococci, although activity against vancomycin-resistant enterococci is lacking. In phase 3 ABSSSI studies, dalbavancin demonstrated similar activity to vancomycin and provides a more convenient dosing regimen. Limited phase 2 data suggest dalbavancin also possesses activity in catheter-related bloodstream infections. Potential further therapeutic uses include conditions that require long-term treatment such as osteomyelitis and infective endocarditis, although data are currently lacking. The extended half-life of dalbavancin, along with its in vitro activity against gram-positive organisms with reduced susceptibility to other anti-MRSA antibiotics, suggest it could have an exciting clinical role going forward.
Project description:Acute bacterial skin and skin structure infections (ABSSSIs) are a cause of significant morbidity and therapy can be a burden to the healthcare system. New antibiotics that simplify treatment and avoid hospitalization are needed. This study compared the safety and efficacy of a single intravenous infusion of 1500 mg of dalbavancin to the 2-dose regimen.This study was a randomized, double-blind trial in patients aged >18 years with ABSSSIs. Patients were randomized to dalbavancin 1500 mg either as a single intravenous (IV) infusion or 1000 mg IV on day 1 followed 1 week later by 500 mg IV. The primary endpoint was a ≥20% reduction in the area of erythema at 48-72 hours in the intent-to-treat population. Noninferiority was to be declared if the lower limit of the 95% confidence interval (CI) on the difference in the outcomes was greater than -10%. Clinical outcome was also assessed at days 14 and 28.Six hundred ninety-eight patients were randomized. Demographic characteristics were similar on each regimen, although there were more patients with methicillin-resistant Staphylococcus aureus (MRSA) at baseline on the 2-dose regimen (36/210 [17.1%] vs 61/220 [27.7%]). Dalbavancin delivered as a single dose was noninferior to a 2-dose regimen (81.4% vs 84.2%; difference, -2.9% [95% CI, -8.5% to 2.8%]). Clinical outcomes were also similar at day 14 (84.0% vs 84.8%), day 28 (84.5% vs 85.1%), and day 14 in clinically evaluable patients with MRSA in a baseline culture (92.9% vs 95.3%) in the single- and 2-dose regimens, respectively. Treatment-emergent adverse events occurred in 20.1% of the single-dose patients and 19.9% on the 2-dose regimen.A single 1500-mg infusion of dalbavancin is noninferior to a 2-dose regimen, has a similar safety profile, and removes logistical constraints related to delivery of the second dose.NCT02127970.
Project description:Background:Omadacycline is an oral and intravenous (IV) once-daily aminomethylcycline antibiotic that is approved in the United States for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI). It has broad-spectrum activity against common causative pathogens of ABSSSI, including methicillin-resistant Staphylococcus aureus. Omadacycline has been shown to be noninferior to linezolid for the treatment of adults with ABSSSI across 2 phase 3 clinical trials. To date, no studies have assessed the budget impact for omadacycline in the treatment of ABSSSI. Objectives:To estimate the potential budget impact of introducing omadacycline as a treatment option in patients who present to the emergency department (ED) with ABSSSI from the hospital perspective (Medicare payer) in the United States. The ED's and observation units were assumed to be hospital-owned. Methods:The base case of this decision model-based analysis was conducted from the perspective of a hospital for a theoretical cohort of 1 million covered Medicare members over a 3-year time horizon. Scenario analyses included the economic impact of (1) shifting inpatient care to the outpatient setting with omadacycline and (2) reducing hospital length of stay (LOS) among hospitalized patients with omadacycline IV to oral therapy relative to the current inpatient standard of care. Costs are presented in 2017 US dollars with no adjustments for inflation, based on the cost model estimates. Results:The annual total incremental cost following the introduction of omadacycline as a treatment of ABSSSI was $11,168, $39,918, and $88,777 in years 1, 2, and 3, respectively. The incremental cost per member treated (cost per case) rose by $0.49, $1.74, and $3.86 over 3 years. Reducing hospital LOS by 1 day among hospitalized patients with omadacycline resulted in incremental costs of $4311, $15,231, and $33,919 in years 1, 2, and 3, respectively. Under the assumption that patients may be discharged sooner when an oral formulation of the same drug with which they are being treated is available, reducing hospital LOS by 2 days reduced costs by $2546, $9455, and $20,939 in years 1, 2, and 3, respectively. Shifting inpatient care to the outpatient setting with omadacycline reduced costs by $38,777, $139,885, and $310,784 in years 1, 2, and 3, respectively. Conclusion:This hypothetical, model-based study determined that omadacycline would result in a modest increase in total cost over 3 years when introduced as a treatment for ABSSSI in adults who present to the ED for their care.
Project description:Dalbavancin is a new lipoglycopeptide that is active against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus. It has a half-life of 14.4 days, permitting intravenous treatment of acute bacterial skin and skin structure infections without the need for daily dosing.The objective of these analyses was to compare the adverse event profile of dalbavancin with that of the comparator agents in the treatment of skin and skin structure infections.Data on adverse events and laboratory assessments collected from 3002 patients enrolled in seven late-stage, randomized clinical trials were analyzed for patients receiving dalbavancin or a comparator antibiotic.Overall adverse event rates were similar or lower for patients receiving dalbavancin (799/1778; 44.9%) compared with those receiving comparator agents (573/1224; 46.8%, p = 0.012). The most common treatment-emergent adverse events were nausea, headache, diarrhea, constipation, vomiting, rash, urinary tract infection, pruritus, and insomnia. The duration and timing of the onset of adverse events were similar for patients receiving dalbavancin relative to the comparators.Dalbavancin exhibits a favorable overall safety profile for treatment of acute bacterial skin and skin structure infections due to Gram-positive bacteria.
Project description:Background:Osteomyelitis is a challenging infection that can involve 4-6 weeks of intravenous (IV) antibiotics. Dalbavancin, approved for acute bacterial skin and skin structure infections, has potent activity against gram-positive pathogens. This study assessed the efficacy and safety of dalbavancin as a 2-dose regimen for osteomyelitis. Methods:This study was a randomized, open-label, comparator-controlled trial in adults with a first episode of osteomyelitis defined by clinical symptoms, radiologic findings, and elevated C-reactive protein. Patients were randomized 7:1 to dalbavancin (1500 mg IV on days 1 and 8) or standard of care (SOC) for osteomyelitis (oral or IV) per investigator judgment for 4-6 weeks. The primary endpoint was clinical response at day 42, defined as recovery without need for additional antibiotics in the clinically evaluable (CE) population. Clinical response was also assessed at day 21, 6 months, and 1 year. Results:Eighty patients were randomized to dalbavancin (n = 70) or SOC (n = 10). All had baseline debridement; Staphylococcus aureus was the most common pathogen (60% of patients). Clinical cure at day 42 was seen in 65/67 (97%) and 7/8 (88%) patients in the dalbavancin group and SOC group in the CE population, respectively. Clinical response was similar in the dalbavancin group at day 21 (94%), 6 months, and 1 year (96%). Treatment-emergent adverse events occurred in 10 patients in the dalbavancin group; no patient discontinued treatment due to an adverse event. Conclusions:A 2-dose regimen of weekly dalbavancin is effective and well tolerated for the treatment of osteomyelitis in adults. Clinical Trials Registration:NCT02685033.
Project description:The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibit in vitro activity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstrate in vitro activity against VRE. These new Gram-positive agents are reviewed here.
Project description:Limited research has assessed patient preferences for treatment disposition and antibiotic therapy of acute bacterial skin and skin structure infection (ABSSSI) in the emergency department (ED). Understanding patient preference for the treatment of ABSSSI may influence treatment selection and improve satisfaction. A survey was conducted across 6 US hospital EDs. Patients with ABSSSI completed a baseline survey assessing preferences for antibiotic therapy (intravenous versus oral) and treatment location. A follow-up survey was conducted within 30-40?days after ED discharge to reassess preferences and determine satisfaction with care. A total of 94 patients completed both baseline and follow-up surveys. Sixty (63.8%) participants had a history of ABSSSI, and 69 (73.4%) were admitted to the hospital. Treatment at home was the most common preference reported on baseline and follow-up surveys. Patients with higher education were 82.2% less likely to prefer treatment in the hospital. Single dose intravenous therapy was the most commonly preferred antibiotic regimen on baseline and follow-up surveys (39.8 and 19.1%, respectively). Median satisfaction scores for care in the ED, hospital, home, and with overall antibiotic therapy were all 8 out of a maximum of 10. In these patients, the most common preference was for outpatient care and single dose intravenous antibiotics. Patient characteristics including higher education, younger age, and current employment were associated with these preferences. Opportunities exist for improving ABSSSI care and satisfaction rates by engaging patients and offering multiple treatment choices.