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Efficacy and Safety of Oritavancin Relative to Vancomycin for Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Outpatient Setting: Results From the SOLO Clinical Trials.

ABSTRACT: BACKGROUND:The objective of this analysis was to evaluate the efficacy and safety of oritavancin compared with vancomycin for patients with acute bacterial skin and skin structure infections (ABSSSIs) who received treatment in the outpatient setting in the Phase 3 SOLO clinical trials. METHODS:SOLO I and SOLO II were 2 identically designed comparative, multicenter, double-blind, randomized studies to evaluate the efficacy and safety of a single 1200-mg dose of intravenous (IV) oritavancin versus 7-10 days of twice-daily IV vancomycin for the treatment of ABSSSI. Protocols were amended to allow enrolled patients to complete their entire course of antimicrobial therapy in an outpatient setting. The primary efficacy outcome was a composite endpoint (cessation of spread or reduction in size of the baseline lesion, absence of fever, and no rescue antibiotic at early clinical evaluation [ECE]) (48 to 72 hours). Key secondary endpoints included investigator-assessed clinical cure 7 to 14 days after end of treatment (posttherapy evaluation [PTE]) and 20% or greater reduction in lesion area at ECE. Safety was assessed until day 60. RESULTS:Seven hundred ninety-two patients (oritavancin, 392; vancomycin, 400) received entire course of treatment in the outpatient setting. Efficacy response rates at ECE and PTE were similar (primary composite endpoint at ECE: 80.4% vs 77.5% for oritavancin and vancomycin, respectively) as was incidence of adverse events. Five patients (1.3%) who received oritavancin and 9 (2.3%) vancomycin patients were subsequently admitted to a hospital. CONCLUSIONS:Oritavancin provides a single-dose alternative to multidose vancomycin for treatment of ABSSSI in the outpatient setting.

SUBMITTER: Lodise TP

PROVIDER: S-EPMC5414048 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Efficacy and Safety of Oritavancin Relative to Vancomycin for Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Outpatient Setting: Results From the SOLO Clinical Trials.

Lodise Thomas P TP Redell Mark M Armstrong Shannon O SO Sulham Katherine A KA Corey G Ralph GR

Open forum infectious diseases 20170119 1

<h4>Background</h4>The objective of this analysis was to evaluate the efficacy and safety of oritavancin compared with vancomycin for patients with acute bacterial skin and skin structure infections (ABSSSIs) who received treatment in the outpatient setting in the Phase 3 SOLO clinical trials.<h4>Methods</h4>SOLO I and SOLO II were 2 identically designed comparative, multicenter, double-blind, randomized studies to evaluate the efficacy and safety of a single 1200-mg dose of intravenous (IV) ori ...[more]

PMID: 28480266

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Project description:IntroductionIntroduction of new antibiotics enabling single-dose administration, such as oritavancin may significantly impact site of care decisions for patients with acute bacterial skin and skin structure infections (ABSSSI). This analysis compared the efficacy of single-dose oritavancin with multiple-dose vancomycin in patients categorized according to disease severity via modified Eron classification and management setting.MethodsSOLO I and II were phase 3 studies evaluating single-dose oritavancin versus 7-10 days of vancomycin for treatment of ABSSSI. Patient characteristics were collected at baseline and retrospectively analyzed. Study protocols were amended, allowing outpatient management at the discretion of investigators. In this post hoc analysis, patients were categorized according to a modified Eron severity classification and management setting (outpatient vs. inpatient) and the efficacy compared.ResultsOverall, 1910 patients in the SOLO trials were categorized into Class I (520, 26.5%), II (790, 40.3%), and III (600, 30.6%). Of the 767 patients (40%) in the SOLO trials who were managed entirely in the outpatient setting 40.3% were categorized as Class II and 30.6% were Class III. Clinical efficacy was similar between oritavancin and vancomycin treatment groups, regardless of severity classification and across inpatient and outpatient settings. Class III patients had lower response rates (oritavancin 73.3%, vancomycin 76.6%) at early clinical evaluation when compared to patients in Class I (82.6%) or II (86.1%); however, clinical cure rates at the post-therapy evaluation were similar for Class III patients (oritavancin 79.8%, vancomycin 79.9%) when compared to Class I and II patients (79.1-85.7%).ConclusionSingle-dose oritavancin therapy results in efficacy comparable to multiple-dose vancomycin in patients categorized according to modified Eron disease severity classification regardless of whether management occurred in the inpatient or outpatient setting.FundingThe Medicines Company, Parsippany, NJ, USA.Trial registrationClinicalTrials.gov identifiers, NCT01252719 (SOLO I) and NCT01252732 (SOLO II).

Project description:IntroductionDalbavancin is a lipoglycopeptide antibiotic approved as a single- and two-dose regimen for adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive organisms. We present nephrotoxicity rates for patients with ABSSSI who received dalbavancin in three pivotal clinical trials and compare the rates with vancomycin.MethodsIn a phase 3b clinical trial (DUR001-303), patients were randomized to dalbavancin single-dose (1500 mg intravenous [IV]) or two-dose regimen (1000 mg IV on day 1, 500 mg IV on day 8). In two phase 3 clinical trials (DISCOVER 1 and DISCOVER 2), patients were randomized to dalbavancin (two-dose regimen) or vancomycin 1 g (or 15 mg/kg) IV every 12 h for at least 3 days with an option to switch to orally administered linezolid 600 mg every 12 h for 10-14 days. Patients on dalbavancin with a creatinine clearance below 30 mL/min not on regular dialysis received a reduced dose of 1000 mg (single-dose arm) or 750 mg IV on day 1, 375 mg IV on day 8 (two-dose arm). Nephrotoxicity was defined as a 50% increase from baseline serum creatinine (SCr) or an absolute increase in SCr of 0.5 mg/dL at any time point. P values were obtained using the Cochran-Mantel-Haenszel test.ResultsIn dalbavancin-treated patients, rates of nephrotoxicity were low. The safety population with available creatinine values included 1325/1347 patients on any regimen of dalbavancin, and 54/651 patients who received vancomycin intravenously for at least 10 days and were not switched to orally administered linezolid. Patients on any regimen of dalbavancin had a lower rate of nephrotoxicity compared with patients receiving vancomycin intravenously for at least 10 days (3.7% vs 9.3%, respectively; P = 0.039).ConclusionsNephrotoxicity rates were lower in patients on dalbavancin relative to vancomycin for at least 10 days. On the basis of this experience, dalbavancin may be less nephrotoxic than intravenously administered vancomycin.

Project description:BACKGROUND:Acute bacterial skin and skin structure infections (ABSSSI) are a frequent cause of hospital admissions in the United States. Safe and effective outpatient treatments may lower ABSSSI-associated health care costs by reducing unnecessary hospital admissions. Using data from 2 phase 3 trials (ESTABLISH-1, NCT01170221; ESTABLISH-2, NCT01421511), this post-hoc analysis explored the efficacy and safety of tedizolid in an outpatient setting. METHODS:Subgroup analysis was performed on US outpatients (defined as patients who were not in hospital at the time of treatment initiation) with ABSSSI caused by presumed or proven gram-positive pathogens. Patients were randomly assigned to receive tedizolid phosphate 200?mg once daily for 6 days (n?=?403) or linezolid 600?mg twice daily for 10 days (n?=?410). The primary end point was early clinical response (48-72?hours after the start of treatment). Secondary end points included investigator-assessed clinical response at end of therapy (EOT) and post-therapy evaluation (PTE; 7-14 days after therapy). Additional assessments included the patient-reported level of pain using a visual analog scale (VAS) and the per-pathogen favorable microbiological response rate at the PTE visit. Compliance with treatment and safety outcomes was also recorded. RESULTS:Early clinical response was similar between treatment groups (tedizolid, 82.4%; linezolid, 79.0%), as was investigator-assessed clinical response at EOT (tedizolid, 87.1%; linezolid, 86.1%) and PTE (tedizolid, 83.1%; linezolid, 83.7%). Mean changes from baseline to days 10 to 13 in VAS scores were identical between treatment groups (tedizolid, -51.9?mm; linezolid, -51.9?mm). Microbiological eradication rates were generally similar in both treatment groups for all key pathogens. Patients in both groups had favorable response at PTE. More tedizolid-treated patients (89.3%) than linezolid-treated patients (77.3%) were compliant with treatment. The most frequently reported drug-related treatment-emergent adverse events were nausea (tedizolid, 10.7%; linezolid, 13.8%), diarrhea (tedizolid, 4.5%; linezolid, 5.9%), and headache (tedizolid, 5.5%; linezolid, 4.4%). Treatment discontinuation rates were low for both treatment groups (tedizolid, 0.7%; linezolid, 1.0%). CONCLUSION:Short-course therapy with tedizolid can successfully treat patients with ABSSSI caused by presumed or proven gram-positive pathogens in an outpatient setting.

Project description:Background and objectiveNearly 10% of all US hospital admissions are attributed to acute bacterial skin and skin structure infections (ABSSSIs). While most antibacterials used to treat these infections require multi-day and multi-dose regimens, a single-dose treatment is now available. The objective of this analysis is to estimate the annual budget impact of using single-dose oritavancin in patients with moderate to severe ABSSSIs receiving intravenous methicillin-resistant Staphylococcus aureus (MRSA)-active antibacterials from a US hospital perspective.MethodsA decision-analytic model based on current clinical practice was developed to estimate the economic impact of oritavancin. Utilization of antibacterials and rates of hospital admission were derived from the Premier Research Database. Demographic and clinical data were informed by the published literature and 2014 wholesale drug acquisition costs were used. Other costs were based on the published literature and Medicare National Limitation amounts. All costs were inflated to 2014 US dollars. Two base-case scenarios were considered: one for hospitals with ambulatory services and one for hospitals without ambulatory services.ResultsFor a US hospital with ambulatory services with 1000 ABSSSI patients receiving intravenous MRSA antibiotics annually, use of oritavancin in 26% of patients is estimated to reduce the total annual budget by 12.9% (US$1.23 million), or approximately US$1234.67 per patient. Total inpatient costs will be reduced by 22.3% (US$1.40 million) and outpatient costs will increase slightly by 1.7% (US$55,310). Pharmaceutical cost increases are offset by savings in the inpatient setting from fewer hospital admissions. Hospitals without ambulatory services are estimated to receive overall cost savings of 9.3% (US$0.63 million).ConclusionUse of single-dose oritavancin in select ABSSSI patients with suspected or confirmed MRSA involvement is estimated to save US hospitals approximately 9.3-12.9% per year by reducing hospital admissions and lowering drug administration burden.

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:INTRODUCTION:Outcomes data for patients who received tedizolid for acute bacterial skin and skin-structure infections (ABSSSIs) are scant. We provide a real-world analysis of economic and clinical outcomes following tedizolid use in the outpatient setting. METHODS:This retrospective study of adults with skin infections treated with tedizolid (index period: 1 July 2014-31 May 2016) used data from the Optum Research and Impact National Benchmark databases. RESULTS:Ninety-one patients received tedizolid for the treatment of skin infections (with complications, n = 18; without complications, n = 73). Some patients had > 1 complication and infection site. Among patients with complications, pre-index complications during the [index date - 30] through [index date + 1] period included osteomyelitis (44.4%), septicemia (44.4%), and prosthetic joint/device/graft infection (16.7%). For the [index date - 7] through [index date + 1] period, the infection site included abscesses (55.6%) and chronic ulcers (38.9%). Mean (standard deviation [SD]) days supplied for the index tedizolid claim was 6.8 (2.3) days. Healthcare resource utilization (HCRU) during the 30-day post-index period included ≥ 1 ambulatory visit (100.0%), ≥ 1 emergency department (ED) visit (16.7%), and ≥ 1 hospitalization (22.2%). Median 30-day post-index all-cause costs were $11,098 [lower quartile (Q1), $5688; upper quartile (Q3), $16,246; mean (SD), $14,637 ($11,435)]. Among patients without complications, the pre-index infection site from ([index date - 7] through [index date + 1]) included abscesses (60.3%), chronic ulcers (37.0%), and cellulitis (2.7%). Mean (SD) days supplied for the index tedizolid claim was 6.6 (2.5) days. Thirty-day post-index HCRU included ≥ 1 ambulatory visit (91.8%), ≥ 1 ED visit (17.8%), and ≥ 1 hospitalization (5.5%). Median 30-day post-index all-cause costs were $3230 (Q1, $2345; Q3, $6847; mean [SD], $6898 [$11,129]). CONCLUSIONS:Patients treated with tedizolid in the outpatient setting experienced a short duration of therapy, low hospital admission, and modest post-index HCRU indicators, suggesting its utility for outpatient therapy of ABSSSIs.

Project description:BackgroundOritavancin, a long-acting lipoglycopeptide approved for use in acute bacterial skin and skin structure infections, has limited data evaluating use in serious infections due to Gram-positive organisms. We aimed to assess the effectiveness and safety of oritavancin for consolidative treatment of Gram-positive bloodstream infections (BSI), including infective endocarditis (IE).MethodsWe conducted a retrospective cohort study evaluating adult patients admitted to University of Colorado Hospital from March 2016 to January 2022 who received ≥ 1 oritavancin dose for treatment of Gram-positive BSI. Patients were excluded if the index culture was drawn at an outside facility or were > 89 years of age. The primary outcome was a 90-day composite failure (clinical or microbiological failure) in those with 90-day follow-up. Secondary outcomes included individual components of the primary outcome, acute kidney injury (AKI), infusion-related reactions (IRR), and institutional cost avoidance.ResultsOverall, 72 patients were included. Mean ± SD age was 54 ± 16 years, 61% were male, and 10% had IE. Organisms most commonly causing BSI were Staphylococcus aureus (68%, 17% methicillin-resistant), followed by Streptococcus spp. (26%), and Enterococcus spp. (10%). Patients received standard-of-care antibiotics before oritavancin for a median (IQR) of 11 (5-17) days. Composite failure in the clinically evaluable population (n = 64) at 90-days occurred in 14% and was composed of clinical and microbiological failure, which occurred in 14% and 5% of patients, respectively. Three patients (4%) experienced AKI after oritavancin, and two (3%) experienced an IRR. Oritavancin utilization resulted in earlier discharge for 94% of patients corresponding to an institutional cost-avoidance of $3,055,804 (mean $44,938/patient) from 1,102 hospital days saved (mean 16 days/patient).ConclusionsThe use of oritavancin may be an effective sequential therapy for Gram-positive BSI to facilitate early discharge resulting in institutional cost avoidance.

Dataset Information

Efficacy and Safety of Oritavancin Relative to Vancomycin for Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Outpatient Setting: Results From the SOLO Clinical Trials.

Publications

Efficacy and Safety of Oritavancin Relative to Vancomycin for Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI) in the Outpatient Setting: Results From the SOLO Clinical Trials.

Similar Datasets

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