Acute Bacterial Skin And Skin Structure Infections Patients Research Articles

Target attainment of intravenous lefamulin for treatment of acute bacterial skin and skin structure infections.

Lefamulin is a pleuromutilin antibiotic approved for the treatment of community-acquired bacterial pneumonia (CABP). Its spectrum of activity, good penetration into soft tissues and low rates of cross-resistance also make lefamulin a potentially valuable option for treatment of acute bacterial skin and skin structure infections (ABSSSIs). A Phase 2 trial of lefamulin for ABSSSI indicated similar efficacy of 100 and 150 mg q12h IV dosing regimens. In the present study, the potential of lefamulin for this indication was further evaluated from a translational pharmacokinetic/pharmacodynamic perspective. PTA was determined for various dosages using Monte Carlo simulations of a population pharmacokinetic model of lefamulin in ABSSSI patients and preclinical exposure targets associated with bacteriostasis and a 1-log reduction in bacterial count. Overall target attainment against MSSA and MRSA was calculated using lefamulin MIC distributions. Overall attainment of the bacteriostasis target was 94% against MSSA and 84% against MRSA for the IV dosage approved for CABP (150 mg q12h). Using the same target, for the 100 mg q12h regimen, overall target attainment dropped to 68% against MSSA and 50% against MRSA. Using the 1-log reduction target, overall target attainment for both regimens was <40%. Lefamulin at the currently approved IV dosage covers most Staphylococcus aureus isolates when targeting drug exposure associated with bacteriostasis, suggesting potential of lefamulin for the treatment of ABSSSIs. Lefamulin may not be appropriate in ABSSSI when rapid bactericidal activity is warranted.

1015. Real World Use of Dalbavancin and Oritavancin for Optimized Outpatient Antimicrobial Therapy in Patients Inappropriate for Standard Therapy

Abstract Background Dalbavancin and oritavancin are long acting lipoglycopeptide antibiotics (LaLGP) approved for treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible gram-positive organisms. These antibiotics have shown promise in treatment of non-FDA approved gram-positive infections including bacteremia, endocarditis, pneumonia, and osteomyelitis. The aim of this review was to determine indication, length of therapy, treatment failures, and adverse drug events (ADE) in patients receiving LaLGP at our institution. Methods Retrospective study of adult patients that received LaLGP within an integrated health system consisting of 3 hospitals and 2 outpatient infusion centers, between July 2016 and February 2022. Data collection included dosing regimen specifics for both LaLGP and non-LaLGP, indication and justification for LaLGP use, culture results, labs, ADE, incidence of readmission and Emergency (ED)/Urgent Care presentation, and treatment failure defined as readmission or return to the ED/Urgent care within 90 days of therapy completion. Results 36 patients received LaLGP during the study period. A majority of patients received LaLGP for an indication other than ABSSSI (64%)(Table 1). Four patients were lost to follow-up but included in analysis of indication and justification for LaLGP use. Staphylococcus aureus (30% MRSA, 26% MSSA) was the most commonly identified pathogen in patients who received LaLGP for non-ABSSSI indications. Justification for use of LaLGP over standard therapy is shown in Table 2. The median duration of standard therapy prior to transitioning to LaLGP was 7 days. Table 3 shows agent selection, number of doses, and outcomes for ABSSSI indications vs non-ABSSSI indications. ABSSSI patients received a maximum of 2 doses; non-ABSSSI indications received 1-8 doses. Re-admission rates were higher in the ABSSSI group compared to non-ABSSSI while ED/Urgent care presentations were higher in non-ABSSSI indications. Conclusion LaLGP is a viable option for therapy completion after improvement is seen while on standard therapy in patients where daily outpatient antimicrobial therapy is not feasible. While LaLGP is currently only approved for ABSSSI, they appear to be safe and effective for other indications. Disclosures All Authors: No reported disclosures.

1385. Pathway with single-dose long-acting intravenous antibiotic dalbavancin is a cost-saving alternative to usual inpatient care of acute bacterial skin and skin structure infections (ABSSSI)

Abstract Background Acute bacterial skin and skin structure infections (ABSSSI) are a common type of bacterial infection, with the cost of hospitalization being the main contributing factor to overall treatment costs. Two pragmatic clinical trials (Table 1) demonstrated that a new treatment pathway in which patients are treated with the intravenous (IV) long-acting antibiotic, dalbavancin, reduced hospital admission rates and length of stay (LOS) in hospitalized patients. The objective of this study is to evaluate the cost-effectiveness of a single dose of dalbavancin administered in the emergency department (ED) compared with IV antibiotics for appropriate patients who would otherwise be admitted to hospital and receive usual care such as vancomycin or daptomycin. Table 1.References of the Two Pragmatic Clinical Trials Methods A decision-analytic cost-effectiveness model was developed from the perspective of the US healthcare system. The population was ABSSSI patients presenting at the ED, who would be eligible to receive IV antibiotic infusion. Patients can receive IV treatment in the ED, and then discharged or followed by hospital admission for continued management (Fig. 1). A 14-day time horizon was used, representing the typical duration of ABSSSI management. Hospital admission rates and LOS were from the two clinical trials. Cost included ED visits, drug cost, inpatient stay, and physician visits. Input parameter uncertainty was examined via one-way and probabilistic sensitivity analyses. Figure 1.Decision Analytic Model Structure Results Providing dalbavancin in the ED resulted in $4,848 savings per patient (2021 USD). The drug cost of dalbavancin treatment was offset by a mean reduction of 4.24 days LOS per patient, which translated as $1,144 savings per hospitalization day avoided. One-way sensitivity analyses demonstrated that the key drivers were the cost of inpatient hospital stay and the LOS with usual care; however, none of the sensitivity analyses resulted in the new pathway being more costly (Fig. 2). Dalbavancin was cost saving in 100% of simulated scenarios. Figure 2.One-way Sensitivity Analysis Conclusion These results could help guide the management of ABSSSI by shifting care for appropriate patients from the inpatient to the outpatient setting where patients can be managed successfully, thereby freeing up hospital resources and reducing the total costs of ABSSSI treatment. Disclosures FRANK LOVECCHIO, DO, MPH, ABBVIE: Speaker|NIH: Grant/Research Support Alasdair D. Henry, PhD, AbbVie: Grant/Research Support Quan V. Doan, PharmD, AbbVie: Advisor/Consultant|AbbVie: Grant/Research Support|Allergan: Advisor/Consultant|Allergan: Grant/Research Support John L. Lock, PharmD, Abbvie: Employee|Abbvie: Stocks/Bonds Rosie D. Lyles, MD, MHA, MSc, AbbVie: AbbVie Employee|AbbVie: Stocks/Bonds Xiaolan Ye, PhD, AbbVie Inc.: AbbVie Employee|AbbVie Inc.: Stocks/Bonds.

Emergency department care of ABSSSI with dalbavancin infusion, direct discharge, and outpatient telemedicine follow up: a study protocol

Novel therapeutic strategies such as the long-acting lipoglycopeptide antibiotics allow for the treatment and discharge of selected emergency department (ED) patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI), who require intravenous antibiotics and would otherwise be hospitalized. The COVID-19 pandemic highlighted the need to develop strategies that may reduce hospitalization. The telehealth approach has shown success in remote management of cellulitis patients and could aid in the remote follow up of overall ABSSSI patients. This article describes a study protocol for the telemedicine follow up of patients diagnosed with ABSSSI in the ED, requiring intravenous treatment, receiving a single dalbavancin dose, and directly discharged. A telehealth system for remote follow up is evaluated as well as the possible inclusion of point-of-care ultrasound for the appropriate diagnosis of ABSSSI. The study will be conducted in compliance with regulatory requirements; and all collected data will be kept strictly confidential and in accordance with all relevant legislation on the control and protection of personal information. Dissemination of the study protocol may help increasing knowledge and awareness on this topic, with the aim of optimizing patient management, reducing hospitalization and lower the impact on healthcare associated costs.

Budget Impact Analysis of Dalbavancin in the Treatment of Acute Bacterial Skin and Skin Structure Infections in Three European Countries.

Acute bacterial skin and skin structure infections (ABSSSIs) have been defined by the US Food and Drug Administration (FDA) in 2013 to include a subset of complicated skin and skin structure infections commonly treated with parenteral antibiotic therapy. Inpatient treatment of ABSSSIs involves a significant economic burden on the healthcare system. This study aimed to evaluate the economic impact on the National Health System associated with the management of non-severe ABSSSIs treated in hospitals with innovative long-acting dalbavancin compared to standard antibiotic therapy in Italy, Spain, and Austria. A budget impact analysis was developed to evaluate the direct costs associated with the management of ABSSSI from the national public health system perspective. The model considered the possibility of early discharge of patients directly from the Emergency Department (ED), after 1 night in the hospital, or after two or three nights in the hospital. A scenario with Standard of Care was compared with a dalbavancin scenario, where patients had the possibility of being discharged early. The epidemiological and cost parameters were extrapolated from national administrative databases and from a systematic literature review for each country. The analysis was conducted in a 3-year time horizon. A one-way deterministic sensitivity analysis was conducted to examine the robustness of the results. The model estimated an average annual number of patients with non-severe ABSSSI in Italy, Spain, and Austria equal to 5396, 7884, and 1788, respectively. A total annual expenditure of about €9.9 million, €13.5 million, and €3.4 million was estimated for treating the full set of ABSSSI patients in Italy, Spain, and Austria, respectively. Dalbavancin reduced the in-hospital length of stay in each country. In the first year of its introduction, dalbavancin significantly reduced the total economic burden in Italy and Spain (-€352,252 and -€233,991, respectively), while it increased the total economic burden in Austria (€80,769, 0.7% of the total expenditure for these patients); in the third year of its introduction, dalbavancin reduced the total economic burden in each Country (-€1.1 million, -€810,650, and -€70,269, respectively). The introduction of dalbavancin in a new patient pathway to treat non-severe ABSSSI could generate a significant reduction in hospitalized patients and the overall patient length of stay in hospital.

A Multicenter Evaluation of Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections.

BackgroundWe sought to determine the real-world incidence of and risk factors for vancomycin-associated acute kidney injury (V-AKI) in hospitalized adults with acute bacterial skin and skin structure infections (ABSSSI).MethodsRetrospective, observational, cohort study at ten U.S. medical centers between 2015 and 2019. Hospitalized patients treated with vancomycin (≥ 72 h) for ABSSSI and ≥ one baseline AKI risk factor were eligible. Patients with end-stage kidney disease, on renal replacement therapy or AKI at baseline, were excluded. The primary outcome was V-AKI by the vancomycin guidelines criteria.ResultsIn total, 415 patients were included. V-AKI occurred in 39 (9.4%) patients. Independent risk factors for V-AKI were: chronic alcohol abuse (aOR 4.710, 95% CI 1.929–11.499), no medical insurance (aOR 3.451, 95% CI 1.310–9.090), ICU residence (aOR 4.398, 95% CI 1.676–11.541), Gram-negative coverage (aOR 2.926, 95% CI 1.158–7.392) and vancomycin duration (aOR 1.143, 95% CI 1.037–1.260). Based on infection severity and comorbidities, 34.7% of patients were candidates for oral antibiotics at baseline and 39.3% had non-purulent cellulitis which could have been more appropriately treated with a beta-lactam. Patients with V-AKI had significantly longer hospital lengths of stay (9 vs. 6 days, p = 0.001), higher 30-day readmission rates (30.8 vs. 9.0%, p < 0.001) and increased all-cause 30-day mortality (5.1 vs. 0.3%, p = 0.024)ConclusionsV-AKI occurred in approximately one in ten ABSSSI patients and may be largely prevented by preferential use of oral antibiotics whenever possible, using beta-lactams for non-purulent cellulitis and limiting durations of vancomycin therapy.Electronic supplementary materialThe online version of this article (10.1007/s40121-019-00278-1) contains supplementary material, which is available to authorized users.

Dalbavancin Reduces Hospital Stay and Improves Productivity for Patients with Acute Bacterial Skin and Skin Structure Infections: The ENHANCE Trial.

IntroductionAdmissions 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.MethodsA 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.ResultsOf 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).ConclusionAfter 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 RegistrationClinicalTrials.gov identifier, NCT03233438.FundingAllergan plc.Electronic supplementary materialThe online version of this article (10.1007/s40121-019-00275-4) contains supplementary material, which is available to authorized users.

456. Dalbavancin, a Long-Acting Lipoglycopeptide Antimicrobial Agent, Reduces Length of Stay and Improves Patient Work Productivity in a Hospital Critical Pathway for Acute Bacterial Skin and Skin Structure Infections (ABSSSI)—the ENHANCE ABSSSI Trial

BackgroundProlonged 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.MethodsA 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.ResultsOf 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.ConclusionAfter 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.

110. Clinical Outcomes of Patients with Secondary Bacteremia in the Omadacycline Phase 3 Acute Bacterial Skin and Skin Structure Infections and Community-Acquired Bacterial Pneumonia Studies

BackgroundLow serum concentrations of tetracycline antibiotics may raise concerns on their efficacy in patients with secondary bacteremia, especially in comorbid patients and in those with higher acuity of illness. Omadacycline (OMC), an aminomethylcycline antibiotic, showed noninferiority to linezolid (LZD) in two acute bacterial skin and skin structure infections (ABSSSI) studies (Omadacycline in Acute Skin and skin structure Infections Study [OASIS]-1 and -2), or to moxifloxacin (MOX) in a community-acquired bacterial pneumonia (CABP) study (Omadacycline for Pneumonia Treatment In the Community study [OPTIC]). This analysis considers clinical outcomes in patients with secondary bacteremia identified in these studies.MethodsBaseline blood cultures were taken from adult patients enrolled in Phase 3 randomized, double-blind clinical studies of OMC. Patients received ≥1 treatment dose: N = 1,347 ABSSSI (OMC n = 676; LZD n = 671); N = 774 CABP (OMC n = 386; MOX n = 388). Efficacy was evaluated by investigator assessment of clinical response at a post-treatment evaluation (PTE) 7–14 days (ABSSSI) or 5–10 days (CABP) after the last dose.ResultsBacteremia was confirmed in 63 patients (3%) across the three studies. Staphylococcus aureus was the most common pathogen in patients with ABSSSI (N = 30: OMC n/N = 7/13; LZD n/N = 9/17), with a median treatment duration of median 9 days (OMC) and median 10 days (LZD). Streptococcus pneumoniae was the most common pathogen in patients with CABP (N = 33; OMC n/N = 11/15; MOX n/N = 11/18), with a median treatment duration of 11 days (OMC) and 14 days (MOX). Clinical success was numerically comparable between treatment groups within each study (figure) after completion of therapy.ConclusionThe clinical successes of patients receiving OMC for ABSSSI or CABP with secondary bacteremia were comparable to results for LZD and MOX, respectively. Although limited by the small sample size, data from ABSSSI and CABP study patients with secondary bacteremia provide reassurance for the use of OMC. Real-world OMC data in patients with ABSSSI and CABP will be needed to assess outcomes in patients with additional comorbidities and/or higher acuity of illness. Disclosures All authors: No reported disclosures.

442. Risk Score for Vancomycin-Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin and Skin Structure Infections

BackgroundVancomycin (VAN) has been the standard empiric antibiotic for the treatment of hospitalized patients with acute bacterial skin and skin structure infections (ABSSSI) for decades but its use can be complicated by acute kidney injury (AKI). The substantial morbidity and mortality associated with AKI underscores the need to identify ABSSSI patients at increased risk for this complication. The objective of this study was to derive a clinical prediction model for VAN-associated AKI (VAN-AKI) in hospitalized patients with ABSSSI and at least one baseline traditional risk factor for AKI.MethodsThis was a multicenter, retrospective, case–control study between 2015 and 2018 conducted at seven academic medical centers in the USA. The population of interest was hospitalized adults with ABSSSI treated with VAN ≥72 h and initiated ≤24 h of admission. Cases consisted of patients who developed AKI according to the RIFLE criteria during VAN or ≤72 h of discontinuation. Patients who did not develop AKI served as controls. Independent predictors of VAN-AKI were identified through multivariable logistic regression. A risk score was derived using a weighted coefficient-based scoring system.ResultsA total of 284 patients (28 cases and 256 controls) were included. Independent predictors of VAN-AKI included in the score were: metastatic cancer, ICU admission at VAN initiation, alcohol abuse, ≥2 nephrotoxins, mental health disease, lower extremity ABSSSI and prior ABSSSI within 1 year. Patients with mental health disease had a variety of advanced chronic comorbidities and substance use. The median risk score in cases and controls was 9 (7, 11) and 4 (3.7) (P < 0.001), respectively. The risk score area under the receiver operator curve was 0.803 (95% CI 0.712, 0.894). The sensitivity, specificity, positive predictive value and negative predictive value of the risk score using a threshold of 5 points was 89.29% (95% CI 70.63%, 97.19%), 51.56% (42.27%, 57.81%), 16.78% (11.35%, 23.97%) and 97.78% (93.14%, 99.42%), respectively.ConclusionThe risk score developed in this study provides a standardized, evidenced-based approach to identify hospitalized patients with ABSSSI at higher risk for VAN-AKI. External validation is required before widespread use.Disclosures All authors: No reported disclosures.

Economic evaluation of the treatment of Acute Bacterial Skin and Skin Structure Infections (ABSSSIs) from the national payer perspective: introduction of a new treatment to the patient journey. A simulation of three European countries

ABSTRACTBackground: The aim of this study was to develop a spending predictor model to evaluate the direct costs associated with the management of ABSSSIs from the National health-care provider’s perspective of Italy, Romania, and Spain.Methodology: A decision-analytic model was developed to evaluate the diagnostic and clinical pathways of hospitalized ABSSSI patients based on scientific guidelines and real-world data. A Standard of Care (SoC) scenario was compared with a dalbavancin scenario in which the patients could be discharged early. The epidemiological and cost parameters were extrapolated from national administrative databases (i.e., hospital information system). A probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OWA) were performed.Results: Overall, the model estimated an average annual number of patients with ABSSSIs of approximately 50,000 in Italy, Spain, and Romania. On average, the introduction of dalbavancin reduced the length of stay by 3.3 days per ABSSSI patient. From an economic perspective, dalbavancin did not incur any additional cost from the National Healthcare perspective, and the results were consistent among the countries. The PSA and OWA demonstrated the robustness of these results.Conclusion: This model represents a useful tool for policymakers by providing information regarding the economic and organizational consequences of an early discharge approach in ABSSSI management.

Ceftaroline fosamil therapy in patients with acute bacterial skin and skin-structure infections with systemic inflammatory signs: A retrospective dose comparison across three pivotal trials

This post-hoc analysis compared the pharmacokinetics and clinical outcomes of ceftaroline fosamil 600 mg every 12 (q12h) versus every 8 hours (q8h) in patients with acute bacterial skin and skin-structure infection (ABSSSI) and signs of sepsis. Clinical outcomes at test-of-cure in patients with ABSSSI and systemic inflammatory signs/systemic inflammatory response syndrome (SIRS) as well as ceftaroline minimum inhibitory concentrations (MICs) against baseline pathogens were compared between the COVERS trial (ceftaroline fosamil 600 mg q8h, 2-h infusion) and the CANVAS 1 and 2 trials (ceftaroline fosamil 600 mg q12h, 1-h infusion). Ceftaroline exposure among patients in COVERS with or without markers of sepsis was compared using population pharmacokinetic modelling. In COVERS, 62% (312/506) and 41% (208/506) of ceftaroline fosamil-treated patients had ≥1 systemic inflammatory sign or SIRS, respectively, compared with 55% (378/693) and 22% (155/693), respectively, in the CANVAS trials. Clinical cure rates for the modified intent-to-treat population in COVERS and CANVAS were similar for ceftaroline fosamil-treated patients with ≥1 sign of sepsis [82% (255/312) and 85% (335/394)] and for those with SIRS [84% (168/199) and 85% (131/155)]. Ceftaroline MIC distributions were similar across trials. Sepsis did not affect predicted individual steady-state ceftaroline exposure. Clinical cure rates in patients with ≥1 systemic inflammatory sign or SIRS were comparable for both ceftaroline fosamil dosage regimens. Pathogen susceptibilities to ceftaroline were similar across trials. Ceftaroline exposure was not affected by disease severity. Ceftaroline fosamil 600 mg q12h is a robust dosage regimen for most ABSSSI patients with sepsis [ClinicalTrials.gov ID: NCT01499277, NCT00424190, NCT00423657].

2378. Resolution of Signs and Symptoms (S&amp;S) of Acute Bacterial Skin and Skin Structure Infections (ABSSSI) With Delafloxacin (DLX) IV/Oral Therapy

BackgroundDelafloxacin, a fluoroquinolone antibiotic with Gram-negative and Gram-positive activity including MRSA, was approved for treatment of ABSSSI. In a phase 3 ABSSSI trial, DLX was non-inferior to VAN/AZ in both objective and clinical response endpoints. Clinical signs and symptoms (S&S) and lesion size measurements also were evaluated in this trial.MethodsA multicenter, double-blind trial of adults with ABSSSI patients randomized 1:1 to receive either DLX monotherapy 300mg q12h IV with switch to oral 450 mg q12h or vancomycin (VAN) 15 mg/kg (actual body weight) with aztreonam (AZ) for 5–14 days. AZ was discontinued once Gram-negative infection was excluded in the VAN arm. The presence or absence of clinical S&S were collected at each evaluation timepoint. Patients with complete resolution of S&S were classified as complete cures. Lesions were measured by digital planimetry. Patient-reported pain was recorded by numerical rating scale (NRS; 0=no pain, 10= worst pain). Assessments were completed at baseline, during and at end of treatment (EOT), at Follow-up (FU day 14) and Late Follow-up (LFU day 21–28).Results850 patients were randomized in United States, Europe, Asia and Latin America. 63% were male with mean age 51 years. 48% had cellulitis, 25% abscesses, 26% wound and 1% burn infections. Baseline erythema and induration were reported in 100% and 93% of patients, respectively. Mean area of erythema and induration at baseline was 353 and 138 cm2 respectively. Most common locations for lesions were lower extremities (56%) and upper extremities (24%). S. aureus was the most common isolate. Mean days of treatment was 7 days in either group. DLX and VAN/AZ patients had comparable impact on S&S with complete resolution in 42% vs. 45% at EOT, and 58% vs. 60% at FU, and 68% vs. 71% at LFU respectively. DLX was comparable to VAN/AZ in percent reduction in erythema over time (figure). There was a mean reduction of 58% vs. 53% at 48–72 h, 90% vs. 87% at EOT, and 98% vs. 97% at LFU for DLX and VAN/AZ respectively (figure). Baseline mean pain scores were 7/10 with scores of ~1/10 at EOT and ~0.5/10 at FU for both treatment groups.ConclusionTreatment with DLX and VAN/AZ provided equally rapid improvement in clinical signs and symptoms in ABSSSI with comparable reductions in S&S, lesion size and pain score. Disclosures J. Pullman, Melinta Therapeutics, Inc.: Investigator, Research support. W. O’ Riordan, Melinta Therapeutics, Inc.: Investigator, Research support. L. Lawrence, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. M. Quintas, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. C. Tseng, Melinta Therapeutics, Inc.: Consultant and Research Contractor, Consulting fee. S. K. Cammarata, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary.

2377. Outcomes in Patients With History of Cardiac or Vascular Disease (CV) During Treatment of Acute Bacterial Skin And Skin Structure Infection (ABSSSI) With Delafloxacin (DLX) vs. Vancomycin/Aztreonam (VAN/AZ)

BackgroundDLX, an anionic fluoroquinolone antibiotic with Gram-positive and Gram-negative activity, was recently approved for treatment of ABSSSI. Two global phase 3 ABSSSI trials (studies 302 and 303) included patients with cardiac or vascular disease.MethodsTwo multicenter, double-blind, double-dummy trials of adults with ABSSSI patients randomized 1:1 to receive either DLX monotherapy or VAN 15 mg/kg (actual body weight) with AZ for 5–14 days. Study 302 used DLX 300 mg BID IV only; study 303 used DLX 300 mg BID IV for 3 days with a mandatory blinded switch to DLX 450 mg oral BID. Key endpoints were objective response at 48–72 hours with ≥20% reduction in lesion size; and Investigator assessment of outcome based on resolution of signs and symptoms at Follow-up (FU day 14) and Late Follow-up (LFU day 21–28).ResultsIn the two studies, 488 CV patients were randomized in United States, Europe, Latin America and Asia. 57% were male with mean age 59 years. Average erythema area at baseline was 446 cm2. 58% had cellulitis, 19% abscesses, 22% wound and 1% burns. Key endpoints are given in the following table.DLX, n/Total (%)VAN/AZ, n/Total (%)Objective response 48–72h (ITT)208/260 (80.0%)183/228 (80.3%)Investigator-Assessed Success (FU CE)204/217 (94.0%)176/185 (95.1%)Investigator-Assessed Success (LFU CE)194/207 (93.7%)173/182 (95.1%)Micro Success (FU ME) for S. aureus72/74 (97.3%)57/61 (93.4%)The % of CV patients with at least one treatment-related adverse event (AE) was similar for DLX (22.7%) compared with VAN/AZ (22.4%). There were 2 DLX and 5 VAN/AZ-treated CV patients discontinued due to related AEs. The most frequent treatment-related AEs were gastrointestinal including diarrhea seen in 8.2% and 3.1% of DLX and VAN/AZ patients respectively, generally mild to moderate in nature with no cases of C. difficile diarrhea. There were no cardiac events or deaths attributed to either study drug.ConclusionIn CV patients, fixed dose DLX monotherapy was comparable to VAN/AZ in treatment of ABSSSI based on the early objective and investigator assessed responses at FU and LFU. DLX was also comparable to VAN/AZ in treating patients with S. aureus. There were no cardiac events or deaths in either study group. DLX appears effective and well tolerated in CV patients with ABSSSI.Disclosures G. Oguchi, Melinta Therapeutics, Inc.: Investigator, Research support. R. Beasley, Melinta Therapeutics, Inc.: Investigator, Research support. L. Lawrence, Melinta Therapeutics, Inc.: Employee and Shareholder, Salary. C. Tseng, Melinta Therapeutics, Inc.: Consultant and Research Contractor, Consulting fee. S. K. Cammarata, Melinta Therapeutics, Inc.: Employee, Salary.

PD56 Economic Evaluation Of Dalbavancin In European Countries

Introduction:Dalbavancin is a new innovative long-acting antimicrobial treatment that allows clinicians to endorse an early discharge program for patients suffering from acute bacterial skin and skin structure Infections (ABSSSI). The aim of this study was to develop a spending predictor model for evaluating the direct costs associated with the management of ABSSSI from the National Health Service (NHS) perspective of Italy, Spain, and Romania. The main purpose is to compare the hospitalization and drug costs due to the treatment of ABSSSI patients treated with standard antibiotics therapy or innovative long-acting treatment dalbavancin.Methods:A decision-analytic model was performed to evaluate the diagnostic and clinical pathways of ABSSSI patients in the hospital, based on clinicians’ expert opinion. The standard of care scenario was compared with the dalbavancin scenario. The epidemiological and cost parameters were extrapolated from national administrative databases (hospital information system) and from a systematic literature review for each country. Only direct costs in the national payer's perspective were considered. Probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OSA) were performed to check the robustness of the model assumptions.Results:Overall, the model estimated an average annual number of patients with ABSSSI equal to around 50,000 in Italy, Spain, and Romania. The introduction of dalbavancin reduced the length of stay of, on average, 3.3 days per ABSSSI patient. From the economic point of view, dalbavancin did not incur any additional cost from the NHS perspective with homogenous results between countries. The PSA and OSA demonstrated the robustness of the results.Conclusions:The preliminary results highlight that the introduction of dalbavancin could generate a significant reduction in term of length of stay with no incremental cost from the NHS perspective. This model could represent a good tool for policymakers to provide information on the early discharge approach in the ABSSSI management.

Current Use of Intravenous (IV) Long Acting Antibiotic (LAA) Therapy in the Aetna Health Plan among Patients with Acute Bacterial Skin and Skin Structure Infection (ABSSSI)

BackgroundIn an effort to lower costs and improve quality of care, there is potential to change the treatment landscape for low-risk (i.e., less severe) ABSSSI patients who historically required inpatient management, a costly option. Outpatient IV treatment pathways have been shown to be a cost-saving option for hospitals and insurers. The objective was to quantify the potential opportunity for reducing cost of ABSSSI treatment in an insured Commercial and Medicare Aetna population.MethodsAdult patients between January 2013 and July 2016 were identified with a primary ABSSSI claim (Table 1) in the Aetna fully-insured Commercial and Medicare insurance claims database. ABSSSI encounters were identified with insurance eligibility for the 7 months prior to and no evidence of ABSSSI in the 30 days prior to the ABSSSI claim. Demographic and clinical data were described, including length of stay (LOS) and allowed cost for inpatient encounters with data. Inpatient encounters without evidence of severity (e.g., codes for major complications or comorbidities) were considered potential candidates for an outpatient LAA pathway. A sensitivity analysis for LOS and cost was run including all ABSSSI patients with LAA dispenses through 2016 (i.e., inclusion/exclusion criteria did not need to be met).Results194,023 ABSSSI encounters were identified, most receiving non-IV treatment (90%). 18,603 received IV treatment, where 83% initially presented to the emergency room and the majority were admitted (97%). Of the 28 encounters with LAA use, 7 were inpatient. Of all current inpatient encounters (N = 9,019 after Jan 1, 2015), the majority (N = 7,005; 78%) where considered potential LAA pathway candidates. Comparing inpatient encounters with vs. without LAA use, mean LOS and cost differed (Table 2: 4.1 days and $14,295 vs. 9.0 days and $23,194, respectively). A sensitivity analysis supported similar mean LOS and cost for all inpatient LAA dispenses.ConclusionCurrent use of LAA in an inpatient population is limited but resulted in potential cost-savings. Most of the inpatient population was identified as potential candidates for an outpatient LAA pathway. Research on utilization and quality of care for outpatient IV treatment pathways with LAA is warranted.Disclosures K. R. Keyloun, Allergan: Employee, Salary N. Bonine, Allergan: Employee, Salary

Risk Factors and Outcomes for Bloodstream Infections (BSI) Among Patients with Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Background ABSSSI are common infections in the community and can result in high morbidity and healthcare costs. While risk factors for ABSSSI have been previously evaluated, risk factors associated with secondary BSI have not, especially in an urban population with limited access to healthcare.Methods This case–control study evaluated risk factors and outcomes associated with secondary S. aureus BSI among adult ABSSSI patients. Patients age ≥ 18 years with an ABSSSI diagnosis presenting to two academic medical centers in Detroit, MI from 2010 to 2015 were included. Baseline/clinical characteristics and outcomes were compared between cases (ABSSSI + BSI) and controls (ABSSSI). Outcomes included in-hospital mortality, hospital length of stay (los) and 30-day reinfection. Fisher’s exact and Student’s t- or Mann–Whitney U-tests were used for bivariate comparisons. Variables associated with ABSSSI + BSI in bivariate analysis at a P-value < 0.1 were included in multivariable logistic regression to examine factors independently associated with ABSSSI + BSI.Results392 patients consisting of 196 ABSSSI + BSI and 196 controls ABSSSI were evaluated. In bivariate analysis, individuals with ABSSSI + BSI were significantly older (P < 0.001), more likely to be male (P = 0.008), be an intravenous drug user (P = 0.012), have chronic renal failure (P = 0.002), prior hospitalization (P <0.001), and more systemic symptoms, such as elevated temperature, white blood cell count, and acute renal failure on hospital admission (P < 0.001). By regression, male gender (aOR 1.85, 95% CI 11–3.66), acute renal failure (aOR 2.08, 95% CI 1.18–3.67), intravenous drug use (aOR 4.38, 95% CI 2.22–8.62), and prior hospitalization (aOR 2.41, 95% CI 1.24–4.93) remained statistically significant. ABSSSI + BSI patients were more likely to experience in-hospital mortality (4.1 vs. 0%, P <0.001), have longer mean loss (7.4 ± 5.7 vs. 2.7 ± 2.2 days, P = <0.001), and experience 30-day reinfection (11.2 vs. 4.1%, P = 0.006).Conclusion Patients with ABSSSI + BSI had worse outcomes than those with ABSSSI alone. Factors associated with ABSSSI + BSI, such as gender, IVDU, prior hospitalization, renal failure, and systemic signs/symptoms of infection, may be used to identify patients at risk for ABSSSI + BSI.Disclosures All authors: No reported disclosures.

Use of Oritavancin in Moderate-to-Severe ABSSSI Patients Requiring IV Antibiotics: A U.S. Payer Budget Impact Analysis.

It is estimated that acute bacterial skin and skin structure infections (ABSSSI) account for nearly 10% of hospital admissions and 3.4-3.8 million emergency department visits per year in the United States. Analyses of hospital discharge records indicate 74% of ABSSSI admissions involve empiric treatment with methicillin-resistant Staphylococcus aureus (MRSA) active antibiotics. Analysis has shown that payer costs could be reduced if moderate-to-severe ABSSSI patients were treated to a greater extent in the observational unit followed by discharge to outpatient parenteral antibiotic therapy (OPAT). Oritavancin is a lipoglycopeptide antibiotic with bactericidal activity against gram-positive bacteria, including MRSA. To estimate the impact on a U.S. payer's budget of using single-dose oritavancin in ABSSSI patients with suspected MRSA involvement who are indicated for intravenous antibiotics. A decision analytic model based on current clinical practice was developed to estimate the economic value of decreased hospital resource consumption by using single-dose oritavancin over a 1-year time horizon. Use of antibiotics was informed by an analysis of the Premier Research Database. Demographic and clinical data were derived from a targeted literature review. Emergency department, observation, laboratory, and administration costs used were Medicare National Limitation amounts. Drug costs were 2014 wholesale acquisition costs. For a hypothetical U.S. payer with 1,000,000 members, it is expected that approximately 14,285 members per year will be diagnosed with ABSSSI severe enough to indicate intravenous antibiotics with MRSA activity. Based on this simulation, use of single-dose oritavancin in 26% of these patients was estimated to reduce the number of inpatient admissions, reduce length of stay for patients requiring admission, and reduce the number of days a patient needs to receive daily infusions in the OPAT clinic. The total patient days decreased from 171,125 to 133,435 with a total annual budget impact of -$12,550,000 or -$1.05 per member per month (PMPM). Total inpatient and outpatient costs were reduced by $9,970,000 (19.7%) and $2,580,000 (4.2%), respectively. Inpatient cost savings were derived from a reduction in admissions, length of stay, and lower drug administration burden. Outpatient costs were reduced by lower drug administration burden in the OPAT setting. A sensitivity analysis demonstrated that the model was most sensitive to population estimates. Use of single-dose oritavancin in moderate-to-severe ABSSSI patients, including those with suspected MRSA, was projected to deliver an estimated cost reduction to U.S. payers of $1.05 PMPM by avoiding hospitalization in appropriate patients and reducing outpatient costs associated with multiday parenteral antibiotic therapy. This work was funded by The Medicines Company. Jensen, Wu, and Cyr are employees of ICON Health Economics, which provides consulting services to the biopharmaceutical industry, including The Medicines Company. Fan and Sulman are employees and shareholders of The Medicines Company. Dufour and Lodise have provided consulting services to The Medicines Company. Nicolau provided model input but did not receive an honorarium for contributions on this project. Nicolau is a speaker for The Medicines Company. Study concept and design were contributed by Jensen and Wu, along with the other authors. Jensen, Wu, Fan, and Sulham collected the data, with assistance from Cyr. Data interpretation was performed by Sulham, Jensen, Wu, and Fan, assisted by Lodise, Nicolau, and Dufour. The manuscript was written by Jensen, Wu, and Sulham, with assistance from Cyr, and revised by Lodise, Nicolau, and Dufour, with assistance from the other authors.

Ceftaroline fosamil as first-line versus second-line treatment for acute bacterial skin and skin structure infections (ABSSSI) or community-acquired bacterial pneumonia (CABP)

The Clinical Assessment Program and Teflaro® Utilization Registry (CAPTURE) is a multicenter registry study of acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP) patients treated with ceftaroline fosamil in the US. Data for this analysis were collected between August 2011 and February 2013 at US study centres by randomly ordered chart review. Clinical success rates among ABSSSI patients were >81% when ceftaroline fosamil was used as first- or second-line therapy, including monotherapy and concurrent therapy. Among CABP patients, clinical success rates were >77% among first-line and second-line patients and patients who received first-line concurrent therapy or second line monotherapy or concurrent therapy. For CABP patients treated with ceftaroline fosamil as first-line monotherapy, the clinical success rate was 70%. Ceftaroline fosamil is an effective treatment option for patients with ABSSSI or CABP with similar clinical success rates when used as first-line or second-line treatment.

Use of Oritavancin in Acute Bacterial Skin and Skin Structure Infections Patients Receiving Intravenous Antibiotics: A US Hospital Budget Impact Analysis.

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s40261-015-0365-8) contains supplementary material, which is available to authorized users.