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  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Open Forum Infectious Diseases Vol. 8, No. Supplement_1 ( 2021-12-04), p. S638-S638
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S638-S638
    Abstract: Dalbavancin is a semi-synthetic glycopeptide with a long half-life, making it a promising alternative for infections requiring prolonged therapy such as complicated Staphylococcus aureus bacteremia. A critical pharmacokinetic consideration with prolonged treatment is the unbound or “free” concentration-time profile, as free antibiotic concentrations may correlate with tissue penetration and therapeutic effects better than total drug. Dalbavancin’s plasma protein binding (PB) remains poorly studied and has been reported to range between 93-99%. A reliable and validated free drug assay is needed to link dalbavancin concentrations with patient outcomes. Methods The ultracentrifugation technique was used to determine free dalbavancin concentrations in plasma at two concentrations (50 and 200 µg/mL) in duplicate. Centrifuge tubes and pipette tips were treated for 24 hours before use with Tween 80 to assess adsorption. PB centrifugation conditions: 400,000 g (106,000 RPM in TLA-120.1 rotor) for 4 hours at 37°C. Dalbavancin concentrations were analyzed from the plasma samples (total) and middle layer samples (free) by liquid chromatography – tandem mass spectrometry (LC/MS/MS) with isotopically labeled internal standard. Warfarin served as a positive control with known high protein binding. Results Measurement of free dalbavancin was sensitive to adsorption onto plastic. Treatment of tubes and pipette tips with ≥2% Tween 80 effectively prevented drug loss during PB experiments (Figure 1). Addition of 2% Tween 80 did not affect PB results of warfarin. In PB experiments with 2% Tween 80 coated tubes, the free fraction of dalbavancin was 0.96% (95% CI: 0.94-0.98) at 50 µg/mL and 1.11% (95% CI: 1.08-1.13) at 200 µg/mL. Figure 1. Percent Free Dalbavancin vs Varying Concentrations of Tween 80 for Pretreatment of Tubes Conclusion By the ultracentrifugation method, dalbavancin’s PB was estimated to be approximately 99%. Given dalbavancin’s high PB, accurate measurement of free dalbavancin concentrations should be a key consideration in future exposure-response studies, especially clinical trials. Future investigations should also determine if the active fraction is best predicted by the free or total fraction, as this remains a subject of debate. Supported by NIAID/NIH grant UM1AI104681. Content is solely the authors’ responsibility and does not represent official NIH views. Disclosures Thomas L. Holland, MD, Aridis (Consultant)Basilea Pharmaceutica (Consultant)Lysovant (Consultant) Thomas L. Holland, MD, Aridis (Individual(s) Involved: Self): Consultant; Basilea Pharmaceutica (Individual(s) Involved: Self): blinded adjudication, Consultant, Other Financial or Material Support; Genentech (Individual(s) Involved: Self): Consultant; Lysovant (Individual(s) Involved: Self): Consultant; Motif Bio (Individual(s) Involved: Self): Consultant Thomas Lodise, Jr., PharmD, PhD, Astra-Zeneca (Consultant)Bayer (Consultant)DoseMe (Consultant, Advisor or Review Panel member)ferring (Consultant)genentech (Consultant)GSK (Consultant)Melinta (Consultant)merck (Consultant, Independent Contractor)nabriva (Consultant)paratek (Consultant, Advisor or Review Panel member, Speaker’s Bureau)shionogi (Consultant, Advisor or Review Panel member, Speaker’s Bureau)Spero (Consultant)tetraphase (Consultant)Venatrox (Consultant) Thomas Lodise, Jr., PharmD, PhD, Melinta Therapeutics (Individual(s) Involved: Self): Consultant; Merck (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Paratek (Individual(s) Involved: Self): Consultant; Shionogi (Individual(s) Involved: Self): Consultant, Speakers’ bureau; Spero (Individual(s) Involved: Self): Consultant; Tetraphase Pharmaceuticals Inc. (Individual(s) Involved: Self): Consultant
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Open Forum Infectious Diseases Vol. 8, No. Supplement_1 ( 2021-12-04), p. S801-S801
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S801-S801
    Abstract: Complicated urinary tract infections (cUTI) are one of the most common bacterial infections and represent substantial burden to the health care system. Here, we examine the epidemiology and treatment patterns associated with cUTI in a large US database containing longitudinal inpatient (IP) and outpatient (OP) patient-level data. Methods We conducted a retrospective cohort study of adult patients in the IBM MarketScan® Commercial or Medicare Supplemental Databases with at least 1 IP or non-diagnostic OP claim with a diagnosis for cUTI between January 1, 2017 and June 30, 2019. Patients meeting the following criteria were included for analysis: (1) ≥18 years of age on the index date, (2) ≥6 months of continuous enrollment (CE) with medical and pharmacy benefits prior to the index date, (3) ≥12 months of CE following the index date or evidence of death, and (4) no evidence of a prior cUTI during the 6-month baseline period. Demographics and clinical characteristics were quantified. Patients were classified as IP if they were hospitalized during 30-day post index date; remaining patients were classified as OP. Antibiotics received in the OP setting in the 12-months post index date were examined. Results 95,423 patients met study criteria. Most (86.4%) patients were Commercially insured, mean (SD) age was 53.6 (18.1) and 70.4% were female. Mean baseline Charlson Comorbidity Index was 0.77. During the 30-day post index date, 22.2% were treated as IP and 77.8% were strictly treated as OP. In the 12-month OP follow-up period among index IP, 78.2% required ≥ 2 antibiotics, 38.2% required ≥4 antibiotics, and 41.6% received an IV antibiotic. In the 12-month OP follow-up period among index OP, 81.8% required ≥2 antibiotics, 38.2% required ≥4 antibiotics, and 46.8% received an IV antibiotic. For both IP and OP, fluoroquinolones were the most common oral antibiotic class (57.7%), followed by cephalosporins (39.2%), penicillins (30.3%), trimethoprim-sulfamethoxazole (29.8%), and nitrofurantoin (25.2%). Cephalosporins were the most common IV antibiotic class (38.5%). Conclusion Regardless of index treatment setting, approximately 40% of all cUTI patients required ≥4 antibiotic therapy and almost half with receive an IV antibiotic in the outpatient setting in the 12-months post index date. Disclosures Thomas Lodise, Jr., PharmD, PhD, Astra-Zeneca (Consultant)Bayer (Consultant)DoseMe (Consultant, Advisor or Review Panel member)ferring (Consultant)genentech (Consultant)GSK (Consultant)Melinta (Consultant)merck (Consultant, Independent Contractor)nabriva (Consultant)paratek (Consultant, Advisor or Review Panel member, Speaker’s Bureau)shionogi (Consultant, Advisor or Review Panel member, Speaker’s Bureau)Spero (Consultant)tetraphase (Consultant)Venatrox (Consultant) Thomas Lodise, Jr., PharmD, PhD, Melinta Therapeutics (Individual(s) Involved: Self): Consultant; Merck (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Paratek (Individual(s) Involved: Self): Consultant; Shionogi (Individual(s) Involved: Self): Consultant, Speakers’ bureau; Spero (Individual(s) Involved: Self): Consultant; Tetraphase Pharmaceuticals Inc. (Individual(s) Involved: Self): Consultant Janna Manjelievskaia, PhD, MPH, IBM Watson Health (Employee)Spero Therapeutics (Consultant) Matthew Brouillette, MPH, Spero Therapeutics, Inc. (Other Financial or Material Support, I am an employee of IBM Watson Health, who received funds from Spero Therapeutics, Inc. to conduct this analysis.) Kate Sulham, MPH, Spero Therapeutics (Consultant)
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 3
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S480-S481
    Abstract: The HAC-RP is a Medicare pay-for-performance program that links Medicare Part A payments to ACH healthcare quality. Starting in 2015, ACHs ranking in the lower 25% for HAC quality measures are subject to a 1% payment reduction. C. difficile infection (CDI) is 1 of 6 quality measures included in the HAC-RP. Hospitals with a CDI-SIR ≥1, indicating that observed yearly CDI cases exceed predicted CDI cases, are subject to a payment reduction, depending on their performance on other HAC quality measures. Little data are available on the CDI-SIR and observed CDI cases among CMS-participating ACH. Methods The HAC hospital data were obtained from CMS (publicly available at https://data.cms.gov/). Definitive Healthcare imported the data using a Structured Query Language based program and linked the CMS data (October yearly reports) with key hospital-level variables in the Definitive Healthcare Data Platform. Data on CDI cases between 2015 - 2018 among CMS-participating short-term ACHs were obtain from Definitive Healthcare and stratified in quartiles by hospital discharges per year. Within each quartile, the number of observed CDI cases were compared descriptively among ACHs with a CDI-SIR ≥1 vs. & lt; 1 by year. Results Number of ACHs with a CDI-SIR ≥1 vs. & lt; 1 within each hospital discharge quartile by year is displayed in Figure 1. The number of ACHs with CDI-SIR ≥1 increased in 2015, were maintained in 2016, declined in 2017 and again in 2018. Within each quartile, the average observed cases per year were higher for ACHs with CDI-SIR ≥ 1 (Figure 2). After 2015 total observed cases declined in ACHs with CDI-SIR ≥ 1 but remained unchanged in ACH with CDI-SIR & lt; 1 (Figure 3). Figure 1. Number of ACH with CDI-SIR ≥1 vs. & lt;1 Within Each Hospital Discharge Quartile Between 2015-2018 Figure 2. Average Number of and Total Observed Cases per ACH within Each Hospital Discharge Quartile by CDI-SIR ≥1 Figure 3. Total Observed Cases by CDI-SIR ≥ between 2015-2018 Conclusion Observed cases were similar regardless of CDI-SIR score, although approximately 75% of ACHs had a CDI-SIR & lt; 1. HAC-RP penalizes short-term ACHs with a CDI-SIR ≥1 and appears to be effective in reducing CDI cases. However, the observed increase of cases over the 4-year period among ACHs with CDI-SIR & lt; 1 post HAC-RP implementation is concerning. Greater focus is needed to reduce CDI cases across all ACHs, irrespective of CDI-SIR given the burden of disease and associated morbidity and mortality. Disclosures Mauricio Rodriguez, Jr., PharmD, BCPS, BCCCP, BCIDP, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Surya Chitra, PhD, Paratek Pharmaceuticals, Inc. (Consultant) Paige Lavallee, BA, Definitive Healthcare (Employee) Thomas Lodise, Jr., PharmD, PhD, Astra-Zeneca (Consultant)Bayer (Consultant)DoseMe (Consultant, Advisor or Review Panel member)ferring (Consultant)genentech (Consultant)GSK (Consultant)Melinta (Consultant)merck (Consultant, Independent Contractor)nabriva (Consultant)paratek (Consultant, Advisor or Review Panel member, Speaker's Bureau)shionogi (Consultant, Advisor or Review Panel member, Speaker's Bureau)Spero (Consultant)tetraphase (Consultant)Venatrox (Consultant) Thomas Lodise, Jr., PharmD, PhD, Melinta Therapeutics (Individual(s) Involved: Self): Consultant; Merck (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Paratek (Individual(s) Involved: Self): Consultant; Shionogi (Individual(s) Involved: Self): Consultant, Speakers' bureau; Spero (Individual(s) Involved: Self): Consultant; Tetraphase Pharmaceuticals Inc. (Individual(s) Involved: Self): Consultant
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 4
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. Supplement_1 ( 2021-12-04), p. S772-S773
    Abstract: Assess 30-day real-world outcomes associated with OMC for the treatment of adults with ABSSSI or CABP. Thirty-day outcomes are an important quality metric for both private and public payers. This retrospective study compared HRU among adult pts treated with OMC for ABSSSI or CABP in the 30-day pre- and post-OMC Rx periods. The pre-post study design was selected to assess how 30-day HRU changed post-OMC RX (proxy for treatment response). Methods Pts who received ≥1 OMC outpatient Rx from a large US claims database (10/2018-9/2020) were identified. Pts were classified as ABSSSI or CABP cohort based on presence of ICD-10 code near (-90 d to +30 d) OMC Rx. Within each diagnosis, pts were classified as complicated if any of the following infections were identified in the pre-period (-90 d to + 5 d) (ABSSSI: osteomyelitis (OST), sepsis/bacteremia (S/B), endocarditis, implant, necrotizing fasciitis, meningitis; CABP: severe pneumonia, lung abscess, S/B, endocarditis, meningitis). Risk of inpatient admissions (IP), ED visits, outpatient visits (OP) were compared between the following 2 periods: 30 days pre- and 30-days post-OMC Rx. Results During study period, 258 OMC outpatient Rx met inclusion criteria: 189 were ABSSSI and 69 were CABP. Among the 189 ABSSSI pts, 83 were complicated. Most common ABSSSI complicated were OST (53%), S/B (33%), and implant infection (21%). Among the 69 CABP pts, 20 were COM. Most common CABP complicated were S/B (80%) and severe pneumonia (25%). Comparison of HRU in the 30 days pre- to the 30-day post-OMC Rx period are shown in Tables 1 and 2. Among complicated ABSSSI pts, IP decreased by 38% (41% vs 25%; p & lt; 0.05) while ED visits and OP were similar. Among non- complicated ABSSSI pts, IP decreased by 61% (17% vs 7%; p & lt; 0.05), ED visits decreased by 88% (16% vs 2%; p & lt; 0.01) while OP were similar. Among complicated CABP pts, IP decreased by 75% (80% vs 20%; p & lt; 0.01), ED decreased by 100% (40% vs 0%; p & lt; 0.001) while OP were similar. Among non- complicated CABP pts, IP decreased by 75% (33% vs 8%; p & lt; 0.01), while ED visits and OP were similar. Table 1. Comparison of HRU in the 30-day pre-OMC Rx vs 30-day post-OMC Rx period among ABSSSI pts Table 2. Comparison of HRU in the 30-day pre-OMC Rx vs 30-day post-OMC Rx period among CABP pts Conclusion This study provided the first real world characterization of pts treated with OMC for ABSSSI or CABP. Patients who received OMC had lower HRU in the 30-days post- OMC Rx period relative to the 30-day pre-OMC Rx period. Disclosures Thomas Lodise, Jr., PharmD, PhD, Astra-Zeneca (Consultant)Bayer (Consultant)DoseMe (Consultant, Advisor or Review Panel member)ferring (Consultant)genentech (Consultant)GSK (Consultant)Melinta (Consultant)merck (Consultant, Independent Contractor)nabriva (Consultant)paratek (Consultant, Advisor or Review Panel member, Speaker’s Bureau)shionogi (Consultant, Advisor or Review Panel member, Speaker’s Bureau)Spero (Consultant)tetraphase (Consultant)Venatrox (Consultant) Thomas Lodise, Jr., PharmD, PhD, Melinta Therapeutics (Individual(s) Involved: Self): Consultant; Merck (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Paratek (Individual(s) Involved: Self): Consultant; Shionogi (Individual(s) Involved: Self): Consultant, Speakers’ bureau; Spero (Individual(s) Involved: Self): Consultant; Tetraphase Pharmaceuticals Inc. (Individual(s) Involved: Self): Consultant Kyle Gunter, PharmD, MBA, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Mauricio Rodriguez, Jr., PharmD, BCPS, BCCCP, BCIDP, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Fan Miu, PhD, Analysis Group (Employee, Other Financial or Material Support, Analysis Group received consulting fees from Paratek Pharmaceuticals, Inc.) Emily Gao, MS, MPH, Merck & Co., Inc. (Consultant) Danni Yang, BA, Analysis Group (Employee, Other Financial or Material Support, Analysis Group received consulting fees from Paratek Pharmaceuticals, Inc.) Steve Sandor, JD, MBA, Paratek Pharmaceuticals, Inc. (Employee, Shareholder) Gail Berman, MD, Paratek Pharmaceuticals, Inc. (Employee, Shareholder)
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 5
    In: International Journal of Antimicrobial Agents, Elsevier BV, Vol. 52, No. 2 ( 2018-08), p. 233-240
    Type of Medium: Online Resource
    ISSN: 0924-8579
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
    detail.hit.zdb_id: 2011829-6
    SSG: 15,3
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  • 6
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 5, No. suppl_1 ( 2018-11-26), p. S409-S409
    Abstract: The objective of this evaluation was to provide an analysis of pooled efficacy data from two parallel Phase 3 trials of iclaprim, a diaminopyrimidine dihydrofolate reducatase inhibitor, compared with vancomycin for the treatment of patients with wound infections including surgical site infections (SSI). Methods A pooled analysis of patients with wound infections was conducted from two parallel Phase 3, double-blind, randomized (1:1), active-controlled, multinational, multicenter trials (REVIVE-1 and REVIVE-2), which included a total of 602 patients with wound infections. The data were analyzed separately and then pooled to determine the efficacy of iclaprim 80 mg fixed dose compared with vancomycin 15 mg/kg. Both drugs were administered intravenously every 12 hours for 5 to 14 days according to the investigator assessment of clinical response. The primary endpoint of these studies was to determine whether iclaprim was noninferior (NI; 10% margin) to vancomycin in achieving a ≥20% reduction in lesion size (early clinical response [ECR] at 48 to 72 hours after initiation of the study drug (early time point [ETP] ), compared with baseline in the intent-to-treat (ITT) population. Results Iclaprim had similar ECR rates at ETP compared with vancomycin among the subset of patients with wound infections (see table). The median treatment duration for both iclaprim and vancomycin was 7 days (range 5–14 days). Conclusion In this post-hoc analysis of the REVIVE studies, iclaprim achieved NI to vancomycin in both studies, based on ECR at ETP, in the subgroup of patients with wound infections. These results suggest that iclaprim may be a valuable treatment option for patients with wound infections, including SSI, suspected or confirmed to be due to Gram-positive pathogens. Disclosures D. Huang, Motif BioSciences: Employee, Salary. G. R. Corey, Motif BioSciences: Board Member, Consulting fee. T. L. Holland, Basilea: Consultant, Consulting fee. Motif Bio: Consultant and Scientific Advisor, Consulting fee. Theravance: Consultant, Speaker honorarium. Genentech: Consultant, Consulting fee. T. P. Lodise Jr., Motif BioSciences: Board Member, Consulting fee. W. O’Rirodan, Motif BioSciences: Board Member, Consulting fee. M. Wilcox, Motif BioSciences: Board Member, Consulting fee. T. M. File Jr., Motif BioSciences: Board Member, Consulting fee. M. Dryden, Motif BioSciences: Board Member, Consulting fee. B. Balser, Motif BioSciences: Consultant, Consulting fee. E. Desplats, Motif BioSciences: Consultant, Consulting fee.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 7
    In: Journal of Medical Microbiology, Microbiology Society, Vol. 69, No. 4 ( 2020-04-01), p. 625-630
    Abstract: Introduction. Iclaprim is a diaminopyrimidine antibiotic for the treatment of acute bacterial skin and skin structure infections (ABSSSI) due to Gram-positive pathogens. Aim. This analysis evaluates patients with wound infections from two Phase 3 trials of ABSSSI. Methodology. Six-hundred-two patients with wound infections from two Phase 3, double-blinded, randomized, multicenter, active controlled trials (REVIVE-1/–2) were evaluated in a post hoc analysis of iclaprim 80 mg compared with vancomycin 15 mg kg –1 administered intravenously every 12 h for 5–14 days. The primary endpoint was to determine whether iclaprim was non-inferior (10 % margin) to vancomycin in achieving a ≥20 % reduction from baseline in lesion size 48–72 h after starting study drug (early clinical response [ECR]). Safety was assessed. Results. In REVIVE-1, ECR was 83.5 % with iclaprim versus 79.7 % with vancomycin (treatment difference 3.77%, 95 % CI −4.50%, 12.04%). In REVIVE-2, ECR was 82.7 % with iclaprim versus 76.3 % with vancomycin (treatment difference 6.38%, 95 % CI −3.35%, 16.12%). In the pooled dataset, iclaprim had similar ECR rates compared with vancomycin among wound infection patients (83.2 % vs 78.2 %) with a treatment difference of 5.01 % (95 % CI −1.29%, 11.32%). The safety profile was similar in iclaprim- and vancomycin-treated patients, except for a higher incidence of diarrhea with vancomycin ( n =17) compared with iclaprim ( n =6) and fatigue with iclaprim ( n =17) compared with vancomycin ( n =8). Conclusion. Based on early clinical response, iclaprim achieved non-inferiority to vancomycin with a similar safety profile in patients with wound infections suspected or confirmed as caused by Gram-positive pathogens. Iclaprim may be a valuable treatment option for wound infections.
    Type of Medium: Online Resource
    ISSN: 0022-2615 , 1473-5644
    RVK:
    Language: English
    Publisher: Microbiology Society
    Publication Date: 2020
    detail.hit.zdb_id: 2083944-3
    SSG: 12
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  • 8
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 62, No. 5 ( 2018-05)
    Abstract: Iclaprim is a novel diaminopyrimidine antibiotic that may be an effective and safe treatment for serious skin infections. The safety and effectiveness of iclaprim were assessed in a global phase 3, double-blind, randomized, active-controlled trial. Six hundred thirteen adults with acute bacterial skin and skin structure infections (ABSSSIs) suspected or confirmed to be due to Gram-positive pathogens were randomized to iclaprim (80 mg) or vancomycin (15 mg/kg of body weight), both of which were administered intravenously every 12 h for 5 to 14 days. The primary endpoint was a ≥20% reduction in lesion size compared with that at the baseline at 48 to 72 h after the start of administration of study drug in the intent-to-treat population. Among patients randomized to iclaprim, 78.3% (231 of 295) met this primary endpoint, whereas 76.7% (234 of 305) of those receiving vancomycin met this primary endpoint (difference, 1.58%; 95% confidence interval, −5.10% to 8.26%). This met the prespecified 10% noninferiority margin. Iclaprim was well tolerated, with most adverse events being categorized as mild. In conclusion, iclaprim was noninferior to vancomycin in this phase 3 clinical trial for the treatment of acute bacterial skin and skin structure infections. On the basis of these results, iclaprim may be an efficacious and safe treatment for skin infections suspected or confirmed to be due to Gram-positive pathogens. (This trial has been registered at ClinicalTrials.gov under identifier NCT02607618.)
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2018
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 9
    In: Trials, Springer Science and Business Media LLC, Vol. 23, No. 1 ( 2022-12)
    Abstract: Staphylococcus aureus bacteremia is a life-threatening infection and leading cause of infective endocarditis, with mortality rates of 15–50%. Treatment typically requires prolonged administration of parenteral therapy, itself associated with high costs and potential catheter-associated complications. Dalbavancin is a lipoglycopeptide with potent activity against Staphylococcus and a long half-life, making it an appealing potential therapy for S. aureus bacteremia without the need for durable central venous access. Methods DOTS is a phase 2b, multicenter, randomized, assessor-blinded, superiority, active-controlled, parallel-group trial. The trial will enroll 200 adults diagnosed with complicated S. aureus bacteremia, including definite or possible right-sided infective endocarditis, who have been treated with effective antibiotic therapy for at least 72 h (maximum 10 days) and with subsequent clearance of bacteremia prior to randomization to study treatment. Subjects will be randomized 1:1 to complete their antibiotic treatment course with either two doses of dalbavancin on days 1 and 8, or with a total of 4–8 weeks of standard intravenous antibiotic therapy. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at day 70 for patients randomized to dalbavancin versus standard of care. Key secondary endpoints include quality of life outcomes and pharmacokinetic analyses of dalbavancin. Discussion The DOTS trial will establish whether dalbavancin is superior to standard parenteral antibiotic therapy for the completion of treatment of complicated S. aureus bacteremia. Trial registration US National Institutes of Health ClinicalTrials.gov NCT04775953 . Registered on 1 March 2021
    Type of Medium: Online Resource
    ISSN: 1745-6215
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2040523-6
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  • 10
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 8, No. 10 ( 2021-10-01)
    Abstract: Pivmecillinam is approved for the treatment of adults with uncomplicated urinary tract infection (uUTI) in Canada and Europe and is pending United States (US) Food and Drug Administration submission for consideration for approval. US-focused health care decision-analytics were developed to define the value of an agent like pivmecillinam relative to current standard-of-care (SOC) agents among adult patients with Enterobacterales uUTIs based on its improved microbiologic activity against common Enterobacterales. Methods The model population was 100 theoretical adult outpatients with Enterobacterales uUTIs under 4 different uUTI first-line empiric treatment scenarios (ie, pivmecillinam, nitrofurantoin, trimethoprim-sulfamethoxazole [SXT], or fluoroquinolones). The total mean uUTI-related 30-day costs, including inappropriate treatment costs, were calculated for each regimen. The range of pivmecillinam regimen costs that conferred cost savings relative to the current SOC agents based on its potentially improved microbiologic activity against common Enterobacterales was determined. Results The 30-day uUTI-related costs associated with nitrofurantoin, SXT, and fluoroquinolones were $655.61, $687.57, and $659.69, respectively. The pivmecillinam neutral regimen cost thresholds that resulted in the same uUTI-related 30-day per-patient costs for nitrofurantoin, SXT, and fluoroquinolones were $83.50, $115.45, and $87.58, respectively. The overall antimicrobial susceptibility improvement required with pivmecillinam fixed at $200/regimen, for it to be cost savings relative to SOC agents, was 28%. Conclusions The analyses suggests that an agent like pivmecillinam, if approved in the US, has the potential to reduce the economic burden associated with inappropriate treatment of adult outpatients with uUTIs, especially in patients at high risk for an Enterobacterales uUTI that is resistant to SOC agents.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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