The Experts below are selected from a list of 327 Experts worldwide ranked by ideXlab platform
George L. Drusano - One of the best experts on this subject based on the ideXlab platform.
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pharmacodynamics of ceftaroline fosamil for complicated Skin and Skin Structure infection rationale for improved anti methicillin resistant staphylococcus aureus activity
Journal of Antimicrobial Chemotherapy, 2010Co-Authors: George L. DrusanoAbstract:Ceftaroline fosamil is a new β-lactam antibiotic with an altered 3' side chain that allows it to interact with penicillin-binding protein (PBP) 2a, resulting in lower MIC values for methicillin-resistant Staphylococcus aureus (MRSA). Large MRSA collections repeatedly demonstrate MIC 90 values of 1 mg/L. The pharmacokinetics for ceftaroline fosamil are straightforward and reminiscent of many other cephalosporin antibiotics, with a terminal half-life of ~2.6 h. Pharmacodynamic evaluation demonstrates that relatively short free drug T> MIC results in stasis or 1 log 10 cfu/g bacterial kill (mean values for four S. aureus isolates of 26% and 33% of the dosing interval, respectively). Monte Carlo simulation demonstrated high expected target attainment rates (>97%) and clinical trial data showed clinically evaluable and microbiologically evaluable cure rates (96.7%) that are highly concordant with the pharmacodynamic analyses. Clinical trial data for ceftaroline fosamil are in excellent concordance with the pharmacodynamic analysis. Ceftaroline fosamil at a dose of 600 mg administered intravenously every 12 h is highly likely to be successful in clinical practice for treatment of complicated Skin and Skin Structure infections.
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Pharmacodynamics of ceftaroline fosamil for complicated Skin and Skin Structure infection: Rationale for improved anti-methicillin-resistant Staphylococcus aureus activity
Journal of Antimicrobial Chemotherapy, 2010Co-Authors: George L. DrusanoAbstract:Ceftaroline fosamil is a new beta-lactam antibiotic with an altered 3' side chain that allows it to interact with penicillin-binding protein (PBP) 2a, resulting in lower MIC values for methicillin-resistant Staphylococcus aureus (MRSA). Large MRSA collections repeatedly demonstrate MIC values of 1 mg/L. The pharmacokinetics for ceftaroline fosamil are straightforward and reminiscent of many other cephalosporin antibiotics, with a terminal half-life of approximately 2.6 h. Pharmacodynamic evaluation demonstrates that relatively short free drug T > MIC results in stasis or 1 log cfu/g bacterial kill (mean values for four S. aureus isolates of 26% and 33% of the dosing interval, respectively). Monte Carlo simulation demonstrated high expected target attainment rates (> 97%) and clinical trial data showed clinically evaluable and microbiologically evaluable cure rates (96.7%) that are highly concordant with the pharmacodynamic analyses. Clinical trial data for ceftaroline fosamil are in excellent concordance with the pharmacodynamic analysis. Ceftaroline fosamil at a dose of 600 mg administered intravenously every 12 h is highly likely to be successful in clinical practice for treatment of complicated Skin and Skin Structure infections
Peter J Petersen - One of the best experts on this subject based on the ideXlab platform.
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in vitro activity of tigecycline against isolates from patients enrolled in phase 3 clinical trials of treatment for complicated Skin and Skin Structure infections and complicated intra abdominal infections
Clinical Infectious Diseases, 2005Co-Authors: Patricia A Bradford, Tasha Weaver D Sands, Peter J PetersenAbstract:The in vitro activity of tigecycline was evaluated against 4913 baseline pathogens isolated from 1986 patients enrolled in 4 pivotal phase 3 clinical trials. The trials, which were conducted in 38 countries worldwide, involved patients with complicated Skin and Skin-Structure infections or complicated intra-abdominal infections. Tigecycline was active against the most prevalent pathogens for each infection type, including gram-positive and gram-negative strains of both aerobic and anaerobic bacteria (MICs, ≤2 μg/mL for most pathogens). The spectrum of activity of tigecycline included important pathogens, such as Staphylococcus aureus (including methicillin-resistant S. aureus), Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, and Bacteroides fragilis. A few genera, such as Pseudomonas aeruginosa and members of the tribe Proteeae, were generally less susceptible to tigecycline than were other gram-negative pathogens. The susceptibility of the pathogens to tigecycline was similar for isolates obtained from patients enrolled in the studies of complicated Skin and Skin-Structure infection or of complicated intra-abdominal infection. For most pathogens, the susceptibility to tigecycline was similar across all geographic regions. The excellent expanded broad-spectrum activity of tigecycline demonstrated in vitro against clinical isolates confirmed its potential utility for pathogens associated with complicated Skin and Skin-Structure infections or complicated intra-abdominal infections.
John Pullman - One of the best experts on this subject based on the ideXlab platform.
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a randomized double blind phase 2 study to evaluate subjective and objective outcomes in patients with acute bacterial Skin and Skin Structure infections treated with delafloxacin linezolid or vancomycin
Journal of Antimicrobial Chemotherapy, 2016Co-Authors: Jeff Kingsley, Purvi Mehra, Laura Lawrence, Sue K Cammarata, Eugenia Henry, Erin Duffy, John PullmanAbstract:Objectives Delafloxacin is an investigational anionic fluoroquinolone being developed to treat infections caused by Gram-positive and -negative organisms. This clinical trial evaluated the efficacy and safety of delafloxacin in the treatment of acute bacterial Skin and Skin Structure infections (ABSSSIs).
Michael J Rybak - One of the best experts on this subject based on the ideXlab platform.
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daptomycin versus vancomycin for complicated Skin and Skin Structure infections clinical and economic outcomes
Pharmacotherapy, 2007Co-Authors: Susan L Davis, Peggy S Mckinnon, Levi M Hall, George Delgado, Warren E Rose, Robert F Wilson, Michael J RybakAbstract:Study Objective. To assess the effect of daptomycin compared with vancomycin on the clinical and economic outcomes in patients with complicated Skin and Skin Structure infections. Design. Prospective, open-label study. Setting. Level 1 trauma center in Detroit, Michigan. Patients. Fifty-three adult patients with complicated Skin and Skin Structure infections at risk for methicillin-resistant Staphylococcus aureus (MRSA) infection who were treated with daptomycin and a matched cohort of 212 patients treated with vancomycin. Intervention. Patients in the prospective arm received intravenous daptomycin 4 mg/kg every 24 hours for at least 3 days but not more than 14 days. Historical controls received at least 3 days of vancomycin dosed to achieve trough concentrations of 5–20 μg/ml. Measurements and Main Results. Outcomes evaluated included blinded assessments of clinical resolution, duration of therapy, and costs. The most common diagnoses were cellulitis (31%), abscess (22%), and both cellulitis with abscess (37%). Microbiology differed significantly between groups, with S. aureus found in 27 patients (51%) in the daptomycin group and 167 patients (79%) in the vancomycin group and MRSA in 22 (42%) and 159 (75%), respectively (p<0.001). The proportions of patients with clinical improvement or resolution of their infections on days 3 and 5 were 90% versus 70% and 98% versus 81% in the daptomycin versus vancomycin groups, respectively (p<0.01 for both comparisons), and 100% at the end of therapy in both groups. Among patients with complete resolution of their infections (41 patients [77%] with daptomycin vs 89 patients [42%] with vancomycin, p<0.05), median duration of intravenous therapy was 4 and 7 days, respectively, (p<0.001), and hospital costs were $5027 and $7552 (p<0.001). Conclusions. Patients receiving daptomycin achieved more rapid resolution of symptoms and clinical cure and had a decreased duration of inpatient therapy compared with those receiving vancomycin. This study suggests that daptomycin is a cost-effective alternative to vancomycin for complicated Skin and Skin Structure infections.
Philippe Prokocimer - One of the best experts on this subject based on the ideXlab platform.
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tedizolid for 6 days versus linezolid for 10 days for acute bacterial Skin and Skin Structure infections establish 2 a randomised double blind phase 3 non inferiority trial
Lancet Infectious Diseases, 2014Co-Authors: Gregory J Moran, Ralph G Corey, Edward Fang, Carisa De Anda, Philippe ProkocimerAbstract:Summary Background New antibiotics are needed to treat infections caused by drug-resistant bacteria. Tedizolid is a novel oxazolidinone antibacterial drug designed to provide enhanced activity against Gram-positive pathogens. We aimed to assess the efficacy and safety of intravenous to oral tedizolid for treatment of patients with acute bacterial Skin and Skin-Structure infections. Methods ESTABLISH-2 was a randomised, double-blind, phase 3, non-inferiority trial done between Sept 28, 2011, and Jan 10, 2013, at 58 centres in nine countries. Patients (aged ≥12 years) with acute bacterial Skin and Skin-Structure infections (cellulitis or erysipelas, major cutaneous abscess, or wound infection) that had a minimum lesion area of 75 cm 2 and were suspected or documented to be associated with a Gram-positive pathogen, were randomly assigned (1:1), via an interactive voice-response system with block randomisation, to receive intravenous once-daily tedizolid (200 mg for 6 days) or twice-daily linezolid (600 mg for 10 days), with optional oral step-down. Randomisation was stratified by geographic region and type of acute bacterial Skin and Skin-Structure infection. The primary endpoint was early clinical response (≥20% reduction in lesion area at 48–72 h compared with baseline), with a non-inferiority margin of −10%. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01421511. Findings 666 patients were randomly assigned to receive tedizolid (n=332) or linezolid (n=334). 283 (85%) patients in the tedizolid group and 276 (83%) in the linezolid group achieved early clinical response (difference 2·6%, 95% CI −3·0 to 8·2), meeting the prespecified non-inferiority margin. Gastrointestinal adverse events were less frequent with tedizolid than linezolid, taking place in 52 (16%) of 331 patients and 67 (20%) of 327 patients in the safety population. Treatment-emergent adverse events leading to discontinuation of study drug were reported by one ( Interpretation Intravenous to oral once-daily tedizolid 200 mg for 6 days was non-inferior to twice-daily linezolid 600 mg for 10 days for treatment of patients with acute bacterial Skin and Skin-Structure infections. Tedizolid could become a useful option for the treatment of acute bacterial Skin and Skin-Structure infections in the hospital and outpatient settings. Funding Cubist Pharmaceuticals.
