12 results on '"Moeck, Greg"'
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2. Comparative in vitro activity of oritavancin and other agents against vancomycin-susceptible and -resistant enterococci.
- Author
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Sweeney D, Stoneburner A, Shinabarger DL, Arhin FF, Belley A, Moeck G, and Pillar CM
- Subjects
- Cross Infection microbiology, Enterococcus isolation & purification, Enterococcus faecalis drug effects, Gram-Positive Bacterial Infections drug therapy, Humans, Lipoglycopeptides, Microbial Sensitivity Tests methods, Vancomycin pharmacology, Vancomycin Resistance, Anti-Bacterial Agents pharmacology, Enterococcus drug effects, Glycopeptides pharmacology
- Published
- 2017
- Full Text
- View/download PDF
3. Comparative in vitro activity of oritavancin and other agents against methicillin-susceptible and methicillin-resistant Staphylococcus aureus.
- Author
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Sweeney D, Shinabarger DL, Arhin FF, Belley A, Moeck G, and Pillar CM
- Subjects
- Lipoglycopeptides, Microbial Sensitivity Tests, Microbial Viability drug effects, Staphylococcus aureus physiology, Anti-Bacterial Agents pharmacology, Glycopeptides pharmacology, Staphylococcus aureus drug effects
- Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) infections constitute a threat to the public health due to their prevalence and associated mortality and morbidity. Several agents have been recently approved to treat MRSA skin infections including lipoglycopeptides (dalbavancin, oritavancin, and telavancin), ceftaroline, and tedizolid. This study compared the MIC, minimum bactericidal concentration (MBC), and time-kill of these agents alongside daptomycin, linezolid, and vancomycin against MRSA (n=15); meropenem, cefazolin, and nafcillin were also included against methicillin-susceptible S. aureus (MSSA [n=12]). MIC and MBC testing was conducted in accordance with Clinical and Laboratory Standards Institute guidelines, and time-kills were evaluated at multiples of the MIC and the free-drug maximum plasma concentration (fC
max ) at both standard and high inoculum densities for a subset of MRSA (n=2) and MSSA (n=2). MRSA and MSSA were highly susceptible to all agents, with the lipoglycopeptides having the most potent activity by MIC50/90 . All agents excluding tedizolid and linezolid were bactericidal by MBC for MRSA and MSSA, though dalbavancin and telavancin exhibited strain-specific bactericidal activity for MRSA. All agents excluding tedizolid and linezolid were bactericidal by time-kill at their respective fCmax against MRSA and MSSA at standard inoculum density, though oritavancin exhibited the most rapid bactericidal activity. Oritavancin and daptomycin at their respective fCmax maintained similar kill curves at high inoculum density. In contrast, the killing observed with other agents was typically reduced or slowed at high inoculum density. These data demonstrate the rapid bactericidal activity of oritavancin and daptomycin against S. aureus relative to other MRSA agents regardless of bacterial burden., (Copyright © 2016 Elsevier Inc. All rights reserved.)- Published
- 2017
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- View/download PDF
4. Effects of Oritavancin on Coagulation Tests in the Clinical Laboratory.
- Author
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Belley A, Robson R, Francis JL, Adcock DM, Tiefenbacher S, Rubino CM, Moeck G, Sylvester D, Dudley MN, and Loutit J
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- Adult, Blood Coagulation Tests, Female, Hemostasis drug effects, Humans, Lipoglycopeptides, Male, Middle Aged, Young Adult, Anti-Bacterial Agents therapeutic use, Blood Coagulation drug effects, Glycopeptides therapeutic use
- Abstract
Previous studies have shown that some lipoglycopeptide and lipopeptide antimicrobial agents may cause falsely elevated values for some phospholipid-dependent coagulation tests. The effect of oritavancin, a lipoglycopeptide antibiotic, on coagulation test results was explored using pooled human plasma samples spiked with drug and in a clinical study after an infusion of a single 1,200-mg intravenous dose of oritavancin in normal healthy volunteers. Pooled plasma with oritavancin added ex vivo showed concentration-dependent prolongation of prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and dilute Russell viper venom time (DRVVT) test results. In contrast, oritavancin had no effect on the activated protein C resistance assay, chromogenic anti-factor Xa assay (anti-FXa), thrombin time, and an immunoassay for the laboratory diagnosis of heparin-induced thrombocytopenia. In participants that received a single dose of oritavancin, elevations in PT/INR result, aPTT, DRVVT, activated clotting time, and silica clotting time occurred, with the maximum times to resolution of test interference determined to be 12, 120, 72, 24, and 18 h, respectively. The anti-FXa assay was unaffected, whereas transient elevations in D dimer levels were observed in 30% of participants, with a maximum time to resolution of 72 h. Although oritavancin has no impact on the coagulation system in vivo, a single dose of oritavancin can produce falsely elevated values of some coagulation tests used to monitor hemostasis. The interference of oritavancin on affected tests is transient, and the test results revert to normal ranges within specified times after dosing., (Copyright © 2017 American Society for Microbiology.)
- Published
- 2017
- Full Text
- View/download PDF
5. Pooled analysis of single-dose oritavancin in the treatment of acute bacterial skin and skin-structure infections caused by Gram-positive pathogens, including a large patient subset with methicillin-resistant Staphylococcus aureus.
- Author
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Corey GR, Arhin FF, Wikler MA, Sahm DF, Kreiswirth BN, Mediavilla JR, Good S, Fiset C, Jiang H, Moeck G, Kabler H, Green S, and O'Riordan W
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Double-Blind Method, Female, Gram-Positive Bacteria classification, Gram-Positive Bacteria drug effects, Humans, Lipoglycopeptides, Male, Microbial Sensitivity Tests, Middle Aged, Treatment Outcome, Young Adult, Anti-Bacterial Agents administration & dosage, Glycopeptides administration & dosage, Gram-Positive Bacteria isolation & purification, Gram-Positive Bacterial Infections drug therapy, Skin Diseases, Bacterial drug therapy
- Abstract
Oritavancin is a lipoglycopeptide antibiotic with bactericidal activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). The phase 3 studies SOLO I and SOLO II demonstrated comparable efficacy and safety of a single dose of oritavancin compared with 7-10 days of twice-daily vancomycin in adults with acute bacterial skin and skin-structure infections (ABSSSIs). The present analysis assessed clinical responses by pathogen at 48-72 h and at study days 14-24 in SOLO patients within the pooled data set. Of the 1959 patients in the pooled SOLO studies, 1067 had at least one baseline Gram-positive pathogen and 405 had MRSA. Clinical response rates were similar for oritavancin- and vancomycin-treated patients by pathogen, including Staphylococcus aureus with or without the Panton-Valentine leukocidin (pvl) gene and from different clonal complexes, and were similar for pathogens within each treatment group. Oritavancin exhibited potent in vitro activity against all baseline pathogens, with MIC
90 values (minimum inhibitory concentration required to inhibit 90% of the isolates) of 0.12 µg/mL for Staphylococcus aureus, 0.25 µg/mL for Streptococcus pyogenes and 0.06 µg/mL for Enterococcus faecalis. Whereas both oritavancin and vancomycin achieved similarly high rates of clinical response by pathogen, including methicillin-susceptible and -resistant Staphylococcus aureus, oritavancin provides a single-dose alternative to 7-10 days of twice-daily vancomycin to treat ABSSSIs., (Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)- Published
- 2016
- Full Text
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6. Comparative In Vitro Activities of Oritavancin, Dalbavancin, and Vancomycin against Methicillin-Resistant Staphylococcus aureus Isolates in a Nondividing State.
- Author
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Belley A, Lalonde Seguin D, Arhin F, and Moeck G
- Subjects
- Lipoglycopeptides, Microbial Sensitivity Tests, Teicoplanin pharmacology, Anti-Bacterial Agents pharmacology, Glycopeptides pharmacology, Methicillin-Resistant Staphylococcus aureus drug effects, Teicoplanin analogs & derivatives, Vancomycin pharmacology
- Abstract
Antibacterial agents that kill nondividing bacteria may be of utility in treating persistent infections. Oritavancin and dalbavancin are bactericidal lipoglycopeptides that are approved for acute bacterial skin and skin structure infections in adults caused by susceptible Gram-positive pathogens. Using time-kill methodology, we demonstrate that oritavancin exerts bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) isolates that are maintained in a nondividing state in vitro, whereas dalbavancin and the glycopeptide vancomycin do not., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Published
- 2016
- Full Text
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7. Results from Oritavancin Resistance Surveillance Programs (2011 to 2014): Clarification for Using Vancomycin as a Surrogate To Infer Oritavancin Susceptibility.
- Author
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Jones RN, Moeck G, Arhin FF, Dudley MN, Rhomberg PR, and Mendes RE
- Subjects
- Gram-Positive Bacteria drug effects, Lipoglycopeptides, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Glycopeptides pharmacology, Vancomycin pharmacology
- Abstract
Measurement of vancomycin susceptibility has been shown to be highly predictive as a surrogate measure of oritavancin susceptibility among clinically indicated Gram-positive species. Results of studying over 30,000 pathogens (from 2011 to 2014) by cross-susceptibility analysis and determining the poor reproducibility of oritavancin-nonsusceptible results showed nearly perfect surrogate testing accuracy (99.86 to 99.94%). Any isolate of an indicated organism species with locally reproducible oritavancin-nonsusceptible results (extremely rare) should be referred to a reference laboratory for confirmation of the results and determination of the resistance mechanism., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)
- Published
- 2016
- Full Text
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8. Use of in vitro vancomycin testing results to predict susceptibility to oritavancin, a new long-acting lipoglycopeptide.
- Author
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Jones RN, Turnidge JD, Moeck G, Arhin FF, and Mendes RE
- Subjects
- Enterococcus drug effects, Gram-Positive Bacteria drug effects, Lipoglycopeptides, Microbial Sensitivity Tests, Predictive Value of Tests, Reference Standards, Staphylococcus aureus drug effects, Streptococcus drug effects, Vancomycin Resistance drug effects, Anti-Bacterial Agents pharmacology, Drug Resistance, Bacterial drug effects, Glycopeptides pharmacology, Vancomycin pharmacology
- Abstract
Oritavancin is a recently approved lipoglycopeptide antimicrobial agent with activity against Gram-positive pathogens. Its extended serum elimination half-life and concentration-dependent killing enable single-dose treatment of acute bacterial skin and skin structure infections. At the time of regulatory approval, new agents, including oritavancin, are not offered in the most widely used susceptibility testing devices and therefore may require application of surrogate testing using a related antimicrobial to infer susceptibility. To evaluate vancomycin as a predictive susceptibility marker for oritavancin, 26,993 recent Gram-positive organisms from U.S. and European hospitals were tested using reference MIC methods. Organisms included Staphylococcus aureus, coagulase-negative staphylococci (CoNS), beta-hemolytic streptococci (BHS), viridans group streptococci (VGS), and enterococci (ENT). These five major pathogen groups were analyzed by comparing results with FDA-approved susceptible breakpoints for both drugs, as well as those suggested by epidemiological cutoff values and supported by pharmacokinetic/pharmacodynamic analyses. Vancomycin susceptibility was highly accurate (98.1 to 100.0%) as a surrogate for oritavancin susceptibility among the indicated pathogen species. Furthermore, direct MIC comparisons showed high oritavancin potencies, with vancomycin/oritavancin MIC90 results of 1/0.06, 2/0.06, 0.5/0.12,1/0.06, and >16/0.06 μg/ml for S. aureus, CoNS, BHS, VGS, and ENT, respectively. In conclusion, vancomycin demonstrated acceptable accuracy as a surrogate marker for predicting oritavancin susceptibility when tested against the indicated pathogens. In contrast, 93.3% of vancomycin-nonsusceptible enterococci had oritavancin MIC values of ≤0.12 μg/ml, indicating a poor predictive value of vancomycin for oritavancin resistance against these organisms. Until commercial oritavancin susceptibility testing devices are readily available, isolates that when tested show vancomycin susceptibility can be inferred to be susceptible to oritavancin by using FDA-approved breakpoints., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Published
- 2015
- Full Text
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9. Single-dose oritavancin versus 7-10 days of vancomycin in the treatment of gram-positive acute bacterial skin and skin structure infections: the SOLO II noninferiority study.
- Author
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Corey GR, Good S, Jiang H, Moeck G, Wikler M, Green S, Manos P, Keech R, Singh R, Heller B, Bubnova N, and O'Riordan W
- Subjects
- Administration, Intravenous, Adolescent, Adult, Aged, Aged, 80 and over, Double-Blind Method, Female, Gram-Positive Bacterial Infections pathology, Humans, Lipoglycopeptides, Male, Middle Aged, Treatment Outcome, Young Adult, Anti-Bacterial Agents therapeutic use, Glycopeptides therapeutic use, Gram-Positive Bacterial Infections drug therapy, Skin Diseases, Bacterial drug therapy, Soft Tissue Infections drug therapy, Vancomycin therapeutic use
- Abstract
Background: Oritavancin is a lipoglycopeptide antibiotic with rapid bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and long half-life allow for single-dose treatment., Methods: In a randomized, double-blind trial, adults with acute bacterial skin and skin structure infections (ABSSSIs) received either a single intravenous 1200-mg dose of oritavancin or 7-10 days of twice-daily vancomycin. Three efficacy endpoints were tested for noninferiority: (1) primary composite endpoint at 48-72 hours (cessation of spreading or reduction in lesion size, absence of fever, and no rescue antibiotic); (2) investigator-assessed clinical cure 7-14 days after end of treatment; and (3) ≥20% reduction in lesion area at 48-72 hours., Results: A total of 503 and 502 patients comprised the modified intent-to-treat population for oritavancin and vancomycin, respectively. All 3 efficacy endpoints met the 10% noninferiority margin: the primary composite endpoint (80.1% vs 82.9%; 95% confidence interval [CI], -7.5 to 2.0), investigator-assessed clinical cure (82.7% vs 80.5%; 95% CI, -2.6 to 7.0), and proportion of patients attaining ≥20% reduction in lesion area (85.9% vs 85.3%; 95% CI, -3.7 to 5.0) for oritavancin vs vancomycin, respectively. Efficacy outcomes by pathogen, including methicillin-resistant Staphylococcus aureus and the frequency of adverse events, were similar between treatment groups., Conclusions: A single 1200-mg dose of oritavancin was noninferior to 7-10 days of vancomycin in treating ABSSSIs caused by gram-positive pathogens, and was well tolerated. Oritavancin provides a single-dose alternative to multidose therapies for the treatment of ABSSSIs. Clinical Trials Registration. NCT01252732., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
- Full Text
- View/download PDF
10. Dalbavancin or oritavancin for skin infections.
- Author
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Corey GR, Jiang H, and Moeck G
- Subjects
- Female, Humans, Male, Anti-Bacterial Agents administration & dosage, Glycopeptides administration & dosage, Skin Diseases, Bacterial drug therapy, Teicoplanin analogs & derivatives, Vancomycin administration & dosage
- Published
- 2014
- Full Text
- View/download PDF
11. Single-dose oritavancin in the treatment of acute bacterial skin infections.
- Author
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Corey GR, Kabler H, Mehra P, Gupta S, Overcash JS, Porwal A, Giordano P, Lucasti C, Perez A, Good S, Jiang H, Moeck G, and O'Riordan W
- Subjects
- Acute Disease, Adolescent, Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents adverse effects, Double-Blind Method, Drug Administration Schedule, Female, Glycopeptides adverse effects, Humans, Infusions, Intravenous, Intention to Treat Analysis, Lipoglycopeptides, Male, Methicillin-Resistant Staphylococcus aureus isolation & purification, Middle Aged, Nausea chemically induced, Skin Diseases, Bacterial microbiology, Vancomycin adverse effects, Young Adult, Anti-Bacterial Agents administration & dosage, Glycopeptides administration & dosage, Skin Diseases, Bacterial drug therapy, Vancomycin administration & dosage
- Abstract
Background: Oritavancin is a lipoglycopeptide with bactericidal activity against gram-positive bacteria. Its concentration-dependent activity and prolonged half-life allow for single-dose treatment., Methods: We conducted a randomized, double-blind trial in which adults with acute bacterial skin and skin-structure infections received either a single intravenous dose of 1200 mg of oritavancin or a regimen of intravenous vancomycin twice daily for 7 to 10 days. Three efficacy end points were tested for noninferiority. The primary composite end point was defined as cessation of spreading or reduction in lesion size, absence of fever, and no need for administration of a rescue antibiotic 48 to 72 hours after administration of oritavancin. Secondary end points were clinical cure 7 to 14 days after the end of treatment, as determined by a study investigator, and a reduction in lesion size of 20% or more 48 to 72 hours after administration of oritavancin., Results: The modified intention-to-treat population comprised 475 patients who received oritavancin and 479 patients who received vancomycin. All three efficacy end points met the prespecified noninferiority margin of 10 percentage points for oritavancin versus vancomycin: primary end point, 82.3% versus 78.9% (95% confidence interval [CI] for the difference, -1.6 to 8.4 percentage points); investigator-assessed clinical cure, 79.6% versus 80.0% (95% CI for the difference, -5.5 to 4.7 percentage points); and proportion of patients with a reduction in lesion area of 20% or more, 86.9% versus 82.9% (95% CI for the difference, -0.5 to 8.6 percentage points). Efficacy outcomes measured according to type of pathogen, including methicillin-resistant Staphylococcus aureus, were similar in the two treatment groups. The overall frequency of adverse events was also similar, although nausea was more common among those treated with oritavancin., Conclusions: A single dose of oritavancin was noninferior to twice-daily vancomycin administered for 7 to 10 days for the treatment of acute bacterial skin and skin-structure infections caused by gram-positive pathogens. (Funded by the Medicines Company; SOLO I ClinicalTrials.gov number, NCT01252719.).
- Published
- 2014
- Full Text
- View/download PDF
12. Pharmacodynamics of a simulated single 1,200-milligram dose of oritavancin in an in vitro pharmacokinetic/pharmacodynamic model of methicillin-resistant staphylococcus aureus infection.
- Author
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Belley A, Arhin FF, Sarmiento I, Deng H, Rose W, and Moeck G
- Subjects
- Analysis of Variance, Area Under Curve, Clinical Trials, Phase III as Topic, Colony Count, Microbial, Culture Media, Drug Dosage Calculations, Humans, Infusion Pumps, Lipoglycopeptides, Methicillin-Resistant Staphylococcus aureus growth & development, Microbial Sensitivity Tests, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Anti-Bacterial Agents pharmacology, Daptomycin pharmacology, Glycopeptides pharmacology, Methicillin-Resistant Staphylococcus aureus drug effects, Models, Biological, Vancomycin pharmacology
- Abstract
The safety and efficacy of a single 1,200-mg dose of the lipoglycopeptide oritavancin are currently being investigated in two global phase 3 studies of acute bacterial skin and skin structure infections. In this study, an in vitro pharmacokinetic/pharmacodynamic model was established to compare the free-drug pharmacodynamics associated with a single 1,200-mg dose of oritavancin to once-daily dosing with daptomycin at 6 mg/kg of body weight and twice-daily dosing with vancomycin at 1,000 mg against three methicillin-resistant Staphylococcus aureus (MRSA) strains over 72 h. The area under the bacterial-kill curve (AUBKC) was used to assess the antibacterial effect of each dosing regimen at 24 h (AUBKC(0-24)), 48 h (AUBKC(0-48)), and 72 h (AUBKC(0-72)). The rapid bactericidal activities of oritavancin and daptomycin contributed to lower AUBKC(0-24)s for the three MRSA strains than with vancomycin (P < 0.05, as determined by analysis of variance [ANOVA]). Oritavancin exposure also resulted in a lower AUBKC(0-48) and AUBKC(0-72) against one MRSA strain and a lower AUBKC(0-48) for another strain than did vancomycin exposure (P < 0.05). Furthermore, daptomycin exposure resulted in a lower AUBKC(0-48) and AUBKC(0-72) for one of the MRSA isolates than did vancomycin exposure (P < 0.05). Lower AUBKC(0-24)s for two of the MRSA strains (P < 0.05) were obtained with oritavancin exposure than with daptomycin. Thus, the antibacterial effect from the single-dose regimen of oritavancin is as effective as that from either once-daily dosing with daptomycin or twice-daily dosing with vancomycin against the MRSA isolates tested in an in vitro pharmacokinetic/pharmacodynamic model over 72 h. These results provide further justification to assess the single 1,200-mg dose of oritavancin for treatment of acute bacterial skin and skin structure infections.
- Published
- 2013
- Full Text
- View/download PDF
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