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116 results on '"Moeck, Greg"'

7. 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

Corey, G. Ralph, Arhin, Francis F., Wikler, Matthew A., Sahm, Daniel F., Kreiswirth, Barry N., Mediavilla, José R., Good, Samantha, Fiset, Claude, Jiang, Hai, Moeck, Greg, Kabler, Heidi, Green, Sinikka, and O'Riordan, William

Published
2016
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8. In Vitro Activity of Cefepime-Taniborbactam and Comparators against Clinical Isolates of Gram-Negative Bacilli from 2018 to 2020: Results from the Global Evaluation of Antimicrobial Resistance via Surveillance (GEARS) Program

Author

Karlowsky, James A., primary, Hackel, Meredith A., additional, Wise, Mark G., additional, Six, David A., additional, Uehara, Tsuyoshi, additional, Daigle, Denis M., additional, Cusick, Susan M., additional, Pevear, Daniel C., additional, Moeck, Greg, additional, and Sahm, Daniel F., additional

Published
2023
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13. 133. ARGONAUT-III: Susceptibility of Carbapenem-resistant Klebsiellae to Cefepime-Taniborbactam

Author

Mack, Andrew R, primary, Bethel, Christopher, additional, Marshall, Steven, additional, Patel, Robin, additional, van Duin, David, additional, Fowler, Vance G, additional, Rhoads, Daniel D, additional, Jacobs, Michael, additional, van den Akker, Focco, additional, Six, David A, additional, Moeck, Greg, additional, Papp-Wallace, Krisztina M, additional, and Bonomo, Robert A, additional

Published
2021
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14. 1055. ARGONAUT-IV: Susceptibility of Carbapenem-resistant Klebsiellae to Ceftibuten/VNRX-5236

Author

Mack, Andrew R, primary, Bethel, Christopher, additional, Marshall, Steven, additional, Patel, Robin, additional, van Duin, David, additional, Fowler, Vance G, additional, Rhoads, Daniel D, additional, Jacobs, Michael, additional, van den Akker, Focco, additional, Six, David A, additional, Moeck, Greg, additional, Papp-Wallace, Krisztina M, additional, and Bonomo, Robert A, additional

Published
2021
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15. 1063. ARGONAUT-V: Susceptibility of Multidrug-Resistant (MDR) Pseudomonas aeruginosa to Cefepime-Taniborbactam

Author

Mack, Andrew R, primary, Bethel, Christopher, additional, Marshall, Steven, additional, Patel, Robin, additional, van Duin, David, additional, Fowler, Vance G, additional, Rhoads, Daniel D, additional, Jacobs, Michael, additional, van den Akker, Focco, additional, Six, David A, additional, Moeck, Greg, additional, Papp-Wallace, Krisztina M, additional, and Bonomo, Robert A, additional

Published
2021
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17. Discovery of VNRX-7145 (VNRX-5236 Etzadroxil): An Orally Bioavailable β-Lactamase Inhibitor for Enterobacterales Expressing Ambler Class A, C, and D Enzymes

Author

Trout, Robert E., primary, Zulli, Allison, additional, Mesaros, Eugen, additional, Jackson, Randy W., additional, Boyd, Steven, additional, Liu, Bin, additional, Hamrick, Jodie, additional, Daigle, Denis, additional, Chatwin, Cassandra L., additional, John, Kaitlyn, additional, McLaughlin, Lisa, additional, Cusick, Susan M., additional, Weiss, William J., additional, Pulse, Mark E., additional, Pevear, Daniel C., additional, Moeck, Greg, additional, Xerri, Luigi, additional, and Burns, Christopher J., additional

Published
2021
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20. Genome annotation and intraviral interactome for the Streptococcus pneumoniae virulent phage Dp-1

Author

Moineau, Sylvain, Häuser, Roman, Sabri, Mourad, Ouellette, Marc, Liu, Jing, Dehbi, Mohammed, Moeck, Greg, García López, Ernesto Ángel, Titz, Björn, Uetz, Peter, Moineau, Sylvain, Häuser, Roman, Sabri, Mourad, Ouellette, Marc, Liu, Jing, Dehbi, Mohammed, Moeck, Greg, García López, Ernesto Ángel, Titz, Björn, and Uetz, Peter

Abstract

Streptococcus pneumoniae causes several diseases, including pneumonia, septicemia, and meningitis. Phage Dp-1 is one of the very few isolated virulent S. pneumoniae bacteriophages, but only a partial characterization is currently available. Here, we confirmed that Dp-1 belongs to the family Siphoviridae. Then, we determined its complete genomic sequence of 56,506 bp. It encodes 72 open reading frames, of which 44 have been assigned a function. We have identified putative promoters, Rho-independent terminators, and several genomic clusters. We provide evidence that Dp-1 may be using a novel DNA replication system as well as redirecting host protein synthesis through queuosine-containing tRNAs. Liquid chromatography-mass spectrometry analysis of purified phage Dp-1 particles identified at least eight structural proteins. Finally, using comprehensive yeast two-hybrid screens, we identified 156 phage protein interactions, and this intraviral interactome was used to propose a structural model of Dp-1.

Published
2020

21. A new class of small molecule RNA polymerase inhibitors with activity against Rifampicin-resistant Staphylococcus aureus

Author

Arhin, Francis, Bélanger, Odette, Ciblat, Stéphane, Dehbi, Mohammed, Delorme, Daniel, Dietrich, Evelyne, Dixit, Dilip, Lafontaine, Yanick, Lehoux, Dario, Liu, Jing, McKay, Geoffrey A., Moeck, Greg, Reddy, Ranga, Rose, Yannick, Srikumar, Ramakrishnan, Tanaka, Kelly S.E., Williams, Daniel M., Gros, Philippe, Pelletier, Jerry, Parr, Thomas R., Jr., and Far, Adel Rafai

Published
2006
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23. VNRX-5133 (Taniborbactam), a Broad-Spectrum Inhibitor of Serine- and Metallo-β-Lactamases, Restores Activity of Cefepime in Enterobacterales and Pseudomonas aeruginosa

Author

Hamrick, Jodie C., primary, Docquier, Jean-Denis, additional, Uehara, Tsuyoshi, additional, Myers, Cullen L., additional, Six, David A., additional, Chatwin, Cassandra L., additional, John, Kaitlyn J., additional, Vernacchio, Salvador F., additional, Cusick, Susan M., additional, Trout, Robert E. L., additional, Pozzi, Cecilia, additional, De Luca, Filomena, additional, Benvenuti, Manuela, additional, Mangani, Stefano, additional, Liu, Bin, additional, Jackson, Randy W., additional, Moeck, Greg, additional, Xerri, Luigi, additional, Burns, Christopher J., additional, Pevear, Daniel C., additional, and Daigle, Denis M., additional

Published
2020
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37. 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

Corey, G. Ralph, primary, Good, Samantha, additional, Jiang, Hai, additional, Moeck, Greg, additional, Wikler, Matthew, additional, Green, Sinikka, additional, Manos, Paul, additional, Keech, Richard, additional, Singh, Rajesh, additional, Heller, Barry, additional, Bubnova, Natalia, additional, and O'Riordan, William, additional

Published
2014
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39. Genome annotation and intraviral interactome for the Streptococcus pneumoniae virulent phage Dp-1

Author

Sabri, Mourad, Häuser, Roman, Ouellette, Marc, Liu, Jing, Dehbi, Mohammed, Moeck, Greg, García López, Ernesto Ángel, Titz, Björn, Uetz, Peter, Moineau, Sylvain, Sabri, Mourad, Häuser, Roman, Ouellette, Marc, Liu, Jing, Dehbi, Mohammed, Moeck, Greg, García López, Ernesto Ángel, Titz, Björn, Uetz, Peter, and Moineau, Sylvain

Abstract

Streptococcus pneumoniae causes several diseases, including pneumonia, septicemia, and meningitis. Phage Dp-1 is one of the very few isolated virulent S. pneumoniae bacteriophages, but only a partial characterization is currently available. Here, we confirmed that Dp-1 belongs to the family Siphoviridae. Then, we determined its complete genomic sequence of 56,506 bp. It encodes 72 open reading frames, of which 44 have been assigned a function. We have identified putative promoters, Rho-independent terminators, and several genomic clusters. We provide evidence that Dp-1 may be using a novel DNA replication system as well as redirecting host protein synthesis through queuosine-containing tRNAs. Liquid chromatography-mass spectrometry analysis of purified phage Dp-1 particles identified at least eight structural proteins. Finally, using comprehensive yeast two-hybrid screens, we identified 156 phage protein interactions, and this intraviral interactome was used to propose a structural model of Dp-1.

Published
2010

40. Antibiotic activity against intracellular Staphylococcus aureus

Author

UCL - SC - Sciences, Tulkens, Paul, Van Bambeke, Françoise, Rezsohazy, René, Moeck, Greg, Schneider, Yves-Jacques, Remacle, Claude, Glupczynski, Youri, Baudoux, Pierre, UCL - SC - Sciences, Tulkens, Paul, Van Bambeke, Françoise, Rezsohazy, René, Moeck, Greg, Schneider, Yves-Jacques, Remacle, Claude, Glupczynski, Youri, and Baudoux, Pierre

Abstract

Staphylococcus aureus is a widespread human pathogen, responsible for nosocomial infections and causing diverse diseases including life-threatening ones. Emergence and spread of multidrug resistant S. aureus compel for development of new active molecules. There are nowadays increasing evidences that S. aureus is able to invade and persist into host cells, where bacteria are partially protected from immune response and action of extracellular antibiotics. Using pharmacological models, we wanted to further understand which factors are critical for antibiotic intracellular activity, characterize antistaphylococcal compounds with strong intracellular activity and investigate the predictive value of our in vitro macrophages model of infection through comparison with in vivo studies. Our results showed that acidic medium influences on antibiotic intrinsic activity is a critical factor for intracellular activity towards S. aureus. However, additional parameters, still not elucidated, must play a role in determining intracellular activity. Through activity testing, we showed that quinupristin-dalfopristin, a streptogramin combination, and oritavancin, a newly developped glycopeptide, yield marked intracellular activity regarding to what has already been described in previous studies, including against strains with clinically relevant resistance phenotypes. In the final phase of this study, we assessed activity of plectasin, an antimicrobial peptide currently under development for use in humans, simultaneously in vitro and in vivo. Intracellular activity results obtained in vivo were globally in line with what was observed from in vitro study, therefore suggesting the latter as a relevant screening tool for assessment of antibiotic intracellular activity, although in vivo studies remain essential to achieve a valuable estimation., (BIOL 3) -- UCL, 2010

Published
2010

43. 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

Corey, G. Ralph, Good, Samantha, Jiang, Hai, Moeck, Greg, Wikler, Matthew, Green, Sinikka, Manos, Paul, Keech, Richard, Singh, Rajesh, Heller, Barry, Bubnova, Natalia, and O'Riordan, William

Subjects
GRAM-positive bacterial infections, METHICILLIN-resistant staphylococcus aureus treatment, VANCOMYCIN, TREATMENT effectiveness, PHARMACOKINETICS, BACTERIAL disease treatment
Abstract

A single 1200-mg dose of oritavancin was noninferior to 7–10 days of vancomycin for treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by gram-positive pathogens. Oritavancin provides a single-dose alternative to multi-dose therapies for ABSSSI.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. [ABSTRACT FROM PUBLISHER]

Published
2015
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44. Antimicrobial drug discovery through bacteriophage genomics

Author

Liu, Jing, primary, Dehbi, Mohammed, additional, Moeck, Greg, additional, Arhin, Francis, additional, Bauda, Pascale, additional, Bergeron, Dominique, additional, Callejo, Mario, additional, Ferretti, Vincent, additional, Ha, Nhuan, additional, Kwan, Tony, additional, McCarty, John, additional, Srikumar, Ramakrishnan, additional, Williams, Dan, additional, Wu, Jinzi J, additional, Gros, Philippe, additional, Pelletier, Jerry, additional, and DuBow, Michael, additional

Published
2004
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46. Comparative In VitroActivities of Oritavancin, Dalbavancin, and Vancomycin against Methicillin-Resistant Staphylococcus aureusIsolates in a Nondividing State

Author

Belley, Adam, Lalonde Seguin, David, Arhin, Francis, and Moeck, Greg

Abstract

ABSTRACTAntibacterial 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.

Published
2016
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47. Use of In VitroVancomycin Testing Results To Predict Susceptibility to Oritavancin, a New Long-Acting Lipoglycopeptide

Author

Jones, Ronald N., Turnidge, John D., Moeck, Greg, Arhin, Francis F., and Mendes, Rodrigo E.

Abstract

ABSTRACTOritavancin 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 MIC90results 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.

Published
2015
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48. Antimicrobial drug discovery through bacteriophage genomics.

Author

Arhin, Francis, Bauda, Pascale, Bergeron, Dominique, Callejo, Mario, Ferretti, Vincent, Nhuan Ha, Vincent, Kwan, Tony, McCarty, John, Srikumar, Ramakrishnan, Williams, Dan, Jinzi J. Wu, Dan, Gros, Philippe, Pelletier, Jerry, DuBow, Michael, Jing Liu, Dehbi, Mohammed, and Moeck, Greg

Subjects
ANTI-infective agents, BACTERIOPHAGE genetics, ANTIBIOTICS, GENETICS of staphylococcus aureus infections, DNA replication, COMMUNICABLE diseases
Abstract

Over evolutionary time bacteriophages have developed unique proteins that arrest critical cellular processes to commit bacterial host metabolism to phage reproduction. Here, we apply this concept of phage-mediated bacterial growth inhibition to antibiotic discovery. We sequenced 26 Staphylococcus aureus phages and identified 31 novel polypeptide families that inhibited growth upon expression in S. aureus. The cellular targets for some of these polypeptides were identified and several were shown to be essential components of the host DNA replication and transcription machineries. The interaction between a prototypic pair, ORF104 of phage 77 and DnaI, the putative helicase loader of S. aureus, was then used to screen for small molecule inhibitors. Several compounds were subsequently found to inhibit both bacterial growth and DNA synthesis. Our results suggest that mimicking the growth-inhibitory effect of phage polypeptides by a chemical compound, coupled with the plethora of phages on earth, will yield new antibiotics to combat infectious diseases. [ABSTRACT FROM AUTHOR]

Published
2004
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49. Pharmacodynamics of a Simulated Single 1,200-Milligram Dose of Oritavancin in an In VitroPharmacokinetic/Pharmacodynamic Model of Methicillin-Resistant Staphylococcus aureusInfection

Author

Belley, Adam, Arhin, Francis F., Sarmiento, Ingrid, Deng, Hong, Rose, Warren, and Moeck, Greg

Abstract

ABSTRACTThe 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 vitropharmacokinetic/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 (AUBKC0-24), 48 h (AUBKC0-48), and 72 h (AUBKC0-72). The rapid bactericidal activities of oritavancin and daptomycin contributed to lower AUBKC0-24s 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 AUBKC0-48and AUBKC0-72against one MRSA strain and a lower AUBKC0-48for another strain than did vancomycin exposure (P< 0.05). Furthermore, daptomycin exposure resulted in a lower AUBKC0-48and AUBKC0-72for one of the MRSA isolates than did vancomycin exposure (P< 0.05). Lower AUBKC0-24s 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 vitropharmacokinetic/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
2012
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50. VNRX-5133 (Taniborbactam), a Broad-Spectrum Inhibitor of Serine- and Metallo-β-Lactamases, Restores Activity of Cefepime in Enterobacteralesand Pseudomonas aeruginosa

Author

Hamrick, Jodie C., Docquier, Jean-Denis, Uehara, Tsuyoshi, Myers, Cullen L., Six, David A., Chatwin, Cassandra L., John, Kaitlyn J., Vernacchio, Salvador F., Cusick, Susan M., Trout, Robert E. L., Pozzi, Cecilia, De Luca, Filomena, Benvenuti, Manuela, Mangani, Stefano, Liu, Bin, Jackson, Randy W., Moeck, Greg, Xerri, Luigi, Burns, Christopher J., Pevear, Daniel C., and Daigle, Denis M.

Abstract

As shifts in the epidemiology of β-lactamase-mediated resistance continue, carbapenem-resistant Enterobacterales(CRE) and carbapenem-resistant Pseudomonas aeruginosa(CRPA) are the most urgent threats.

Published
2020
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