scholarly journals New Gram-Positive Agents: the Next Generation of Oxazolidinones and Lipoglycopeptides

2016 ◽  
Vol 54 (9) ◽  
pp. 2225-2232 ◽  
Author(s):  
Matthew P. Crotty ◽  
Tamara Krekel ◽  
Carey-Ann D. Burnham ◽  
David J. Ritchie
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Next Generation ◽  
Gram Positive ◽  
Content Type ◽  
Skin Structure ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
The U.S

The growing problem of antimicrobial resistance among bacterial pathogens, including methicillin-resistantStaphylococcus aureus(MRSA) and vancomycin-resistant enterococci (VRE), has reached a critical state. Tedizolid phosphate, dalbavancin, and oritavancin have recently been approved by the U.S. Food and Drug Administration (FDA) for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and represent the next generation of oxazolidinones and lipoglycopeptides. All three agents exhibitin vitroactivity and clinical efficacy against MRSA. Tedizolid phosphate and oritavancin demonstratein vitroactivity against VRE. These new Gram-positive agents are reviewed here.

scholarly journals In Vitro and In Vivo Activities of DA-7867, a New Oxazolidinone, against Aerobic Gram-Positive Bacteria

2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Infection Models ◽  
Vancomycin Resistant

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.

scholarly journals Activities of Oxadiazole Antibacterials against Staphylococcus aureus and Other Gram-Positive Bacteria

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Sara Ceballos ◽  
Choon Kim ◽  
Derong Ding ◽  
Shahriar Mobashery ◽  
Mayland Chang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Mrsa Strains

ABSTRACT The activities of four oxadiazoles were investigated with 210 methicillin-resistant Staphylococcus aureus (MRSA) strains. MIC50 and MIC90 values of 1 to 2 and 4 μg/ml, respectively, were observed. We also evaluated the activity of oxadiazole ND-421 against other staphylococci and enterococci and in the presence of oxacillin for selected MRSA strains. The MIC for ND-421 is lowered severalfold in combination with oxacillin, as they synergize. The MIC90 of ND-421 against vancomycin-resistant enterococci is ≤1 μg/ml.

scholarly journals In VitroActivities of Tedizolid and Linezolid against Gram-Positive Cocci Associated with Acute Bacterial Skin and Skin Structure Infections and Pneumonia

2015 ◽  
Vol 59 (10) ◽  
pp. 6262-6265 ◽  
Author(s):  
Ko-Hung Chen ◽  
Yu-Tsung Huang ◽  
Chun-Hsing Liao ◽  
Wang-Hui Sheng ◽  
Po-Ren Hsueh
Keyword(s):  
Staphylococcus Aureus ◽  
Dilution Method ◽  
Agar Dilution Method ◽  
Gram Positive ◽  
Content Type ◽  
Skin Structure ◽  
Streptococcus Anginosus ◽  
Wide Range ◽  
Gram Positive Cocci

ABSTRACTTedizolid is a novel, expanded-spectrum oxazolidinone with potent activity against a wide range of Gram-positive pathogens. A total of 425 isolates of Gram-positive bacteria were obtained consecutively from patients with acute bacterial skin and skin structure infections (ABSSSIs) or pneumonia. These isolates included methicillin-susceptibleStaphylococcus aureus(MSSA) (n= 100), methicillin-resistantStaphylococcus aureus(MRSA) (n= 100),Streptococcus pyogenes(n= 50),Streptococcus agalactiae(n= 50),Streptococcus anginosusgroup (n= 75),Enterococcus faecalis(n= 50), and vancomycin-resistant enterococci (VRE) (Enterococcus faecium) (n= 50). The MICs of tedizolid and linezolid were determined by the agar dilution method. Tedizolid exhibited betterin vitroactivities than linezolid against MSSA (MIC90s, 0.5 versus 2 μg/ml), MRSA (MIC90s, 0.5 versus 2 μg/ml),S. pyogenes(MIC90s, 0.5 versus 2 μg/ml),S. agalactiae(MIC90s, 0.5 versus 2 μg/ml),Streptococcus anginosusgroup (MIC90s, 0.5 versus 2 μg/ml),E. faecalis(MIC90s, 0.5 versus 2 μg/ml), and VRE (MIC90s, 0.5 versus 2 μg/ml). The tedizolid MICs againstE. faecalis(n= 3) and VRE (n= 2) intermediate to linezolid (MICs, 4 μg/ml) were 1 μg/ml and 0.5 μg/ml, respectively. The tedizolid MIC90s against S. anginosus,S. constellatus, andS. intermediuswere 0.5, 1, and 0.5 μg/ml, respectively, and the rates of susceptibility based on the U.S. FDA MIC interpretive breakpoints to the isolates were 16%, 28%, and 72%, respectively. Tedizolid exhibited 2- to 4-fold betterin vitroactivities than linezolid against a variety of Gram-positive cocci associated with ABSSSIs and pneumonia. The lower susceptibilities of tedizolid against isolates ofS. anginosusandS. constellatusthan against those ofS. intermediusin Taiwan were noted.

scholarly journals JNJ-Q2, a New Fluoroquinolone with PotentIn VitroActivity against Staphylococcus aureus, Including Methicillin- and Fluoroquinolone-Resistant Strains

2011 ◽  
Vol 55 (7) ◽  
pp. 3631-3634 ◽  
Author(s):  
David J. Farrell ◽  
Lisa C. Liverman ◽  
Douglas J. Biedenbach ◽  
Ronald N. Jones
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
Broad Spectrum ◽  
The United States ◽  
Gram Positive ◽  
Content Type ◽  
Skin Structure ◽  
Resistant Strains

ABSTRACTJNJ-Q2 is a broad-spectrum bactericidal fluoroquinolone with potent activity against Gram-positive and -negative pathogens. In this study, thein vitroactivity of JNJ-Q2 was evaluated against 511 selectedStaphylococcus aureussamples isolated in 2008-2009 from patients with acute bacterial skin and skin structure infections in the United States by using reference methodology. JNJ-Q2 was the most potent fluoroquinolone tested overall (MIC50and MIC90, 0.12 and 0.5 μg/ml, respectively) and against methicillin- and fluoroquinolone-resistant subgroups in direct comparisons to moxifloxacin, levofloxacin, and ciprofloxacin (each being ≥16-fold less potent than JNJ-Q2).

scholarly journals Oritavancin Disrupts Membrane Integrity of Staphylococcus aureus and Vancomycin-Resistant Enterococci To Effect Rapid Bacterial Killing

2010 ◽  
Vol 54 (12) ◽  
pp. 5369-5371 ◽  
Author(s):  
Adam Belley ◽  
Geoffrey A. McKay ◽  
Francis F. Arhin ◽  
Ingrid Sarmiento ◽  
Sylvain Beaulieu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Death ◽  
Membrane Integrity ◽  
Clinical Development ◽  
Bacterial Membrane ◽  
Gram Positive ◽  
Bacterial Killing ◽  
Skin Structure ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

ABSTRACT Oritavancin is an investigational lipoglycopeptide in clinical development for the treatment of acute bacterial skin and skin structure infections. In this study, we demonstrate that oritavancin causes bacterial membrane depolarization and permeabilization leading to cell death of Gram-positive pathogens and that these effects are attributable to the 4′-chlorobiphenylmethyl group of the molecule.

scholarly journals In VivoAntibacterial Activity of MRX-I, a New Oxazolidinone

2014 ◽  
Vol 58 (4) ◽  
pp. 2418-2421 ◽  
Author(s):  
Cong-Ran Li ◽  
Qian-Qian Zhai ◽  
Xiu-Kun Wang ◽  
Xin-Xin Hu ◽  
Guo-Qing Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Local Infection ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Infection Models ◽  
Vancomycin Resistant

ABSTRACTMRX-I is a potent oxazolidinone antibiotic against Gram-positive pathogens, including methicillin-resistantStaphylococcus aureus(MRSA), penicillin-resistantStreptococcus pneumoniae(PRSP), penicillin-intermediateS. pneumoniae(PISP), and vancomycin-resistant enterococci (VRE). In this study, thein vivoefficacy of orally administered MRX-I was evaluated using linezolid as a comparator. MRX-I showed the same or better efficacy than linezolid in both systemic and local infection models against the tested strains.

scholarly journals Oritavancin Combinations with β-Lactams against Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci

2016 ◽  
Vol 60 (4) ◽  
pp. 2352-2358 ◽  
Author(s):  
Jordan R. Smith ◽  
Juwon Yim ◽  
Animesh Raut ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Single Agent ◽  
Multidrug Resistant ◽  
Content Type ◽  
Vancomycin Resistant Enterococci ◽  
Complex Models ◽  
Vancomycin Resistant ◽  
Mrsa Strains ◽  
Time Kill

ABSTRACTOritavancin possesses activity against vancomycin-resistant enterococci (VRE) and methicillin-resistantStaphylococcus aureus(MRSA).In vitrodata suggest synergy between beta-lactams (BLs) and vancomycin or daptomycin, agents similar to oritavancin. We evaluated the activities of BLs combined with oritavancin against MRSA and VRE. Oritavancin MICs were determined for 30 strains, 5 each of MRSA, daptomycin-nonsusceptible (DNS) MRSA, vancomycin-intermediate MRSA (VISA), heteroresistant VISA (hVISA), vancomycin-resistantEnterococcus faecalis, and vancomycin-resistantEnterococcus faecium. Oritavancin MICs were determined in the presence of subinhibitory concentrations of BLs. Oritavancin combined with ceftaroline, cefazolin, or nafcillin was evaluated for lethal synergy against MRSA, and oritavancin combined with ceftaroline, ampicillin, or ertapenem was evaluated for lethal synergy against VRE in 24-h time-kill assays. Oritavancin at 0.5× the MIC was combined with BLs at 0.5× the MIC or the biological free peak concentration, whichever one was lower. Synergy was defined as a ≥2-log10-CFU/ml difference between the killing achieved with the combination and that achieved with the most active single agent at 24 h. Oritavancin MICs were ≤0.125 μg/ml for all MRSA isolates except three VISA isolates with MICs of 0.25 μg/ml. Oritavancin MICs for VRE ranged from 0.03 to 0.125 μg/ml. Oritavancin in combination with ceftaroline was synergistic against all MRSA phenotypes and statistically superior to all other combinations against DNS MRSA, hVISA, and MRSA isolates (P< 0.02). Oritavancin in combination with cefazolin and oritavancin in combination with nafcillin were also synergistic against all MRSA strains. Synergy between oritavancin and all BLs was revealed against VRE strain 8019, while synergy between oritavancin and ampicillin or ertapenem but not ceftaroline was demonstrated against VRE strain R7164. The data support the potential use of oritavancin in combination with BLs, especially oritavancin in combination with ceftaroline, for the treatment of infections caused by MRSA. The data from the present study are not as strong for oritavancin in combination with BLs for VRE. Further study of both MRSA and VRE in more complex models is warranted.

scholarly journals In Vitro Activities of the Rx-01 Oxazolidinones against Hospital and Community Pathogens

2008 ◽  
Vol 52 (5) ◽  
pp. 1653-1662 ◽  
Author(s):  
Laura Lawrence ◽  
Paul Danese ◽  
Joe DeVito ◽  
Francois Franceschi ◽  
Joyce Sutcliffe
Keyword(s):  
Staphylococcus Aureus ◽  
Moraxella Catarrhalis ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Gram Negative ◽  
Vancomycin Resistant Enterococci ◽  
The Family ◽  
Vancomycin Resistant ◽  
Gram Negative Organisms

ABSTRACT Rx-01_423 and Rx-01_667 are two members of the family of oxazolidinones that were designed using a combination of computational and medicinal chemistry and conventional biological techniques. The compounds have a two- to eightfold-improved potency over linezolid against serious gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant streptococci, and vancomycin-resistant enterococci. This enhanced potency extends to the coverage of linezolid-resistant gram-positive microbes, especially multidrug-resistant enterococci and pneumococci. Compounds from this series expand the spectrum compared with linezolid to include fastidious gram-negative organisms like Haemophilus influenzae and Moraxella catarrhalis. Like linezolid, the Rx-01 compounds are bacteriostatic against MRSA and enterococci but are generally bactericidal against S. pneumoniae and H. influenzae.

scholarly journals Antimicrobial Activity of Omadacycline Tested against Clinical Bacterial Isolates from Hospitals in Mainland China, Hong Kong, and Taiwan: Results from the SENTRY Antimicrobial Surveillance Program (2013 to 2016)

2019 ◽  
Vol 63 (3) ◽  
Author(s):  
Cecilia G. Carvalhaes ◽  
Michael D. Huband ◽  
Harald H. Reinhart ◽  
Robert K. Flamm ◽  
Helio S. Sader
Keyword(s):  
Staphylococcus Aureus ◽  
Hong Kong ◽  
Klebsiella Oxytoca ◽  
Surveillance Program ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Geographic Regions

ABSTRACTOmadacycline is a derivative of minocycline and the first agent of the aminomethylcycline class. A total of 3,282 organisms (1 per patient) were consecutively collected from patients hospitalized in China (including Hong Kong) and Taiwan. Susceptibility testing was performed by broth microdilution methods in a central laboratory (JMI Laboratories). The collection included Gram-positive and Gram-negative organisms from patients with pneumonia, bloodstream, skin, community-acquired respiratory, and other infections. Omadacycline was very potent againstStaphylococcus aureus(n= 689; MIC50/90, 0.12/0.25 mg/liter), including methicillin-resistantStaphylococcus aureus(MRSA;n= 299; MIC50/90, 0.12/0.5 mg/liter), and had similar activity across geographic regions. Omadacycline was very active againstStreptococcus pneumoniae(highest MIC, 0.25 mg/liter), β-hemolytic streptococci (highest MIC, 1 mg/liter), viridans group streptococci (highest MIC, 0.25 mg/liter), andEnterococcusspp. (highest MIC, 0.5 mg/liter) from all geographic regions. Overall, 53.8% ofS. pneumoniaeisolates were penicillin resistant (penicillin MIC, ≥2 mg/liter) and 10.7% of enterococci (21.2% amongE. faeciumisolates) were vancomycin resistant. Omadacycline was active againstHaemophilus influenzae(MIC50/90, 0.5/1 mg/liter) regardless of β-lactamase production and was active againstMoraxella catarrhalis(MIC50/90, ≤0.12/0.25 mg/liter). AgainstEnterobacteriaceae, omadacycline was most active againstEscherichia coli(MIC50/90, 1/2 mg/liter),Klebsiella oxytoca(MIC50/90, 1/4 mg/liter), andEnterobacter cloacae(MIC50/90, 2/4 mg/liter). Omadacycline had potentin vitroactivity against Gram-positive and Gram-negative pathogens isolated from China and Taiwan and retained activity against problem pathogens, such as MRSA, vancomycin-resistant enterococci (VRE), penicillin-resistantS. pneumoniae(PRSPN), and extended-spectrum β-lactamase-producingE. coli. The observed MIC profile in Chinese isolates was very similar to that seen in the U.S. and European surveillance studies.

scholarly journals In Vitro Activities of LY333328 and Comparative Agents against Nosocomial Gram-Positive Pathogens Collected in a 1997 Global Surveillance Study

2000 ◽  
Vol 44 (5) ◽  
pp. 1370-1374 ◽  
Author(s):  
Michael L. Zeckel ◽  
David A. Preston ◽  
Bradley S. Allen
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Gram Positive ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant

ABSTRACT The in vitro activity of LY333328 was evaluated for 1,479 nosocomial gram-positive pathogens isolated in 12 countries during 1997. LY333328 MICs at which 90% of the isolates tested were inhibited for Enterococcus faecalis (n = 351),Enterococcus faecium (n = 100),Staphylococcus aureus (n = 593), coagulase-negative Staphylococcus species (n = 325), and Streptococcus pneumoniae(n = 110) were 1, 1, 2, 2, and 0.015 μg/ml, respectively. LY333328 demonstrated potent activity against isolates of vancomycin-resistant enterococci, oxacillin-resistant staphylococci, and penicillin-resistant pneumococci.

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