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 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 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 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 Comparative Genomics of Vancomycin-Resistant Staphylococcus aureus Strains and Their Positions within the Clade Most Commonly Associated with Methicillin-Resistant S. aureus Hospital-Acquired Infection in the United States

mBio ◽  
2012 ◽  
Vol 3 (3) ◽  
Author(s):  
Veronica N. Kos ◽  
Christopher A. Desjardins ◽  
Allison Griggs ◽  
Gustavo Cerqueira ◽  
Andries Van Tonder ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Infection ◽  
Vancomycin Resistant ◽  
Foreign Dna ◽  
Mrsa Strains ◽  
Hospital Acquired

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) strains are leading causes of hospital-acquired infections in the United States, and clonal cluster 5 (CC5) is the predominant lineage responsible for these infections. Since 2002, there have been 12 cases of vancomycin-resistantS. aureus(VRSA) infection in the United States—all CC5 strains. To understand this genetic background and what distinguishes it from other lineages, we generated and analyzed high-quality draft genome sequences for all available VRSA strains. Sequence comparisons show unambiguously that each strain independently acquired Tn1546and that all VRSA strains last shared a common ancestor over 50 years ago, well before the occurrence of vancomycin resistance in this species. In contrast to existing hypotheses on what predisposes this lineage to acquire Tn1546, the barrier posed by restriction systems appears to be intact in most VRSA strains. However, VRSA (and other CC5) strains were found to possess a constellation of traits that appears to be optimized for proliferation in precisely the types of polymicrobic infection where transfer could occur. They lack a bacteriocin operon that would be predicted to limit the occurrence of non-CC5 strains in mixed infection and harbor a cluster of unique superantigens and lipoproteins to confound host immunity. A frameshift indprA, which in other microbes influences uptake of foreign DNA, may also make this lineage conducive to foreign DNA acquisition.IMPORTANCEInvasive methicillin-resistantStaphylococcus aureus(MRSA) infection now ranks among the leading causes of death in the United States. Vancomycin is a key last-line bactericidal drug for treating these infections. However, since 2002, vancomycin resistance has entered this species. Of the now 12 cases of vancomycin-resistantS. aureus(VRSA), each was believed to represent a new acquisition of the vancomycin-resistant transposon Tn1546from enterococcal donors. All acquisitions of Tn1546so far have occurred in MRSA strains of the clonal cluster 5 genetic background, the most common hospital lineage causing hospital-acquired MRSA infection. To understand the nature of these strains, we determined and examined the nucleotide sequences of the genomes of all available VRSA. Genome comparison identified candidate features that position strains of this lineage well for acquiring resistance to antibiotics in mixed infection.

scholarly journals Daptomycin versus Vancomycin in a Methicillin-Resistant Staphylococcus aureus Endophthalmitis Rabbit Model: Bactericidal Effect, Safety, and Ocular Pharmacokinetics

2012 ◽  
Vol 56 (5) ◽  
pp. 2485-2492 ◽  
Author(s):  
Sophie Lefèvre ◽  
Maher Saleh ◽  
Luc Marcellin ◽  
Audrey Subilia ◽  
Tristan Bourcier ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Rabbit Model ◽  
Bacterial Count ◽  
Ocular Inflammation ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Content Type ◽  
Gram Positive Bacteria ◽  
Bactericidal Efficacy ◽  
The Mean

ABSTRACTStaphylococcus aureusis a frequent cause of acute endophthalmitis, and infection with this virulent bacterium is often associated with a poor visual outcome. In this study, we investigated the bactericidal efficacy and the safety of intravitreal daptomycin (DAP), a lipopeptide antibiotic with broad-spectrum activity against Gram-positive bacteria, compared with those of intravitreal vancomycin (VAN) in a methicillin-resistantS. aureusendophthalmitis rabbit model. The pharmacokinetics and pharmacodynamics of daptomycin in the infected eyes were also studied. Rabbits were randomly divided into three treatment groups (n= 8) and one untreated group (n= 4), to compare the effect of single intravitreal injections of 0.2 mg and 1 mg of daptomycin (DAP 0.2 and DAP 1 groups, respectively) with that of 1 mg of intravitreal vancomycin (VAN 1 group). Vitreal aspirates were regularly collected and grading of ocular inflammation was regularly performed until euthanasia on day 7. In the DAP 0.2 group, 62.5% of the eyes were sterilized and the mean bacterial count presented a reduction of 1 log unit. In the DAP 1 and VAN 1 groups, the infection was eradicated (100% and 87.5% of eyes sterilized, respectively), with a 4-log-unit reduction of the mean bacterial count. The bactericidal efficacy in the DAP 1 group was not inferior to that in the VAN 1 group and was superior to that of the other regimens in limiting the ocular inflammation and preserving the architecture of the ocular structures (P< 0.05). The elimination half-life (t1/2β) of daptomycin was independent of the administered dose (38.8 ± 16.5 h and 40.9 ± 6.7 h, respectively, for the DAP 0.2 and DAP 1 groups) and was significantly longer than thet1/2βof vancomycin (20.5 ± 2.0 h for the VAN 1 group) (P< 0.05). This antibiotic could therefore be considered for the treatment of intraocular infections caused by Gram-positive bacteria.

scholarly journals Use of Pristinamycin for Infections by Gram-Positive Bacteria: Clinical Experience at an Australian Hospital

2010 ◽  
Vol 54 (9) ◽  
pp. 3949-3952 ◽  
Author(s):  
A. B. Reid ◽  
J. R. Daffy ◽  
P. Stanley ◽  
K. L. Buising
Keyword(s):  
Staphylococcus Aureus ◽  
Side Effects ◽  
Epidural Abscess ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Prosthetic Joints ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
Australian Hospital

ABSTRACT Thirty-six patients were treated with pristinamycin for 46 different microbiological isolates between April 2007 and July 2009. Pathogens included 9 methicillin-resistant Staphylococcus aureus isolates, 13 methicillin-resistant coagulase negative staphylococci, and 9 vancomycin-resistant enterococci. Sites of infections included 12 osteomyelitis cases, 10 prosthetic joints, 4 other prostheses, and 1 epidural abscess. Five patients ceased treatment due to side effects. Ten patients were cured of their infections, and 21 patients had infections successfully suppressed.

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 Survival of Enterococci and Staphylococci on Hospital Fabrics and Plastic

2000 ◽  
Vol 38 (2) ◽  
pp. 724-726 ◽  
Author(s):  
Alice N. Neely ◽  
Matthew P. Maley
Keyword(s):  
Staphylococcus Aureus ◽  
Antibiotic Sensitivity ◽  
Critical Aspect ◽  
Gram Positive ◽  
Consistent Effect ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Control Procedures ◽  
Contact Control ◽  
Vancomycin Resistant

The transfer of gram-positive bacteria, particularly multiresistantStaphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), among patients is a growing concern. One critical aspect of bacterial transfer is the ability of the microorganism to survive on various common hospital surfaces. The purpose of this study was to determine the survival of 22 gram-positive bacteria (vancomycin-sensitive and -resistant enterococci and methicillin-sensitive and -resistant staphylococci) on five common hospital materials: smooth 100% cotton (clothing), 100% cotton terry (towels), 60% cotton–40% polyester blend (scrub suits and lab coats), 100% polyester (privacy drapes), and 100% polypropylene plastic (splash aprons). Swatches were inoculated with 104to 105 CFU of a microorganism, assayed daily by placing the swatches in nutritive media, and examining for growth after 48 h. All isolates survived for at least 1 day, and some survived for more than 90 days on the various materials. Smaller inocula (102) survived for shorter times but still generally for days. Antibiotic sensitivity had no consistent effect on survival. The long survival of these bacteria, including MRSA and VRE, on commonly used hospital fabrics, such as scrub suits, lab coats, and hospital privacy drapes, underscores the need for meticulous contact control procedures and careful disinfection to limit the spread of these bacteria.

scholarly journals Mode of Action of Van-M-02, a Novel Glycopeptide Inhibitor of Peptidoglycan Synthesis, in Vancomycin-Resistant Bacteria

2009 ◽  
Vol 54 (2) ◽  
pp. 960-962 ◽  
Author(s):  
Kenji Miura ◽  
Hidenori Yamashiro ◽  
Kouichi Uotani ◽  
Satoshi Kojima ◽  
Takashi Yutsudo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Inhibitory Activity ◽  
Mode Of Action ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Peptidoglycan Synthesis ◽  
Vancomycin Resistant Enterococci ◽  
Resistant Strains ◽  
Vancomycin Resistant

ABSTRACT Van-M-02, a novel glycopeptide, was revealed to exert potent activities against Gram-positive bacteria, including vancomycin-resistant enterococci (VRE) and vancomycin-resistant Staphylococcus aureus (VRSA). A crude assay system was then used to study the mode of action of Van-M-02 as a peptidoglycan synthesis model of both vancomycin-susceptible and -resistant strains. The results suggested that Van-M-02 inhibits the synthesis of lipid intermediates irrespective of their termini. This inhibitory activity may contribute to the anti-VRE and anti-VRSA activities observed.

scholarly journals In Vitro Activities of a New Ketolide, ABT-773, against Multidrug-Resistant Gram-Positive Cocci

2001 ◽  
Vol 45 (12) ◽  
pp. 3640-3643 ◽  
Author(s):  
Kavindra V. Singh ◽  
Kumthorn Malathum ◽  
Barbara E. Murray
Keyword(s):  
Staphylococcus Aureus ◽  
Enterococcus Faecium ◽  
Multidrug Resistant ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant ◽  
Almost All ◽  
Gram Positive Cocci

ABSTRACT The in vitro activities of ABT-773 were evaluated against 324 strains of gram-positive bacteria, including multidrug-resistantStaphylococcus spp. and Enterococcus spp. ABT-773 had lower MIC ranges, MICs at which 50% of isolates are inhibited (MIC50s), and MIC90s than erythromycin or clindamycin for almost all isolates tested. The MICs of ABT-773 were also lower than those of quinupristin-dalfopristin (Q-D) for methicillin-susceptible Staphylococcus aureus,Rhodococcus spp., and Streptococcus spp., while the MICs of Q-D were lower than those of ABT-773 for methicillin-resistant S. aureus and Enterococcus faecium, including vancomycin-resistant isolates.

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