scholarly journals In VitroActivities of LTX-109, a Synthetic Antimicrobial Peptide, against Methicillin-Resistant, Vancomycin-Intermediate, Vancomycin-Resistant, Daptomycin-Nonsusceptible, and Linezolid-Nonsusceptible Staphylococcus aureus

2012 ◽  
Vol 56 (8) ◽  
pp. 4478-4482 ◽  
Author(s):  
Louis D. Saravolatz ◽  
Joan Pawlak ◽  
Leonard Johnson ◽  
Hector Bonilla ◽  
Louis D. Saravolatz ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Peptide ◽  
Bactericidal Activity ◽  
Antimicrobial Agents ◽  
Methicillin Resistant ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Time Kill ◽  
Dose Dependent

ABSTRACTLTX-109 and eight other antimicrobial agents were evaluated against 155 methicillin-resistantStaphylococcus aureus(MRSA) isolates, including strains resistant to vancomycin and strains with decreased susceptibility to daptomycin and linezolid, by microdilution tests to determine MICs. Time-kill assays were performed against representative MRSA, vancomycin-intermediateS. aureus(VISA), and vancomycin-resistantS. aureus(VRSA) isolates. LTX-109 demonstrated a MIC range of 2 to 4 μg/ml and dose-dependent rapid bactericidal activity againstS. aureus. This activity was not influenced by resistance to other antistaphylococcal agents.

scholarly journals In VitroActivity of Retapamulin against Staphylococcus aureus Resistant to Various Antimicrobial Agents

2013 ◽  
Vol 57 (9) ◽  
pp. 4547-4550 ◽  
Author(s):  
Louis D. Saravolatz ◽  
Joan Pawlak ◽  
Stephanie N. Saravolatz ◽  
Leonard B. Johnson
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Agents ◽  
Good Activity ◽  
Methicillin Resistant ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Time Kill

ABSTRACTRetapamulin and six other antimicrobial agents were evaluated against 155 methicillin-resistantStaphylococcus aureus(MRSA) isolates, including strains resistant to vancomycin, linezolid, daptomycin, and mupirocin by microdilution tests. Time-kill assays were performed against representative MRSA, vancomycin-intermediateS. aureus(VISA), and vancomycin-resistantS. aureus(VRSA) isolates. Retapamulin and mupirocin demonstrated MIC90s of 0.12 μg/ml and 8 μg/ml, respectively, with resistance seen in 2.6% and 10% of isolates, respectively. Retapamulin maintained good activity against 94% (15/16) of mupirocin-resistant isolates.

scholarly journals Antistaphylococcal Activity of Oritavancin and Its Synergistic Effect in Combination with Other Antimicrobial Agents

2014 ◽  
Vol 58 (10) ◽  
pp. 6251-6254 ◽  
Author(s):  
Gengrong Lin ◽  
Glenn Pankuch ◽  
Peter C. Appelbaum ◽  
Klaudia Kosowska-Shick
Keyword(s):  
Staphylococcus Aureus ◽  
Synergistic Effect ◽  
Antimicrobial Agents ◽  
Methicillin Resistant ◽  
Content Type ◽  
Antistaphylococcal Activity ◽  
Vancomycin Resistant ◽  
Time Kill

ABSTRACTOritavancin exhibitedin vitroactivity against 169 strains of vancomycin-susceptible, methicillin-resistantStaphylococcus aureus(MRSA) with MICs ranging from 0.03 to 1 μg/ml and against vancomycin-intermediate MRSA (VISA;n= 29), heterogeneous vancomycin-intermediate MRSA (hVISA;n= 5), and vancomycin-resistant MRSA (n= 5) strains, with MICs ranging from 0.12 to 4 μg/ml. For 10 MRSA isolates comprising 5 VISA and 5 hVISA strains, synergy between oritavancin and gentamicin, linezolid, or rifampin was observed against most of the strains tested using a time-kill method.

scholarly journals ComparativeIn VitroActivities of Oritavancin, Dalbavancin, and Vancomycin against Methicillin-Resistant Staphylococcus aureus Isolates in a Nondividing State

2016 ◽  
Vol 60 (7) ◽  
pp. 4342-4345 ◽  
Author(s):  
Adam Belley ◽  
David Lalonde Seguin ◽  
Francis Arhin ◽  
Greg Moeck
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Antibacterial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Skin Structure ◽  
Persistent Infections ◽  
Time Kill

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-resistantStaphylococcus aureus(MRSA) isolates that are maintained in a nondividing statein vitro, whereas dalbavancin and the glycopeptide vancomycin do not.

scholarly journals The Combination of Daptomycin and Fosfomycin Has Synergistic, Potent, and Rapid Bactericidal Activity against Methicillin-ResistantStaphylococcus aureusin a Rabbit Model of Experimental Endocarditis

2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Cristina García-de-la-Mària ◽  
Oriol Gasch ◽  
Javier García-Gonzalez ◽  
Dolors Soy ◽  
Evelyn Shaw ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Combined Therapy ◽  
Rabbit Model ◽  
Bactericidal Effect ◽  
Methicillin Resistant ◽  
Content Type ◽  
Mrsa Strains ◽  
Time Kill

ABSTRACTWe investigated whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistantStaphylococcus aureus(MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to performin vitrotime-kill studies using standard (106) and high (108) inocula. Combined therapy was compared to daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied, and the equivalents of cloxacillin at 2 g/4 h, fosfomycin at 2 g/6 h, and daptomycin at 6 to 10 mg/kg/day were administered intravenously. A combination of daptomycin and either fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 μg/ml) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/day in terms of both the proportion of sterile vegetations (100% versus 72%,P= 0.046) and the decrease in the density of bacteria within the vegetations (P= 0.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/day (100% versus 93%,P= 1.00) and had activity similar to that of daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/day (100% versus 88%,P= 0.48). Daptomycin nonsusceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.

scholarly journals Novel Combinations of Vancomycin plus Ceftaroline or Oxacillin against Methicillin-Resistant Vancomycin-Intermediate Staphylococcus aureus (VISA) and Heterogeneous VISA

2013 ◽  
Vol 57 (5) ◽  
pp. 2376-2379 ◽  
Author(s):  
B. J. Werth ◽  
C. Vidaillac ◽  
K. P. Murray ◽  
K. L. Newton ◽  
G. Sakoulas ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Wall ◽  
Inverse Correlation ◽  
Fluorescent Dye ◽  
Beta Lactam ◽  
Significant Inverse Correlation ◽  
Methicillin Resistant ◽  
Content Type ◽  
Time Kill ◽  
Wall Interactions

ABSTRACTWe demonstrated a significant inverse correlation between vancomycin and beta-lactam susceptibilities in vancomycin-intermediateStaphylococcus aureus(VISA) and heterogeneous VISA (hVISA) isolates. Using time-kill assays, vancomycin plus oxacillin or ceftaroline was synergistic against 3 of 5 VISA and 1 of 5 hVISA isolates or 5 of 5 VISA and 4 of 5 hVISA isolates, respectively. Beta-lactam exposure reduced overall vancomycin-Bodipy (dipyrrometheneboron difluoride [4,4-difluoro-4-bora-3a,4a-diaza-s-indacene] fluorescent dye) binding but may have improved vancomycin-cell wall interactions to improve vancomycin activity. Further research is warranted to elucidate the mechanism behind vancomycin and beta-lactam synergy.

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 Novel Antibiotic Combinations of Diverse Subclasses for Effective Suppression of Extensively Drug-Resistant Methicillin-Resistant Staphylococcus aureus (MRSA)

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Shumyila Nasir ◽  
Muhammad Sufyan Vohra ◽  
Danish Gul ◽  
Umm E Swaiba ◽  
Maira Aleem ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Clavulanic Acid ◽  
Antimicrobial Agents ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Methicillin Resistant ◽  
Development Of Resistance ◽  
Amoxicillin Clavulanic Acid ◽  
Combination Antibiotics ◽  
Time Kill

The emergence of multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), the chief etiological agent for a range of refractory infections, has rendered all β-lactams ineffective against it. The treatment process is further complicated with the development of resistance to glycopeptides, primary antibiotics for treatment of MRSA. Antibiotic combination therapy with existing antimicrobial agents may provide an immediate treatment option. Minimum inhibitory concentrations (MICs) of 18 different commercially available antibiotics were determined along with their 90 possible pairwise combinations and 64 triple combinations to filter out 5 best combinations. Time-Kill kinetics of these combinations were then analyzed to find collateral bactericidal combinations which were then tested on other randomly selected MRSA isolates. Among the top 5 combinations including levofloxacin-ceftazidime; amoxicillin/clavulanic acid-tobramycin; amoxicillin/clavulanic acid-cephradine; amoxicillin/clavulanic acid-ofloxacin; and piperacillin/tazobactam-tobramycin, three combinations were found to be collaterally effective. Levofloxacin-ceftazidime acted synergistically in 80% of the tested clinical MRSA isolates. First-line β-lactams of lower generations can be used effectively against MRSA infection when used in combination. Antibiotics other than glycopeptides may still work in combination.

scholarly journals β-Lactamase Inhibitors Enhance the Synergy between β-Lactam Antibiotics and Daptomycin against Methicillin-Resistant Staphylococcus aureus

2016 ◽  
Vol 61 (1) ◽  
Author(s):  
Karl Evans R. Henson ◽  
Juwon Yim ◽  
Jordan R. Smith ◽  
George Sakoulas ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Synergistic Effect ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Time Kill ◽  
Lactamase Inhibitor

ABSTRACT The evidence for using combination therapy for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections is growing. In this study, we investigated the synergistic effect of daptomycin (DAP) combined with piperacillin-tazobactam and ampicillin-sulbactam against MRSA in time-kill experiments. Six of eight strains demonstrated synergy between DAP and the β-lactam–β-lactamase inhibitor (BLI) combination. In 5/8 strains, the synergy occurred only in the presence of the BLI, highlighting a role for BLIs in peptide–β-lactam synergy.

scholarly journals In vitro activities of oxazolidinone compounds U100592 and U100766 against Staphylococcus aureus and Staphylococcus epidermidis.

1996 ◽  
Vol 40 (3) ◽  
pp. 799-801 ◽  
Author(s):  
G W Kaatz ◽  
S M Seo
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Inhibitory Activity ◽  
Antimicrobial Agents ◽  
Methicillin Resistant ◽  
Clinical Strains ◽  
Time Kill

The new oxazolidinone antimicrobial agents U100592 and U100766 demonstrated good in vitro inhibitory activity against clinical strains of Staphylococcus aureus and Staphylococcus epidermidis regardless of methicillin susceptibility. Both agents appeared bacteriostatic by time-kill analysis. Stable resistance to low multiples of the MIC of either drug could be produced only in methicillin-resistant S. aureus.

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