scholarly journals High-Dose Daptomycin plus Fosfomycin Is Safe and Effective in Treating Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus Endocarditis

2012 ◽  
Vol 56 (8) ◽  
pp. 4511-4515 ◽  
Author(s):  
José M. Miró ◽  
José M. Entenza ◽  
Ana del Río ◽  
Maria Velasco ◽  
Ximena Castañeda ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
High Dose ◽  
Native Valve ◽  
Methicillin Resistant ◽  
Content Type ◽  
Native Valve Endocarditis ◽  
Prosthetic Aortic Valve ◽  
Staphylococcus Aureus Endocarditis

ABSTRACTWe describe 3 patients with left-sided staphylococcal endocarditis (1 with methicillin-susceptibleStaphylococcus aureus[MSSA] prosthetic aortic valve endocarditis and 2 with methicillin-resistantS. aureus[MRSA] native-valve endocarditis) who were successfully treated with high-dose intravenous daptomycin (10 mg/kg/day) plus fosfomycin (2 g every 6 h) for 6 weeks. This combination was testedin vitroagainst 7 MSSA, 5 MRSA, and 2 intermediately glycopeptide-resistantS. aureusisolates and proved to be synergistic against 11 (79%) strains and bactericidal against 8 (57%) strains. This combination deserves further clinical study.

scholarly journals In VitroActivities of Daptomycin-, Vancomycin-, and Teicoplanin-Loaded Polymethylmethacrylate against Methicillin-Susceptible, Methicillin-Resistant, and Vancomycin-Intermediate Strains of Staphylococcus aureus

2011 ◽  
Vol 55 (12) ◽  
pp. 5480-5484 ◽  
Author(s):  
Yuhan Chang ◽  
Wen-Chien Chen ◽  
Pang-Hsin Hsieh ◽  
Dave W. Chen ◽  
Mel S. Lee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
High Performance ◽  
Low Dose ◽  
Antibacterial Activities ◽  
High Dose ◽  
Bone Cements ◽  
Antibacterial Effects ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACTThe objective of this study was to evaluate the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with daptomycin, vancomycin, and teicoplanin against methicillin-susceptibleStaphylococcus aureus(MSSA), methicillin-resistantStaphylococcus aureus(MRSA), and vancomycin-intermediateStaphylococcus aureus(VISA) strains. Standardized cement specimens made from 40 g PMMA loaded with 1 g (low-dose), 4 g (middle-dose) or 8 g (high-dose) antibiotics were tested for elution characteristics and antibacterial activities. The patterns of release of antibiotics from the cement specimens were evaluated usingin vitrobroth elution assay with high-performance liquid chromatography. The activities of broth elution fluid against differentStaphylococcus aureusstrains (MSSA, MRSA, and VISA) were then determined. The antibacterial activities of all the tested antibiotics were maintained after being mixed with PMMA. The cements loaded with higher dosages of antibiotics showed longer elution periods. Regardless of the antibiotic loading dose, the teicoplanin-loaded cements showed better elution efficacy and provided longer inhibitory periods against MSSA, MRSA, and VISA than cements loaded with the same dose of vancomycin or daptomycin. Regarding the choice of antibiotics for cement loading in the treatment ofStaphylococcus aureusinfection, teicoplanin was superior in terms of antibacterial effects.

scholarly journals Susceptibility of Methicillin-Resistant Staphylococcus aureus to Five Quinazolinone Antibacterials

2019 ◽  
Vol 64 (1) ◽  
Author(s):  
Sara Ceballos ◽  
Choon Kim ◽  
Yuanyuan Qian ◽  
Shahriar Mobashery ◽  
Mayland Chang ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Amino Acid ◽  
Binding Proteins ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Penicillin Binding Proteins

ABSTRACT The in vitro activities of five quinazolinone antibacterials, compounds Q1 to Q5, were tested against 210 strains of methicillin-resistant Staphylococcus aureus (MRSA). The MIC50/MIC90 values (in μg/ml) were as follows: Q1, 0.5/2; Q2, 1/4; Q3, 2/4; Q4, 0.06/0.25; and Q5, 0.125/0.5. Several strains with high MIC values (from 8 to >32 μg/ml) for some of these compounds exhibited amino acid changes in the penicillin-binding proteins, which are targeted by these antibacterials.

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 Classical β-Lactamase Inhibitors Potentiate the Activity of Daptomycin against Methicillin-Resistant Staphylococcus aureus and Colistin against Acinetobacter baumannii

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
George Sakoulas ◽  
Warren Rose ◽  
Andrew Berti ◽  
Joshua Olson ◽  
Jason Munguia ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Acinetobacter Baumannii ◽  
Murine Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Peptide Antibiotic ◽  
Peptide Antibiotics ◽  
Methicillin Resistant ◽  
Content Type ◽  
Host Defense Peptide

ABSTRACT We asked whether beta-lactamase inhibitors (BLIs) increased the activity of daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA), the peptide antibiotic colistin (COL) against the emerging Gram-negative nosocomial pathogen Acinetobacter baumannii, and the human host defense peptide cathelicidin LL37 against either pathogen. DAP and LL37 kill curves were performed with or without BLIs against MRSA, vancomycin-intermediate S. aureus (VISA), and heterogeneous VISA (hVISA). COL and LL37 kill curves were performed against A. baumannii. Boron-dipyrromethene (BODIPY)-labeled DAP binding to MRSA grown with the BLI tazobactam (TAZ) was assessed microscopically. The combination of COL plus TAZ was studied in a murine model of A. baumannii pneumonia. TAZ alone lacked in vitro activity against MRSA or A. baumannii. The addition of TAZ to DAP resulted in a 2- to 5-log10 reduction in recoverable MRSA CFU at 24 h compared to the recoverable CFU with DAP alone. TAZ plus COL showed synergy by kill curves for 4 of 5 strains of A. baumannii tested. Growth with 20 mg/liter TAZ resulted in 2- to 2.5-fold increases in the intensity of BODIPY-DAP binding to MRSA and hVISA strains. TAZ significantly increased the killing of MRSA and A. baumannii by LL37 in vitro. TAZ increased the activity of COL in a murine model of A. baumannii pneumonia. Classical BLIs demonstrate synergy with peptide antibiotics. Since BLIs have scant antimicrobial activity on their own and are thus not expected to increase selective pressure toward antibiotic resistance, their use in combination with peptide antibiotics warrants further study.

scholarly journals Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

1996 ◽  
Vol 40 (5) ◽  
pp. 1219-1224 ◽  
Author(s):  
B Fantin ◽  
J Pierre ◽  
N Castéla-Papin ◽  
L Saint-Julien ◽  
H Drugeon ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Body Weight ◽  
Synergistic Effect ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Limiting Factor ◽  
High Dose ◽  
Methicillin Resistant

The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations. The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h). This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03). In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01). We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S. aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S. aureus.

scholarly journals Evaluation of Ceftaroline, Vancomycin, Daptomycin, or Ceftaroline plus Daptomycin against Daptomycin-Nonsusceptible Methicillin-Resistant Staphylococcus aureus in anIn VitroPharmacokinetic/Pharmacodynamic Model of Simulated Endocardial Vegetations

2014 ◽  
Vol 58 (6) ◽  
pp. 3177-3181 ◽  
Author(s):  
Brian J. Werth ◽  
Katie E. Barber ◽  
Cortney E. Ireland ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Bactericidal Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Active Agent ◽  
Minimum Concentration ◽  
Ceftaroline Fosamil ◽  
Methicillin Resistant ◽  
Content Type ◽  
Sustained Activity

ABSTRACTInfective endocarditis (IE) caused by methicillin-resistantStaphylococcus aureus(MRSA) with reduced susceptibility to vancomycin and daptomycin has few adequate therapeutic options. Ceftaroline (CPT) is bactericidal against daptomycin (DAP)-nonsusceptible (DNS) and vancomycin-intermediate MRSA, but supporting data are limited for IE. This study evaluated the activities of ceftaroline, vancomycin, daptomycin, and the combination of ceftaroline plus daptomycin against DNS MRSA in a pharmacokinetic/pharmacodynamic (PK/PD) model of simulated endocardial vegetations (SEVs). Simulations of ceftaroline-fosamil (600 mg) every 8 h (q8h) (maximum concentration of drug in serum [Cmax], 21.3 mg/liter; half-life [t1/2], 2.66 h), daptomycin (10 mg/kg of body weight/day) (Cmax, 129.7 mg/liter;t1/2, 8 h), vancomycin (1 g) q8h (minimum concentration of drug in serum [Cmin], 20 mg/liter;t1/2, 5 h), and ceftaroline plus daptomycin were evaluated against 3 clinical DNS, vancomycin-intermediate MRSA in a two-compartment,in vitro, PK/PD SEV model over 96 h with a starting inoculum of ∼8 log10CFU/g. Bactericidal activity was defined as a ≥3-log10CFU/g reduction from the starting inoculum. Therapeutic enhancement of combinations was defined as ≥2-log10CFU/g reduction over the most active agent alone. MIC values for daptomycin, vancomycin, and ceftaroline were 4 mg/liter, 4 to 8 mg/liter, and 0.5 to 1 mg/liter, respectively, for all strains. At simulated exposures, vancomycin was bacteriostatic, but daptomycin and ceftaroline were bactericidal. By 96 h, ceftaroline monotherapy offered significantly improved killing compared to other agents against one strain. The combination of DAP plus CPT demonstrated therapeutic enhancement, resulting in significantly improved killing versus either agent alone against 2/3 (67%) strains. CPT demonstrated bactericidal activity against DNS, vancomycin-intermediate MRSA at high bacterial densities. Ceftaroline plus daptomycin may offer more rapid and sustained activity against some MRSA in the setting of high-inoculum infections like IE and should also be considered.

scholarly journals Rapid Detection of Methicillin-Resistant Staphylococcus aureus and Methicillin-Susceptible S. aureus Directly from Positive Blood Cultures by Use of the BD Max StaphSR Assay

2015 ◽  
Vol 53 (12) ◽  
pp. 3900-3904 ◽  
Author(s):  
Justin A. Ellem ◽  
Tom Olma ◽  
Matthew V. N. O'Sullivan
Keyword(s):  
Staphylococcus Aureus ◽  
Predictive Value ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Direct Detection ◽  
Blood Cultures ◽  
Coagulase Negative Staphylococcus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Standard Culture

The BD Max StaphSR assay is an automated qualitativein vitrodiagnostic test for the direct detection and differentiation of methicillin-susceptibleStaphylococcus aureus(MSSA) and methicillin-resistantS. aureus(MRSA). A total of 460 specimens were tested, and the results were compared with standard culture-based identification. MRSA was detected in 48 samples (sensitivity of 100%; positive predictive value [PPV] of 100%). MSSA was detected in 112 samples (sensitivity of 99.1%; PPV of 100%), and 299 samples containing coagulase-negative staphylococcus and nonstaphylococcal species were negative by the BD Max StaphSR assay (specificity of 100%; negative predictive value [NPV] of 99.7 to 100%).

scholarly journals Impact of Dose De-Escalation and Escalation on Daptomycin's Pharmacodynamics against Clinical Methicillin-Resistant Staphylococcus aureus Isolates in anIn VitroModel

2011 ◽  
Vol 55 (5) ◽  
pp. 2160-2165 ◽  
Author(s):  
Celine Vidaillac ◽  
Molly E. Steed ◽  
Michael J. Rybak
Keyword(s):  
Staphylococcus Aureus ◽  
Dose Escalation ◽  
High Dose ◽  
Standard Regimen ◽  
Patient Response ◽  
Killing Effect ◽  
Methicillin Resistant ◽  
Content Type

ABSTRACTDe-escalation and escalation therapeutic strategies are commonly employed by clinicians on the basis of susceptibility results and patient response. Since noin vitroorin vivodata are currently available to support one strategy over the other for daptomycin, we attempted to evaluate the effects of dose escalation and de-escalation on daptomycin activity against methicillin-resistantStaphylococcus aureus(MRSA) isolates using anin vitropharmacokinetic/pharmacodynamic (PK/PD) model with simulated endocardial vegetations. Three clinical MRSA isolates, including one heterogeneous vancomycin-intermediateS. aureus(hVISA) isolate and one vancomycin-intermediateS. aureus(VISA) isolate, were exposed to daptomycin at 10 or 6 mg/kg of body weight/day for 8 days using a starting inoculum of ∼109CFU/g of vegetations, with dose escalation and de-escalation initiated on the fourth day. Daptomycin MIC values ranged from 0.5 to 1 μg/ml. In the PK/PD model, high-dose daptomycin (10 mg/kg/day) and de-escalation simulation (10 to 6 mg/kg/day) appeared to be the most efficient regimens against the three tested isolates, exhibiting the fastest bactericidal activity (4 to 8 h) compared to that of the standard regimen of 6 mg/kg/day and the escalation therapy of 6 to 10 mg/kg/day. The differences in the numbers of CFU/g observed between dose escalation and de-escalation were significant for the hVISA strain, with the de-escalation simulation exhibiting a better killing effect than the escalation simulation (P< 0.024). Although our results need to be carefully considered, the use of high-dose daptomycin up front demonstrated the most efficient activity against the tested isolates. Different therapeutic scenarios including isolates with higher MICs and prolonged drug exposures are warranted to better understand the outcomes of escalation and de-escalation strategies.

scholarly journals Antibacterial Properties of MagnesiumIn Vitroand in anIn VivoModel of Implant-Associated Methicillin-Resistant Staphylococcus aureus Infection

2014 ◽  
Vol 58 (12) ◽  
pp. 7586-7591 ◽  
Author(s):  
Yang Li ◽  
Guangwang Liu ◽  
Zanjing Zhai ◽  
Lina Liu ◽  
Haowei Li ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Formation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Periprosthetic Infection ◽  
Antibacterial Properties ◽  
Methicillin Resistant ◽  
Content Type ◽  
Aureus Infection

ABSTRACTPeriprosthetic infection remains a challenging clinical complication. We investigated the antibacterial properties of pure (99.9%) magnesium (Mg)in vitroand in anin vivorat model of implant-related infection. Mg was highly effective against methicillin-resistantStaphylococcus aureus-induced osteomyelitis and improved new peri-implant bone formation. BacterialicaAandagrRNAIII transcription levels were also assessed to characterize the mechanism underlying the antibacterial properties of the Mg implant.

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