scholarly journals Repurposing of the Tamoxifen Metabolites to Treat Methicillin-Resistant Staphylococcus epidermidis and Vancomycin-Resistant Enterococcus faecalis Infections

2021 ◽  
Author(s):  
Andrea Miró-Canturri ◽  
Andrea Vila-Domínguez ◽  
Marta Caretero-Ledesma ◽  
Rafael Ayerbe-Algaba ◽  
Jerónimo Pachón ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Enterococcus Faecalis ◽  
Staphylococcus Epidermidis ◽  
Bacterial Infections ◽  
Therapeutic Strategies ◽  
Vancomycin Resistant Enterococcus ◽  
Methicillin Resistant ◽  
Content Type ◽  
Tamoxifen Metabolites ◽  
Vancomycin Resistant

The development of new antimicrobial therapeutic strategies requires immediate attention to avoid the tens of millions of deaths predicted to occur by 2050 as a result of MDR bacterial infections. In this study, we assessed the antibacterial activity of three major tamoxifen metabolites, N -desmethyltamoxifen (DTAM), 4-hydroxytamoxifen (HTAM), and endoxifen (ENDX), against methicillin-resistant Staphylococcus epidermidis (MRSE) and Enterococcus spp. ( E. faecalis and E. faecium ).

scholarly journals Ampicillin in Combination with Ceftaroline, Cefepime, or Ceftriaxone Demonstrates Equivalent Activities in a High-Inoculum Enterococcus faecalis Infection Model

2016 ◽  
Vol 60 (5) ◽  
pp. 3178-3182 ◽  
Author(s):  
Megan K. Luther ◽  
Louis B. Rice ◽  
Kerry L. LaPlante
Keyword(s):  
Combination Therapy ◽  
Enterococcus Faecalis ◽  
Pharmacodynamic Model ◽  
Infection Model ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
Time Profiles ◽  
Concentration Time ◽  
Vancomycin Resistant

ABSTRACTAmpicillin-ceftriaxone combination therapy has become a predominant treatment for seriousEnterococcus faecalisinfections, such as endocarditis. Unfortunately, ceftriaxone use is associated with future vancomycin-resistant enterococcus colonization. We evaluatedE. faecalisin anin vitropharmacodynamic model against simulated human concentration-time profiles of ampicillin plus ceftaroline, cefepime, ceftriaxone, or gentamicin. Ampicillin-cefepime and ampicillin-ceftaroline demonstrated activities similar to those of ampicillin-ceftriaxone againstE. faecalis.

scholarly journals β-Lactams Enhance Daptomycin Activity against Vancomycin-Resistant Enterococcus faecalis and Enterococcus faecium inIn VitroPharmacokinetic/Pharmacodynamic Models

2015 ◽  
Vol 59 (5) ◽  
pp. 2842-2848 ◽  
Author(s):  
Jordan R. Smith ◽  
Katie E. Barber ◽  
Animesh Raut ◽  
Michael J. Rybak
Keyword(s):  
Body Weight ◽  
Combination Therapy ◽  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Single Agent ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
Vancomycin Resistant ◽  
Combination Regimens

ABSTRACTEnterococcus faecalisandEnterococcus faeciumare frequently resistant to vancomycin and β-lactams. In enterococcal infections with reduced glycopeptide susceptibility, combination therapy is often administered. Our objective was to conduct pharmacokinetic/pharmacodynamic (PK/PD) models to evaluate β-lactam synergy with daptomycin (DAP) against resistant enterococci. OneE. faecalisstrain (R6981) and twoE. faeciumstrains (R6370 and 8019) were evaluated. DAP MICs were obtained. All strains were evaluated for response to LL37, an antimicrobial peptide, in the presence and absence of ceftaroline (CPT), ertapenem (ERT), and ampicillin (AMP). After 96 h,in vitromodels were run simulating 10 mg DAP/kg body weight/day, 600 mg CPT every 8 h (q8h), 2 g AMP q4h, and 1 g ERT q24h, both alone and in combination against all strains. DAP MICs were 2, 4, and 4 μg/ml for strains R6981, R6370, and 8019, respectively. PK/PD models demonstrated bactericidal activity with DAP-CPT, DAP-AMP, and DAP-ERT combinations against strain 8019 (P< 0.001 and log10CFU/ml reduction of >2 compared to any single agent). Against strains R6981 and R6370, the DAP-AMP combination demonstrated enhancement against R6370 but not R6981, while the combinations of DAP-CPT and DAP-ERT were bactericidal, demonstrated enhancement, and were statistically superior to all other regimens at 96 h (P< 0.001) against both strains. CPT, ERT, and AMP similarly augmented LL37 killing against strain 8019. In strains R6981 and R6370, CPT and ERT aided LL37 more than AMP (P< 0.001). Compared to DAP alone, combination regimens provide better killing and prevent resistance. Clinical research involving DAP combinations is warranted.

scholarly journals Comparison of the Clinical Characteristics and Outcomes Associated with Vancomycin-Resistant Enterococcus faecalis and Vancomycin-Resistant E. faecium Bacteremia

2012 ◽  
Vol 56 (5) ◽  
pp. 2452-2458 ◽  
Author(s):  
Kayoko Hayakawa ◽  
Dror Marchaim ◽  
Emily T. Martin ◽  
Namita Tiwari ◽  
Adnan Yousuf ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
Lower Risk ◽  
Clinical Characteristics ◽  
Medical Center ◽  
Blood Cultures ◽  
Study Cohort ◽  
Vancomycin Resistant Enterococcus ◽  
Content Type ◽  
The Mean ◽  
Vancomycin Resistant

ABSTRACTIn published studies, cohorts of patients with bacteremia due to vancomycin-resistantEnterococcus(VRE) have predominantly been infected withEnterococcus faecium. Little is known about the epidemiology and outcomes associated with bacteremia due to VREnterococcus faecalis. A retrospective study of isolates obtained from January 2008 to October 2010 was conducted at Detroit Medical Center (DMC). Unique patients with blood cultures positive for VRE were reviewed. Outcomes were analyzed using logistic regression. During the study period, 105 cases of bacteremia due to VRE. faecalisand 197 cases of bacteremia due to VRE. faeciumwere identified. The mean age in the study cohort was 61.5 ± 15 years; 162 subjects (53.6%) were male. After controlling for a propensity score, bacteremia due to VRE. faecaliswas associated with >2-fold-lower in-hospital mortality than bacteremia due to VRE. faecium. Interestingly, bacteremia due to VRE. faecaliswas associated with longer hospital stay after VRE isolation, although total length of stay was similar for groups with VRE. faecalisand VRE. faecium. Bacteremia due to VRE. faecaliswas associated with a >2-fold-lower risk for mortality than bacteremia due to VRE. faecium, possibly due to the availability of β-lactam therapeutics for treatment of VRE. faecalis.

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