scholarly journals In Vitro Synergism of Penicillin and Ceftriaxone against Enterococcus faecalis

2021 ◽  
Vol 9 (10) ◽  
pp. 2150
Author(s):  
Lara Thieme ◽  
Simon Briggs ◽  
Eamon Duffy ◽  
Oliwia Makarewicz ◽  
Mathias W. Pletz
Keyword(s):  
Infective Endocarditis ◽  
Combination Therapy ◽  
Enterococcus Faecalis ◽  
Synergistic Effects ◽  
Case Series ◽  
Standard Strain ◽  
Parenteral Antibiotic ◽  
Trough Concentrations ◽  
The Relationship

Enterococcus faecalis infective endocarditis is commonly treated with intravenous ampicillin/ceftriaxone combination therapy. Ampicillin, however, is unsuitable for outpatient parenteral antibiotic therapy (OPAT) regimens due to its instability in 24 h continuous infusors, and has been successfully replaced by benzylpenicillin used together with ceftriaxone in a few small case series. Since in vitro synergy data of penicillin/ceftriaxone against E. faecalis are still lacking, checkerboard assays were performed for 28 clinical E. faecalis isolates and one laboratory standard strain. Synergistic effects (both lowest and median FICI) were observed for penicillin/ceftriaxone in 15/29 isolates, while ampicillin/ceftriaxone exhibited synergism in 22/29 isolates. For isolates with ceftriaxone MICs ≤ 256 mg/L, the addition of free ceftriaxone trough concentrations to penicillin or ampicillin resulted in comparable synergistic effects for both combinations. In contrast, for isolates with ceftriaxone MICs ≥ 512 mg/L free ceftriaxone trough concentrations were only sufficient to exhibit synergistic effects in combination with ampicillin, but not penicillin. This study suggests that benzylpenicillin/ceftriaxone would be expected to be suitable for the OPAT treatment of enterococcal endocarditis for E. faecalis isolates with ceftriaxone MICs ≤ 256 mg/L. However, combination therapy would be expected to provide no advantage over benzylpenicillin monotherapy for isolates with ceftriaxone MICs ≥ 512 mg/L. Further investigation is required to analyse the relationship between ceftriaxone susceptibility and penicillin/ceftriaxone synergy, especially for isolates with ceftriaxone MICs of 64 to 512 mg/L.

scholarly journals Rifampin Combination Therapy for Nonmycobacterial Infections

2010 ◽  
Vol 23 (1) ◽  
pp. 14-34 ◽  
Author(s):  
Graeme N. Forrest ◽  
Kimberly Tamura
Keyword(s):  
Combination Therapy ◽  
Prosthetic Heart Valve ◽  
Case Series ◽  
Source Control ◽  
Retrospective Case ◽  
Coagulase Negative Staphylococci ◽  
Joint Infections ◽  
Prosthetic Joint Infections

SUMMARY The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.

scholarly journals Anti-Ace monoclonal antibody reduces Enterococcus faecalis aortic valve infection in a rat infective endocarditis model

2018 ◽  
Vol 76 (8) ◽  
Author(s):  
Kavindra V Singh ◽  
Kenneth L Pinkston ◽  
Peng Gao ◽  
Barrett R Harvey ◽  
Barbara E Murray
Keyword(s):  
Monoclonal Antibody ◽  
Infective Endocarditis ◽  
Enterococcus Faecalis ◽  
Collagen Iv ◽  
Aortic Valves ◽  
Collagen Binding ◽  
Passive Protection ◽  
A Cell ◽  
Pre Treatment

AbstractAce (Adhesin to collagen from Enterococcus faecalis) is a cell-wall anchored protein that is expressed conditionally and is important for virulence in a rat infective endocarditis (IE) model. Previously, we showed that rats immunized with the collagen binding domain of Ace (domain A), or administered anti-Ace domain A polyclonal antibody, were less susceptible to E. faecalis endocarditis than sham-immunized controls. In this work, we demonstrated that a sub nanomolar monoclonal antibody (mAb), anti-Ace mAb70, significantly diminished E. faecalis binding to ECM collagen IV in in vitro adherence assays and that, in the endocarditis model, anti-Ace mAb70 pre-treatment significantly reduced E. faecalis infection of aortic valves. The effectiveness of anti-Ace mAb against IE in the rat model suggests it might serve as a beneficial agent for passive protection against E. faecalis infections.

scholarly journals Is Once-Daily High-Dose Ceftriaxone plus Ampicillin an Alternative for Enterococcus faecalis Infective Endocarditis in Outpatient Parenteral Antibiotic Therapy Programs?

2020 ◽  
Vol 65 (1) ◽  
pp. e02099-20
Author(s):  
Laura Herrera-Hidalgo ◽  
Arístides de Alarcón ◽  
Luis Eduardo López-Cortes ◽  
Rafael Luque-Márquez ◽  
Luis Fernando López-Cortes ◽  
...  
Keyword(s):  
Single Dose ◽  
Infective Endocarditis ◽  
Antibiotic Therapy ◽  
Enterococcus Faecalis ◽  
High Dose ◽  
Synergistic Activity ◽  
Parenteral Antibiotic ◽  
Once Daily ◽  
Content Type ◽  
Outpatient Parenteral Antibiotic Therapy

ABSTRACTCeftriaxone administered as once-daily high-dose short infusion combined with ampicillin has been proposed for the treatment of Enterococcus faecalis infective endocarditis in outpatient parenteral antibiotic therapy programs (OPAT). This combination requires synergistic activity, but the attainment of ceftriaxone synergic concentration (Cs) with the regimen proposed for OPAT has not been studied. This phase II pharmacokinetic study enrolled healthy adult volunteers who underwent two sequential treatment phases. During phase A, volunteers received 2 g of ceftriaxone each 12 h during 24 h followed by a 7-day wash-out. Then the participants received phase B, which consisted of a single dose of 4 g of ceftriaxone. Throughout both phases, each volunteer underwent intensive pharmacokinetic (PK) sampling over 24 h. Ceftriaxone total and unbound concentrations were measured. Twelve participants were enrolled and completed both phases. Mean ceftriaxone total and free concentrations 24 h after the administration of 2 g each 12 h were 86.44 ± 25.90 mg/liter and 3.59 ± 1.35 mg/liter, respectively, and after the 4-g single dose were 34.60 ± 11.16 mg/liter and 1.40 ± 0.62 mg/liter, respectively. Only 3 (25%) patients in phase A maintained unbound plasma concentrations superior to the suggested Cs = 5 mg/liter during 24 h, and none (0%) in phase B. No grade 3 to 4 adverse events or laboratory abnormalities were observed. Ceftriaxone optimal exposure combined with ampicillin to achieve maximal synergistic activity against E. faecalis required for the treatment of infective endocarditis remains unknown. However, the administration of a single daily dose of 4 g of ceftriaxone implies a reduction in the time of exposure to the proposed Cs. (This study has been registered in the European Union Drug Regulating Authorities Clinical Trials [EudraCT] database under identifier 2017-003127-29.)

scholarly journals Antibodies to a Surface-Exposed, N-terminal Domain of Aggregation Substance Are Not Protective in the Rabbit Model of Enterococcus faecalis Infective Endocarditis

2001 ◽  
Vol 69 (5) ◽  
pp. 3305-3314 ◽  
Author(s):  
John K. McCormick ◽  
Helmut Hirt ◽  
Christopher M. Waters ◽  
Timothy J. Tripp ◽  
Gary M. Dunny ◽  
...  
Keyword(s):  
Infective Endocarditis ◽  
Enterococcus Faecalis ◽  
Rabbit Model ◽  
Surface Protein ◽  
Conjugative Plasmid ◽  
Aggregation Substance ◽  
Exposed Region ◽  
Correct Sequence

ABSTRACT The aggregation substance (AS) surface protein fromEnterococcus faecalis has been implicated as an important virulence factor for the development of infective endocarditis. To evaluate the role of antibodies specific for Asc10 (the AS protein from the conjugative plasmid pCF10) in protective immunity to infective endocarditis, an N-terminal region of Asc10 lacking the signal peptide and predicted to be surface exposed (amino acids 44 to 331; AS44–331) was cloned with a C-terminal histidine tag translational fusion and expressed fromEscherichia coli. N-terminal amino acid sequencing of the purified protein revealed the correct sequence, and rabbit polyclonal antisera raised against AS44–331 reacted specifically to Asc10 expressed from E. faecalis OG1SSp, but not to other proteins as judged by Western blot analysis. Using these antisera, flow cytometry analysis demonstrated that antibodies to AS44–331 bound to a surface-exposed region of Asc10. Furthermore, antibodies specific for AS44–331were opsonic for E. faecalis expressing Asc10 in vitro but not for cells that did not express Asc10. New Zealand White rabbits immunized with AS44–331 were challenged intravenously withE. faecalis cells constitutively expressing Asc10 in the rabbit model of experimental endocarditis. Highly immune animals did not show significant differences in clearance of organisms from the blood or spleen or in formation of vegetations on the aortic valve, in comparison with nonimmune animals. Although in vivo expression of Asc10 was demonstrated by immunohistochemistry, these experiments provide evidence that immunity to Asc10 does not play a role in protection from experimental infective endocarditis due toE. faecalis and may have important implications for the development of immunological approaches to combat enterococcal endocarditis.

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 In VitroPharmacodynamics of Vancomycin and Cefazolin Alone and in Combination against Methicillin-Resistant Staphylococcus aureus

2011 ◽  
Vol 56 (1) ◽  
pp. 202-207 ◽  
Author(s):  
Mao Hagihara ◽  
Dora E. Wiskirchen ◽  
Joseph L. Kuti ◽  
David P. Nicolau
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Synergistic Effects ◽  
Bacterial Density ◽  
Bacterial Killing ◽  
Methicillin Resistant ◽  
Content Type ◽  
Vancomycin Mics ◽  
Time Kill

ABSTRACTPrevious studies employing time-kill methods have observed synergistic effects against methicillin-resistantStaphylococcus aureus(MRSA) when a β-lactam is combined with vancomycin. However, these time-kill studies have neglected the importance of human-simulated exposures. We evaluated the effect of human simulated exposures of vancomycin at 1 g every 8 h (q8h) in combination with cefazolin at 1 g q8h against various MRSA isolates. Four clinical isolates (two MRSA isolates [vancomycin MICs, 0.5 and 2.0 μg/ml], a heterogeneous vancomycin-intermediateS. aureus[hVISA] isolate [MIC, 2.0 μg/ml], and a vancomycin-intermediateS. aureus[VISA] isolate [MIC, 8.0 μg/ml]) were evaluated in anin vitropharmacodynamic model with a starting inoculum of 106or 108CFU/ml. Bacterial density was measured over 48 to 72 h. Time-kill curves were constructed, and the area under the bacterial killing and regrowth curve (AUBC) was calculated. During 106CFU/ml studies, combination therapy achieved greater log10CFU/ml changes than vancomycin alone at 12 h (−4.31 ± 0.58 versus −2.80 ± 0.59,P< 0.001), but not at 48 h. Combination therapy significantly reduced the AUBC from 0 to 48 h (122 ± 14) compared with vancomycin alone (148 ± 22,P= 0.017). Similar results were observed during 108CFU/ml studies, where combination therapy achieved greater log10CFU/ml changes at 12 h than vancomycin alone (−4.00 ± 0.20 versus −1.10 ± 0.04,P< 0.001) and significantly reduced the AUBC (275 ± 30 versus 429 ± 37,P< 0.001) after 72 h of incubation. In this study, the combination of vancomycin and cefazolin at human-simulated exposures improved the rate of kill against these MRSA isolates and resulted in greater overall antibacterial effect, but no differences in bacterial density were observed by the end of the experiments.

scholarly journals In vitro bactericidal activity of amoxicillin combined with different cephalosporins against endocarditis-associated Enterococcus faecalis clinical isolates

2019 ◽  
Vol 74 (12) ◽  
pp. 3511-3514 ◽  
Author(s):  
Nathan Peiffer-Smadja ◽  
Elena Guillotel ◽  
David Luque-Paz ◽  
Naouale Maataoui ◽  
F -Xavier Lescure ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Infective Endocarditis ◽  
Enterococcus Faecalis ◽  
Bactericidal Activity ◽  
Empirical Therapy ◽  
The Mean ◽  
Time Kill ◽  
Reference Strains ◽  
Free Plasma

Abstract Background The combination of amoxicillin with cefazolin could be an interesting regimen for the empirical therapy of severe infective endocarditis, but its activity against enterococci is unknown. Objectives To evaluate in vitro the bactericidal activity of the combination of amoxicillin with different cephalosporins including cefazolin. Methods Combinations of amoxicillin (at MIC×¼) with cefazolin, cefotaxime, ceftriaxone, cefepime, ceftaroline or ceftobiprole (at the mean free plasma concentration) were studied using time–kill experiments for 10 endocarditis-associated Enterococcus faecalis strains and 2 reference strains. Results The combinations amoxicillin/cefazolin, amoxicillin/cefotaxime, amoxicillin/ceftriaxone and amoxicillin/cefepime were synergistic at 12 and 24 h against 12/12 strains and amoxicillin/ceftobiprole and amoxicillin/ceftaroline against 10/12 strains. The combination amoxicillin/cefepime was bactericidal at 24 h against 9/12 strains, the combination amoxicillin/cefazolin against 8/12 strains, the combinations amoxicillin/ceftaroline, amoxicillin/cefotaxime and amoxicillin/ceftobiprole against 7/12 strains and the combination amoxicillin/ceftriaxone against 6/12 strains. Conclusions The combination amoxicillin/cefazolin is as synergistic and bactericidal in vitro as amoxicillin/cefotaxime or amoxicillin/ceftriaxone against E. faecalis.

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