Vancomycin-Resistant
            <i>Enterococcus faecalis</i>
            Endocarditis: Linezolid Failure and Strain Characterization of Virulence Factors

Tsigrelis, Constantine; Singh, Kavindra V.; Coutinho, Thais; Murray, Barbara E.; Baddour, Larry M.

doi:10.1128/jcm.02188-06

Cited by 45 publications

(27 citation statements)

References 37 publications

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“…206 On the basis of these susceptibility data, a fluoroquinolone (ciprofloxacin, levofloxacin, or moxifloxacin) may be considered as an alternative agent in patients unable to tolerate ceftriaxone (or other third-or fourth-generation cephalosporins) therapy. There are only a few case reports of HACEK IE treated with a fluoroquinolone, however.…”

Section: Hacek Microorganismsmentioning

confidence: 99%

“…However, linezolid treatment failures of E faecium IE also were reported. 206 The advantages of linezolid therapy include high bioavailability of the oral formulation, approval for pediatric patients, and a lack of many therapeutic alternatives. The disadvantages are toxicity (mild to severe neutropenia and thrombocytopenia that is reversible); peripheral and optic neuritis, which is more often seen with longer durations of therapy and may not be reversible; multidrug interactions, especially serotonin uptake inhibitors; and emergence of resistance during treatment.…”

Section: Linezolidmentioning

confidence: 99%

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Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications

Baddour¹,

Wilson²,

Bayer³

et al. 2015

Circulation

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2,467

1,421

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Background— Infective endocarditis is a potentially lethal disease that has undergone major changes in both host and pathogen. The epidemiology of infective endocarditis has become more complex with today’s myriad healthcare-associated factors that predispose to infection. Moreover, changes in pathogen prevalence, in particular a more common staphylococcal origin, have affected outcomes, which have not improved despite medical and surgical advances. Methods and Results— This statement updates the 2005 iteration, both of which were developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It includes an evidence-based system for diagnostic and treatment recommendations used by the American College of Cardiology and the American Heart Association for treatment recommendations. Conclusions— Infective endocarditis is a complex disease, and patients with this disease generally require management by a team of physicians and allied health providers with a variety of areas of expertise. The recommendations provided in this document are intended to assist in the management of this uncommon but potentially deadly infection. The clinical variability and complexity in infective endocarditis, however, dictate that these recommendations be used to support and not supplant decisions in individual patient management.

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Section: Hacek Microorganismsmentioning

confidence: 99%

Section: Linezolidmentioning

confidence: 99%

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications

Baddour¹,

Wilson²,

Bayer³

et al. 2015

Circulation

Self Cite

2,467

1,421

View full text Add to dashboard Cite

show abstract

“…Moreover, we determined high-resolution crystal structures of the best inhibitors in complex with cholix toxin to reveal important criteria for inhibitor binding and mechanism of action. These results provide new insight into development of antivirulence compounds for treating many bacterial diseases.Bacteria use virulence factors as tools to facilitate disease in plants, animals, and humans (14,26,30,34); one strategy to combat infection is to inhibit these factors by small-molecule therapy, thereby helping to neutralize the offending microbe (5,6,12,19,22). It is now generally appreciated that an antivirulence approach is a powerful alternative strategy for antibacterial treatment and vaccine development (27) and that it may require multiple tactics to resolve the current drug resistance dilemma (6,8).…”

mentioning

confidence: 99%

Newly Discovered and Characterized Antivirulence Compounds Inhibit Bacterial Mono-ADP-Ribosyltransferase Toxins

Turgeon

Jørgensen

Visschedyk

et al. 2011

Antimicrob Agents Chemother

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The mono-ADP-ribosyltransferase toxins are bacterial virulence factors that contribute to many disease states in plants, animals, and humans. These toxins function as enzymes that target various host proteins and covalently attach an ADP-ribose moiety that alters target protein function. We tested compounds from a virtual screen of commercially available compounds combined with a directed poly(ADP-ribose) polymerase (PARP) inhibitor library and found several compounds that bind tightly and inhibit toxins from Pseudomonas aeruginosa and Vibrio cholerae. The most efficacious compounds completely protected human lung epithelial cells against the cytotoxicity of these bacterial virulence factors. Moreover, we determined high-resolution crystal structures of the best inhibitors in complex with cholix toxin to reveal important criteria for inhibitor binding and mechanism of action. These results provide new insight into development of antivirulence compounds for treating many bacterial diseases.Bacteria use virulence factors as tools to facilitate disease in plants, animals, and humans (14,26,30,34); one strategy to combat infection is to inhibit these factors by small-molecule therapy, thereby helping to neutralize the offending microbe (5,6,12,19,22). It is now generally appreciated that an antivirulence approach is a powerful alternative strategy for antibacterial treatment and vaccine development (27) and that it may require multiple tactics to resolve the current drug resistance dilemma (6,8). Antivirulence compounds offer significant advantages over conventional antibiotics since these inhibitors are directed toward specific mechanisms (targets) in the offending pathogen that promote infection rather than against an essential metabolic factor (12). Neutralizing the cytotoxic properties of virulence factors from microorganisms without threatening their survival offers reduced selection pressure, making the induction of drug resistance mutations less likely (6). Additionally, virulence-specific therapeutics avoid the undesirable effects on the host microbiota that are associated with current antibiotics.The mono-ADP-ribosyltransferase (mART) family is a group of toxic bacterial enzymes, some of which possess a long history against human civilization. The best-characterized and wellknown members of this lethal family are cholera toxin (CT) from Vibrio cholerae, diphtheria toxin (DT) produced by Corynebacterium diphtheriae, pertussis toxin (PT) from Bordella pertussis, heat-labile enterotoxin from Escherichia coli, C3-like exoenzyme produced by Clostridium botulinum and Clostridium limosum, and exotoxin A (ExoA) from Pseudomonas aeruginosa. These enzymes act on NAD ϩ and facilitate the scission of the glycosidic bond (C-N) between nicotinamide and its conjugated ribose followed by the transfer of the ADPribose group to a nucleophilic residue on a target macromolecule (35). This family can be divided into the CT and DT groups. The CT group consists of an ExoS-like subgroup (enzymatic A domain alone or paired with ano...

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“…However, linezolid showed excellent activity in vitro against E. faecalis and for this high diffusion in tissue it could be used in IE therapy, even if its activity is bacteriostatic. Berdal and Eskesen [30] and Tsigrelis et al [31] have reported failures in the treatment of enterococcal endocarditis with this drug.…”

Section: Discussionmentioning

confidence: 99%

In vitro Activity Effects of Twelve Antibiotics Alone and in Association against Twenty-Seven <i>Enterococcus faecalis</i> Strains Isolated from Italian Patients with Infective Endocarditis: High in vitro Synergistic Effect of the Association Ceftriaxone-Fosfomycin

et al. 2011

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Background: In 2004–2008, the epidemiological and clinical Infective Endocarditis Study Group (SEI) evaluated 852 cases of infective endocarditis. Staphylococcus aureus was the main involved pathogen (24.5%) and Enterococcus faecalis etiology was described in 11% of the cases. The aim of this study was to evaluate the in vitro activity of 12 antibiotics alone and in association against 27 strains of E. faecalis isolated from blood cultures of patients with infective endocarditis. Results: The results showed high in vitro activity of tigecycline, daptomycin and linezolid. A high synergistic effect was obtained with the association ceftriaxone-fosfomycin [fractional inhibitory concentration (FIC)₅₀ = 0.34, FIC₉₀ = 0.78]. Furthermore, ceftriaxone plus ampicillin presented additive results (FIC₅₀ = 0.66, FIC₉₀ = 1.00), and ceftriaxone plus fosfomycin and ceftriaxone plus ampicillin were significantly more active in vitro than each drug alone. The efficacy of ceftriaxone plus fosfomycin was confirmed by the association testing using the broth dilution technique. Conclusion: Fosfomycin seems particularly significant and its association with ceftriaxone could be considered as a useful therapeutic option in medical treatment of E. faecalis infective endocarditis.

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Vancomycin-Resistant Enterococcus faecalis Endocarditis: Linezolid Failure and Strain Characterization of Virulence Factors

Cited by 45 publications

References 37 publications

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications

Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications

Newly Discovered and Characterized Antivirulence Compounds Inhibit Bacterial Mono-ADP-Ribosyltransferase Toxins

In vitro Activity Effects of Twelve Antibiotics Alone and in Association against Twenty-Seven <i>Enterococcus faecalis</i> Strains Isolated from Italian Patients with Infective Endocarditis: High in vitro Synergistic Effect of the Association Ceftriaxone-Fosfomycin

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