In vitroActivity of Linezolid and Eperezolid, Two Novel Oxazolidinone Antimicrobial Agents, Against Anaerobic Bacteria

Yagi, Betty H.; Zurenko, Gary E.

doi:10.1006/anae.1997.0115

Cited by 15 publications

(7 citation statements)

References 8 publications

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“…Linezolid also appeared to have modest in vitro activity against the medically significant anaerobes Bacteroides fragilis, Clostridium spp., and Peptostreptococcus spp., which is consistent with the spectrum of activity of other antibiotics active against Gram-positive bacteria, for example, clindamycin ( Table 2). [39] A very interesting conundrum arose during early SAR work on the oxazolidinones. We were quite aware that the spectrum of oxazolidinone activity did not include the Gramnegative bacilli and yet some of the biologists on the team were measuring oxazolidinone inhibition of bacterial protein synthesis in a cell-free system.…”

Section: Methodsmentioning

confidence: 99%

Oxazolidinone Structure–Activity Relationships Leading to Linezolid

Barbachyn¹,

Ford²

2003

Angew Chem Int Ed

485

219

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The development of bacterial resistance to currently available antibacterial agents is a growing global health problem. Of particular concern are infections caused by multidrug-resistant Gram-positive pathogens which are responsible for significant morbidity and mortality in both the hospital and community settings. A number of solutions to the problem of bacterial resistance are possible. The most common approach is to continue modifying existing classes of antibacterial agents to provide new analogues with improved attributes. Other successful strategies are to combine existing antibacterial agents with other drugs as well as the development of improved diagnostic procedures that may lead to rapid identification of the causative pathogen and permit the use of antibacterial agents with a narrow spectrum of activity. Finally, and most importantly, the discovery of novel classes of antibacterial agents employing new mechanisms of action has considerable promise. Such agents would exhibit a lack of cross-resistance with existing antimicrobial drugs. This review describes the work leading to the discovery of linezolid, the first clinically useful oxazolidinone antibacterial agent.

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Section: Methodsmentioning

confidence: 99%

Oxazolidinone Structure–Activity Relationships Leading to Linezolid

Barbachyn¹,

Ford²

2003

Angew Chem Int Ed

485

219

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“…[30] 3. Biologische Evaluierung von Linezolid [39] In der frühen Phase des Oxazolidinon-SAR-Programms tauchte ein zunächst unerklärlicher Befund auf: Wir wussten, dass das Aktivitätsspektrum der Oxazolidinone Gram-negative Erreger nicht umfasst, dennoch konnten Biologen [40] Die fehlende Aktivität der Oxazolidinone gegen Gram-negative Bakterien beruht demzufolge auf der Wirkung der zellulären Transmembranpumpen, die das Oxazolidinon -zusammen mit anderen Molekülen -relativ schnell aus dem Zellinneren herauspumpen und so dessen Anreicherung verhindern.…”

Section: Synthese Von Linezolid Im Verfahrensmaßstabunclassified

Struktur‐Wirkungs‐Beziehungen von Oxazolidinonen: Grundlage der Entwicklung von Linezolid

Barbachyn¹,

Ford²

2003

Angewandte Chemie

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Die zunehmende Resistenz von Bakterien gegen Antibiotika ist gegenwärtig eines der drängendsten Probleme in der Medizin. In dieser Hinsicht besonders bedenklich sind durch mehrfachresistente Gram‐positive Pathogene verursachte Infektionen, die signifikante Krankheits‐ und Sterblichkeitsziffern verursachen. Eine Reihe von Lösungsansätzen wurde zur Bekämpfung der Bakterienresistenz eingeführt. Der am häufigsten angewendete Ansatz beruht auf der Modifizierung existierender Klassen von Antibiotika zur Herstellung neuer Analoga mit verbesserten Eigenschaften. Weitere Strategien sind die Kombination von antibakteriellen mit anderen Wirkstoffen und die Anwendung von Zusatztherapeutika wie Immunmodulatoren. Die größte Bedeutung hat aber zweifellos die Entwicklung neuer Klassen antibakterieller Wirkstoffe mit neuartigen Wirkmechanismen, die sich durch das Fehlen von Kreuzresistenzen mit existierenden antimikrobiellen Wirkstoffen auszeichnen. Dieser Aufsatz schildert die Arbeiten, die zur Entwicklung von Linezolid führten, dem ersten klinisch nutzbaren Oxazolidinon‐Antibiotikum.

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“…It has potent activity against many gram-positive organisms, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci (5,9,26), and several anaerobic species (24). Linezolid is usually bacteriostatic against staphylococci and enterococci (11,12).…”

mentioning

confidence: 99%

Accuracy of Six Antimicrobial Susceptibility Methods for Testing Linezolid against Staphylococci and Enterococci

et al. 2007

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A challenge panel of enterococci (n ‫؍‬ 50) and staphylococci (n ‫؍‬ 50), including 17 and 15 isolates that were nonsusceptible to linezolid, respectively, were tested with the Clinical and Laboratory Standards Institute broth microdilution and disk diffusion reference methods. In addition, all 100 isolates were tested in parallel by Etest (AB Biodisk, Solna, Sweden), MicroScan WalkAway (Dade, West Sacramento, CA), BD Phoenix (BD Diagnostic Systems, Sparks, MD), VITEK (bioMérieux, Durham, NC), and VITEK 2 (bioMérieux) by using the manufacturers' protocols. Compared to the results of the broth microdilution method for detecting linezolidnonsusceptible staphylococci and enterococci, MicroScan results showed the highest category agreement (96.0%). The overall categorical agreement levels for VITEK 2, Etest, Phoenix, disk diffusion, and VITEK were 93.0%, 90.0%, 89.6%, 88.0%, and 85.9%, respectively. The essential agreement levels (results within ؎1 doubling dilution of the MIC determined by the reference method) for MicroScan, Phoenix, VITEK 2, Etest, and VITEK were 99.0%, 95.8%, 92.0%, 92.0%, and 85.9%, respectively. The very major error rates for staphylococci were the highest for VITEK (35.7%), Etest (40.0%), and disk diffusion (53.3%), although the total number of resistant isolates tested was small. The very major error rate for enterococci with VITEK was 20.0%. Three systems (MicroScan, VITEK, and VITEK 2) provided no interpretations of nonsusceptible results for staphylococci. These data, from a challenge panel of isolates, illustrate that the recent emergence of linezolidnonsusceptible staphylococci and enterococci is providing a challenge for many susceptibility testing systems.

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In vitroActivity of Linezolid and Eperezolid, Two Novel Oxazolidinone Antimicrobial Agents, Against Anaerobic Bacteria

Cited by 15 publications

References 8 publications

Oxazolidinone Structure–Activity Relationships Leading to Linezolid

Oxazolidinone Structure–Activity Relationships Leading to Linezolid

Struktur‐Wirkungs‐Beziehungen von Oxazolidinonen: Grundlage der Entwicklung von Linezolid

Accuracy of Six Antimicrobial Susceptibility Methods for Testing Linezolid against Staphylococci and Enterococci

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