Efficacy of Linezolid in Treatment of Experimental Endocarditis Caused by Methicillin-Resistant
            <i>Staphylococcus aureus</i>

Dailey, Charlene F; Dileto-Fang, Christine L.; Buchanan, Lewis V.; Oramas-Shirey, M. P.; Batts, Donald H.; Ford, Charles W.; Gibson, John K.

doi:10.1128/aac.45.8.2304-2308.2001

Cited by 81 publications

(53 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In several animal infection models, a T >MIC >40% significantly M a n u s c r i p t enhanced bacterial killing of pneumococci, and AUC/MIC ratios of 48-147 were necessary for a bacteriostatic effect [38,38,40]. Linezolid serum levels with T >MIC >50% for pathogens with MICs of 2-4 mg/L can be obtained in healthy volunteers by administration of 600 mg every 12 h [41].…”

Section: Linezolidmentioning

confidence: 99%

Pharmacokinetic/pharmacodynamic (PK/PD) considerations in the management of Gram-positive bacteraemia

Scaglione

2010

International Journal of Antimicrobial Agents

View full text Add to dashboard Cite

Section: Linezolidmentioning

confidence: 99%

Pharmacokinetic/pharmacodynamic (PK/PD) considerations in the management of Gram-positive bacteraemia

Scaglione

2010

International Journal of Antimicrobial Agents

View full text Add to dashboard Cite

“…A few cephalosporins have been identified, of which a handful has now advanced into clinical trials for MRSA treatment (6 -8). Also, the clinical urgency has been met in the past few years by the introduction of Synercid (a combination of quinupristin and dalfopristin) (9), daptomycin (10), and linezolid (an oxazolidinone) (11) for treatment of MRSA. However, resistance to all of these agents exists, and the recent emergence of variants of MRSA resistant to linezolid (12) and glycopeptide antibiotics (13)(14)(15)(16) has created a situation in which certain strains of S. aureus are either treatable only with a single class of antibiotics or are simply not treatable, which is a disconcerting situation clinically.…”

mentioning

confidence: 99%

The Basis for Resistance to β-Lactam Antibiotics by Penicillin-binding Protein 2a of Methicillin-resistant Staphylococcus aureus

Fuda

Suvorov

Vakulenko

et al. 2004

Journal of Biological Chemistry

223

200

View full text Add to dashboard Cite

Penicillin-binding protein 2a (PBP2a) of Staphylococcus aureus is refractory to inhibition by available ␤-lactam antibiotics, resulting in resistance to these antibiotics. The strains of S. aureus that have acquired the mecA gene for PBP2a are designated as methicillin-resistant S. aureus (MRSA). The mecA gene was cloned and expressed in Escherichia coli, and PBP2a was purified to homogeneity. The kinetic parameters for interactions of several ␤-lactam antibiotics (penicillins, cephalosporins, and a carbapenem) and PBP2a were evaluated. The enzyme manifests resistance to covalent modification by ␤-lactam antibiotics at the active site serine residue in two ways. First, the microscopic rate constant for acylation (k 2 ) is attenuated by 3 to 4 orders of magnitude over the corresponding determinations for penicillinsensitive penicillin-binding proteins. Second, the enzyme shows elevated dissociation constants (K d ) for the non-covalent pre-acylation complexes with the antibiotics, the formation of which ultimately would lead to enzyme acylation. The two factors working in concert effectively prevent enzyme acylation by the antibiotics in vivo, giving rise to drug resistance. Given the opportunity to form the acyl enzyme species in in vitro experiments, circular dichroism measurements revealed that the enzyme undergoes substantial conformational changes in the course of the process that would lead to enzyme acylation. The observed conformational changes are likely to be a hallmark for how this enzyme carries out its catalytic function in cross-linking the bacterial cell wall.

show abstract

“…Although indifference is often observed for linezolid combinations against S. aureus (including methicillin-resistant strains), some cases of antagonism and synergism were reported and studied in vivo using the experimental model of endocarditis. (Dailey et al, 2001). After 5 days of treatment, linezolid displayed a stepwise decrease in the mean bacterial counts from the valve vegetation with a significant decrease for both 50 and 75 mg/kg.…”

Section: In Vitro Antibacterial Activity Of Linezolid Alone and In Comentioning

confidence: 99%

“…After 5 days of treatment, linezolid displayed a stepwise decrease in the mean bacterial counts from the valve vegetation with a significant decrease for both 50 and 75 mg/kg. Showing a 4-to 5-log reduction in valvular bacterial counts, linezolid acted as a bactericidal drug in this study (Dailey et al, 2001). …”

Section: In Vitro Antibacterial Activity Of Linezolid Alone and In Comentioning

confidence: 99%

Antibiotics Against Endocarditis – Past, Present and Future (Experimental Data)

Jacqueline¹,

Amador²,

Batard³

et al. 2012

Endocarditis

View full text Add to dashboard Cite

Efficacy of Linezolid in Treatment of Experimental Endocarditis Caused by Methicillin-Resistant Staphylococcus aureus

Cited by 81 publications

References 18 publications

Pharmacokinetic/pharmacodynamic (PK/PD) considerations in the management of Gram-positive bacteraemia

Pharmacokinetic/pharmacodynamic (PK/PD) considerations in the management of Gram-positive bacteraemia

The Basis for Resistance to β-Lactam Antibiotics by Penicillin-binding Protein 2a of Methicillin-resistant Staphylococcus aureus

Antibiotics Against Endocarditis – Past, Present and Future (Experimental Data)

Contact Info

Product

Resources

About