Comparative activity of the new lipoglycopeptide telavancin in the presence and absence of serum against 50 glycopeptide non-susceptible staphylococci and three vancomycin-resistant Staphylococcus aureus

Leuthner, Kimberly D.; Cheung, Chrissy M.; Rybak, Michael J.

doi:10.1093/jac/dkl235

Cited by 118 publications

(90 citation statements)

References 21 publications

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“…They have been combined to generate a water-soluble intravenous preparation. Quinupristin-dalfopristin (QD) is active against MRSA and has also demonstrated in vitro activity against a range of hVISA and VISA strains (MIC 90 for hVISA and VISA of 1 g per ml) (146,177).…”

Section: Potentially Active Antimicrobials Currently Availablementioning

confidence: 99%

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

et al. 2010

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SUMMARY The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) over the past decade has provided a challenge to diagnostic microbiologists to detect these strains, clinicians treating patients with infections due to these strains, and researchers attempting to understand the resistance mechanisms. Recent data show that these strains have been detected globally and in many cases are associated with glycopeptide treatment failure; however, more rigorous clinical studies are required to clearly define the contribution of hVISA to glycopeptide treatment outcomes. It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the division septum; however, the phenotypic features of these strains can vary because the mutations leading to resistance can vary. Interestingly, changes in the staphylococcal surface and expression of agr are likely to impact host-pathogen interactions in hVISA and VISA infections. Given the subtleties of vancomycin susceptibility testing against S. aureus, it is imperative that diagnostic laboratories use well-standardized methods and have a framework for detecting reduced vancomycin susceptibility in S. aureus.

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Section: Potentially Active Antimicrobials Currently Availablementioning

confidence: 99%

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

et al. 2010

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“…For example, telavancin and daptomycin display bactericidal activity against Gram-positive organisms despite being highly protein bound, 93 and 92%, respectively (21,23,125). Various factors have been proposed to explain these observations.…”

Section: In Vitro Studiesmentioning

confidence: 99%

“…In vitro, the impact of protein binding on antimicrobial activity is often investigated through determination of the MIC, time-kill curves, and cell culture assays (13,16). Numerous in vitro studies have been published, which evaluated the impact of protein binding on antimicrobials (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28), antivirals (29,30), and antifungals (31,32) by using protein supplements and/or serum to mimic in vivo conditions. In the majority of studies, free drug concentrations are not measured directly in the experimental setting, and the extent of protein binding is accounted for by the using binding values reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

2013

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SUMMARY For the optimization of dosing regimens of anti-infective agents, it is imperative to have a good understanding of pharmacokinetics (PK) and pharmacodynamics (PD). Whenever possible, drug efficacy needs to be related to unbound concentrations at the site of action. For anti-infective drugs, the infection site is typically located outside plasma, and a drug must diffuse through capillary membranes to reach its target. Disease- and drug-related factors can contribute to differential tissue distribution. As a result, the assumption that the plasma concentration of drugs represents a suitable surrogate of tissue concentrations may lead to erroneous conclusions. Quantifying drug exposure in tissues represents an opportunity to relate the pharmacologically active concentrations to an observed pharmacodynamic parameter, such as the MIC. Selection of an appropriate specimen to sample and the advantages and limitations of the available sampling techniques require careful consideration. Ultimately, the goal will be to assess the appropriateness of a drug and dosing regimen for a specific pathogen and infection.

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“…In contrast, telavancin, an investigational lipoglycopeptide with a dual mechanism of action, is potent, with MICs of Յ1 g/ml against all MRSA phenotypes (including hVISA and VISA) with the exception of some VRSA strains (12,13,19,23). Telavancin was recently approved in the United States and Canada for treatment of complicated skin and skin structure infections due to Gram-positive pathogens (26)(27)(28), including MRSA, and is under investigation as a oncedaily treatment for hospital-acquired pneumonia caused by Gram-positive bacteria (25).…”

mentioning

confidence: 99%

Antistaphylococcal Activities of Telavancin Tested Alone and in Combination by Time-Kill Assay

Lin

Pankuch

Ednie

et al. 2010

Antimicrob Agents Chemother

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Synergy time-kill studies against 40 methicillin-resistant Staphylococcus aureus (MRSA) strains of differing resistance phenotypes were conducted. Subinhibitory concentrations of telavancin were combined with sub-MIC concentrations of other antimicrobial agents that might be used in combination with telavancin to provide Gram-negative coverage. The highest incidence of synergy was found after 24 h with gentamicin (90% of strains), followed by ceftriaxone (88%), rifampin and meropenem (each 65%), cefepime (45%), and ciprofloxacin (38%) for combinations tested at or below the intermediate breakpoint for each agent.

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Comparative activity of the new lipoglycopeptide telavancin in the presence and absence of serum against 50 glycopeptide non-susceptible staphylococci and three vancomycin-resistant Staphylococcus aureus

Cited by 118 publications

References 21 publications

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents

Antistaphylococcal Activities of Telavancin Tested Alone and in Combination by Time-Kill Assay

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