Activity of simulated serum concentrations of daptomycin versus vancomycin during the first 24h of treatment in the presence of physiological albumin concentrations against vancomycin-susceptible, -tolerant or -intermediate-resistant Staphylococcus aureus

Torrico, M.; Aguilar, Lorenzo; Sevillano, David; Giménez, María-José; Alou, Luís; González, Natalia; Cafini, Fabio; Cleeland, Roy; Prieto, J.

doi:10.1016/j.ijantimicag.2010.12.007

Cited by 5 publications

(4 citation statements)

References 35 publications

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“…Using an immunocompromised thigh infection model and a bacterial inoculum of 10 7 CFU/mL, Dandekar et al reported that a f AUC/MIC ratio of 171-442 and 38-157 were required to achieve bactericidal activity against MRSA and Enterococcus spp., respectively (Dandekar et al 2003 ). Similar values were recently reported by Torrico et al with slight variations attributed to changes in the vancomycin-susceptibility profi le (Torrico et al 2011 ). …”

Section: In Vitro and In Vivo Assessment Of Daptomycin Pd Parameterssupporting

confidence: 89%

Daptomycin: Pharmacokinetic, Pharmacodynamic, and Dose Optimization

Vidaillac

Rybak

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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Daptomycin is a parenteral cyclic lipopeptide antibiotic approved for the treatment of infections caused by Gram-positive pathogens including multidrug resistant Staphylococci and Enterococci sp. In addition to its unique mechanism of action daptomycin also displays unique pharmacological properties, with a linear pharmacokinetic profi le, a good tolerability, a rapid and concentration-dependent bactericidal effect, and a low clinical resistance rate. Daptomycin dosages up to 12 mg/kg/day and antimicrobial combinations have been recently suggested to increase and preserve the effectiveness of daptomycin from the development of resistance. This chapter aims to provide medical and scientifi c readers with main pharmacokinetic and pharmacodynamic properties of daptomycin and discuss available and potential strategies developed to optimize its clinical use.

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Section: In Vitro and In Vivo Assessment Of Daptomycin Pd Parameterssupporting

confidence: 89%

Daptomycin: Pharmacokinetic, Pharmacodynamic, and Dose Optimization

Vidaillac

Rybak

2013

Fundamentals of Antimicrobial Pharmacokinetics and Pharmacodynamics

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“…We suspect that the dismal in vivo efficacy of DAB-10 can be attributed to serum albumin binding as both DAB-6 and DAB-10 exhibited a 32-fold higher activity against Mtb in growth medium containing casitone in place of BSA (DAB-6 MIC = 0.5 μM and DAB-10 MIC = 0.06 μM). Not surprisingly, albumin binding has been shown to significantly lower the activity of cationic antimicrobial peptides. , Because albumin binding by AMPs is largely a result of physicochemical interactions, fine-tuning the sequence, length, and lipophilicity of DAB-10 might increase its serum bioavailability and consequently increase its antimycobacterial activity. Indeed, in a study of tripeptides, greater lipophilic character largely resulted in higher albumin binding .…”

Section: Resultsmentioning

confidence: 99%

“…Not surprisingly, albumin binding has been shown to significantly lower the activity of cationic antimicrobial peptides. 37,38 Because albumin binding by AMPs is largely a result of physicochemical interactions, 39 fine-tuning the sequence, length, and lipophilicity of DAB-10 might increase its serum bioavailability and consequently increase its antimycobacterial activity. Indeed, in a study of tripeptides, greater lipophilic character largely resulted in higher albumin binding.…”

Section: ■ Resultsmentioning

confidence: 99%

Phagosomal Copper-Promoted Oxidative Attack on Intracellular Mycobacterium tuberculosis

et al. 2018

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Copper (Cu) ions are critical in controlling bacterial infections, and successful pathogens like Mycobacterium tuberculosis (Mtb) possess multiple Cu resistance mechanisms. We report, as proof of concept, that a novel Cu hypersensitivity phenotype can be generated in mycobacteria, including Mtb, through a peptide, DAB-10, that is able to form reactive oxygen species (ROS) following Cu-binding. DAB-10 induces intramycobacterial oxidative stress in a Cu-dependent manner in vitro and during infection. DAB-10 penetrates murine macrophages and encounters intracellular mycobacteria. Significant intracellular Cu-dependent protection was observed when Mtb-infected macrophages were treated with DAB-10 alongside a cell-permeable Cu chelator. Treatment with the Cu chelator reversed the intramycobacterial oxidative shift induced by DAB-10. We conclude that DAB-10 utilizes the pool of phagosomal Cu ions in the host-Mtb interface to augment the mycobactericidal activity of macrophages while simultaneously exploiting the susceptibility of Mtb to ROS. DAB-10 serves as a model with which to develop next-generation, multifunctional antimicrobials.

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“…The four cartridges (for each of the two experiments) consisted of a growth control (drug free) and three vancomycin dosing arms that were designed to achieve a total AUC/MIC ratio of Ն400 over 168 h. The three vancomycin regimens simulated the steady-state human concentrations of unbound vancomycin at a percent protein binding of 45% (1,26). The mean pharmacokinetic parameters and creatinine clearance (CL CR ) values for these vancomycin regimens were derived from a vancomycin population pharmacokinetic model (6,17,18).…”

Section: Time-kill Assaymentioning

confidence: 99%

Evaluation of Once-Daily Vancomycin against Methicillin-Resistant Staphylococcus aureus in a Hollow-Fiber Infection Model

Nicasio

Bulitta

Lodise

et al. 2012

Antimicrob Agents Chemother

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For methicillin-resistant Staphylococcus aureus (MRSA) infections, data suggest that the clinical response is significantly better if the total vancomycin area under the concentration-time curve (AUC)/MIC ratio is >400. While the AUC/MIC ratio is the accepted pharmacokinetic/pharmacodynamic (PK/PD) index for vancomycin, this target has been achieved using multiple daily doses. We are unaware of a systematically designed dose fractionation study to compare the bactericidal activity of once-daily administration to that of traditional twice-daily administration. A dose fractionation study was performed with vancomycin in an in vitro hollow-fiber infection model against an MRSA USA300 strain (MIC of 0.75 g/ml) using an inoculum of ϳ10 6 CFU/ ml. The three vancomycin regimens evaluated for 168 h were 2 g every 24 h (q24h) as a 1-h infusion, 1 g q12h as a 1-h infusion, and 2 g q24h as a continuous infusion. Free steady-state concentrations (assuming 45% binding) for a total daily AUC/MIC ratio of >400 were simulated for all regimens. A validated liquid chromatography-tandem mass spectrometry method was used to determine vancomycin concentrations. Although once-daily and twice-daily dosage regimens exhibited total trough concentrations of <15 g/ml, all regimens achieved similar bactericidal activities between 24 and 168 h and suppressed the amplification of nonsusceptible subpopulations. No colonies were found on agar plates with 3؋ MIC for any of the treatment arms. Overall, the results suggest that once-daily vancomycin administration is feasible from a PK/PD perspective and merits further inquiry in the clinical arena. Given the dual threat of diminishing vancomycin efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and recent reports of rising nephrotoxicity (10, 22) (albeit potentially due to concomitant dosing increases), new vancomycin dosing strategies are urgently needed. From a pharmacodynamic viewpoint, there is an opportunity to alter standard dosage regimens of vancomycin in clinical practice to optimize outcomes and minimize toxicity. Data suggest that killing by vancomycin is concentration dependent, and a near-maximal bactericidal effect is achieved against MRSA when the ratio of the area under the total vancomycin concentration-time curve (AUC) to the MIC exceeds 400 (22). While an AUC/MIC ratio of 400 is a well-recognized pharmacokinetic/pharmacodynamic (PK/PD) target for vancomycin, this target has been determined using multiple daily doses, which has resulted in the default stance of using multiple-daily-dosing regimens in clinical practice (4,5,7,9,12,13,20,21). The possibility of once-daily administration is appealing from a PK/PD perspective, as it affords the ability to achieve more robust AUCs in a defined interval (i.e., during the first 6 to 12 h) while minimizing trough concentrations, which predicts nephrotoxicity (10). However, we are unaware of a systematically designed dose fractionation study that compared the bactericidal activity of a once-daily administration of vanc...

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Activity of simulated serum concentrations of daptomycin versus vancomycin during the first 24h of treatment in the presence of physiological albumin concentrations against vancomycin-susceptible, -tolerant or -intermediate-resistant Staphylococcus aureus

Cited by 5 publications

References 35 publications

Daptomycin: Pharmacokinetic, Pharmacodynamic, and Dose Optimization

Daptomycin: Pharmacokinetic, Pharmacodynamic, and Dose Optimization

Phagosomal Copper-Promoted Oxidative Attack on Intracellular Mycobacterium tuberculosis

Evaluation of Once-Daily Vancomycin against Methicillin-Resistant Staphylococcus aureus in a Hollow-Fiber Infection Model

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