Linezolid tissue penetration and serum activity against strains of methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility in diabetic patients with foot infections

Stein, Gary E.; Schooley, Sharon; Peloquin, Charles A.; Missavage, Anne E.; Havlichek, Daniel H.

doi:10.1093/jac/dkm271

Cited by 62 publications

(45 citation statements)

References 25 publications

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“…infused over 1 h in a study by Stein et al (27). The mean value for C max in the current study (11.99 Ϯ 3.67 g/ml) was comparable to that of the previous study (14.7 Ϯ 6.1 g/ml).…”

Section: Discussionsupporting

confidence: 85%

“…One study conducted with 6 patients undergoing lower limb amputation found a mean linezolid concentration in infected soft tissue samples collected at the time of amputation that was 51% of the corresponding concentration in serum (27). A second study, conducted with 15 patients with diabetic wound infections, found a mean linezolid concentration in infected wound tissue samples that was 102% of that in plasma at 3 h (15).…”

mentioning

confidence: 99%

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Determination of Tissue Penetration and Pharmacokinetics of Linezolid in Patients with Diabetic Foot Infections Using In Vivo Microdialysis

Wiskirchen

Shepard

Kuti

et al. 2011

Antimicrob Agents Chemother

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Staphylococcus aureus and other Gram-positive organisms, including methicillin-resistant S. aureus, continue to be the predominant pathogens associated with diabetic foot infections. Consequently, linezolid is often used to treat these infections. The purpose of the current study was to describe the pharmacokinetic profile and determine the level of penetration of linezolid into healthy thigh tissue and infected wound tissue of the same extremity in 9 diabetic patients with chronic lower limb infections by use of in vivo microdialysis. Hourly plasma and dialysate samples were obtained over a 12-h dosing interval following 3 to 4 doses of linezolid (600 mg intravenously every 12 h). Plasma protein binding was also assessed at 1, 6, and 12 h postdose. The means ؎ standard deviations (SD) for the maximum concentration in serum (C max ), the volume of distribution at terminal phase (V z ), and the half-life (t 1/2 ) for linezolid in plasma were 11.99 ؎ 3.67 g/ml,

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“…infused over 1 h in a study by Stein et al (27). The mean value for C max in the current study (11.99 Ϯ 3.67 g/ml) was comparable to that of the previous study (14.7 Ϯ 6.1 g/ml).…”

Section: Discussionsupporting

confidence: 85%

mentioning

confidence: 99%

Determination of Tissue Penetration and Pharmacokinetics of Linezolid in Patients with Diabetic Foot Infections Using In Vivo Microdialysis

Wiskirchen

Shepard

Kuti

et al. 2011

Antimicrob Agents Chemother

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“…However, interindividual variations in linezolid pharmacokinetics have been observed (47,48). C max data obtained with 200 and 800 mg matched human data fluctuation well, but the AUC 0-24 values were lower, essentially due to different modes of calculation (13).…”

Section: Vol 54 2010 Linezolid Against Hypermutator Cocci In a Pk-pmentioning

confidence: 77%

“…Moreover, the volume of distribution at steady state in healthy adults is 0.5 to 0.6 liters/kg of body weight, which approximates that of body water (30), and linezolid concentrations in interstitial fluid are very close to those of plasma (20). Thus, therapeutic failures could be explained by achieving inefficient concentrations at the infection site at the usual doses due to interindividual variability of drug pharmacokinetics (13,35,48). This might be particularly critical for strains, called mutators, that exhibit unusually high spontaneous mutation rates (53) due to altered systems of correction and prevention of errors during DNA replication (11).…”

mentioning

confidence: 99%

Activity of Linezolid in anIn VitroPharmacokinetic-Pharmacodynamic Model Using Different Dosages andStaphylococcus aureusandEnterococcus faecalisStrains with and without a Hypermutator Phenotype

Arpin

Nso

et al. 2010

Antimicrob Agents Chemother

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-, 600-, or 800-mg dose for 48 h was simulated against four strains (MIC, 2 g/ml): Staphylococcus aureus RN4220 and its mutator derivative MutS2, Enterococcus faecalis ATCC 29212, and a mutator clinical strain of E. faecalis, Ef1497. The peak concentrations (4.38 to 4.79, 13.4 to 14.6, and 19.2 to 19.5 g/ml) and half-lives at ␤-phase (5.01 to 6.72 h) fit human plasma linezolid pharmacokinetics. Due to its bacteriostatic property, the cumulative percentages of the dosing interval during which the drug concentration exceeded the MIC (T > MIC), 66.6 and 69.1% of the dosing interval, were not significant, except for Ef1497, with an 800-mg dose and a T > MIC of 80.9%. At the standard 600-mg dosage, resistant mutants (2-to 8-fold MIC increases) were selected only with Ef1497. A lower, 200-mg dosage did not select resistant mutants of E. faecalis ATCC 29212, but a higher, 800-mg dosage against Ef1497 did not prevent their emergence. For the most resistant mutant (MIC, 16 g/ml), characterization of 23S rRNA genes revealed the substitution A2453G in two of the four operons, which was previously described only in in vitro mutants of archaebacteria. Nevertheless, this mutant did not yield further mutants under 600-or 200-mg treatment. In conclusion, linezolid was consistently efficient against S. aureus strains. The emergence of resistant E. faecalis mutants was probably favored by the rapid decline of linezolid concentrations against a strong mutator, a phenotype less exceptional in E. faecalis than in S. aureus.

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“…This research characterized by a reduced susceptibility to vancomycin in patients with peripheral vascular disease and infectious complications, requiring surgery. It is shown that the concentration of linezolid in the tissues of 51% (from 18% to 78%), leads to the conclusion that the effectiveness of linezolid in the treatment of MRSA patients with diabetic foot with reduced concentrations of the drug at the site of blood flow disturbances [41].…”

Section: Malorodova Tn Pokrovskaya Tg каZаkоvа Ee Urojevskaymentioning

confidence: 99%

Diabetic Foot Syndrome: Importance of Microbiological Monitoring and Antimicrobial Penetration of Chemotherapeutic Agents Into the Soft Tissue Lower Limb in Determining the Treatment

Malorodova¹,

Pokrovskaya²,

Kazakova³

et al. 2016

RR.P and CP

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Linezolid tissue penetration and serum activity against strains of methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility in diabetic patients with foot infections

Abstract: These findings suggest that linezolid could be effective in the treatment of multidrug-resistant MRSA even when concentrations at the infection site are diminished due to impaired blood flow.

Cited by 62 publications

References 25 publications

Determination of Tissue Penetration and Pharmacokinetics of Linezolid in Patients with Diabetic Foot Infections Using In Vivo Microdialysis

Determination of Tissue Penetration and Pharmacokinetics of Linezolid in Patients with Diabetic Foot Infections Using In Vivo Microdialysis

Activity of Linezolid in anIn VitroPharmacokinetic-Pharmacodynamic Model Using Different Dosages andStaphylococcus aureusandEnterococcus faecalisStrains with and without a Hypermutator Phenotype

Diabetic Foot Syndrome: Importance of Microbiological Monitoring and Antimicrobial Penetration of Chemotherapeutic Agents Into the Soft Tissue Lower Limb in Determining the Treatment

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