Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis

Song, Taeksun; Lee, Myungsun; Jeon, Han Seung; Park, Yumi; Dodd, Lori E.; Dartois, Véronique; Follman, Dean; Wang, Jing; Cai, Ying; Goldfeder, Lisa C.; Olivier, Kenneth N.; Xie, Yingda L.; Via, Laura E.; Cho, Sang Nae; Barry, Clifton E.; Chen, Ray Y.

doi:10.1016/j.ebiom.2015.09.051

Cited by 110 publications

(109 citation statements)

References 33 publications

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“…This is because a C min higher than the IC 50 without recovery time has been associated with mitochondrial toxicity 81. Similarly, an association between an higher C min of linezolid and lower mitochondrial function has been observed in other studies,82 and this fact has been associated with a greater proportion of adverse events related to mitochondrial toxicity.…”

Section: Tolerabilitysupporting

confidence: 74%

Critical role of tedizolid in the treatment of acute bacterial skin and skin structure infections

Ferrández¹,

Urbina²,

Grau³

2016

DDDT

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Tedizolid phosphate has high activity against the Gram-positive microorganisms mainly involved in acute bacterial skin and skin structure infections, such as strains of Staphylococcus aureus (including methicillin-resistant S. aureus strains and methicillin-sensitive S. aureus strains), Streptococcus pyogenes, Streptococcus agalactiae, the Streptococcus anginosus group, and Enterococcus faecalis, including those with some mechanism of resistance limiting the use of linezolid. The area under the curve for time 0–24 hours/minimum inhibitory concentration (MIC) pharmacodynamic ratio has shown the best correlation with the efficacy of tedizolid, versus the time above MIC ratio and the maximum drug concentration/minimum inhibitory concentration ratio. Administration of this antibiotic for 6 days has shown its noninferiority versus administration of linezolid for 10 days in patients with skin and skin structure infections enrolled in two Phase III studies (ESTABLISH-1 and ESTABLISH-2). Tedizolid’s more favorable safety profile and dosage regimen, which allow once-daily administration, versus linezolid, position it as a good therapeutic alternative. However, whether or not the greater economic cost associated with this antibiotic is offset by its shorter treatment duration and possibility of oral administration in routine clinical practice has yet to be clarified.

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Section: Tolerabilitysupporting

confidence: 74%

Critical role of tedizolid in the treatment of acute bacterial skin and skin structure infections

Ferrández¹,

Urbina²,

Grau³

2016

DDDT

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“…Acquired linezolid resistance has been reported, particularly with a daily linezolid dose of 300 mg . Mitochondrial toxicity risk was found to increase with linezolid trough concentrations, suggesting the possibility of better tolerance for intermittent dosing …”

Section: Novel Treatment Regimensmentioning

confidence: 99%

Drug‐resistant tuberculosis: An update on disease burden, diagnosis and treatment

et al. 2018

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The emergence of antimicrobial resistance against Mycobacterium tuberculosis, the leading cause of mortality due to a single microbial pathogen worldwide, represents a growing threat to public health and economic growth. The global burden of multidrug-resistant tuberculosis (MDR-TB) has recently increased by an annual rate of more than 20%. According to the World Health Organization approximately only half of all patients treated for MDR-TB achieved a successful outcome. For many years, patients with drug-resistant tuberculosis (TB) have received standardized treatment regimens, thereby accelerating the development of MDR-TB through drug-specific resistance amplification. Comprehensive drug susceptibility testing (phenotypic and/or genotypic) is necessary to inform physicians about the best drugs to treat individual patients with tailor-made treatment regimens. Phenotypic drug resistance can now often, but with variable sensitivity, be predicted by molecular drug susceptibility testing based on whole genome sequencing, which in the future could become an affordable method for the guidance of treatment decisions, especially in high-burden/resource-limited settings. More recently, MDR-TB treatment outcomes have dramatically improved with the use of bedaquiline-based regimens. Ongoing clinical trials with novel and repurposed drugs will potentially further improve cure-rates, and may substantially decrease the duration of MDR-TB treatment necessary to achieve relapse-free cure.

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“…(3) Intermittent dosing may help prevent or alleviate neuropathy by shortening exposure at toxic levels . Therapeutic drug monitoring may help reduce toxicity, as adverse events are reportedly associated with mean linezolid trough >2 mg/L…”

Section: Mdr‐tb: Repurposed and Novel Drugsmentioning

confidence: 99%

“…(2) The optimal linezolid dosing schedule remains open. Reducing linezolid dosage from 600 mg bd to 600 mg once daily, and from 600 mg once daily to 300 mg once daily, significantly reduces adverse events. Prolonged use of linezolid 300 mg once daily is still associated with a substantial risk of neuropathy, with concerns about possibly acquiring bacillary linezolid resistance…”

Section: Mdr‐tb: Repurposed and Novel Drugsmentioning

confidence: 99%

New drugs and regimens for tuberculosis

et al. 2018

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Since standardized rifampin-based first-line regimens and fluoroquinolone-based second-line regimens were used to treat tuberculosis (TB), unfortunately without timely modification according to the drug resistance profile, TB and drug-resistant disease are still important public health threats worldwide. Although the last decade has witnessed advances in rapid diagnostic tools and use of repurposed and novel drugs for better managing drug-resistant TB, we need an appropriate TB control strategy and a well-functioning health infrastructure to ensure optimal operational use of rapid tests, judicious use of effective treatment regimens that can be rapidly tailored according to the drug resistance profile and timely management of risk factors and co-morbidities that promote infection and its progression to disease. We searched the published literature to discuss (i) standardized versus individualized therapies, including the choice between a single one-size-fit-all regimen versus different options with different key drugs determined mainly by rapid drug susceptibility testing, (ii) alternative regimens for managing drug-susceptible TB, (iii) evidence for using the World Health Organization (WHO) longer and shorter regimens for multidrug-resistant TB and (iv) evidence for using repurposed and novel drugs. We hope an easily applicable combination of biomarkers that accurately predict individual treatment outcome will soon be available to ultimately guide individualized therapy.

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Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis

Cited by 110 publications

References 33 publications

Critical role of tedizolid in the treatment of acute bacterial skin and skin structure infections

Critical role of tedizolid in the treatment of acute bacterial skin and skin structure infections

Drug‐resistant tuberculosis: An update on disease burden, diagnosis and treatment

New drugs and regimens for tuberculosis

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