Pharmacokinetics and Pharmacodynamics of Tedizolid

Abstract

Tedizolid is an oxazolidinone antibiotic with high potency against Gram-positive bacteria and currently prescribed in bacterial skin and skin-structure infections. The aim of the review was to summarize and critically review the key pharmacokinetic and pharmacodynamic aspects of tedizolid. Tedizolid displays linear pharmacokinetics with good tissue penetration. In in vitro susceptibility studies, tedizolid exhibits activity against the majority of Gram-positive bacteria (minimal inhibitory concentration [MIC] of ≤ 0.5 mg/L), is four-fold more potent than linezolid, and has the potential to treat pathogens being less susceptible to linezolid. Area under the unbound concentration-time curve (fAUC) related to MIC (fAUC/MIC) was best correlated with efficacy. In neutropenic mice, fAUC/MIC of ~ 50 and ~ 20 induced bacteriostasis in thigh and pulmonary infection models, respectively, at 24 h. The presence of granulocytes augmented its antibacterial effect. Hence, tedizolid is currently not recommended for immunocompromised patients. Clinical investigations with daily doses of 200 mg for 6 days showed non-inferiority to twice-daily dosing of linezolid 600 mg for 10 days in patients with acute bacterial skin and skin-structure infections. In addition to its use in skin and skin-structure infections, the high pulmonary penetration makes it an attractive option for respiratory infections including Mycobacterium tuberculosis. Resistance against tedizolid is rare yet effective antimicrobial surveillance and defining pharmacokinetic/pharmacodynamic targets for resistance suppression are needed to guide dosing strategies to suppress resistance development.

Developmental Pharmacokinetics of Antibiotics Used in Neonatal ICU: Focus on Preterm Infants

“…PPB for tedizolid is from 70 to 90% [ 162 ]. It is thought that in critically ill patients, in a hypoalbuminemia state, the PPB of tedizolid will be changed resulting in increased clearance [ 163 ].…”

The Struggle to End a Millennia-Long Pandemic: Novel Candidate and Repurposed Drugs for the Treatment of Tuberculosis

“…Tedizolid is a newer oxazolidinone prodrug converted in serum to its active form, and subsequently inhibits the 50S subunit of the ribosome, impairing protein synthesis [ 108 ]. It exhibits excellent penetration into cutaneous and pulmonary tissue (superior to linezolid), making it an optimistic option for treatment of TB [ 109 ]. It demonstrates vast Gram-positive inhibitory activity, and in addition demonstrated activity against both rapidly and slowly growing nontuberculous mycobacteria, including TB [ 109 ].…”

“…It exhibits excellent penetration into cutaneous and pulmonary tissue (superior to linezolid), making it an optimistic option for treatment of TB [ 109 ]. It demonstrates vast Gram-positive inhibitory activity, and in addition demonstrated activity against both rapidly and slowly growing nontuberculous mycobacteria, including TB [ 109 ]. It demonstrates the most potent in vitro activity of any of the oxazolidinones against rapidly-growing M. abscessus [ 110 ].…”

“…Tedizolid seems to have a superior safety profile to linezolid [ 109 ]. Its more common side effects were mild AEs including headache and gastrointestinal (GI) intolerance, and it seems to have a better hematologic safety profile to that shown by linezolid [ 96 , 102 ].…”

“…Delpazolid is a novel oxazolidinone that contains a cyclic amidrazone group. It is highly bactericidal, and similar to other oxazolidinones exerts its antimycobacterial function by inhibiting protein synthesis at the 23s rRNA [ 109 ]. Similar to other oxazolidinones, it possesses broad Gram-positive activity and also seems to have potent activity against M. abscessus [ 40 ].…”