tedizolid
Regulatory sources consulted
Approved indications
- Acute bacterial skin and skin-structure infections caused by susceptible gram-positive organisms.
Contraindications
Absolute
- Hypersensitivity to tedizolid.
Clinical warnings
- Major warning · Consider another treatment if neutrophils are <1,000 cells/mm³. Monitor cytopenias and neuropathy if treatment extends beyond the approved duration. — CIMA/AEMPS, ficha técnica 115991001
- Major warning · It may cause serotonin syndrome and C. difficile colitis; monitor symptoms and discontinue if severe. — CIMA/AEMPS, ficha técnica 115991001
Drug interactions
- ModerateIntestinal BCRP substrates such as methotrexate, topotecan, or rosuvastatin
Mechanism: Oral tedizolid inhibits intestinal BCRP and may increase exposure.
Recommendation: If possible, interrupt the BCRP substrate during the 6 days of oral tedizolid; if it cannot be interrupted, monitor toxicity and concentrations when appropriate.
CIMA/AEMPS, ficha técnica 115991001
- HighSerotonergic drugs
Mechanism: They may increase the risk of serotonin syndrome.
Recommendation: Consider alternatives; if the combination is necessary, closely monitor for serotonin-syndrome signs.
CIMA/AEMPS, ficha técnica 115991001
Adverse events
Common (≥1%)
Nausea, headache, diarrhea, and vomiting
Rare but serious
Serotonin syndrome, severe cytopenia, and neuropathy
Pregnancy and lactation
It may cause fetal harm. Decide whether to discontinue breastfeeding or treatment according to maternal benefit.
Recent literature (PubMed)
The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antimicrobial Susceptibility Testing (AST) develops and publishes standards and guidelines for AST methods and results interpretation in an annual update to the Performance Standards for Antimicrobial Susceptibility Testing (M100). This minireview will discuss changes to M100 for the 31st edition, including new and revised breakpoints and testing recommendations. New MIC and disk diffusion breakpoints are described for azithromycin (Shigella spp.), imipenem-relebactam (Enterobacterales, Pseudomonas aeruginosa, and anaerobes), and lefamulin (Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pneumoniae), and disk breakpoints are described for azithromycin and Neisseria gonorrhoeae. The rationale behind revised oxacillin MIC breakpoints for select staphylococci is discussed. Updates to test methods include a method for disk diffusion using positive blood culture broth and use of linezolid to predict tedizolid susceptibility. There is clarification on which drugs to suppress on bacteria isolated from the cerebrospinal fluid and clarification on the use of a caret symbol attached to the intermediate category ("I^") to indicate those antimicrobials that concentrate in the urine.
Vancomycin is a first-line drug for the treatment of MRSA infection. However, overuse of vancomycin can cause bacteria to become resistant, forming resistant strains and making infections more difficult to treat. This study aimed to evaluate the efficacy and safety of different antibiotics in the treatment of MRSA infections and to compare them, mainly with vancomycin, to find better vancomycin alternatives. All studies were obtained from the PubMed and Embase databases from inception to 13 April 2023. The three comprehensive indicators of clinical cure success rate, clinical microbiological success rate, and adverse reactions were evaluated, and the clinical cure success rates of three disease types, complex skin and skin structure infections (cSSSIs), complex skin and soft tissue infections (cSSTIs), and pneumonia, were analyzed in subgroups. All statistical analyses were performed using R and STATA 14.0 software for network meta-analysis. A total of 38 trials with 6281 patients were included, and 13 drug treatments were evaluated. For MRSA infections, the results of network meta-analysis showed that the clinical success rates of linezolid, the combination of vancomycin and rifampin, and the combination of minocycline and rifampin were better than that of vancomycin (RR 1.71; 95%-CI 1.45-2.02), (RR 2.46; 95%-CI 1.10-5.49) (RR, 2.77; 95%-CI 1.06-7.21). The success rate of clinical microbiological treatment with vancomycin was inferior to that with telavancin (RR 0.74; 95%-CI 0.55-0.99). Linezolid had a higher rate of adverse reactions than teicoplanin (RR 5.35; 95%-CI 1.10-25.98). Subgroup analysis showed that vancomycin had a lower clinical success rate than linezolid in the treatment of MRSA-induced cSSSIs, cSSTIs, and pneumonia (RR 0.59; 95%-CI 0.44-0.80) (RR 0.55; 95%-CI 0.35-0.89) (RR 0.55; 95%-CI 0.32-0.93). This systematic review and NMA provide a new comparison framework for the clinical treatment of MRSA infection. The NMA suggests that linezolid may be th
2-Oxazolidinone is well known as a pharmacophore for antibacterial agents represented by two marketed medicines, Linezolid and Tedizolid. On the other hand, there are growing reports on the various biological activities of 2-oxazolidinones beyond antibacterial activities. Therefore, in this review, we provide an overview of the progress of this untraditional area of 2-oxazolidinones in the past 10 years (2011-2021).
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.
This review discusses small molecule antibiotics approved for clinical use in the time frame 2010-2022. This time span saw the approval of four synthetic antibiotics (bedaquiline, pretomanid, delafloxacin, tedizolid), nine natural product derivatives (ceftaroline fosamil, cefiderocol, plazomicin, omadacycline, eravacycline, sarecycline, lefamulin, dalbavancin, oritavancin), and one natural product (fidaxomicin).