Latest research on Linezolid

Linezolid is a synthetic antibiotic, the first of the oxazolidinone class, used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA). The drug works by inhibiting the initiation of bacterial protein synthesis.

Linezolid dosage

Patients received either two doses of dalbavancin, 1 g initially followed by 500 mg on day 8 of treatment, or Vancomycin 1 g every 12 hours for ≥3 days, with the option of transitioning to oral Linezolid to Complete 10–14 days of therapy. [source, 2016]
Preliminary, unpublished results suggest that bedaquiline or Linezolid can successfully replace high-dose fourth-generation FQs in the context of high-level FQ resistance. [source, 2016]
We think there are four major points to highlight: (1) Signs/symptoms of TB and SLE can mimic each other posing a diagnostic challenge, (2) Drug toxicities of MDR-TB treatment, including skin rash, arthralgias, nephrotoxicity, anemia, thrombocytopenia and CNS symptoms could also mimic signs/symptoms of SLE and thus complicate management, (3) Drug-drug interactions and overlapping toxicities can complicate management of SLE and MDR-TB, especially in the face of mycobacterial resistance to fluoroquinolones and/or aminoglycosides where more toxic drugs like Linezolid may have to be used, which share similar hematological toxicity profile with immuno-suppressive agents such as Azathioprine used for SLE [5], and (4) Absent clear-cut guidelines, use of immunosuppressant agents and their dose adjustments in an SLE patient with MDR-TB could be clinically challenging for the treating physician. [source, 2015]
While AUC0–24 for Linezolid in epithelial lining fluid (ELF) have been reported to be around fivefold those seen in plasma, tedizolid was found to have an ELF AUC0–24 40-fold higher (approximately 100 mg h/L for a 200 mg dose) than plasma. [source, 2015]
A Phase I trial examining the effect of 200, 300, or 400 mg of tedizolid phosphate daily compared to 600 mg of Linezolid twice daily for 21 days in healthy volunteers found less thrombocytopenia in the 200 mg tedizolid group (mean reduction 15% versus 22% for tedizolid and Linezolid, respectively; data presented in poster form by Prokocimer and colleagues at the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy) Higher doses of tedizolid, however, were not found to be different when compared to Linezolid. [source, 2015]
In the Phase III ESTABLISH studies, more patients receiving Linezolid (12.6%) exhibited platelet counts <150,000 cells/mm3 than in the tedizolid group (6.4%) through last dose of study drug (P = 0.0016) [50–52]. [source, 2015]
Clinical data from two large Phase III studies have demonstrated that ceftobiprole medocaril is noninferior to the combination of high-dose Ceftazidime and Linezolid for the treatment of HAP (excluding VAP) and noninferior to high-dose Ceftriaxone with or without Linezolid for the treatment of CAP requiring hospitalization. [source, 2015]
For example, in the study claiming superiority for Linezolid over Vancomycin in hospital-acquired pneumonia, Vancomycin may not have been dosed optimally as the Vancomycin trough did not reach the recommended 15–20 mg/L range until day 9 of therapy (Wunderink et al. 2012). [source, 2015]
All antibiotics exhibited a dose-dependent effect, except for Linezolid, rifampicin, and Tigecycline. [source, 2015]
Linezolid was employed in pre-XDR-TB patients with limited second-line drug options and despite the small number of patients appeared to be tolerated at a 600 mg daily dose (in no patient was Linezolid stopped due to toxicity). [source, 2015]