tedizolid and Skin-Diseases--Infectious

Tedizolid is a second-generation oxazolidinone with activity against Gram-positive bacteria, including MRSA isolates resistant to linezolid. Pivotal clinical trials showed that tedizolid at 200 mg once-daily for 6 days is not inferior to linezolid 600 mg twice daily for 10 days in patients with SSTI. The comparison of adverse events is favorable to tedizolid under the circumstances of the clinical trials. This is a review of recent literature on tedizolid, its use in special populations and potential adverse effects.. Findings suggest that tedizolid can be used in SSTI in adolescents, those older than 65 years, obese individuals and patients with diabetic foot infections. Forthcoming research to determine the future uses of this drug in other clinical syndromes requires demonstration of tolerance whenever tedizolid is administered for longer than 6 days.We also speculate on missing data and potential future indications of tedizolid in the highly competitive field of the treatment of severe Gram-positive infections other than SSTI.. Tedizolid is a second-generation oxazolidinone, very convenient for treatment of SSTI, in search for other indications including nosocomial pneumonia and bone and joint infections. VIDEO ABSTRACT.

Topics: Anti-Bacterial Agents; Drug-Related Side Effects and Adverse Reactions; Gram-Positive Bacterial Infections; Humans; Oxazolidinones; Skin Diseases, Infectious; Soft Tissue Infections; Tetrazoles; Treatment Outcome

Tedizolid, a novel oxazolidinone with activity against a wide range of Gram-positive pathogens, was evaluated in two noninferiority phase 3 acute bacterial skin and skin structure infection trials. The data from individual trials showed its noninferior efficacy compared to that of linezolid and a favorable tolerability profile. To evaluate potential differences, the pooled data were analyzed. The patients received 200 mg of tedizolid once daily for 6 days or 600 mg of linezolid twice daily for 10 days. Efficacy was evaluated at 48 to 72 h (primary endpoint), on days 11 to 13 (end of therapy [EOT]), and 7 to 14 days after the EOT (posttherapy evaluation). Treatment-emergent adverse events and hematologic and clinical laboratory parameters were collected. The baseline characteristics were comparable between the treatment groups: 852/1,333 (64%) patients were from North America, and the majority of infections were caused by Staphylococcus aureus. Tedizolid was noninferior to linezolid (early clinical responses, 81.6% versus 79.4%, respectively). The early responses remained relatively consistent across various host/disease factors and severity measures. Nausea was the most frequently reported adverse event (tedizolid, 8.2%; linezolid, 12.2%; P=0.02), with onset occurring primarily during the first 6 days. Fewer tedizolid than linezolid patients had platelet counts of <150,000 cells/mm3 at the EOT (tedizolid, 4.9%; linezolid, 10.8%; P=0.0003) and during the postbaseline period through the last day of active drug visit (tedizolid, 6.4%; linezolid, 12.6%; P=0.0016). Efficacy was achieved with a 6-day once-daily course of therapy with the option of an intravenous/oral regimen, and fewer low platelet counts and gastrointestinal side effects were reported with tedizolid than with linezolid, all of which aligns well with antimicrobial stewardship principles. (These studies have been registered at ClinicalTrials.gov under registration no. NCT01170221 and NCT01421511.).

Topics: Acetamides; Anti-Bacterial Agents; Double-Blind Method; Female; Humans; Linezolid; Male; Oxazolidinones; Skin Diseases, Bacterial; Skin Diseases, Infectious; Staphylococcal Skin Infections; Tetrazoles