Tedizolid proven safe, effective for acute bacterial skin and skin structure infections
Tedizolid is a safe and effective treatment option for adolescents with acute bacterial skin and skin structure infections (ABSSSIs), particularly those with S. aureus-susceptible strains, a study has shown.
“No new safety concerns were identified in the adolescent population,” the researchers said. “Efficacy rates for tedizolid were high and similar to those of comparators.”
This randomized, assessor-blind, global phase III study stratified 120 Gram-positive ABSSSIs in adolescents (12 to <18 years of age) by region and randomly assigned them 3:1 to receive tedizolid phosphate 200 mg (oral and/or intravenous; n=91) once daily for 6 days or active comparator (n=29), selected from an allowed list per local standard of care, for 10 days. Statistical comparisons between treatment groups were not performed.
Treatment-emergent adverse events (TEAEs) were comparable between the two groups (tedizolid: 14.3 percent; comparator: 10.3 percent). Three participants (3.3 percent) in the tedizolid group and one (3.4 percent) in the comparator group suffered a single TEAE. In addition, clinical success rates were high in both groups: 96.7 percent for the tedizolid group and 93.1 percent for the comparator group at the test-of-cure (TOC) visit. [Pediatr Infect Dis J 2021;40:238-244]
In the phase III ESTABLISH-1 and -2 trials, tedizolid was well-tolerated and noninferior to linezolid, another oxazolidine-class antibacterial agent, for the treatment of ABSSSIs in adults. [JAMA 2013;309:559-569; Lancet Infect Dis 2014;14:696-705]
“The incidences of reported AEs and drug-related AEs were lower in the adolescent tedizolid group compared with adults with ABSSSI in the phase III adult studies,” the researchers noted. “Rates of drug-related serious AEs and discontinuations due to an AE were low in the adolescent population and similar to rates observed in adults.”
Of note, previous studies also reported haematologic toxicity in adults treated with linezolid. The current study, however, found no clinically significant between-group differences in change from baseline through the TOC visit for haematologic parameters, including absolute neutrophil count, leukocyte count, platelet count, and haemoglobin. [J Antimicrob Chemother 2012;67:727-735; Clin Infect Dis 2002;34:695-698]
“These results are consistent with previous phase II and III clinical trials of tedizolid in adults, in which low incidences of reduced platelet counts and reduced absolute neutrophil counts were observed with tedizolid therapy,” the researchers said. [Antimicrob Agents Chemother 2011;55:583-592; Antimicrob Agents Chemother 2014;58:7198-7204]
The current study was limited by its small population size. In addition, it was not powered for inferential statistics and had no hypothesis testing planned for the efficacy endpoints. However, clinical and microbiological response rates appeared high and similar between treatment groups.
“Tedizolid, the active moiety of the tedizolid phosphate prodrug, is an oxazolidinone-class antibacterial agent that binds to the 50S bacterial ribosome subunit, inhibiting protein synthesis, and has broad in vitro activity against Gram-positive bacteria, including methicillin-resistant S. aureus and vancomycin- and linezolid-resistant strains,” the researchers said. [J Chemother 2019;31:188-194; Antimicrob Agents Chemother 2012;56:4608-4613; Antimicrob Agents Chemother 2009;53:3236-3239]