“While on your advanced hospital rotation you are asked by the pharmacy director to write up a monograph on Sivextro for the next P&T Committee meeting. Provide the recommendation section of your monograph explaining if Sivextro should or should not be added to the hospital formulary.”
Tedizolid phosphate was approved by the FDA in June 2014 as a second-generation oxazolidinone with potentially four- to 16-fold potency against MRSA when compared to linezolid.1 Favorable results from clinical trials have led to its indication for the treatment of ABSSSIs in adult patients with susceptible bacteria.1
Tedizolid phosphate is a prodrug that is converted by plasma phosphatases to its active form. It interacts with the bacterial 23S ribosome initiation complex and binds to the 50S subunit to prevent the formation of the 70S complex. Therefore, it inhibits bacterial translation and protein synthesis.1 Tedizolid is active against clinically relevant Gram-positive pathogens (MRSA, MSSA, Strep pyogenes, Strep agalactiae, enterococci, and coagulase-negative staph). This drug has also demonstrated activity against linezolid-resistant staphylococci ESTABLISH-12 Looked at efficacy and safety of tedizolid phosphate versus linezolid in ABSSSI (multicenter, randomized, dounble-blind, double-dummy, noninferiority, phase 3 trial). Inclusion criteria: at least 18 years old with cellulitis, major cutaneous abscess, or wound infection. Must have erythema and a total lesion size of at least 75 cm2 and at least one local, regional, or systemic sign of infection and a documented or suspected Gram-positive bacterium. Exclusion criteria: uncomplicated ABSSSI, a vascular catheter site-associated ABSSSI, thrombophlebitis, or surgery other than clean surgery; if they received any other antibiotics with similar spectrum of activity within 96 hours of the first dose of the study drug, or if they previously failed therapy at the same infection site. Eligible patients were randomized 1:1 to receive either tedizolid phosphate 200 mg PO once daily for six days or linezolid 600 mg PO twice daily for 10 days. Primary Endpoint: early clinical response at the 48- to 72-hour assessment in the intent-to-treat analysis group. …show more content…
Treatment responder: patient who was afebrile, had no growth in lesion area, width, or length from baseline, and did not receive other antimicrobial therapy identified by the exclusion criteria, and did not die of any cause.
667 patients were randomized with a median age of 43 years. About 41% had cellulitis, about 30% had major cutaneous abscess and about 30% had a wound infection. S. aureus was the most commonly detected pathogen and MRSA was present in about 42% of both treatment groups.
Results: Treatment response rates were similar at the 48- to 72-hour assessment in both groups, noninferiority was achieved, and sustained clinical success rates at the end of treatment using the ITT data were comparable between the two groups.
ESTABLISH-23
Randomized, double-blind, parallel-group, noninferiority phase 3 trial that evaluated the use of IV tedizolid phosphate or linezolid with an option to switch to oral therapy.
Inclusion and exclusion criteria were similar to that of ESTABLISH-1, as were the randomization and treatment of the two groups. (Except IV instead of PO) After two doses of therapy, patients could switch to oral therapy if they met at least 2 of the following criteria: no increase in lesion size compared with baseline, temperature of 37.7 degrees Celsius or less, or absence of worsening signs and symptoms of the affected area. Primary outcome was similar to ESTABLISH-1. Treatment responders: patients who had at least
Tedizolid phosphate was approved by the FDA in June 2014 as a second-generation oxazolidinone with potentially four- to 16-fold potency against MRSA when compared to linezolid.1 Favorable results from clinical trials have led to its indication for the treatment of ABSSSIs in adult patients with susceptible bacteria.1
Tedizolid phosphate is a prodrug that is converted by plasma phosphatases to its active form. It interacts with the bacterial 23S ribosome initiation complex and binds to the 50S subunit to prevent the formation of the 70S complex. Therefore, it inhibits bacterial translation and protein synthesis.1 Tedizolid is active against clinically relevant Gram-positive pathogens (MRSA, MSSA, Strep pyogenes, Strep agalactiae, enterococci, and coagulase-negative staph). This drug has also demonstrated activity against linezolid-resistant staphylococci ESTABLISH-12 Looked at efficacy and safety of tedizolid phosphate versus linezolid in ABSSSI (multicenter, randomized, dounble-blind, double-dummy, noninferiority, phase 3 trial). Inclusion criteria: at least 18 years old with cellulitis, major cutaneous abscess, or wound infection. Must have erythema and a total lesion size of at least 75 cm2 and at least one local, regional, or systemic sign of infection and a documented or suspected Gram-positive bacterium. Exclusion criteria: uncomplicated ABSSSI, a vascular catheter site-associated ABSSSI, thrombophlebitis, or surgery other than clean surgery; if they received any other antibiotics with similar spectrum of activity within 96 hours of the first dose of the study drug, or if they previously failed therapy at the same infection site. Eligible patients were randomized 1:1 to receive either tedizolid phosphate 200 mg PO once daily for six days or linezolid 600 mg PO twice daily for 10 days. Primary Endpoint: early clinical response at the 48- to 72-hour assessment in the intent-to-treat analysis group. …show more content…
Treatment responder: patient who was afebrile, had no growth in lesion area, width, or length from baseline, and did not receive other antimicrobial therapy identified by the exclusion criteria, and did not die of any cause.
667 patients were randomized with a median age of 43 years. About 41% had cellulitis, about 30% had major cutaneous abscess and about 30% had a wound infection. S. aureus was the most commonly detected pathogen and MRSA was present in about 42% of both treatment groups.
Results: Treatment response rates were similar at the 48- to 72-hour assessment in both groups, noninferiority was achieved, and sustained clinical success rates at the end of treatment using the ITT data were comparable between the two groups.
ESTABLISH-23
Randomized, double-blind, parallel-group, noninferiority phase 3 trial that evaluated the use of IV tedizolid phosphate or linezolid with an option to switch to oral therapy.
Inclusion and exclusion criteria were similar to that of ESTABLISH-1, as were the randomization and treatment of the two groups. (Except IV instead of PO) After two doses of therapy, patients could switch to oral therapy if they met at least 2 of the following criteria: no increase in lesion size compared with baseline, temperature of 37.7 degrees Celsius or less, or absence of worsening signs and symptoms of the affected area. Primary outcome was similar to ESTABLISH-1. Treatment responders: patients who had at least