Tedizolid Effective for Acute Bacterial Skin and Skin-Structure Infections
By Will Boggs MD
NEW YORK - Six days of tedizolid is as effective as 10 days of linezolid for treating acute bacterial skin and skin-structure infections, according to results from the ESTABLISH-2 noninferiority trial.
"Once daily dosing and the shorter six-day course with tedizolid could improve outcomes if there is concern about medication compliance," Dr. Gregory J. Moran from Geffen School of Medicine at UCLA, Los Angeles, California told Reuters Health. "There are several advantages of tedizolid versus vancomycin, including less toxicity, no need for monitoring drug levels, and availability of an oral form with the same dosing regardless of renal or hepatic insufficiency."
An earlier study, ESTABLISH-1, showed oral tedizolid given once daily for six days was noninferior to oral linezolid given twice daily for 10 days for acute bacterial skin infections.
In 666 participants in the ESTABLISH-2 trial, Dr. Moran and colleagues compared IV-to-oral tedizolid against IV-to-oral linezolid for treating acute bacterial skin and skin-structure infections.
The primary efficacy endpoint was early clinical response (48 to 72 hours after the start of treatment). They also examined responses at day 7, end of treatment, and post-therapy (7-14 days after the end of treatment).
Similar percentages of patients in the tedizolid group (283/332, 85%) and in the linezolid group (276/334, 83%) achieved early clinical responses, demonstrating noninferiority of tedizolid to linezolid, the authors reported online June 6th in The Lancet Infectious Diseases.
There were no meaningful differences between groups in rates of early clinical response, regardless of type of acute bacterial skin or skin-structure infection, geographic region, baseline pathogen, and timing of oral step-down.
Similarly, among patients evaluable at the post-therapy assessment, there was no significant difference in the investigator-assessed clinical response rate between tedizolid (268/290, 92%) and linezolid (269/280, 96%).
The overall incidence of treatment-emergent adverse events was similar between the study groups, but gastrointestinal disorders (mostly diarrhea, nausea, and vomiting) were somewhat less common with tedizolid (16%) than with linezolid (20%).
"Tedizolid is a new, once-daily option for six-day short-course treatment of skin infections, including those caused by MRSA," Dr. Moran concluded.
"Cost effectiveness data are difficult to establish given the regional variations in payment structures for health care," Dr. Moran explained. "However, number of hospital days is the biggest driver of health care costs. Any drug that could potentially reduce hospital days is likely to be cost effective."
In an editorial, Dr. Evelina Tacconelli from University Hospital Tuebingen, Germany and Dr. Winfried V. Kern from University Hospital, Freiburg, Germany, write, "This new drug should be further studied and could even be used to address unmet needs for new indicators to define superiority in other settings."
"Furthermore," they continue, "future randomized clinical trials could focus on selected populations admitted to or in hospital (e.g., elderly populations) for whom de-escalation brings greatest benefit."
Dr. David P. Nicolau from Hartford Hospital in Connecticut told Reuters Health by email, "This compound has the potential to improve clinical and economic outcomes due to its enhanced potency against Gram-positive pathogens such as staphylococci and streptococci, as well as its activity against defined genotypic resistance profiles in staphylococci that currently exist to the marketed oxazolidinone, linezolid."
"It will be a tough battle for tedizolid despite these advantages (since) linezolid will go off patent in 2015," Dr. Nicolau explained. "Since the clinical trial was not powered for superiority, thus noninferiority means they have the same efficacy and despite concerns of higher toxicity of linezolid when used in clinical setting without the parameters of clinical trial and polypharmacy, you'll see increased advocacy for linezolid in the hospital setting due to drastic reductions in (cost)."
"Unfortunately the value of antibiotics in many of our institutional settings is based on acquisition cost only, as its much more difficult to value based on differences in efficacy (due to study design), or toxicity since many of these AEs are not catastrophic events even though they have the potential to require other medical intervention or increased length of stay," Dr. Nicolau said.
Dr. Henry F. Chambers from the University of California and San Francisco General Hospital reached a similar conclusion. He told Reuters Health, "The drug is not superior, but the shorter duration of therapy with comparable efficacy is a potential advantage."
He added that whether or not it is favored over another antibiotic "depends on cost, really. If the cost of a six-day regimen is less than that of an alternative, then the six-day tedizolid regimen would be preferred."
On 31 March, the U.S. Food and Drug Administration (FDA) Anti-Infective Drugs Advisory Committee (AIDAC) voted to recommend approval of tedizolid in a unanimous 14 - 0 decision.
Cubist Pharmaceuticals funded the trial, employed three of the six authors, and had various relationships with the other authors.
SOURCE: https://bit.ly/1jyMo64
Lancet Infect Dis 2014.
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