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Omadacycline is not inferior to other antibiotics commonly used for the treatment of community-acquired pneumonia (CAP) and skin infections or lesions of the skin structure, d? after two phase III trials. The results were published online on February 6, 2019, in the New England Journal of Medicine.
Omadacycline is a modernized tetracycline approved by the US Food and Drug Administration (FDA) in October 2017 to treat CAP and acute infections of skin and skin structures. Omadacycline is available in oral and intravenous formulations.
Both studies were conducted in accordance with FDA guidelines, using randomized, double-blind, double-dummy models. Both had a primary efficacy endpoint of early clinical response (48 to 72 hours for skin and skin infections and 72 to 120 hours for CAP), with a prespecified margin of non-inferiority of 10%.
In the first study, entitled OPTIC Trial (Omadacycline for Treatment of Pneumonia in the Community), Roman Stets MD, Ph.D., of Zaporizhzhia City Clinical Hospital No. 6, Ukraine, and colleagues compared 39, omadacycline with moxifloxacin for the treatment of CAP.
The study was conducted at 86 sites in Europe, North America, South America, the Middle East, Africa and Asia between November 2015 and February 2017. It included hospitalized adults with CAP but not requiring treatment in an intensive care unit. The researchers randomly badigned 386 participants to receive 100 mg intravenous omadacycline every 12 hours for the first two doses, then every 24 hours, or 400 mg IV moxifloxacin every 24 hours. Both groups had the option of switching to oral treatment after 3 days.
The early clinical response rates were similar for omadacycline compared with moxifloxacin (81.1% and 82.7%, respectively, difference, -1.6 percentage points, 95% confidence interval). [CI], -7.1 to 3.8), which respect the pre-specified margin of non-inferiority.
Five to ten days after the last dose, the clinical response to omadacycline remained non-inferior to moxifloxacin (87.6% vs 85.1%, difference of 2.5 percentage points, 95% CI -2.4 to 7.4).
In the second study, entitled Omadacycline in the OASIS-1 Study on Acute Skin Infections and Skin Structures, William O. Riordan, MD, of eStudySite, San Diego, CA, and his colleagues compared omadacycline with linezolid for the treatment of skin and skin structures such as those resulting from injection drug use or major abscess usually caused by a gram-positive bacterium, in particular Staphylococcus aureus.
The study was conducted at 55 sites in the United States, Peru, South Africa and Europe between June 2015 and May 2016. The researchers randomized 316 adults under omadacycline 100 mg IV every 12 hours for the first two doses, then every 24 hours thereafter. and 311 adults receiving 600 mg linezolid intravenously every 12 hours, with the option of switching to oral therapy after 3 days.
The results also showed similar rates of early clinical response for omadacycline compared with linezolid (84.8% vs. 85.5%, difference, -0.7 percentage points, 95% CI, 6.3 to 4.9), which corresponds to the prespecified margin of non-inferiority.
Similarly, the clinical response to omadacycline remained non-inferior to linezolid 7-14 days after completion of treatment (86.1% and 83.6%, respectively, 2.5 percentage point difference; at 95% from -3.2 to 8.2).
In both studies, omadacycline and linezolid exhibited similar adverse effects, with gastrointestinal problems being the most common.
These results may seem like good news, but Henry F Chambers, MD, of the University of San Francisco, California, asked, "So what? in an accompanying editorial.
The chambers recognized some advantages of omadacycline over older tetracyclines and other clbades of antibiotics. These included broad-spectrum activity against a variety of gram-positive and negative bacteria, including methicillin-resistant Staph aureus (MRSA) and atypical organisms responsible for CAP, such as Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydia Pneumoniae; the possibility of overcoming certain types of bacterial resistance that infest older tetracyclines and other clbades of antibiotics; lack of cross-resistance with other clbades of antibiotics; and an oral formulation once a day.
Nevertheless, he argues that omadacycline has little benefit over antibiotics already available. Notably, the two studies, despite their high quality, do not make it possible to determine the role of omadacycline in the treatment of multidrug – resistant infections.
He mentions several limitations of the studies. For example, the OASIS-1 study does not determine the activity of omadacycline with respect to Gram-negative bacteria, because the study excludes patients with this type of skin infections. The role of the antibiotic in the treatment of common infections such as diabetic foot bites and ulcers thus remains unclear.
In particular, eight patients died in the omadacycline group, compared to four in the moxifloxacin group in the OPTIC study. Causes of death included progression of pneumonia, hospital-acquired pneumonia, cardiac or vascular events, and cancer. However, the reasons for the imbalance in mortality between omadacycline and moxifloxacin remain unclear.
Despite these caveats, Chambers admits that omadacycline has "at least some promise" for the treatment of some bacterial infections, particularly those caused by some carbapenem and Gram-negative organisms.
"Well-designed clinical trials of omadacycline for the treatment of infections caused by multidrug-resistant Gram-negative pathogens are needed to determine its true value as an antibacterial agent," he concludes.
The study by Stets and his colleagues was supported by Paratek Pharmaceuticals.
Seven authors report a job and a maintenance stick at Paratek Pharmaceuticals.
One or more authors report personal fees, grants and / or consultant fees to one or more of the following departments: Paratek Pharmaceuticals, Achaogen, IterumTx, Nabriva, ContraFect, Wockhardt, UTILITY, Zavante, Tetraphase, Therapance , Cubist, Cempra, Cempra, Spero Therapeutic, InClin, Inc., MicuRx. A complete list is available on the journal's website.
O & # 39; Riordan's study was funded by Paratek Pharmaceuticals. Garrity-Ryan, Tzanis, Eckburg, Manley, Villano, Steenbergen and Loh are employees of Paratek Pharmaceuticals.
One or more authors report personal expenses, non-financial support, and / or other of one or more of the following: Paratek Pharmaceuticals, Achaogen, IterumTx, Nabriva, Contrast, Wockhardt, UTILITY, Zavante, Tetraphase, Theravance, Cubist, Cempra, Cempra, Spero Therapeutics, InClin, Inc. , Basilea, The Medicines Company, GSK Advisory Board, Debiopharm, Cellceutix and / or Paratek Pharmaceuticals COACH (Considerations for Omadacycline and Antibiotics in Communities and Hospitals). A complete list is available on the journal's website.
Chambers reports on Allergan's personal fees and grants.
N Engl J Med. Posted online February 6, 2019. Summary
N Engl J Med. Posted online February 6, 2019. Summary
N Engl J Med. Posted online 6 February 2019. Editorial
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