Omadacycline Similar to Commonly Used Antibiotics for CAP and Skin Infections

Veronica Hackethal, MD

February 06, 2019

Omadacycline is not inferior to other commonly used antibiotics for treating community-acquired pneumonia (CAP) and skin or skin-structure infections, two phase 3 trials have found. Findings 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 skin and skin-structure infections. Omadacycline is available in oral and intravenous formulations.

Both studies were conducted according to FDA guidance using double-blind, double-dummy, randomized designs. Both had a primary efficacy endpoint of early clinical response (48 to 72 hours for skin and skin-structure infections and 72 to 120 hours for CAP), with a prespecified noninferiority margin of 10%.

In the first study, called the Omadacycline for Pneumonia Treatment in the Community (OPTIC) trial, Roman Stets MD, PhD, from City Clinical Hospital #6, Zaporizhzhia, Ukraine, and colleagues compared omadacycline to moxifloxacin for treating CAP. 

The study took place at 86 sites in Europe, North America, South America, the Middle East, Africa, and Asia between November 2015 and February 2017. It included adults hospitalized with CAP but not requiring treatment in an intensive care unit. Researchers randomly assigned 386 participants to receive omadacycline 100 mg intravenously (IV) every 12 hours for the first two doses, then every 24 hours or moxifloxacin 400 mg IV every 24 hours. Both groups had the option to transition to oral therapy after 3 days. 

Rates of early clinical response were similar for omadacycline vs moxifloxacin (81.1% and 82.7%, respectively; difference, −1.6 percentage points; 95% confidence interval [CI], −7.1 to 3.8), which met the prespecified noninferiority margin.

Five to 10 days after the last dose, clinical response to omadacycline remained noninferior to moxifloxacin (87.6% vs 85.1%, respectively;  difference, 2.5 percentage points; 95% CI, −2.4 to 7.4).

In the second study, called the Omadacycline in Acute Skin and Skin Structure Infections Study (OASIS-1), William O'Riordan, MD, from eStudySite, San Diego, California, and colleagues compared omadacycline with linezolid for treating skin and skin-structure infections, such as those resulting from injection drug use or major abscesses commonly caused by gram-positive bacteria, especially Staphylococcus aureus.

The study took place at 55 sites in the United States, Peru, South Africa, and Europe between June 2015 and May 2016. Researchers randomized 316 adults to receive omadacycline 100 mg IV every 12 hours for the first two doses then every 24 hours after that and 311 adults to receive linezolid 600 mg IV every 12 hours, with the option to transition after 3 days to oral therapy.

Results also showed similar rates of early clinical response for omadacycline compared with linezolid (84.8% vs 85.5%, respectively; difference, −0.7 percentage points; 95% CI, −6.3 to 4.9), which met the prespecified noninferiority margin.

Likewise, clinical response to omadacycline remained noninferior to linezolid 7 to 14 days after finishing therapy (86.1% and 83.6%, respectively; difference, 2.5 percentage points; 95% CI, −3.2 to 8.2).

In both studies, omadacycline and linezolid had similar adverse events, with gastrointestinal issues most common.

These results may sound like good news, but Henry F Chambers, MD, from the University of San Francisco, California, asked, "So what?" in an accompanying editorial.

Chambers acknowledged some advantages of omadacycline over older tetracyclines and other classes of antibiotics. These included broad-spectrum activity against a variety of gram-positive and gram-negative bacteria, including methicillin-resistant staph aureus (MRSA) and atypical organisms that cause CAP such as Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydia Pneumoniae; the potential to overcome some types of bacterial resistance that plague older tetracyclines and other classes of antibiotics; lack of cross-resistance with other antibiotic classes; and a once-daily oral formulation.

Nevertheless, he contends that omadacycline has few advantages over already available antibiotics. Notably, the two studies, despite their high quality, cannot determine the role of omadacycline in treating multidrug-resistant infections.

He mentions several limitations of the studies. For example, the OASIS-1 study cannot determine omadacycline's activity against gram-negative bacteria because the trial excluded patients with these types of skin infections. So the antibiotic's role in treating common types of infections like bite wounds and diabetic foot ulcers remains unclear.

Most notably, eight patients died in the omadacycline group compared with four in the moxifloxacin group in the OPTIC trial. Causes of death included progression of pneumonia, hospital-acquired pneumonia, cardiac or vascular events, and cancer. Yet the reasons for the imbalance in mortality between omadacycline and moxifloxacin remain unclear.

Despite these reservations, Chambers concedes that omadacycline has "at least some promise" for treating certain bacterial infections, particularly those caused by certain carbapenem-resistant and gram-negative organisms.

"Well designed clinical trials of omadacycline for the treatment of infections caused by multiple-drug–resistant gram negative pathogens are needed to determine its real value as an antibacterial agent," he concludes.

The study by Stets and colleagues was supported by Paratek Pharmaceuticals.

Seven authors report employment and holding stick with Paratek Pharmaceuticals.

One or more authors reports personal fees, grants, and/or consulting fees from one or more of the following: Paratek Pharmaceuticals, Achaogen, IterumTx, Nabriva, ContraFect, Wockhardt, UTILITY, Zavante, Tetraphase, Theravance, Cubist, Cempra, Spero Therapeutics, InClin, Inc, MicuRx. A complete list is available on the journal's website.

The study by O'Riordan was supported by Paratek Pharmaceuticals. Garrity-Ryan, Tzanis, Eckburg, Manley, Villano, Steenbergen, and Loh are employees of Paratek Pharmaceuticals.

One or more authors reports personal fees, nonfinancial support, and/or other from one or more of the following: Paratek Pharmaceuticals, Achaogen, IterumTx, Nabriva, ContraFect, Wockhardt, UTILITY, Zavante, Tetraphase, Theravance, Cubist, Cempra, Spero Therapeutics, InClin, Inc, MicuRx, Motif, Basilea, The Medicines Company, GSK, Debiopharm, Cellceutix, and/or Paratek Pharmaceuticals COACH (Considerations for Omadacycline and Antibiotics in Community & Hospital) Advisory Board. A complete list is available on the journal's website.

Chambers reports personal fees and grants from Allergan.

N Engl J Med. Published online February 6, 2019. Abstract

N Engl J Med. Published online February 6, 2019. Abstract

N Engl J Med. Published online February 6, 2019. Editorial

Follow Medscape on Facebook , Twitter , Instagram, and YouTube

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....