Omadacycline noninferior to moxifloxacin in patients with PORT risk class III, IV CABP

In the treatment of patients with community-acquired bacterial pneumonia (CABP), omadacycline is as effective as moxifloxacin at inducing response in patients with Pneumonia Patient Outcomes Research Team (PORT) risk class III and IV severity, according to data from the phase III OPTIC* trial.

“Both treatments showed high rates of clinical success overall in patients with an identified CABP pathogen as well as against individual baseline Gram-positive, Gram-negative, and atypical pathogens, and there was no evidence of decreasing susceptibility to omadacycline during therapy,” the investigators said.

They cited that evaluating response at 5–10 days after the last dose confirmed the durability of clinical success—defined as survival with resolution of baseline signs and symptoms of CABP, without development of new symptoms, complications, or need for further antibacterial therapy—following completion of treatment.

OPTIC randomized 660 patients (mean age, 63.4 years) with PORT risk class III/IV to receive omadacycline 100 mg intravenously (every 12 hours for two doses, then every 24 hours; n=329) or moxifloxacin 400 mg intravenously (every 24 hours; n=331) for 7–14 days. The patients had the option to take their medications orally (at 300 mg or at the same dose in the respective groups) after 3 days.

About 76 percent of the patients had systemic inflammatory response syndrome (SIRS) and 50.2 percent had at least one causative bacterial pathogen detected at baseline. Overall, clinical success rates at post-treatment evaluation (PTE) indicated the noninferioriority of omadacycline to moxifloxacin (intent-to-treat population: 88.4 percent vs 85.2 percent, respectively; clinically evaluable population: 92.5 percent vs 90.5 percent, respectively). [Int J Infect Dis 2021;doi:10.1016/j.ijid.2021.01.032]

When assessed by baseline pathogen, clinical success was generally similar between omadacycline- and moxifloxacin-treated patients. For example, the corresponding rates were 89.7 percent vs 90.6 percent for Streptococcus pneumoniae, 70.0 percent vs 77.8 percent for Staphylococcus aureus, 80.8 percent vs 100 percent for Haemophilus influenzae, and 89.7 percent vs 88.5 percent for Mycoplasma pneumoniae.

Results were similar across key patient subgroups defined by PORT risk class, prior antibiotic use, geographic region (Western Europe/North America, Eastern Europe, and rest of the world), and presence of SIRS at baseline, among others.

None of the isolated from patients showed diminished susceptibility to either test treatment. At the PTE visit, 90.3 percent and 88.5 percent of patients treated with omadacycline and moxifloxacin, respectively, had a favourable microbiological response (proven or presumed eradication of pathogen/s).

Safety had been documented earlier, with omadacycline having an adverse event (AE) profile consistent with the known effects of drugs in the tetracycline class. The most frequent AEs were alanine aminotransferase increase, blood pressure elevation, insomnia, vomiting, and nausea, among others. None of the patients on omadacycline developed Clostridioides difficile infection, whereas five on moxifloxacin did. [N Engl J Med 2019; 380:517-527]

“Though multiple treatment options are available for CABP, our findings add to the evidence of in vitro activity of omadacycline against resistant pathogens, including macrolide- and tetracycline-resistant bacteria. This broad response … indicates the potentially important role of [the drug] as an empirical treatment for CABP,” according to the investigators.

The data have important implications, given the need for new antibiotics for treating CABP across the range of disease severity, they added. This need is predicated on increasing resistance to standard antibiotics in key pathogens, including S. pneumoniae and H. influenzae, as well as a global warning about the side-effects associated with fluoroquinolone use (eg, confusion, diarrhoea, tendinitis, aortic dissection), especially in the elderly. [Expert Rev Respir Med 2019;13:139-152; Am J Ther 2017;24:e361-e369; Int J COPD 2017;12:1507-1518.; https://www.fda.gov/media/114192/download; bit.ly/366WNaY; BMJ 2018;360:k678]

*Omadacycline for Pneumonia Treatment In the Community