Did the study by Stets et al. show that omadacycline was noninferior to moxifloxacin for the treatment of adults with community-acquired bacterial pneumonia?
Community-acquired pneumonia is the most common infection leading to hospitalization and death in all age groups, especially the elderly. For pathogens such as Streptococcus pneumoniae and Haemophilus influenzae, increased rates of resistance to beta-lactams, macrolides, and earlier-generation tetracyclines highlight the need for new antibiotic agents. Stets et al. conducted a noninferiority trial that compared omadacycline to moxifloxacin for the treatment of hospitalized adults (not in an intensive care unit) who had community-acquired bacterial pneumonia. Read the NEJM Original Article here.
Q: What is omadacycline?
A: Omadacycline is a new once-daily aminomethylcycline antibiotic that reaches high concentrations in pulmonary tissues and is active against common pathogens that cause community-acquired bacterial pneumonia. It is derived from the tetracycline class, and overcomes the efflux and ribosomal protection mechanisms of tetracycline resistance.
Q: How is omadacyline administered?
A: In the trial by Stets et al., patients were randomly assigned in a 1:1 ratio to receive 7 to 14 days of omadacycline (100 mg administered intravenously every 12 hours for two doses, then 100 mg administered intravenously every 24 hours, with the option to transition to 300 mg taken orally every 24 hours after ≥3 days) or moxifloxacin (400 mg administered intravenously every 24 hours, with the option to transition to 400 mg taken orally every 24 hours after ≥3 days).
Morning Report Questions
Q: Did the study by Stets et al. show that omadacycline was noninferior to moxifloxacin for the treatment of adults with community-acquired bacterial pneumonia?
A: In the trial by Stets et al., the primary efficacy end point was early clinical response, assessed at 72 to 120 hours after the first dose of trial drug in the intention-to-treat population, determined programmatically on the basis of the investigator’s assessment of symptoms of community-acquired bacterial pneumonia (cough, sputum production, pleuritic chest pain, and dyspnea) on a 4-point scale (absent, mild, moderate, or severe). Omadacycline was noninferior to moxifloxacin with regard to early clinical response (response rate, 81.1% and 82.7%, respectively; difference, –1.6 percentage points; 95% confidence interval [CI], −7.1 to 3.8). Durable efficacy was also shown for investigator-assessed clinical response at the post-treatment evaluation 5 to 10 days after the end of therapy. The efficacy results were consistent across analysis populations, Pneumonia Severity Index risk classes (PSI risk classes range from I to V, with higher class numbers indicating a greater risk of death), and causative pathogens. The patients with the most severe community-acquired bacterial pneumonia (i.e., PSI risk class V) and immunocompromised patients were excluded, which limits the generalizability of the results to these important subpopulations of patients.
Q: What were the most frequent adverse events among patients who received omadacylcine in the trial by Stets et al.?
A: Adverse events that emerged after treatment initiation occurred in 41.1% of the patients in the omadacycline group and 48.5% of the patients in the moxifloxacin group. Gastrointestinal events were the most frequent (10.2% of patients in the omadacycline group and 18.0% of those in the moxifloxacin group). The largest difference between the groups was in the incidence of diarrhea (1.0% in the omadacycline group and 8.0% in the moxifloxacin group). Serious adverse events that emerged after treatment initiation occurred with similar incidence in the two groups (6.0% in the omadacycline group and 6.7% in the moxifloxacin group). The mortality rate was 2.1% in the omadacycline group, as compared with 1.0% in the moxifloxacin group. The cause of the mortality imbalance was not established.
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