Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. In this randomized controlled trial, oral lefamulin was noninferior to oral moxifloxacin for treating community-acquired pneumonia, with regards to early clinical response at 96 hours post first dose.

2. Patients who received lefamulin reported more diarrhea and nausea than those who received moxifloxacin.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

The rate of microbial resistance is growing among patients suffering from community acquired bacterial pneumonia (CABP). As a result, new antibiotics are required to overcome this resistance and further help manage the outstanding safety concerns. Lefamulin, a novel pleuromutilin antibiotic, is the first of its class to be approved for enteral or parenteral use in humans. In this randomized controlled trial, a 5-day oral lefamulin course was shown to be noninferior to a 7-day oral moxifloxacin course. Both medications were reported to produce a high clinical response with respect to Pneumonia Outcomes Research Team (PORT) risk class, typical and atypical pathogens, polymicrobial infections, and demographic and baseline characteristics at 96 hours post first dose. In addition, there were similar rates of adverse events between groups, though there were more episodes of diarrhea and nausea in the lefamulin group.

The study successfully randomized a high proportion of patients with more severe forms of CABP, limited use of prior antibiotics, and demonstrated low drug and study discontinuation rates, which strengthens the trial findings. The trial is limited by its extensive exclusion criteria, which restricts the results from being applied to the general patient population with comorbid diseases.

In-Depth [randomized control trial]:

The Lefamulin Evaluation Against Pneumonia (LEAP) 2 trial recruited 738 patients, of which 47.6% were women with a mean age of 57.5 years. The study was conducted from August 2016 to January 2018 across 19 countries throughout Europe, North America, South America, Asia, and Africa. 99 sites participated in this phase 3, double-blind, double-dummy, parallel-group randomized clinical trial, where participants aged 18 and over were followed for 30 days. Participants were included based on the presence of PORT risk class II, III, or IV radiographically documented pneumonia, acute illness (≤7 days), and 3 or more CABP symptoms (dyspnea, new or increased cough, purulent sputum production, and chest pain). The excluded participants had one or more indications of 1 dose of a short-acting (having a dosing interval more frequent than every 24 hours) oral or intravenous antibacterial for CABP within 72 hours before randomization, hospitalization for 2 days or longer within 90 days, confirmed or suspected methicillin-resistant S. aureus, being at risk for major cardiac events or dysfunction, and having significant hepatic disease. The study demonstrated that after the first dose, early clinical response at 96 hours (within a 24-hour window) of 90.8% response was detected in the lefamulin group and 90.8% in the moxifloxacin group, a difference that met the noninferiority margin of 10% (difference 0.1%; 1-sided CI97.5 -4.4% to ∞). Those treated with lefamulin had a higher rate of diarrhea (12.2% vs 1.1%) and nausea (5.2% vs 1.9%) than those treated with moxifloxacin.

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