Новый антибиотик для лечения бактериальной пневмонии.
Выпуск новых антибиотиков является редкостью в наши дни, не говоря уже о новых классах антибиотиков. В августе 2019 года FDA одобрило лефамулин (Xenleta), ингибитор синтеза бактериального белка из класса плевромутилинов широкого спектра действия, для лечения пациентов с бактериальной пневмонией.
В двух плацебо-контролируемых исследованиях, на основании которых препарат был одобрен FDA, исследователи рандомизировали 738 амбулаторных пациентов (средний возраст 57 лет) с внебольничной пневмонией. Одна группа перорально принимала лефамулин (два раза в день в течение 5 дней), вторая - пероральный моксифлоксацин (ежедневно в течение 7 дней). Пациенты были набраны из 19 стран, главным образом в Восточной Европе; 40% были курильщиками. У большинства пациентов были сопутствующие заболевания. В целом, препараты показали одинаково хорошие результаты. Клинически состояние пациентов улучшилось через 4 дня и оставалось стабильным после прекращения лечения. Результаты также были одинаково хорошими для подгруппы, в которых были идентифицированы лекарственно-устойчивый пневмококк или метициллин-устойчивый золотистый стафилококк. Необходимо отметить, что у пациентов принимавших лефамулин, значительно чаще имели место побочные желудочно-кишечные реакции (18% против 8%), в основном в виде диареи и рвоты.
Источник: JAMA. 2019 Sep 27. doi: 10.1001/jama.2019.15468. [Epub ahead of print]
Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial.
Alexander E et al
IMPORTANCE:
New antibacterials are needed to treat community-acquired bacterial pneumonia (CABP) because of growing antibacterial resistance and safety concerns with standard care.
OBJECTIVE:
To evaluate the efficacy and adverse events of a 5-day oral lefamulin regimen in patients with CABP.
DESIGN, SETTING, AND PARTICIPANTS:
A phase 3, noninferiority randomized clinical trial conducted at 99 sites in 19 countries that included adults aged 18 years or older with a Pneumonia Outcomes Research Team (PORT) risk class of II, III, or IV; radiographically documented pneumonia; acute illness; 3 or more CABP symptoms; and 2 or more vital sign abnormalities. The first patient visit was on August 30, 2016, and patients were followed up for 30 days; the final follow-up visit was on January 2, 2018.
INTERVENTIONS:
Patients were randomized 1:1 to receive oral lefamulin (600 mg every 12 hours for 5 days; n = 370) or moxifloxacin (400 mg every 24 hours for 7 days; n = 368).
MAIN OUTCOMES AND MEASURES:
The US Food and Drug Administration (FDA) primary end point was early clinical response at 96 hours (within a 24-hour window) after the first dose of either study drug in the intent-to-treat (ITT) population (all randomized patients). Responders were defined as alive, showing improvement in 2 or more of the 4 CABP symptoms, having no worsening of any CABP symptoms, and not receiving any nonstudy antibacterial drug for current CABP episode. The European Medicines Agency coprimary end points (FDA secondary end points) were investigator assessment of clinical response at test of cure (5-10 days after last dose) in the modified ITT population and in the clinically evaluable population. The noninferiority margin was 10% for early clinical response and investigator assessment of clinical response.
RESULTS:
Among 738 randomized patients (mean age, 57.5 years; 351 women [47.6%]; 360 had a PORT risk class of III or IV [48.8%]), 707 (95.8%) completed the trial. Early clinical response rates were 90.8% with lefamulin and 90.8% with moxifloxacin (difference, 0.1% [1-sided 97.5% CI, -4.4% to ∞]). Rates of investigator assessment of clinical response success were 87.5% with lefamulin and 89.1% with moxifloxacin in the modified ITT population (difference, -1.6% [1-sided 97.5% CI, -6.3% to ∞]) and 89.7% and 93.6%, respectively, in the clinically evaluable population (difference, -3.9% [1-sided 97.5% CI, -8.2% to ∞]) at test of cure. The most frequently reported treatment-emergent adverse events were gastrointestinal (diarrhea: 45/368 [12.2%] in lefamulin group and 4/368 [1.1%] in moxifloxacin group; nausea: 19/368 [5.2%] in lefamulin group and 7/368 [1.9%] in moxifloxacin group).
CONCLUSIONS AND RELEVANCE:
Among patients with CABP, 5-day oral lefamulin was noninferior to 7-day oral moxifloxacin with respect to early clinical response at 96 hours after first dose.