Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial.
Aged; Humans; Male; Adult; Female; Middle Aged; Double-Blind Method; Administration Intravenous; Microbial Sensitivity Tests; pneumonia; Randomized Controlled Trials as Topic; antibiotic; lefamulin; moxifloxacin; pleuromutilin; Anti-Bacterial Agents/administration & dosage/adverse effects/therapeutic use; Diterpenes/administration & dosage/adverse effects/therapeutic use; Linezolid/adverse effects/therapeutic use; Moxifloxacin/administration & dosage/adverse effects/therapeutic use; Pneumonia Bacterial/drug therapy/metabolism; Polycyclic Compounds/administration & dosage/adverse effects/therapeutic use; Thioglycolates/administration & dosage/adverse effects/therapeutic use
BACKGROUND: Lefamulin, a pleuromutilin antibiotic, is active against pathogens commonly causing community-acquired bacterial pneumonia (CABP). The Lefamulin Evaluation Against Pneumonia (LEAP 1) study was a global noninferiority trial to evaluate the efficacy and safety of lefamulin for the treatment of CABP. METHODS: In this double-blind study, adults with CABP of Pneumonia Outcomes Research Team risk class ≥III were randomized 1:1 to receive lefamulin at 150 mg intravenously (IV) every 12 hours or moxifloxacin at 400 mg IV every 24 hours. After 6 doses, patients could be switched to an oral study drug if prespecified improvement criteria were met. If methicillin-resistant Staphylococcus aureus was suspected, either linezolid or placebo was added to moxifloxacin or lefamulin, respectively. The US Food and Drug Administration primary endpoint was an early clinical response (ECR) 96 ± 24 hours after the first dose of the study drug in the intent-to-treat (ITT) population (noninferiority margin, 12.5%). The European Medicines Agency co-primary endpoints were an investigator assessment of clinical response (IACR) 5-10 days after the last dose of the study drug in the modified ITT (mITT) and clinically evaluable (CE) populations (noninferiority margin, 10%). RESULTS: There were 551 patients randomized (n = 276 lefamulin; n = 275 moxifloxacin). Lefamulin was noninferior to moxifloxacin for ECR (87.3% vs 90.2%, respectively; difference -2.9%, 95% confidence interval [CI] g -8.5 to 2.8) and IACR (mITT, 81.7% vs 84.2%, respectively; difference -2.6%, 95% CI -8.9 to 3.9; CE, 86.9% vs 89.4%, respectively; difference -2.5%, 95% CI -8.4 to 3.4). Rates of study drug discontinuation due to treatment-emergent adverse events were 2.9% for lefamulin and 4.4% for moxifloxacin. CONCLUSIONS: Lefamulin was noninferior to moxifloxacin for the primary efficacy endpoints and was generally safe and well tolerated. CLINICAL TRIALS REGISTRATION: NCT02559310.
File TM; Goldberg L; Das A; Sweeney C; Saviski J; Gelone SP; Seltzer E; Paukner S; Wicha WW; Talbot GH; Gasink LB
Clinical Infectious Diseases
2019
2019-11-13
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1093/cid/ciz090" target="_blank" rel="noreferrer noopener">10.1093/cid/ciz090</a>
Impact of the expansion of antimicrobial stewardship services during transitions of care at an academic hospital.
Antimicrobial stewardship of anti-infectives prescribed upon hospital discharge was implemented to improve the rate of appropriate prescribing at discharge. Appropriate prescribing significantly improved from 47.5% to 85.2% (P < .001), antimicrobial days of therapy decreased, and 30-day readmission rates decreased. Discharge antimicrobial stewardship was effective in improving anti-infective prescribing practices.
Zampino ST; Politis PA; Fosnight SM; File TM; Gothard MD
Infection Control and Hospital Epidemiology
2020
2020-06
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1017/ice.2020.216" target="_blank" rel="noreferrer noopener">10.1017/ice.2020.216</a>