Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials
Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/10/12/1489 |
| _version_ | 1797506874329792512 |
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| author | Susanne Paukner David Mariano Anita F. Das Gregory J. Moran Christian Sandrock Ken B. Waites Thomas M. File |
| author_facet | Susanne Paukner David Mariano Anita F. Das Gregory J. Moran Christian Sandrock Ken B. Waites Thomas M. File |
| author_sort | Susanne Paukner |
| collection | DOAJ |
| description | Lefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens (<i>Mycoplasma pneumoniae</i>, <i>Legionella pneumophila</i>, and <i>Chlamydia pneumoniae</i>). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5–7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5–10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality (<i>M. pneumoniae</i> 71.2% [52/73]; <i>L.</i> <i>pneumophila</i> 96.9% [63/65]; <i>C. pneumoniae</i> 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0–2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4–96.6%; moxifloxacin 90.3–96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1–89.7%; moxifloxacin 74.2–97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens. |
| first_indexed | 2024-03-10T04:39:38Z |
| format | Article |
| id | doaj.art-76c7e81345964cbda5fd2343e3fce190 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T04:39:38Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-76c7e81345964cbda5fd2343e3fce1902023-11-23T03:30:37ZengMDPI AGAntibiotics2079-63822021-12-011012148910.3390/antibiotics10121489Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 TrialsSusanne Paukner0David Mariano1Anita F. Das2Gregory J. Moran3Christian Sandrock4Ken B. Waites5Thomas M. File6Nabriva Therapeutics GmbH, Leberstrasse 20, 1110 Vienna, AustriaNabriva Therapeutics US, Inc., Fort Washington, PA 19034, USADas Consulting, Guerneville, CA 95446, USAOlive View-UCLA Medical Center, Los Angeles, CA 91342, USADepartment of Internal Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USADepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USASumma Health, Akron, OH 44304, USALefamulin was the first systemic pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia based on two phase 3 trials (Lefamulin Evaluation Against Pneumonia [LEAP]-1 and LEAP-2). This pooled analysis evaluated lefamulin efficacy and safety in adults with community-acquired bacterial pneumonia caused by atypical pathogens (<i>Mycoplasma pneumoniae</i>, <i>Legionella pneumophila</i>, and <i>Chlamydia pneumoniae</i>). In LEAP-1, participants received intravenous lefamulin 150 mg every 12 h for 5–7 days or moxifloxacin 400 mg every 24 h for 7 days, with optional intravenous-to-oral switch. In LEAP-2, participants received oral lefamulin 600 mg every 12 h for 5 days or moxifloxacin 400 mg every 24 h for 7 days. Primary outcomes were early clinical response at 96 ± 24 h after first dose and investigator assessment of clinical response at test of cure (5–10 days after last dose). Atypical pathogens were identified in 25.0% (91/364) of lefamulin-treated patients and 25.2% (87/345) of moxifloxacin-treated patients; most were identified by ≥1 standard diagnostic modality (<i>M. pneumoniae</i> 71.2% [52/73]; <i>L.</i> <i>pneumophila</i> 96.9% [63/65]; <i>C. pneumoniae</i> 79.3% [46/58]); the most common standard diagnostic modality was serology. In terms of disease severity, more than 90% of patients had CURB-65 (confusion of new onset, blood urea nitrogen > 19 mg/dL, respiratory rate ≥ 30 breaths/min, blood pressure <90 mm Hg systolic or ≤60 mm Hg diastolic, and age ≥ 65 years) scores of 0–2; approximately 50% of patients had PORT (Pneumonia Outcomes Research Team) risk class of III, and the remaining patients were more likely to have PORT risk class of II or IV versus V. In patients with atypical pathogens, early clinical response (lefamulin 84.4–96.6%; moxifloxacin 90.3–96.8%) and investigator assessment of clinical response at test of cure (lefamulin 74.1–89.7%; moxifloxacin 74.2–97.1%) were high and similar between arms. Treatment-emergent adverse event rates were similar in the lefamulin (34.1% [31/91]) and moxifloxacin (32.2% [28/87]) groups. Limitations to this analysis include its post hoc nature, the small numbers of patients infected with atypical pathogens, the possibility of PCR-based diagnostic methods to identify non-etiologically relevant pathogens, and the possibility that these findings may not be generalizable to all patients. Lefamulin as short-course empiric monotherapy, including 5-day oral therapy, was well tolerated in adults with community-acquired bacterial pneumonia and demonstrated high clinical response rates against atypical pathogens.https://www.mdpi.com/2079-6382/10/12/1489atypical pathogenslefamulincommunity-acquired bacterial pneumonia<i>Mycoplasma pneumoniae</i><i>Chlamydia pneumoniae</i><i>Legionella pneumophila</i> |
| spellingShingle | Susanne Paukner David Mariano Anita F. Das Gregory J. Moran Christian Sandrock Ken B. Waites Thomas M. File Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials Antibiotics atypical pathogens lefamulin community-acquired bacterial pneumonia <i>Mycoplasma pneumoniae</i> <i>Chlamydia pneumoniae</i> <i>Legionella pneumophila</i> |
| title | Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials |
| title_full | Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials |
| title_fullStr | Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials |
| title_full_unstemmed | Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials |
| title_short | Lefamulin in Patients with Community-Acquired Bacterial Pneumonia Caused by Atypical Respiratory Pathogens: Pooled Results from Two Phase 3 Trials |
| title_sort | lefamulin in patients with community acquired bacterial pneumonia caused by atypical respiratory pathogens pooled results from two phase 3 trials |
| topic | atypical pathogens lefamulin community-acquired bacterial pneumonia <i>Mycoplasma pneumoniae</i> <i>Chlamydia pneumoniae</i> <i>Legionella pneumophila</i> |
| url | https://www.mdpi.com/2079-6382/10/12/1489 |
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