1320. In Vitro Activity of Lefamulin against <i>Staphylococcus aureus</i> Isolated from the Lower Respiratory Tract of Children with Cystic Fibrosis
Bibliographic record
Abstract
Abstract Background Lefamulin is a first-in-class, oral and IV pleuromutilin antibiotic approved in the US, EU, and Canada for the treatment of community-acquired bacterial pneumonia (CABP) in adults. Lefamulin inhibits bacterial protein synthesis via a unique mechanism of action and its potency against S. aureus has been well established. We evaluated the in vitro activity of lefamulin against S. aureus from patients with cystic fibrosis (CF). Methods Unique isolates (n=224) were collected from the lower respiratory tract (LRT) of children (≤17 years old) with CF and LRT infection. Organisms were from qualified respiratory specimens and determined to be the probable cause of infection by the participant center. The isolates were collected in 2018-2020 from 22 medical centers in 11 countries and tested by broth microdilution methods at JMI Laboratories. Most isolates were from the US (43.3%), Spain (24.1%), France (20.5%), and Costa Rica (7.1%). Results Lefamulin was highly active against the CF S. aureus collection (MIC5090, 0.06/0.12 mg/L), with 99.6% of isolates inhibited at ≤0.25 mg/L, consistent with the susceptible [S] breakpoint published by the US FDA, CLSI, and EUCAST. Only 1 lefamulin-non-S (MIC, 1 mg/L) isolate was observed, a methicillin-susceptible (MSSA) collected in Costa Rica in 2018 and carrying a vga(A) gene. Lefamulin retained potent activity against methicillin-resistant (R) S. aureus (MRSA, n=52; MIC50/90, 0.06/0.12 mg/L), azithromycin-R (n=115; MIC50/90, 0.06/0.12 mg/L), levofloxacin-R (n=23; MIC50/90, 0.06/0.12 mg/L), clindamycin-R (n=11; MIC50/90, 0.06/0.12 mg/L), and gentamicin-R (n=9; MIC range of 0.03-0.12 mg/L) isolates as well as those isolates with multiple resistance phenotypes. Against MRSA, susceptibility to azithromycin was 23.5% and to levofloxacin 64.7%. All isolates were susceptible to vancomycin, linezolid and ceftaroline (Table). Among isolates from the US (n=97), the MRSA rate was 30.9% and all isolates were Lefamulin-S (MIC5090, 0.06/0.12 mg/L). Conclusion Lefamulin demonstrated potent in vitro antibacterial activity against S. aureus from children with CF, regardless of resistance phenotype. Lefamulin may represent a valuable treatment option for CF patients with S. aureus LRT infections. Disclosures Helio S. Sader, MD, PhD, FIDSA, AbbVie (formerly Allergan) (Research Grant or Support)Basilea Pharmaceutica International, Ltd. (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support, Contract no. HHSO100201600002C)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Susanne Paukner, PhD, Nabriva Therapeutics GmbH (Employee) Steven P. Gelone, PharmD, Nabriva Therapeutics US, Inc. (Employee) S J Ryan Arends, PhD, AbbVie (formerly Allergan) (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Spero Therapeutics (Research Grant or Support) Rodrigo E. Mendes, PhD, AbbVie (Research Grant or Support)AbbVie (formerly Allergan) (Research Grant or Support)Cipla Therapeutics (Research Grant or Support)Cipla USA Inc. (Research Grant or Support)ContraFect Corporation (Research Grant or Support)GlaxoSmithKline, LLC (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, LLC (Research Grant or Support)Nabriva Therapeutics (Research Grant or Support)Pfizer, Inc. (Research Grant or Support)Shionogi (Research Grant or Support)Spero Therapeutics (Research Grant or Support)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".