Antibacterial Activity of Lefamulin against Pathogens Most Commonly Causing Community-Acquired Bacterial Pneumonia:
Susanne Paukner1, Steven P Gelone2, S J Ryan Arends3
1Nabriva Therapeutics GmbH, Vienna, Austria Susanne.Paukner@nabriva.com.
Abstract:
Lefamulin, the first semisynthetic pleuromutilin antibacterial for intravenous and oral treatment of community-acquired bacterial pneumonia (CABP), and comparators were evaluated for in vitro activity against a global collection of pathogens commonly causing CABP (n = 8595) from the 2015 and 2016 SENTRY Antimicrobial Surveillance Program. Lefamulin was highly active against the pathogens Streptococcus pneumoniae, including multidrug-resistant and extensively drug-resistant strains (MIC50/90 for total and resistant subsets, 0.06/0.12 μg/ml; 100% inhibited at ≤1 μg/ml), Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA; both MIC50/90, 0.06/0.12 μg/ml; 99.8% and 99.6% inhibited at ≤1 μg/ml, respectively), Haemophilus influenzae (MIC50/90, 0.5/1 μg/ml; 93.8% inhibited at ≤1 μg/ml), and Moraxella catarrhalis (MIC50/90, 0.06/0.12 μg/ml; 100% inhibited at ≤0.25 μg/ml), and its activity was unaffected by resistance to other antibacterial classes.
Insights
Lefamulin demonstrates potent in vitro activity against key community-acquired bacterial pneumonia pathogens, including resistant strains. This novel antibacterial agent shows consistent efficacy unaffected by existing resistance mechanisms.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Community-acquired bacterial pneumonia (CABP) poses a significant global health challenge.
- Emerging antimicrobial resistance necessitates the development of novel therapeutic agents.
- Lefamulin represents a new class of antibiotics, pleuromutilins, for treating bacterial pneumonia.
Purpose of the Study:
- To evaluate the in vitro activity of lefamulin against a broad spectrum of CABP pathogens.
- To compare lefamulin's efficacy with existing antibiotics against resistant bacterial strains.
- To assess the impact of existing resistance mechanisms on lefamulin's antibacterial spectrum.
Main Methods:
- In vitro susceptibility testing of 8,595 global bacterial isolates.
- Utilized data from the 2015-2016 SENTRY Antimicrobial Surveillance Program.
- Determined minimum inhibitory concentrations (MIC50/90) for lefamulin and comparators.
Main Results:
- Lefamulin exhibited high potency against Streptococcus pneumoniae (MIC50/90, 0.06/0.12 μg/ml), including resistant strains.
- Excellent activity was observed against methicillin-resistant Staphylococcus aureus (MRSA) (MIC50/90, 0.06/0.12 μg/ml).
- Lefamulin was effective against Haemophilus influenzae and Moraxella catarrhalis, with activity independent of resistance to other antibiotic classes.
Conclusions:
- Lefamulin demonstrates broad-spectrum in vitro activity against major CABP pathogens.
- Its efficacy against drug-resistant strains, including MRSA, highlights its potential clinical utility.
- Lefamulin offers a promising new option for treating bacterial pneumonia, even in the face of antimicrobial resistance.
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