In Vitro Activities of Lefamulin and Other Antimicrobial Agents against Macrolide-Susceptible and Macrolide-Resistant Mycoplasma pneumoniae from the United States, Europe, and China

Abstract

Lefamulin, an investigational pleuromutilin, was tested against a collection of 18 macrolide-susceptible and 42 macrolide-resistant Mycoplasma pneumoniae strains, and the results were compared with those of azithromycin, erythromycin, tetracycline, doxycycline, and moxifloxacin testing. Lefamulin was highly active against all strains tested, with all MICs at Յ0.008 g/ml. The lefamulin MIC 90 (0.002 g/ml) for macrolide-resistant strains was the lowest among all drugs tested. Minimum bactericidal concentrations were within 2 dilutions of the MIC values, indicating a bactericidal effect.

Antibacterial Activity of Lefamulin against Pathogens Most Commonly Causing Community-Acquired Bacterial Pneumonia: SENTRY Antimicrobial Surveillance Program (2015–2016)

“…MDR, multidrug resistant; XDR, extensive drug resistant. Our results are consistent with previous studies reporting on the in vitro activity of lefamulin against typical and atypical respiratory pathogens (e.g., M. pneumoniae, C. pneumoniae, and L. pneumophila) (18,19,26,27). Furthermore, the in vitro activity of lefamulin has translated to clinical efficacy in two phase 3 clinical trials in adults with CABP, demonstrating the noninferiority of 5 to 10 days of lefamulin versus 7 to 10 days of moxifloxacin given in intravenous-to-oral or oral administration (28,29).…”

“…The unique interaction in this highly conserved region confers a low propensity for the development of bacterial resistance and is thought to be the reason for the lack of cross-resistance with other antibacterial classes, including macrolides, ketolides, lincosamides, fluoroquinolones, and tetracyclines (17). The antibacterial spectrum of lefamulin covers the typical Gram-positive and fastidious Gram-negative respiratory pathogens known to cause CABP and atypical pathogens, such as M. pneumoniae (including macrolide-resistant strains), C. pneumoniae, and L. pneumophila (18,19). Pharmacokinetic and pharmacodynamic analyses demonstrated that lefamulin has rapid and predictable penetration into plasma (ϳ1 to 2 g/ml after a single 150-mg intravenous or 600-mg oral dose) (20) and target tissues, such as the epithelial lining fluid in the lung (21), reaching area under the concentration-time curve (AUC):MIC ratios that support the proposed tentative breakpoints of 1 g/ml for S. pneumoniae and 0.5 g/ml for S. aureus (22).…”

The good, the bad and the tasty: The many roles of mushrooms

“…Research is still ongoing to develop novel pleuromutilin derivatives that could be employed as systemic antibiotics in human medicine (Ling et al., 2014, Zhang et al., 2015). One very promising compound is lefamulin, a pleuromutilin derivative developed by Nabriva Therapeutics that is soon to be entering phase III clinical trials for the treatment of moderate to severe CAPB (community-acquired bacterial pneumonia) (Prince et al., 2013, Rubino et al., 2015, Waites et al., 2016). Fig.…”

Capsular Polysaccharide is a Main Component ofMycoplasma ovipneumoniaein the Pathogen-Induced Toll-Like Receptor-Mediated Inflammatory Responses in Sheep Airway Epithelial Cells

“…Airway epithelium has recently been recognized as the first line of defense against M. pneumoniae infection, which is responsible for initiating an innate immune response by producing various array inflammatory mediators thus mediating lung inflammation [15, 19, 20]. Additionally, it plays a key role in regulating adaptive immune responses via expressing pattern recognition receptors such as toll-like receptors (TLRs) to trigger host defense responses, by interacting with dendritic cells to regulate antigen sensitization and by releasing cytokines and chemokines to recruit effector cells [19, 21].…”