Ralf Schmid, Chief Executive Officer of Nabriva, commented: “The rapid spread of multi-drug resistance in Gram-positive and Gram-negative pathogens has led to an urgent need for new and effective treatment options to fight serious infections.”
Zrinka Ivezic Schoenfeld, PhD, Vice President Non-Clinical of Nabriva, noted: “Our new generation of pleuromutilins – the extended spectrum pleuromutilins (ESP) – has demonstrated a potent antibacterial profile which covers the most prevalent Gram-positive and Gram-negative bacterial organisms, including multi-drug resistant strains. These ESP offer potential as new, effective treatment options.”
The four posters are as follows:
Antibacterial In Vitro Activity of Novel Extended Spectrum Pleuromutilins Against Gram-Positive and -Negative Bacterial Pathogens
S. Paukner, H. Kollmann, K. Thirring, W. Heilmayer, Z. Ivezic-Schoenfeld
This study investigated the antimicrobial activity of various novel derivatives of the new generation of pleuromutilin antibiotics - the extended spectrum pleuromutilins (ESP). Novel ESP demonstrated potent activity against the most prevalent Gram-positive and Gram-negative organisms including not only common multi-drug resistant isolates, but also carbapenemase-producing strains. The improved activity against Enterobacteriaceae represents a significant extension of the antibacterial profile of conventional pleuromutilins. Thus, further development of ESP is aimed at offering additional treatment options for patients with infections caused by multi-drug resistant bacteria such as carbapenemase-producing E. coli and K. pneumoniae.
In Vitro Metabolism and In Vivo Pharmacokinetics of Novel Extended Spectrum Pleuromutilin Antibiotics
D.B. Strickmann, W.W. Wicha, H. Kollmann, Z. Ivezic-Schoenfeld
Extended spectrum pleuromutilins the second generation of pleuromutilin antibiotics that demonstrates an enhanced antimicrobial spectrum, showed good in vitro metabolic stability and in vivo PK properties after s.c. administration. In murine models of infection, the ESP achieved exposures that resulted in high in vivo efficacy against S. aureus and E. coli infections.
In Vivo Activity of Extended Spectrum Pleuromutilins in Murine Sepsis Model
W. W. Wicha and Z. Ivezic-Schoenfeld
Extended spectrum pleuromutilins demonstrated excellent efficacy in severe murine septicemia caused by S. aureus and E. coli. Activity of the tested ESP against sepsis caused by S. aureus and E. coli was comparable to that of benchmark antibiotics linezolid and tigecycline. Based on these data, ESP will be further investigated in in vivo efficacy models including initial pre-clinical PK/PD studies.
Extended Spectrum Pleuromutilins: Mode-of-Action Studies
S. Paukner, D.B. Strickmann, Z. Ivezic-Schoenfeld
Novel ESP translated potent inhibition of prokaryotic protein synthesis in Gram-negative and Gram-positive organisms into potent antibacterial activity, thereby differentiating the ESP from first-generation pleuromutilins. The ESP displayed high uptake by target cells and appeared less subject to AcrAB-TolC mediated efflux than first-generation pleuromutilins. Thus, ESP are a new generation of pleuromutilins with a broad antimicrobial profile covering not only the most prevalent bacterial pathogens (e.g. staphylococci, streptococci, typical and atypical respiratory pathogens) but also multi-drug-resistant Enterobacteriaceae.