Antimicrobial activity of the novel pleuromutilin antibiotic BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs)
Helio S. Sader,Susanne Paukner,Zrinka Ivezic-Schoenfeld,Douglas J. Biedenbach,Franz J Schmitz,Ronald N. Jones +5 more
TLDR
BC-3781 was very active against organisms commonly associated with CARTIs and its activity was not negatively influenced by resistance to other antimicrobials.Abstract:
Background BC-3781 is an investigational semi-synthetic pleuromutilin antibiotic, which recently finished a clinical Phase 2 trial in acute bacterial skin and skin structure infections. BC-3781 binds to the 50S ribosomal subunit and cross-resistance with other antimicrobial classes is uncommon. We evaluated the activity of BC-3781 against organisms responsible for community-acquired respiratory tract infections (CARTIs). Methods BC-3781 and comparator agents were susceptibility tested against Streptococcus pneumoniae (157 isolates; 33% penicillin resistant), Haemophilus influenzae (102; 50% β-lactamase producers), Moraxella catarrhalis (50) and Legionella pneumophila (30) by broth microdilution and the agar dilution method. Mycoplasma pneumoniae (50 strains) was tested by broth microdilution, while Chlamydophila pneumoniae (50 strains) MIC values were determined using HEp-2 cells. Results Against S. pneumoniae (MIC(50/90) 0.12/0.25 mg/L) BC-3781 was 16- and 8-fold more active than azithromycin (MIC(50/90) 2/>16 mg/L) and levofloxacin (MIC(50/90) 1/1 mg/L), respectively, and its activity was not adversely affected by resistance to penicillin. S. pneumoniae showed high resistance rates to azithromycin (50.3%) and clindamycin (31.2%), all being inhibited by BC-3781 at concentrations ≤0.5 mg/L. H. influenzae and M. catarrhalis exhibited low BC-3781 MIC values independent of β-lactamase production. BC-3781 activity against L. pneumophila (MIC(50/90) 0.06/0.5 mg/L) was similar to that of erythromycin, but lower than that of azithromycin. BC-3781 also showed potent activity against M. pneumoniae and C. pneumoniae, with MIC(50/90) of 0.006/0.006 and 0.02/0.04 mg/L, respectively. Conclusions BC-3781 was very active against organisms commonly associated with CARTIs and its activity was not negatively influenced by resistance to other antimicrobials.read more
Citations
More filters
Journal ArticleDOI
Natural product and natural product derived drugs in clinical trials
TL;DR: The next few years will be critical for NP-driven lead discovery, and a concerted effort is required to identify new biologically active pharmacophores and to progress these and existing compounds through pre-clinical drug development into clinical trials.
Journal ArticleDOI
Antibiotics in the clinical pipeline in 2013
TL;DR: The continued emergence of multi-drug-resistant bacteria is a major public health concern and the identification and development of new antibiotics, especially those with new modes of action, is imperative to help treat these infections.
Journal ArticleDOI
New antibiotics for bad bugs: where are we?
TL;DR: The need of new antibiotics still does not cover the increasing prevalence of antibiotic-resistant bacterial infections, so the management of antimicrobial resistance should also include fostering coordinated actions by all stakeholders, creating policy guidance, support for surveillance and technical assistance.
Journal ArticleDOI
Mycoplasma pneumoniae from the Respiratory Tract and Beyond
TL;DR: This review focuses on the many new developments that have occurred over the past several years that enhance the understanding of this microbe, which is among the smallest bacterial pathogens but one of great clinical importance.
Journal ArticleDOI
Antibiotics in the clinical pipeline at the end of 2015
TL;DR: There is growing global recognition that the continued emergence of multidrug-resistant bacteria poses a serious threat to human health and action plans released by the World Health Organization and governments of the UK and USA in particular recognize that discovering new antibiotics, particularly those with new modes of action, is one essential element required to avert future catastrophic pandemics.
References
More filters
Journal ArticleDOI
Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults
Lionel A. Mandell,Richard G. Wunderink,Antonio Anzueto,John G. Bartlett,G. Douglas Campbell,Nathan C. Dean,Nathan C. Dean,Scott F. Dowell,Daniel M. Musher,Daniel M. Musher,Michael S. Niederman,Michael S. Niederman,Antoni Torres,Cynthia G. Whitney,Michael E. DeBakey Veterans +14 more
TL;DR: This work presents a meta-analyses of the immune system’s response to chronic obstructive pulmonary disease and shows clear patterns of decline in the immune systems of elderly patients with compromised immune systems.
Journal ArticleDOI
Methodologies and Cell Lines Used for Antimicrobial Susceptibility Testing of Chlamydia spp.
TL;DR: All strains of chlamydia tested demonstrated survival after exposure to high levels of antimicrobials, and this phenomenon does not reflect selection of antimicrobial-resistant mutants but rather survival of some organisms in high antimicrobial concentrations (heterotypic survival).
Journal Article
The pleuromutilin antibiotics: a new class for human use.
Rodger Novak,David M Shlaes +1 more
TL;DR: The key properties of pleuromutilin derivatives, designed primarily through modifications at the C(14) side chain, are presented, and the potential of these compounds in systemic therapy in humans is discussed.