Ceftibuten—in-vitro activity against respiratory pathogens, β-lactamase stability and mechanism of action

1990 ◽  
Vol 26 (2) ◽  
pp. 209-213 ◽  
Author(s):  
R. Wise ◽  
J. M. Andrews ◽  
J. P. Ashby ◽  
D. Thornber
Keyword(s):  
Mechanism Of Action ◽  
Vitro Activity ◽  
Respiratory Pathogens ◽  
In Vitro Activity

Comparative in-vitro activity of carbapenem antibiotics against respiratory pathogens isolated between 1999 and 2000

2001 ◽  
Vol 7 (4) ◽  
pp. 267-271 ◽  
Author(s):  
Akira Watanabe ◽  
Yutaka Tokue ◽  
Hiroshi Takahashi ◽  
Tohru Kikuchi ◽  
Takao Kobayashi ◽  
...  
Keyword(s):  
Vitro Activity ◽  
Respiratory Pathogens ◽  
In Vitro Activity

scholarly journals Diphenyl Furans and Aza Analogs: Effects of Structural Modification on In Vitro Activity, DNA Binding, and Accumulation and Distribution in Trypanosomes

2007 ◽  
Vol 51 (8) ◽  
pp. 2801-2810 ◽  
Author(s):  
Amanda M. Mathis ◽  
Arlene S. Bridges ◽  
Mohamed A. Ismail ◽  
Arvind Kumar ◽  
Iris Francesconi ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Structural Modification ◽  
Human African Trypanosomiasis ◽  
Treatment Options ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Antitrypanosomal Activity ◽  
Specific Accumulation ◽  
High Concentrations

ABSTRACT Human African trypanosomiasis is a devastating disease with only a few treatment options, including pentamidine. Diamidine compounds such as pentamidine, DB75, and DB820 are potent antitrypanosomal compounds. Previous investigations have shown that diamidines accumulate to high concentrations in trypanosomes. However, the mechanism of action of this class of compounds remains unknown. A long-hypothesized mechanism of action has been binding to DNA and interference with DNA-associated enzymes. The fluorescent diamidines, DB75 and DB820, have been shown to localize not only in the DNA-containing nucleus and kinetoplast of trypanosomes but also to the acidocalcisomes. Here we investigate two series of analogs of DB75 and DB820 with various levels of in vitro antitrypanosomal activity to determine whether any correlation exists between trypanosome accumulation, distribution, and in vitro activity. Despite wide ranges of in vitro antitrypanosomal activity, all of the compounds investigated accumulated to millimolar concentrations in trypanosomes over a period of 8 h. Interestingly, some of the less potent compounds accumulated to concentrations much higher than those of more potent compounds. All of the compounds were localized to the DNA-containing nucleus and/or kinetoplast, and many were also found in the acidocalcisomes. Accumulation in the nucleus and kinetoplast should be important to the mechanism of action of these compounds. The acidocalcisomes may also play a role in the mechanism of action of these compounds. This investigation suggests that the extent of accumulation alone is not responsible for killing trypanosomes and that organelle-specific accumulation may not predict in vitro activity.

scholarly journals In Vitro Activity of Lefamulin Against a Global Collection of Bacterial Pathogens Commonly Causing Community-Acquired Bacterial Pneumonia (CABP, SENTRY 2015)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S373-S373 ◽  
Author(s):  
Susanne Paukner ◽  
Helio S Sader ◽  
Jennifer M Streit ◽  
Robert K Flamm ◽  
Steven P Gelone
Keyword(s):  
Respiratory Tract ◽  
Bacterial Pathogens ◽  
Bloodstream Infections ◽  
Vitro Activity ◽  
Asia Pacific ◽  
Respiratory Pathogens ◽  
In Vitro Activity ◽  
Tract Infections ◽  
Research Grant

Abstract Background CABP is the number one reason for death by infectious diseases worldwide and emerging resistance complicates its treatment. Lefamulin is the first semi-synthetic pleuromutilin antibiotic for IV and oral use in humans. It is currently in Phase 3 trials for the treatment of CABP in adults. Lefamulin effectively and selectively inhibits bacterial translation by binding to the peptidyl transferase center (PTC) via four H-bonds and other interactions at the A- and P-site resulting in an “induced fit.” This study investigated the activity of lefamulin and comparators against a contemporary set of bacterial pathogens associated with community-acquired respiratory infections collected worldwide. Methods Unique patients’ isolates (n = 2817) were collected globally in US (19.7%), Europe (36.9%), Latin America (5.7%) and Asia-Pacific region (37.6%) (30 countries, 116 sites) from adult and pediatric patients with respiratory tract infection (88.0%), bloodstream infections (5.5%) and other infections (2.4%). Lefamulin and comparators were tested by CLSI broth microdilution and susceptibility was determined using the CLSI (2017) breakpoints. Results LEF was the most potent compound tested, with 99.7% of all S. pneumoniae isolates being inhibited at a concentration of ≤0.25 mg/L (MIC50/90 values of 0.06/0.12 mg/L) and its activity was not affected by resistance to other antibiotic classes. S. pneumoniae isolates were largely susceptible to levofloxacin (99.1%) and ceftriaxone (96.5%), while 34.5%, 23.3% and 16.8% of isolates were resistant to macrolides, tetracycline and clindamycin, respectively. Lefamulin also showed potent activity against H. influenzae (MIC50/90 of 0.5/1 mg/L), including 22.0% of ß-lactamase producing strains, and M. catarrhalis (0.06/0.12 mg/L). Conclusion Lefamulin demonstrated potent in vitro activity against this global collection of contemporary respiratory pathogens and its activity was unchanged regardless of resistance phenotype to the other antibiotic classes including macrolides, ß-lactams, tetracyclines or fluoroquinolones. These data support the continued clinical development of lefamulin for the treatment of respiratory tract infections, including CABP. Disclosures S. Paukner, Nabriva Therapeutics: Employee and Shareholder, Salary; H. S. Sader, Nabriva Therapeutics: Research Contractor, Research grant; J. M. Streit, Nabriva Therapeutics: Research Contractor, Research grant; R. K. Flamm, Nabriva Therapeutics: Research Contractor, Research grant; S. P. Gelone, Nabriva Therapeutics: Employee and Shareholder, Salary

scholarly journals 1353. In Vitro Activity of Lefamulin (LEF) Against Bacterial Pathogens Commonly Causing Community-Acquired Bacterial Pneumonia (CABP): 2016 SENTRY Data From the United States

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S414-S414 ◽  
Author(s):  
Susanne Paukner ◽  
Robert K Flamm ◽  
Steven P Gelone ◽  
Helio S Sader
Keyword(s):  
United States ◽  
Ribosomal Subunit ◽  
The United States ◽  
Vitro Activity ◽  
Surveillance Program ◽  
Respiratory Pathogens ◽  
In Vitro Activity ◽  
Medical Centers ◽  
Tract Infections

Abstract Background LEF, the first pleuromutilin antibiotic for IV and oral use in humans, is in Phase 3 clinical trials for the treatment of CABP in adults. In the first of these to be completed, LEF demonstrated noninferiority to moxifloxacin ± linezolid. LEF inhibits bacterial translation by binding the 50S ribosomal subunit at the A- and P-sites in the peptidyl transferase center. CABP is a leading cause of infectious diseases in the United States and increasing antibacterial resistance complicates its treatment. This study investigated the in vitro activity of LEF and comparators against a contemporary set of bacterial respiratory pathogens collected in the United States. Methods Isolates (n = 1674, 1/patient) were collected from 32 medical centers in the United States as part of the SENTRY Surveillance Program. LEF and comparators were tested by CLSI broth microdilution methods, and susceptibility was determined using the CLSI (2018) breakpoints. Results LEF was the most active compound against Streptococcus pneumoniae (MIC50/90 of 0.12/0.12 µg/mL), and its activity was not affected by resistance to other antibiotic classes. S. pneumoniae isolates were susceptible to levofloxacin (99.1%) and ceftriaxone (97.7%), whereas only 53.9%, 63.9%, and 80.4% of isolates were susceptible to macrolides, penicillin (oral), and tetracycline, respectively. LEF also showed potent activity against Staphylococcus aureus (MIC50/90 of 0.06/0.12 µg/mL), including methicillin-resistant (MRSA) isolates (MIC50/90 of 0.06/0.12 µg/mL, 87.1% resistant to erythromycin), Haemophilus influenzae, (MIC50/90 of 0.5/1 µg/mL, 26.9% β-lactamase producing), and Moraxella catarrhalis (MIC50/90 0.06/0.06 µg/mL, 96.5% β-lactamase positive) (figure). Conclusion LEF displayed potent in vitro activity against a contemporary collection of respiratory pathogens from the United States. LEF was active regardless of resistance phenotype to other antibiotic classes including β-lactams, tetracyclines, or macrolides. These results further support the clinical development of lefamulin for the treatment of CABP or other respiratory tract infections. Disclosures S. Paukner, Nabriva: Employee and Shareholder, Salary. R. K. Flamm, Nabriva: Research Contractor, Research grant. S. P. Gelone, Nabriva Therapeutics: Employee, Equity, Shareholder and Salary. Achaogen: Shareholder, Equity, Shareholder. H. S. Sader, Nabriva Therapeutics: Research Contractor, Research support.

scholarly journals Design, Synthesis and In Vitro Activity of Anticancer Styrylquinolines. The p53 Independent Mechanism of Action

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142678 ◽  
Author(s):  
Anna Mrozek-Wilczkiewicz ◽  
Ewelina Spaczynska ◽  
Katarzyna Malarz ◽  
Wioleta Cieslik ◽  
Marzena Rams-Baron ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Design Synthesis ◽  
Independent Mechanism

scholarly journals In vitro activity and mechanism of action of a duplex and multidrug of ethynylcytidine and 5-fluorodeoxyuridine

2008 ◽  
Vol 52 (1) ◽  
pp. 651-651 ◽  
Author(s):  
I. Bijnsdorp ◽  
R. Schwendener ◽  
H Schott ◽  
S Schott ◽  
I Fichtner ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Vitro Activity ◽  
In Vitro Activity
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