The success of linezolid stimulated significant efforts to discover new agents in the oxazolidinone class. Over a dozen oxazolidinones have reached the clinic, but many were discontinued due to lack of differentiated potency, inadequate pharmacokinetics, and safety risks that included myelosuppression. Four oxazolidinones are currently undergoing clinical evaluation. The Trius Therapeutics compound tedizolid phosphate (formerly known as torezolid phosphate, TR-701, DA-7218), the most advanced, is in phase 3 clinical trials for acute bacterial skin and skin structure infections. Rib-X completed two phase 2 studies for radezolid (Rx-01_667, RX-1741) in uncomplicated skin and skin structure infections and community-acquired pneumonia. Pfizer and AstraZeneca have each identified antitubercular compounds that have completed phase 1 studies: sutezolid (PNU-100480, PF-02341272) and AZD5847 (AZD2563), respectively. The oxazolidinones share a relatively low frequency of resistance largely due to the requirement of mutations in 23S ribosomal RNA genes. However, maintaining potency against strains carrying the mobile cfr gene poses a challenge for the oxazolidinone class, as well as other 50S ribosome inhibitors that target the peptidyl transferase center.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1749-6632.2011.06330.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Florfenicol administration in piglets co-selects for multiple antimicrobial resistance genes.
mSystems
December 2024
Lacombe Research and Development Centre, Agriculture and Agri-Food Canada, Lacombe, Alberta, Canada.
Antimicrobial use in food-producing animals such as pigs is a significant issue due to its association with antimicrobial resistance. Florfenicol is a broad-spectrum phenicol antibiotic used in swine for various indications; however, its effect on the swine microbiome and resistome is largely unknown. This study investigated these effects in piglets treated intramuscularly with florfenicol at 1 and 7 days of age.
View Article and Find Full Text PDFBackground And Aim: Infections caused by pathogenic bacteria increase patient morbidity and mortality and significantly raise treatment costs. The use of silver nanoparticles as an alternative treatment for and indicates their antibacterial effect and prompts medical research to consider the next generation of antibacterial drugs that could change antibiotic therapy. By combining silver nanoparticles with different classes of antibiotics, the antibacterial effect is evidenced by increased values of the inhibition zone compared to the values obtained for some antibiotics commonly used in the treatment of bacterial infections.
View Article and Find Full Text PDFExposure to doxycycline increases risk of carrying a broad range of enteric antimicrobial resistance determinants in an elderly cohort.
J Infect
October 2024
Microbiome and Host Health Program, South Australian Health and Medical Research Institute, Adelaide, SA, Australia; Infection and Immunity, Flinders Health and Medical Research Institute, College of Medicine and Public Health, Flinders University, Bedford Park, SA, Australia. Electronic address:
Article Synopsis
- High antibiotic prescriptions in aged care could lead to increased antibiotic-resistant pathogens in residents, raising concerns about treatment failures.
- A study analyzed stool samples from 164 residents in South Australia, linking antibiotic use over the past year to the presence and quantity of antibiotic resistance genes (ARGs).
- Findings revealed that over 1100 unique ARGs were identified, with doxycycline being a major risk factor for high ARG levels, particularly influencing resistance to penicillins and cephalosporins, highlighting the need for cautious antibiotic use in this population.
Discovery of Broad-Spectrum Herpes Antiviral Oxazolidinone Amide Derivatives and Their Structure-Activity Relationships.
ACS Med Chem Lett
August 2024
Discovery Chemistry, Merck & Co., Inc., West Point, Pennsylvania 19486, United States.
Herpesvirus infections are ubiquitous, with over 95% of the adult population infected by at least one strain. While most of these infections resolve without treatment in healthy individuals, they can cause significant morbidity and mortality in immunocompromised, stem cell, or organ transplant patients. Current nucleoside standards of care provide meaningful benefit but are limited due to poor tolerability, resistance, and generally narrow spectrum of activity.
View Article and Find Full Text PDFInteractions between Zoliflodacin and Gyrase and Topoisomerase IV: Enzymological Basis for Cellular Targeting.
ACS Infect Dis
August 2024
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.
Article Synopsis
- * Spiropyrimidinetriones (SPTs), like zoliflodacin, have been developed to fight this resistance and show effectiveness against uncomplicated gonorrhea during human trials.
- * Zoliflodacin is more potent against gyrase than topoisomerase IV, producing more DNA cleavage, and the new SPT H3D-005722 shows promise for achieving balanced targeting of both enzymes.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!