Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains
| Autor: | Tirado-Velez, José M, Carreño, David, Sevillano, David, Alou, Luis, Yuste, Jose Enrique, de la Campa, Adela G, de la Campa |
|---|---|
| Přispěvatelé: | Ministerio de Economía, Industria y Competitividad (España), Instituto de Salud Carlos III |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Microbiology (medical) invasive pneumococcal disease Topoisomerase IV DNA topoisomerase I inhibitor Farmacología 030106 microbiology Resistance Cmax Inmunología RM1-950 seconeolitsine Pharmacology medicine.disease_cause Biochemistry Microbiology DNA gyrase Article Oncología resistance 03 medical and health sciences Antibiotic resistance Levofloxacin Streptococcus pneumoniae medicine Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics biology Chemistry Topoisomerase Invasive pneumococcal disease Seconeolitsine Blood proteins 030104 developmental biology Infectious Diseases biology.protein Therapeutics. Pharmacology medicine.drug |
| Zdroj: | Repisalud Instituto de Salud Carlos III (ISCIII) E-Prints Complutense. Archivo Institucional de la UCM Universidad Europea (UEM) Antibiotics Volume 10 Issue 5 Antibiotics, Vol 10, Iss 573, p 573 (2021) |
| Popis: | Antibiotic resistance in Streptococcus pneumoniae has increased worldwide, making fluoroquinolones an alternative therapeutic option. Fluoroquinolones inhibit the type II DNA topoisomerases (topoisomerase IV and gyrase). In this study we have evaluated the in vivo activity of seconeolitsine, an inhibitor of topoisomerase I. Levofloxacin (12.5 to 50 mg/kg) or seconeolitsine (5 to 40 mg/kg) were administered every 12 h during two days in mice infected with a serotype 8-resistant strain. At 48 h, a 70% protection was obtained with seconeolitsine (40 mg/kg p < 0.001). However, survival with levofloxacin was 20%, regardless of the dose. In addition, seconeolitsine decreased bacteremia efficiently. Levofloxacin had higher levels in serum than seconeolitsine (Cmax of 14.7 vs. 1.6 0.01) and higher values of area under the serum concentration-time curve (AUC0-12h of 17.3 vs. 5 0.01). However, seconeolitsine showed higher levels of time to peak concentration and elimination half-life. This is consistent with the higher binding of seconeolitsine to plasma proteins (40% and 80% when used at 1 µg/mL and 50 µg/mL, respectively) in comparison to levofloxacin (12% at 5 µg/mL and 33% at 50 µg/mL). Our results suggest that seconeolitsine would be a promising therapeutic alternative against pneumococcal isolates with high fluoroquinolone resistance levels. |
| Databáze: | OpenAIRE |
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