» Articles » PMID: 34198513

Activity of Oritavancin and Its Synergy with Other Antibiotics Against Infection In Vitro and In Vivo

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2021 Jul 2
PMID 34198513
Citations 2
Authors
Affiliations
Soon will be listed here.
Abstract

Background: Pulmonary disease caused by () spreads around the world, and this disease is extremely difficult to treat due to intrinsic and acquired resistance of the pathogen to many approved antibiotics. is regarded as one of the most drug-resistant mycobacteria, with very limited therapeutic options.

Methods: Whole-cell growth inhibition assays was performed to screen and identify novel inhibitors. The IC of the target compounds were tested against THP-1 cells was determined to calculate the selectivity index, and then time-kill kinetics assay was performed against . Subsequently, the synergy of oritavancin with other antibiotics was evaluated by using checkerboard method. Finally, in vivo efficacy was determined in an immunosuppressive murine model simulating infection.

Results: We have identified oritavancin as a potential agent against . Oritavancin exhibited time-concentration dependent bactericidal activity against and it also displayed synergy with clarithromycin, tigecycline, cefoxitin, moxifloxacin, and meropenem in vitro. Additionally, oritavancin had bactericidal effect on intracellular . Oritavancin significantly reduced bacterial load in lung when it was used alone or in combination with cefoxitin and meropenem.

Conclusions: Our in vitro and in vivo assay results indicated that oritavancin may be a viable treatment option against infection.

Citing Articles

Drugs for treating infections caused by non-tubercular mycobacteria: a narrative review from the study group on mycobacteria of the Italian Society of Infectious Diseases and Tropical Medicine.

Calcagno A, Coppola N, Sarmati L, Tadolini M, Parrella R, Matteelli A Infection. 2024; 52(3):737-765.

PMID: 38329686 PMC: 11142973. DOI: 10.1007/s15010-024-02183-3.


The role of long-acting antibiotics in the clinical practice: a narrative review.

Micheli G, Chiuchiarelli M, Taccari F, Fantoni M Infez Med. 2023; 31(4):449-465.

PMID: 38075413 PMC: 10705857. DOI: 10.53854/liim-3104-4.

References
1.
Hamad B . The antibiotics market. Nat Rev Drug Discov. 2010; 9(9):675-6. DOI: 10.1038/nrd3267. View

2.
Wu M, Aziz D, Dartois V, Dick T . NTM drug discovery: status, gaps and the way forward. Drug Discov Today. 2018; 23(8):1502-1519. PMC: 6078814. DOI: 10.1016/j.drudis.2018.04.001. View

3.
Griffith D, Aksamit T, Brown-Elliott B, Catanzaro A, Daley C, Gordin F . An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007; 175(4):367-416. DOI: 10.1164/rccm.200604-571ST. View

4.
Egorova A, Jackson M, Gavrilyuk V, Makarov V . Pipeline of anti-Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities. Med Res Rev. 2021; 41(4):2350-2387. PMC: 8217127. DOI: 10.1002/med.21798. View

5.
Chew K, Octavia S, Go J, Ng S, Tang Y, Soh P . In vitro susceptibility of Mycobacterium abscessus complex and feasibility of standardizing treatment regimens. J Antimicrob Chemother. 2020; 76(4):973-978. DOI: 10.1093/jac/dkaa520. View