Active Ingredients: Azithromycin
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The approach using a drug repurposing screen with a pathogen sample isolated from a patient and a high throughput bacterial growth assay led to the successful identification of new drug combinations to overcome a multidrug resistant bacterial infection.
Introduction The emergence and dissemination of drug-resistant bacterial infections are a public health issue.
Acinetobacter baumannii is one of the major causes for the nosocomial infections in critically ill patients. Treatment of Acinetobacter baumannii can be extremely difficult, especially for the carbapenem resistant strains.
Colistin and tigecycline are the last resorts for carbapenem resistant Acinetobacter baumannii.
However, colistin and tigecycline resistant strains have been reported worldwide Deng et al. Antibiotic development mainly relies on two strategies, a target-based approach and isolation of bioactive secondary metabolites from microorganisms Demain, 1999; Marinelli,.
New antibiotic drug development is a long-term process; for example, a target-based method takes time to go through the steps of target selection, lead discovery and optimization, preclinical development, then clinical trials before the FDA gives approval for marketing for a new indication.
Drug repurposing and drug combinations have emerged as promising alternative approaches to provide novel therapeutic options for multidrug resistant bacteria Zheng et al. Drug repurposing of approved drugs bypasses the need for novel molecules in nature or from a synthetic chemical library, and alleviates the need for preclinical development and phase I clinical trials as the data for pre-clinical experiments, human pharmacokinetics, and drug safety are already established.
Thus, drug repurposing accelerates the drug development process and reduces the development costs. In addition, drug combination therapy with a synergistic effect of two or three drugs in combination can overcome drug resistance by inhibiting multiple targets and reducing occurrence of further drug resistance.
A multidrug resistant Acinetobacter baumannii clinical isolate, Acinetobacter baumannii 5075 AB 5075 Jacobs et al.
Strain AB 5075 was first isolated from the osteomyelitis of a patient's tibia bone in. The detailed genomic analysis of AB 5075 in unveiled some antibiotic resistant mechanisms Gallagher et al.
We report here the identification of seven non-antimicrobial drugs that suppressed AB 5075 growth in vitro by a drug repurposing screen using the AB 5075 strain.
The results demonstrate the usefulness of a drug repurposing screen using patient derived pathogens.
These newly identified compounds with inhibitory activities against multidrug resistant Acinetobacter baumannii can be further studied for use as new therapeutic agents.
Other chemicals were purchased from Sigma-Aldrich St.
The bacterial cultures were mixed with sterile glycerol in a 9:1 ratio when the optical density at 600 nm OD 600 reached about 0.
The NPC library consists of 2,816 small molecule compounds, 38.