Drug Repurposing for the Treatment of Bacterial and Fungal Infections

Abstract

Multidrug-resistant (MDR) pathogens pose a well-recognized global health threat that demands effective solutions; the situation is deemed a global priority by the World Health Organization and the European Centre for Disease Prevention and Control. Therefore, the development of new antimicrobial therapeutic strategies requires immediate attention to avoid the ten million deaths predicted to occur by 2050 as a result of MDR bacteria. The repurposing of drugs as therapeutic alternatives for infections has recently gained renewed interest. As drugs approved by the United States Food and Drug Administration, information about their pharmacological characteristics in preclinical and clinical trials is available. Therefore, the time and economic costs required to evaluate these drugs for other therapeutic applications, such as the treatment of bacterial and fungal infections, are mitigated. The goal of this review is to provide an overview of the scientific evidence on potential non-antimicrobial drugs targeting bacteria and fungi. In particular, we aim to: (i) list the approved drugs identified in drug screens as potential alternative treatments for infections caused by MDR pathogens; (ii) review their mechanisms of action against bacteria and fungi; and (iii) summarize the outcome of preclinical and clinical trials investigating approved drugs that target these pathogens.

Mosquito Larvicidal Activity, Antimicrobial Activity, and Chemical Compositions of Essential Oils from Four Species of Myrtaceae from Central Vietnam

“…Microbial infections continue to be a problem, for humans [5], as well as for livestock and other agriculture settings [6][7][8]. Compounding this problem are newly emerging pathogenic microorganisms, in addition to re-emerging multidrug-resistant pathogens [9,10].…”

Tamoxifen repurposing to combat infections by multidrug-resistant Gram-negative bacilli

“…This is consistent with the immune system modulation that improves the bacterial infection clearance (4). Exploiting immunomodulatory drugs, approved by the regulatory agencies for clinical indication different to bacterial infection therapy, has several advantages (30); thus, information of their pharmacological characteristics (toxicity and pharmacokinetics) in preclinical and clinical trials is available. Therefore, the time and the economic costs of the evaluation of these drugs in other therapeutic applications, such as the treatment of bacterial infections, will be reduced (31).…”

The global preclinical antibacterial pipeline

“…Fewer projects will use oral administration (for systemic treatment, in a few projects this is combined with intravenous treatment), inhalation, local administration (mostly non-absorbable oral administration) and topical formulation for the skin. different use 12,40 . The development process for repurposed drugs benefits from a large body of available knowledge and reduces the time and cost of development 12 .…”

“…different use 12,40 . The development process for repurposed drugs benefits from a large body of available knowledge and reduces the time and cost of development 12 . The value of such an approach in the clinical setting remains to be shown.…”

“…To assess the global preclinical bacterial pipeline, we considered all projects from several databases and research and development programmes (Box 1) and included all antibacterial projects that were at least in the lead generation phase (hit-to-lead phase) but had not yet reached first-in-human studies. We grouped all preclinical projects that met these criteria into the following categories: direct-acting traditional agents (traditional antibiotics that directly inhibit growth or kill the bacteria); antibacterial vaccines, antibodies and antibody-drug conjugates; phages or phage-derived proteins and microbiota-modulating therapies; antivirulence agents that augment other agents; potentiators that enhance and augment or transform other agents; repurposed approved drugs; and immunomodulators that are developed for a bacterial disease [8][9][10][11][12][13][14][15] . We also looked at the type and location of institutions carrying Lead generation phase (hit-to-lead phase) Drug discovery phase where promising molecules (hits) are evaluated and undergo limited optimization to identify suitable lead compounds.…”