Antibiotic resistant bacteria: current situation and treatment options to accelerate the development of a new antimicrobial arsenal

ABSTRACT

Introduction

Antibiotic resistance is one of the biggest public health threats worldwide. Currently, antibiotic-resistant bacteria kill 700,000 people every year. These data represent the near future in which we find ourselves, a ‘post-antibiotic era’ where the identification and development of new treatments are key. This review is focused on the current and emerging antimicrobial therapies which can solve this global threat.

Areas covered

Through a literature search using databases such as Medline and Web of Science, and search engines such as Google Scholar, different antimicrobial therapies were analyzed, including pathogen-oriented therapy, phagotherapy, microbiota and antivirulent therapy. Additionally, the development pathways of new antibiotics were described, emphasizing on the potential advantages that the combination of a drug repurposing strategy with the application of mathematical prediction models could bring to solve the problem of AMRs.

Expert opinion

This review offers several starting points to solve a single problem: reducing the number of AMR. The data suggest that the strategies described could provide many benefits to improve antimicrobial treatments. However, the development of new antimicrobials remains necessary. Drug repurposing, with the application of mathematical prediction models, is considered to be of interest due to its rapid and effective potential to increase the current therapeutic arsenal.

Plain Language Summary

• Antibiotic resistance is currently one of the biggest public health threats worldwide. Right now, antibiotic-resistant bacteria kill 700,000 people every year. Many of the available antibiotics are useless against drug resistant bacteria. The present and near future in which we find ourselves is a post-antibiotic era, where the antibiotics we have are unable to combat the bacterial infections that are emerging. In this review, published studies were accessed to explore different techniques that are available to improve existing treatment options. Currently, these strategies cannot replace antibiotic therapy. The reviewed knowledge presents these alternatives as adjuvants to antibiotic treatments. Therefore, research into new antibiotics remains important. This review exposes that the repurposing of known drugs as antibiotics could contribute to the cost-effective search of new antibiotics in a faster and cost-effective way compared to traditional development methods of new antibiotics. The review emphasizes the urgency of identifying new pharmacological targets that can aid in the development of new therapies, and to improve known alternative therapies. Drug repurposing can greatly shorten the time and cost of development of new antibiotics. This strategy adds to the value of certain commercialized molecules, recovering part of the investment made by the pharmaceutic industry. In addition, it provides greater knowledge about other alternative antibiotic therapies and about the mechanisms by which bacteria develop antibiotic resistance.

KEYWORDS:

• Antibiotic resistance
• antivirulent therapy
• drug repurposing
• mathematical prediction model
• microbiota therapy
• POT
• phagotherapy

Article highlights

• The present and near future in which we find ourselves is a ‘post-antibiotic era’, where the therapeutic arsenal we have is unable to combat the bacterial infections that are emerging

• Different techniques are being studied to act as adjuvants of traditional antibiotic treatments by prolonging the efficacy of current antibiotics and providing more time to discover new drugs and new effective alternatives to AMRs.

• Alternative treatments can provide many benefits to improve infection treatments but the development of new antimicrobials remains necessary.

• As for the development of new molecules, the costs, the low success rate and long periods of time make it impossible to obtain an effective therapeutic arsenal against current AMRs.

• Drug repurposing could contribute to the cost-effective search of new antibiotics in a faster and cost-effective way compared to traditional methods.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

A.T-P., B.S-G., and M.T.P-G. contributed to the implementation of the research, to the analysis of the results and to the writing of the manuscript. B.S-G. and M.T.P-G. designed and directed the project.

Additional information

Funding

A.T-P. was supported by CEINDO-SANTANDER (Spain). Work cited in this review from the author<apos;>s laboratory was supported in part by grants from the Universidad CEU Cardenal Herrera (INDI18/34, INDI 19/39, INDI20/38 and INDI21/44).