Circumventing antimicrobial-resistance and preventing its development in novel, bacterial infection-control strategies

ABSTRACT

Introduction

Development of new antimicrobials with ever ‘better’ bacterial killing has long been considered the appropriate response to the growing threat of antimicrobial-resistant infections. However, the time-period between the introduction of a new antibiotic and the appearance of resistance amongst bacterial pathogens is getting shorter and shorter. This suggests that alternative pathways than making ever ‘better’ antimicrobials should be taken.

Areas covered

This review aims to answer the questions (1) whether we have means to circumvent existing antibiotic-resistance mechanisms, (2) whether we can revert existing antibiotic-resistance, (3) how we can prevent the development of antimicrobial-resistance against novel infection-control strategies, including nano-antimicrobials.

Expert opinion

Relying on relieving antibiotic-pressure and natural outcompeting of antimicrobial-resistant bacteria seems an uncertain way out of the antibiotic-crisis facing us. Novel, non-antibiotic, nanotechnology-based infection control-strategies are promising. At the same time, rapid development of new resistance mechanisms once novel strategies is taken into global clinical use, may not be ruled out and must be closely monitored. This suggests focusing research and development on designing suitable combinations of existing antibiotics with new nano-antimicrobials in a way that induction of new antimicrobial-resistance mechanisms is avoided. The latter suggestion, however, requires a change of focus in research and development.

KEYWORDS:

• Antibiotic-resistance
• bacterial infections
• combination strategies
• infection therapy
• infection prophylaxis
• nano-antimicrobials
• reactive-oxygen species

Article highlights

• Nano-antimicrobials have entirely different mechanisms of action than current antimicrobials, including antibiotics.

• Combination of novel nano-antimicrobials with an existing antibiotic is a good way to eradicate antimicrobial-resistant infections.

• Development of novel antimicrobials is futile with the speed at which bacteria develop new resistance-mechanisms.

• Development of infection-control strategies that do not induce resistance in bacterial pathogens should be prioritized.

• Advanced animal models for evaluation of infection-control strategies are required to speed up clinical use of novel antimicrobials.

This box summarizes the key points contained in the article.

Declaration of interest

HJ Busscher is also director of a consulting company, SASA BV (GN Schutterlaan 4, 9797 PC Thesinge, The Netherlands). The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This work was financially supported by National Key Research and Development Program of China (2017YFE0131700), the National Natural Science Foundation of China (21874096), the 111 Project, Collaborative Innovation Center of Suzhou Nano Science and Technology, Joint International Research Laboratory of Carbon-Based Functional Materials and Devices, Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) and UMCG, Groningen, The Netherlands.