Novel treatment dynamics for biofilm-related infections

ABSTRACT

Introduction: As a result of progress in medical care, a huge number of medical devices are used in the treatment of human diseases. In turn, biofilm-related infection has become a growing threat due to the tolerance of biofilms to antimicrobials, a problem magnified by the development of antimicrobial resistance worldwide. As a result, successful treatment of biofilm-disease using only antimicrobials is problematic.

Areas covered: We summarize some alternative approaches to classic antimicrobials for the treatment of biofilm disease. This review is not intended to be exhaustive but to give a clinical picture of alternatives to antimicrobial agents to manage biofilm disease. We highlight those strategies that may be closer to application in clinical practice.

Expert opinion: There are a number of outstanding challenges in the development of novel antibiofilm therapies. Screening for effective antibiofilm compounds requires models relevant to all clinical scenarios. Although in vitro research of anti-biofilm strategies has progressed significantly over the past decade, there is a lack of in vivo research. In addition, the complexity of biofilm biology makes it difficult to develop a compound that is likely to provide the single ‘magic bullet’. The multifaceted nature of biofilms imposes the need for multi-targeted or combinatorial therapies.

KEYWORDS:

• Biofilm disease
• recalcitrance
• antibiofilm
• coatings
• biofilm dispersal
• quorum quenching
• phages
• photodynamic therapy
• persister
• bioelectric effect

Article highlights

• Most antimicrobials are often useless when facing biofilm microorganisms.

• Design of functionalized implant surfaces, including stimuli-triggered activation, with locally controlled release of drugs after bacterial attachment is an appealing approach to treat biofilm related infections.

• Targeting the biofilm matrix can be achieved by inhibiting exopolysaccharide production and degrading exopolysaccharides in established biofilms.

• Modulating c-di-GMP signaling pathways in bacteria could be a new method of preventing biofilm formation.

• Phage activity against biofilms might include the use of natural phages, genetically manipulated phages, phage cocktails, phage-derived enzymes, and phages in combination with antimicrobials

• Some examples of drugs that retain bactericidal efficacy against persisters include colistin and mitomycin C, however, toxicity to eukaryotic human cells limits the widespread use of these molecules in daily medical practice.

• All prototypes including the use of electrical current, radiofrequency, electromagnetic fields and ultrasounds are still in preclinical stages of development.

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.

Additional information

Funding

This paper is not funded.