Alternatives to antibiotics in an era of difficult-to-treat resistance: new insights

ABSTRACT

Introduction: The rise of antibiotic resistance, the limited efficacy and the adverse events associated with antibiotics have urged the development of alternative measures to treat bacterial infections. Novel therapies which are pathogen specific and are safer to the healthy microbiome are being developed.

Areas covered: This manuscript provides a compact overview of the feasibility and clinical impact of the latest novel therapies, with a focus on monoclonal antibodies (mAbs), vaccines, stem cells, bacteriophages, and liposomes. This is a follow-up of a previous manuscript (doi: 10.1080/17512433.2016.1241141); a database search (PubMed, EMBASE, Cochrane) was used to identify recently published literature (from January 2016) which was not covered in the previous publication.

Expert opinion: Among non-traditional agents, monoclonal antibodies have not been as successful as in other therapeutic areas. In particular many are developed to prevent hospital-acquired infections caused by S. aureus or P. aeruginosa and, so far, results have been overall disappointing. Stem cells and bacteriophages still have a long way to go. Vaccines are always desirable to prevent infections but again there is a lack of confirmatory results. Broad spectrum liposomes have shown promising results in treating severely infected patients and could be game changers in patient management.

KEYWORDS:

• Monoclonal antibodies
• bacteriophages
• antimicrobial agents
• stem cells
• vaccines
• liposomes

Article Highlights

• The increase in multidrug-resistant organisms (MDROs) poses a threat to public health and to the provision of health care worldwide.

• These are an urgent need to release to improve the management of MDR organisms.

• Randomized Clinical Trials with different end-points, such as time of resolution and adaptive trials need to be developed.

• Resources need to be invested in the development on NIC-drugs.

• Monoclonal antibodies have not been successful, like in other diseases.

• Timing of progression of sepsis and effects on multiorgan dysfunction explains the challenge of these approaches.

• One Health Initiative and Difficult-to-treat resistance are newer concepts that would facilitate more rational and effective control.

Declaration of interest

J Rello received research grants and honoraria by participation in consultancies from Valneva & ROCHE. A Perez is Chief Medical Officer of Combioxin and served as consultant in infectious diseases from Debiopharm and Abionic. 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 article has been developed with the support of a Grant from the Observership Programme from the European Society of Clinical Microbiology & Infectious Diseases (ESCMID).