LITERATURE UPDATE
Bacteriophages vs. antibiotic resistance: opportunities in the latest scientific literature
In a post-pandemic world, it is perhaps counter-intuitive to suggest that viral agents could contribute to medicine’s fight against the rise of antimicrobial resistance. However, the use of bacteriophages against bacterial infection predates the antibiotic era, so what are some of the opportunities currently being explored? Here, Pathology in Practice Science Editor Brian Nation compiles a small selection of recent research interest.
Phage therapy for antibiotic-resistant bacterial infections Hatfull GF, Dedrick RM, Schooley RT. Annu Rev Med. 2022 Jan 27; 73: 197–211. doi: 10.1146/annurev- med-080219-122208.
Antibiotic resistance in bacterial pathogens presents a substantial threat to the control of infectious diseases. Development of new classes of antibiotics has slowed in recent years due to pressures of cost and market profitability, and there is a strong need for new antimicrobial therapies.
The therapeutic use of bacteriophages has long been considered, with numerous anecdotal reports of success. Interest in phage therapy has been renewed by recent clinical successes in case studies with personalised phage cocktails, and several clinical trials are in progress. In this study, the authors discuss
recent progress in the therapeutic use of phages and contemplate the key factors influencing the opportunities and challenges. With strong safety profiles, the main challenges of phage therapeutics involve strain variation among clinical isolates of many pathogens, battling phage resistance, and the potential limitations of host immune responses. However, the opportunities are considerable, with the potential to enhance current antibiotic efficacy, protect newly developed antibiotics, and provide a last resort in response to complete antibiotic failure.
Novel antimicrobial agents for combating antibiotic-resistant bacteria Chang RYK, Nang SC, Chan HK, Li J. Adv Drug Deliv Rev. 2022 Aug; 187: 114378. doi: 10.1016/
j.addr.2022.114378.
Antibiotic therapy has become increasingly ineffective against bacterial infections due to the rise of resistance. In particular, ESKAPE pathogens (Enterococcus faecium,
Bacteriophage T2, a member of the Myoviridae family (transmission electron micrograph).
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Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species) have caused life-threatening infections in humans and represent a major global health
threat due to a high degree of antibiotic resistance. To respond to this urgent call, novel strategies are urgently needed, such as bacteriophages (phages), phage- encoded enzymes, immunomodulators and monoclonal antibodies. This review critically analyses these
promising antimicrobial therapies for the treatment of multidrug-resistant bacterial infections. Recent advances in these novel therapeutic strategies are discussed, focusing on preclinical and clinical investigations, as well as combinatorial approaches. In this ‘Bad Bugs, No Drugs’ era, novel therapeutic strategies can play a key role in treating deadly infections and help extend the lifetime of antibiotics.
Considerations for the use of phage therapy in clinical practice Suh GA, Lodise TP, Tamma PD et al.; Antibacterial Resistance Leadership Group. Antimicrob Agents Chemother. 2022 Mar 15; 66 (3): e0207121. doi: 10.1128/AAC.02071-21.
Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, and clinical situations in which phage therapy might be considered. Large gaps in knowledge contribute to heterogeneity in approach and lack of consensus in many important clinical areas.
The Antibacterial Resistance Leadership Group (ARLG) has convened a panel of experts in phage therapy, clinical microbiology, infectious diseases, and pharmacology, who worked with regulatory experts and a funding agency to identify questions based on a clinical framework and divided them
JUNE 2023
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