Phage therapy: From biological mechanisms to future directions

Cell, Journal Year: 2023, Volume and Issue: 186(1), P. 17 - 31

Published: Jan. 1, 2023

Increasing antimicrobial resistance rates have revitalized bacteriophage (phage) research, the natural predators of bacteria discovered over 100 years ago. In order to use phages therapeutically, they should (1) preferably be lytic, (2) kill bacterial host efficiently, and (3) fully characterized exclude side effects. Developing therapeutic takes a coordinated effort multiple stakeholders. Herein, we review state art in phage therapy, covering biological mechanisms, clinical applications, remaining challenges, future directions involving naturally occurring genetically modified or synthetic phages.

Language: Английский

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ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics

Nature Reviews Microbiology, Journal Year: 2024, Volume and Issue: 22(10), P. 598 - 616

Published: June 3, 2024

Language: Английский

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Clinical Impact of Staphylococcus aureus Skin and Soft Tissue Infections

Antibiotics, Journal Year: 2023, Volume and Issue: 12(3), P. 557 - 557

Published: March 11, 2023

The pathogenic bacterium Staphylococcus aureus is the most common pathogen isolated in skin-and-soft-tissue infections (SSTIs) United States. Most S. SSTIs are caused by epidemic clone USA300 USA. These can be serious; 2019, with were associated an all-cause, age-standardized mortality rate of 0.5 globally. Clinical presentations vary from superficial local symptoms to monomicrobial necrotizing fasciitis, which cause systemic manifestations and may lead serious complications or death. In order skin infections, employs a host virulence factors including cytolytic proteins, superantigenic factors, cell wall-anchored molecules used for immune evasion. response involves initial responders such as keratinocytes neutrophils, supported dendritic cells T-lymphocytes later during infection. Treatment usually oral therapy, parenteral therapy reserved severe presentations; it ranges cephalosporins penicillin agents oxacillin, generally methicillin-sensitive (MSSA), vancomycin methicillin-resistant (MRSA). challenges include adverse effects, risk Clostridioides difficile infection, potential antibiotic resistance.

Language: Английский

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Fighting antibiotic resistance—strategies and (pre)clinical developments to find new antibacterials

EMBO Reports, Journal Year: 2022, Volume and Issue: 24(1)

Published: Dec. 19, 2022

Language: Английский

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Personalized bacteriophage therapy outcomes for 100 consecutive cases: a multicentre, multinational, retrospective observational study

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(6), P. 1434 - 1453

Published: June 4, 2024

Abstract In contrast to the many reports of successful real-world cases personalized bacteriophage therapy (BT), randomized controlled trials non-personalized products have not produced expected results. Here we present outcomes a retrospective observational analysis first 100 consecutive BT difficult-to-treat infections facilitated by Belgian consortium in 35 hospitals, 29 cities and 12 countries during period from 1 January 2008 30 April 2022. We assessed how often positive clinical outcome (general efficacy) performed regression identify functional relationships. The most common indications were lower respiratory tract, skin soft tissue, bone infections, involved combinations 26 bacteriophages 6 defined cocktails, individually selected sometimes pre-adapted target causative bacterial pathogens. Clinical improvement eradication targeted bacteria reported for 77.2% 61.3% respectively. our dataset cases, was 70% less probable when no concomitant antibiotics used (odds ratio = 0.3; 95% confidence interval 0.127–0.749). vivo selection resistance vitro bacteriophage–antibiotic synergy documented 43.8% (7/16 patients) 90% (9/10) evaluated patients, observed combination antibiotic re-sensitization reduced virulence bacteriophage-resistant isolates that emerged BT. Bacteriophage immune neutralization 38.5% (5/13) screened patients. Fifteen adverse events reported, including seven non-serious drug reactions suspected be linked While is limited uncontrolled nature these data, it indicates can effective with inform design future trials. BT100 study, ClinicalTrials.gov registration: NCT05498363 .

Language: Английский

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Current Clinical Landscape and Global Potential of Bacteriophage Therapy

Viruses, Journal Year: 2023, Volume and Issue: 15(4), P. 1020 - 1020

Published: April 21, 2023

In response to the global spread of antimicrobial resistance, there is an increased demand for novel and innovative antimicrobials. Bacteriophages have been known their potential clinical utility in lysing bacteria almost a century. Social pressures concomitant introduction antibiotics mid-1900s hindered widespread adoption these naturally occurring bactericides. Recently, however, phage therapy has re-emerged as promising strategy combatting resistance. A unique mechanism action cost-effective production promotes phages ideal solution addressing antibiotic-resistant bacterial infections, particularly lower- middle-income countries. As number phage-related research labs worldwide continues grow, it will be increasingly important encourage expansion well-developed trials, standardization storage cocktails, advancement international collaboration. this review, we discuss history, benefits, limitations bacteriophage its current role setting resistance with specific focus on active trials case reports administration.

Language: Английский

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Translating phage therapy into the clinic: Recent accomplishments but continuing challenges

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(5), P. e3002119 - e3002119

Published: May 23, 2023

Phage therapy is a medical form of biological control bacterial infections, one that uses naturally occurring viruses, called bacteriophages or phages, as antibacterial agents. Pioneered over 100 years ago, phage nonetheless currently experiencing resurgence in interest, with growing numbers clinical case studies being published. This renewed enthusiasm due large part to holding promise for providing safe and effective cures infections traditional antibiotics acting alone have been unable clear. Essay introduces basic biology, provides an outline the long history therapy, highlights some advantages using phages agents, overview recent successes. Although has clear potential, it faces biological, regulatory, economic challenges its further implementation more mainstream acceptance.

Language: Английский

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Phage Therapy—Challenges, Opportunities and Future Prospects

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(12), P. 1638 - 1638

Published: Nov. 22, 2023

The increasing drug resistance of bacteria to commonly used antibiotics creates the need search for and develop alternative forms treatment. Phage therapy fits this trend perfectly. Phages that selectively infect kill are often only life-saving therapeutic option. Full legalization treatment method could help solve problem multidrug-resistant infectious diseases on a global scale. aim review is present prospects development phage therapy, ethical legal aspects form given current situation such benefits using products in persons whom available options have been exhausted or do not exist at all. In addition, challenges faced by fight against bacterial infections also described. More clinical studies needed expand knowledge about phages, their dosage, standardized delivery system. These activities necessary ensure phage-based does take an experiment but standard medical Bacterial viruses will probably become miracle cure—a panacea infections—but they chance find important place medicine.

Language: Английский

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Regulations of phage therapy across the world

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 6, 2023

Phage therapy, a century-long treatment targeting bacterial infection, was widely abandoned after the clinical availability of antibiotics in mid-20th century. However, crisis antimicrobial resistance today led to its revival many countries. While articles dive into application now, little research is presenting phage therapy from regulatory perspective. Here, we focus on regulations by dividing sections Eastern Europe where it never and Western Europe, Australia, United States, India, China only re-attracted researchers' attention recent decades. New insights about are provided as English literature has specifically discussed this previously. Ultimately, introducing for human health across representative countries, hope provide ideas how countries may borrow each other's adapting legislation best overcome current hurdles.

Language: Английский

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Bacteriophage therapy for drug-resistant Staphylococcus aureus infections

Frontiers in Cellular and Infection Microbiology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 31, 2024

Drug-resistant Staphylococcus aureus stands as a prominent pathogen in nosocomial and community-acquired infections, capable of inciting various infections at different sites patients. This includes bacteremia (SaB), which exhibits severe infection frequently associated with significant mortality rate approximately 25%. In the absence better alternative therapies, antibiotics is still main approach for treating infections. However, excessive use has, turn, led to an increase antimicrobial resistance. Hence, it imperative that new strategies are developed control drug-resistant S. Bacteriophages viruses ability infect bacteria. Bacteriophages, were used treat bacterial before advent antibiotics, but subsequently replaced by due limited theoretical understanding inefficient preparation processes time. Recently, phages have attracted attention many researchers again because serious problem antibiotic article provides comprehensive overview phage biology, animal models, diverse clinical case treatments, trials context therapy. It also assesses strengths limitations therapy outlines future prospects research directions. review expected offer valuable insights engaged phage-based treatments

Language: Английский

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