Phage Therapy in the Postantibiotic Era

Abstract

SUMMARY Antibiotic resistance is arguably the biggest current threat to global health. An increasing number of infections are becoming harder or almost impossible to treat, carrying high morbidity, mortality, and financial cost. The therapeutic use of bacteriophages, viruses that infect and kill bacteria, is well suited to be part of the multidimensional strategies to combat antibiotic resistance. Although phage therapy was first implemented almost a century ago, it was brought to a standstill after the successful introduction of antibiotics. Now, with the rise of antibiotic resistance, phage therapy is experiencing a well-deserved rebirth. Among the admittedly vast literature recently published on this topic, this review aims to provide a forward-looking perspective on phage therapy and its role in modern society. We cover the key points of the antibiotic resistance crisis and then explain the biological and evolutionary principles that support the use of phages, their interaction with the immune system, and a comparison with antibiotic therapy. By going through up-to-date reports and, whenever possible, human clinical trials, we examine the versatility of phage therapy. We discuss conventional approaches as well as novel strategies, including the use of phage-antibiotic combinations, phage-derived enzymes, exploitation of phage resistance mechanisms, and phage bioengineering. Finally, we discuss the benefits of phage therapy beyond the clinical perspective, including opportunities for scientific outreach and effective education, interdisciplinary collaboration, cultural and economic growth, and even innovative use of social media, making the case that phage therapy is more than just an alternative to antibiotics.

A systematic review: Current trends and take rates of cultured epithelial autografts in the treatment of patients with burn injuries

“…In the current era of antibiotic resistance, phage therapy may prove to be a useful adjunct in wound bed preparation to address the high rates of wound colonization, potential infection, and CEA loss. 86 Pluripotent, high proliferative capacity and self-renewing nature of stem cells may have much to offer especially if these cells can be isolated consistently from the adipose layer of burned skin obtained during debridement. 87 Since this systematic review was conducted, more clinical data involving treatment of burn patients with CEA have been published.…”

Phage therapy for severe bacterial infections: a narrative review

“…There are case series with generally good outcomes, particularly in osteoarticular infections, diabetic foot infections, and chronic prostatitis . Two reviews detail the history of phage therapy in Russia and Eastern European countries and its application in specific human infections, a 2012 article provides a historical review of phage therapy over the years, and comprehensive up‐to‐date reviews are now also available …”

“…19-21 Two reviews 22,23 detail the history of phage therapy in Russia and Eastern European countries and its application in specific human infections, a 2012 article 24 provides a historical review of phage therapy over the years, and comprehensive up-to-date reviews are now also available. 25 However, randomised controlled trial (RCT) experience in humans is less impressive (Box 2). The largest reported RCT was conducted in Russia in 1963-64.…”

A New High-throughput Screening (HiTS) Method for Phages – Enabling Crude Isolation and Fast Identification of Diverse Phages with Therapeutic Potential

“…The upsurge of antibiotic resistant bacteria is one of the main health concerns of our time [1]. when applied as a combination therapy together with conventional antimicrobials, foreseen to play an essential role in the multifaceted strategy required to combat the lurking antibiotic crisis [1], [9].…”

“…The upsurge of antibiotic resistant bacteria is one of the main health concerns of our time [1]. when applied as a combination therapy together with conventional antimicrobials, foreseen to play an essential role in the multifaceted strategy required to combat the lurking antibiotic crisis [1], [9]. a promising potential [10], and could be a sustainable alternative to traditional chemicals facing to facilitate the transfer of lysate from every second well in a chequered pattern into two new 156 microtiter plates with pierceable sealing tape, number #4 (A) and #5 (B) ( Figure S1).…”