Phage therapy for severe bacterial infections: a narrative review

Abstract

Summary Bacteriophage (phage) therapy is re‐emerging a century after it began. Activity against antibiotic‐resistant pathogens and a lack of serious side effects make phage therapy an attractive treatment option in refractory bacterial infections. Phages are highly specific for their bacterial targets, but the relationship between in vitro activity and in vivo efficacy remains to be rigorously evaluated. Pharmacokinetic and pharmacodynamic principles of phage therapy are generally based on the classic predator–prey relationship, but numerous other factors contribute to phage clearance and optimal dosing strategies remain unclear. Combinations of fully characterised, exclusively lytic phages prepared under good manufacturing practice are limited in their availability. Safety has been demonstrated but randomised controlled trials are needed to evaluate efficacy.

Meningitis and the military: the remarkable story of the first use of penicillin in Australia (1943)

“…We also need to rediscover non-antibiotic approaches to treating infections, including serotherapy 21 and bacteriophage therapy. 22 Both were widely and successfully employed in the early 20th century, and Peter's ultimate recovery in August 1943 appeared to require type-specific anti-pneumococcal serum treatment. However, our reliance on antibiotics over the past century has led to clinical and research neglect of alternative treatment modalities, although interest has revived in recent years, particularly in bacteriophage therapy.…”

“…We also need to rediscover non‐antibiotic approaches to treating infections, including serotherapy21 and bacteriophage therapy 22. Both were widely and successfully employed in the early 20th century, and Peter's ultimate recovery in August 1943 appeared to require type‐specific anti‐pneumococcal serum treatment.…”

“…Both were widely and successfully employed in the early 20th century, and Peter's ultimate recovery in August 1943 appeared to require type‐specific anti‐pneumococcal serum treatment. However, our reliance on antibiotics over the past century has led to clinical and research neglect of alternative treatment modalities, although interest has revived in recent years, particularly in bacteriophage therapy 22. Greater investment in alternative treatment options is needed, as well as investigation of novel therapeutic and infection prevention strategies.…”

A Phage Therapy Guide for Clinicians and Basic Scientists: Background and Highlighting Applications for Developing Countries

“…The century-old science of bacteriophage (phage) therapy was largely neglected after the advent of antibiotics (Summers, 2001) but there remain distinct advantages. Phages are highly specific antibacterial agents that cause much less collateral damage to the microflora than conventional antibiotics that can be applied directly to human tissues without causing harm (d 'Herelle, 1931;Weber-Dabrowska et al, 1987;Petrovic Fabijan et al, 2020a) and their abundance means they can be locally sourced, processed and packaged (Nagel et al, 2016).…”

Are Bordetella bronchiseptica Siphoviruses (Genus Vojvodinavirus) Appropriate for Phage Therapy—Bacterial Allies or Foes?

“…In addition, the increased degree of resistance to B. bronchiseptica isolates against commonly used antibiotics, including β-lactams, macrolides and tetracyclines, has become a serious concern [ 13 , 14 , 15 ]. In the last few years, the use of bacteriophages in the treatment of bacterial infections has gained the attention of the scientific community [ 16 , 17 , 18 , 19 ]. Accordingly, bacteriophage therapy offers an alternative or complementary strategy to conventional antimicrobials for more efficient B. bronchiseptica control.…”