The Belgian-led consortium consisting of groups from The Queen Astrid Military Hospital (QAMH), KU Leuven and the public health institute Sciensano recently made the cover of Nature Microbiology. Their paper details 100 consecutive cases of personalized phage therapy facilitated by the consortium along with collaborators around the world. This definitive retrospective analysis demonstrates that phage therapy can be a very effective treatment for antibiotic resistant or other difficult-to-treat bacterial infections when given with concomitant antibiotics.
Addressing one of humanity's greatest challenges
The World Health Organization (WHO) considers antimicrobial resistance (AMR) one of the top threats to global health. Given the stagnation in traditional antibacterial development, there is a critical need to provide a treatment for patients with antibiotic resistant infections. The lead author, Jean-Paul Pirnay heads the group at QAMH to provide phage therapy to patients, together with Maya Merabishvili and drawing upon expertise and protocols from the Eliava Institute of Bacteriophages in Georgia. Phages are omnipresent tiny viruses that 'feed' on bacteria. Phages need specific bacteria hosts, which they inject with their own genetic material, first transforming the bacteria into a phage producing factory, finally destroying it.
Working closely with Professor Rob Lavigne from the Lab of Gene Technology (LoGT) at KU Leuven for the past decade, this group has been able to amass the data needed to substantiate personalized phage therapy as an effective approach to combat antibiotic resistant infections. Further data will be provided with the ongoing prospective study at UZ Leuven, PhageForce, which seeks to evaluate the safety and efficacy of phage therapy.
Largest retrospective case study on phage therapy
To date this consortium has facilitated personalized phage therapy for 155 patients in Belgium and abroad. Medical professionals from around the world helped facilitate treatments, and Sarah Djebara, a physican at QAMH, led the clinical aspects of this study. Within this study, the first 100 consecutive cases were evaluated to provide an objective analysis that included both successful outcomes and treatment failures. Among the cases detailed, bacterial eradication and clinical improvement was noted for 77.2% and 61.3%, respectively. Statistical analysis showed that bacterial eradication was more probable with the use of phage and concomitant antibiotics.
Making Antibiotics Great Again
Analysis of phage resistant bacterial isolates performed by Sabrina Green postdoctoral research associate at LoGT revealed that resistance trade-offs occur, where bacteria developed resistance to phages but also exhibited reduced virulence and increased susceptibility to antibiotics it had previously been resistant to. The strategic use of these types of phages that target regions of the bacteria important for antibiotic resistance could be utilized to resensitize bacteria to antibiotics again essentially "Making Antibiotics Great Again."
Our phage phuture
This study by this consortium underscores the significant amount of effort and collaboration that may be required to provide phage therapy for 100 patients, emphasizing the urgent need to develop technological innovations that facilitate the production and global distribution of phage therapy. Such innovations may include the on-sight production of personalized phage productions based on synthetic biology and artificial intelligence approaches. Moreover, the establishment of a practical regulatory framework, similar to that used in Belgium to provide personalized phage therapy, is essential to enable the wide-spread implementation of this life-saving treatment.
