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Episode #52 – Phage Hunt

52 Cover Art

Summary

Dr. Saima Aslam gives an introduction to bacteriophage therapy!

Table of Contents

Credits

Host: Sara Dong

Guest: Saima Aslam

Writing/Producing/Editing/Cover Art: Sara Dong

Our Guests

Saima Aslam, MBBS

Dr. Aslam is a Professor of Medicine at the Division of Infectious Diseases and Global Public Health at the University of California San Diego (UCSD). She is a transplant infectious diseases physician and is the Director of the Solid Organ Transplant Infectious Diseases service at UCSD. She has been engaged in phage therapy since 2017 and is the Clinical Lead at the Center for Innovative Phage Applications and Therapeutics (IPATH) at UCSD.

Dr Aslam currently has funding through the Cystic Fibrosis Foundation for a pilot study to develop a clinical registry of Burkholderia infected patients with CF and develop an associated bacteriophage library. She is also co-investigator in a U01 grant from NIH/ NIAID to combat multi-drug resistance through innovative applications, including phage therapy. Dr. Aslam is involved in multiple transplant-related clinical trials as well as an ongoing study investigating the use of phage-lysin for Staphylococcus aureus bacteremia.

Culture

Saima shared some recent bonding with family and friends with henna during Eid!

Consult Notes

Consult Q

Lung transplant recipient with multidrug resistant Pseudomonas – can we use phage therapy?

Case Summary

55 year old female with a history of cystic fibrosis s/p bilateral lung transplant and chronic colonization with MDR Pseudomonas aeruginosa who was treated with IV and nebulized bacteriophage therapy

Key Points

Introduction to bacteriophages / phage therapy

  • Bacteriophages = viruses that bind to bacterial surface receptors and get internalized within the bacterial cell >> transfer their viral DNA/RNA into the host >> produce virions that lyse bacterial cell >> phage progeny then infect other bacterial cells
  • Most phages are specific to one or a few strains of bacteria
      • Phages do not infect eukaryotic cells, which reduces adverse events (large differences between bacterial prokaryotic and human eukaryotic cells prevent cross-infection)
  • Bacteriophage therapy involves identifying and administering phages to target specific pathogenic bacteria, and the limited antibiotic options for MDR bacteria and mycobacteria + technical advances in phage purification have led to renewed clinical interest/use
  • Phages were initially discovered in the pre-antibiotic era, and there have been phage preparations used for GI and upper respiratory illnesses!  There is little published information about these uses, so the effectiveness is unknown

What types of infections can we use phage therapy for?

What are the steps and timeframe for undergoing the process of assessing patients for phage therapy?

How is bacteriophage susceptibility determined?

There are two commonly used methods for susceptibility testing:

  • Double agar overlay plaque assay: bacterial lawns on agar plate > assess clear plaques with successive dilutions of phage
  • Biolog method: measures color change when various phage dilutions are combined with a standard bacterial suspension

As Saima mentioned, there can be incongruity between these two methods, and we don’t know which is the better test.  There is ongoing investigation to understand susceptibility testing and how that translates to their clinical response.

Phage cocktails (combinations of phages) are sometimes used due to concern for the risk of resistance to single phage. What causes resistance to phages?

  • Usually you want to use a combination of phages (phage cocktail) that have different receptors for attaching to a certain organism >> so if the bacteria does develop resistance, there would be other phages that can still kill the bacteria
  • Development of phage resistance doesn’t always occur, as Saima discussed.  We’re still trying to understand whether its a particular phage and bacterial interaction that is more susceptible to resistance?

What are some of the challenges and unanswered questions that remain?

  • Optimal dosing concentration, interval, route of administration (are certain routes preferred for certain infections? need for PK/PD studies)
  • Ability to mass manufacture
  • Storage stability
  • Understanding susceptibility and resistance testing
  • Role of immune response
  • Will we eventually be able to use phage alone without antibiotics?  Or is there a synergistic combination?

Check out these additional items mentioned from the show

Check out Saima Aslam on the podcast ASM Editors in Conversation: Phages as Therapeutic Tools Against Multidrug Resistant Bacteria

You can view the UC San Diego Center for Innovative Phage Applications and Therapeutics (iPATH) in the Division of Infectious Diseases & Global Public Health here

Here is the direct link to the Patient Stories that Saima mentioned

Goal

Listeners will be able to understand the role of bacteriophages as an investigational tool against multidrug resistant bacterial infection

Learning Objectives

After listening to this episode, listeners will be able to:

  • Describe how a bacteriophage can lead to bacterial cell lysis
  • Discuss clinical scenarios that might benefit from bacteriophage therapy

Disclosures

Our guest (Saima Aslam) as well as Febrile podcast and hosts report no relevant financial disclosures

Citation

Aslam, S., Dong, S. “#52: Phage Hunt”. Febrile: A Cultured Podcast. https://player.captivate.fm/episode/d691fc9d-e027-4e15-b21b-15846157a626

Transcript

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