Prefect Predator

Personal Lens on Phage Biology

Introduction

  • Personal and emotional context provided by the speaker.
  • Disclosures: speaker’s husband and speaker own stock in a phage company.
  • Speaker is an unpaid adviser to another phage company, Felix Biosciences.
  • Warning issued regarding disturbing patient photos to be shown during the presentation.

Background Story

  • The story began in 2015 during a vacation to Egypt over Thanksgiving.
  • Both speaker and husband are scientists: husband is an experimental psychologist and evolutionary sociobiologist, speaker is an infectious disease epidemiologist.
  • The husband, described as overweight (6'5" and approximately 300 pounds), crawled into the red pyramid, showcasing the extent of physical activity.
Initial Health Concerns
  • Following a seafood meal, the husband becomes violently ill while preparing to visit King Tut's tomb.
  • Initial assumption of food poisoning due to violent vomiting and abdominal pain.
  • Speaker calculates incubation periods for gastroenteritis based on potential tainted food exposure.
  • Concerns heightened with the development of back pain.
  • Decides to call a doctor on the ship as conditions worsened.
  • Reached out to personal acquaintance, Dr. Chip Scooley, head of infectious diseases at UC San Diego, for advice.
First Medical Actions
  • Encouraged to take the husband to the closest hospital, which was actually a clinic in Luxor lacking formal hospital facilities.
  • Clinic had a CT scanner, diagnosing the husband with pancreatitis.
  • Pancreatitis identified as a symptom of a larger issue, prompting a medevac to Germany due to severity.
  • Lesson learned: importance of travel insurance, particularly for medical evacuation in lower-middle-income countries.

Hospitalization in Germany

  • Arrived in the ICU; all personnel were in full PPE due to potential contagious microorganisms from the Middle East.
  • Endoscopy performed revealing a gallstone lodged in the common bile duct, which had caused an abscess filled with murky fluid.
  • Abscess size likened to a small football, indicating a long-standing issue.
  • Lab cultures revealed the presence of Acinetobacter baumannii, recognized now for its resistance.
    • Historical context: once considered benign in the past, now known as a multidrug-resistant organism.
Dimensions of Infection
  • Acinetobacter baumannii is adept at acquiring resistance genes from others and forming biofilms, complicating antibiotic treatment.
  • The antibiogram revealed significant resistance: 15 antibiotics tested, most labeled "r" for resistant.
  • Identified as needing heavy-duty antibiotics, highlighting concern regarding limited treatment options.
  • The speaker expresses realization that modern medicine's efficacy against resistant strains is not guaranteed.
Impact of Superbugs
  • Statistics shared: by 2050, superbugs could kill 10 million annually and cost 100 trillion globally.
  • Highlighted keyword: superbug mortality rates were documented (1.2 million deaths known to be attributable to resistant bacteria in 2019).
  • Push for awareness: Tom's case amplified recognition of a global health crisis.

Urgent Interventions

  • Medi-vac completion back to San Diego, collaborative care from the speaker's colleagues.
  • Too weak for immediate surgery, effort to establish drainage via interventional radiologists.
  • Complications arising from an internal drain leading to septic shock.
  • Ensuing symptoms characterized as a cytokine storm with escalated heart rate and severe physiological distress.

Phage Therapy Search Initiated

  • The husband fell into a coma, and the speaker decided to explore phage therapy as an alternative treatment.
  • Definition of phage therapy provided: uses bacteriophages (viruses targeting bacteria) as a means of treatment, dating back over 100 years.
  • Historical context discussed: discovery tied to cholera research conducted in India.
    • Mention of significant contributors like Ernest Hankins and Felix de Harrel, who first identified and named bacteriophages.
  • Phage therapy records indicate it was overshadowed by antibiotics in Western medicine.
Recognition of Phage Potential
  • Detailed description of phage biology and mechanisms:
    • Scanning electron micrograph shows phages attaching to bacteria and injecting genetic material.
    • Phages are selectively lethal, targeting specific bacteria without harm to others, contrasting traditional antibiotics.

Treatment Preparation

  • Speaker reached out to researchers for phage isolation compatible with the husband’s bacteria.
  • Collaborative efforts detailed with researchers in Texas and Europe emerging from initial communications.
  • The FDA was contacted for compassionate use approval based on patient’s dire condition.
Logistics and Challenges
  • Discussion of procedural challenges within the clinical treatment framework, including dosage and administration routes for phages.
  • Risks associated with endotoxins and identifying safe phage preparations.

Treatment and Recovery

  • Initiation of phage therapy in March 2016.
    • Documented as a pioneering treatment within the U.S. context.
  • Multisystem organ failure noted prior to therapy, underscoring the patient’s critical condition.
  • Sequential phage administrations began yield successful results; initial coma lifted within three days.
  • Comprehensive effect of treatment observed, leading to the husband’s gradual recovery, exit from the hospital in August 2016.

Broader Implications of Phage Therapy

  • Publication of Tom’s case report, illustrating the clinical importance.
  • Establishment of the first dedicated phage therapy center in North America (iPATH).
  • Notable cases of phage success and ongoing efforts to expand applications and trial bases.
Next Steps in the Field
  • Call for continued clinical trials to validate efficacy and safety of phage therapy alongside traditional antibiotics.
  • Strategies needed to develop libraries for phages against different pathogens and narrow host ranges.

Future Research Directions

  • Exploration of synthetic biology in phage engineering potentially altering bacterial interaction outcomes.
  • Potential applications in agriculture, food safety, and public health.
  • Discussion on new pathogens and consideration of alternative uses for phages.
Conclusion
  • Acknowledge the importance of continued vigilance against antimicrobial resistance exacerbated by crises (COVID-19).
  • Ongoing dialogue around equitable access to phage therapy globally, recognizing community support fundamental for advancing the field.
  • Final thoughts shared about the integration of phage therapies into routine clinical practices for systemic infections.