Phage Hunt NZ Guest Post: A First Hand Experience with Phage Therapy, Post 1

The following is the first of two guest posts by SamD* from Auckland New Zealand who describes his first hand account of his recent experiences with unsuccessful Phage Therapy in Georgia. Sam has a complicated infection that was treated with antibiotics for many years. Post 1 will be his tale and Post 2 will be his thoughts about phage therapy considering his experiences.

Sam is very interested in thoughts or suggestions regarding his case and can be contacted at nicois@gmail.com *This is a pseudomonym.

Phage Therapy in Georgia: A Clinical Perspective

In this post I detail my recent experience with Bacteriophage treatment in Georgia, the challenges the treatment presented, the lessons learned, a “Where to from Here” and my thoughts about how Bacteriophage therapy needs to be developed for my situation.

Phage therapy has increasingly gripped the Western world lately with media headlines of great wonder and promise. After a longtime on the receiving end of increasingly severe, resistant, urogenital infections, the potential promise of bacteriophages was not new to me, it had long been my plan “Y”; when and if absolutely all else failed, phages would be my salvation.

Phage Treatment in Georgia
Plan “Y” came early in March 2015 in New Zealand, after 29 years of antibiotic-dependency, including 15 years of continuous antibiotics, subsequent complications from long-term antibiotic side-effects and finally, unyielding nosocomial infections, a casualty of prior successful medical treatment. Preparations were made to go to a Tbilisi phage Clinic with the only initial reservation being that my phage research had always lacked one vital factor; reported, verifiable (male) urogenital-related clinical outcomes were virtually non-existent. I had found most phage clinical material in general very dated with narrow repetitive treatment topics. A new perplexing factor crept in at the 11th hour; the treating Clinic mentioned they sometimes administered antibiotics concurrently with phages. Apart from a few very specific PAS studies, this conflicted with my idea of the principles of the specificity of bacteriophages v. broad-spectrum medications and got me thinking about a pathogen acquiring resistance in mid-course treatment with the two technologies. I attached no more importance to this apart from it remaining as a mild irritant in the back of my mind. But, I was to find it was probably to be one of two specific things crucial to my medical treatment success.

An image of Félix d’Herelle.

On arrival in Tbilisi, the high apartment window view, coincidentally, was very “phage”;  there was a leafy view of Félix d’Herelle’s residence, totally obscured at street level, having been a KGB and now State Security facility, walled up like Fort Knox and bristling with cameras, as well as an aerial view of the actual Eliava Institute building and more distantly, the Zoo which was soon to be destroyed in disastrous flooding.

The Tbilisi Phage Clinic took samples and using a third-party laboratory, identified a “strong” infection of Enterococcus faecalis and “non-pathogenic” Staphylococcus haemolyticus (both the infections a casualty of prior treatment referred to above) with detailed report results including a wide range of graduated drug sensitivities, antibody counts and other non-translated information. These test results confirmed results obtained two weeks earlier in China en route to Georgia. Frustratingly, in the preceding 18 months in New Zealand, all similar tests were pronounced negative, in spite of debilitating, ongoing symptoms.

My too-Simplistic Perception of Phages becomes Apparent
The Eliava Institute, as another third-party entity, successfully located a match for the Enterococcus; enhancing and producing an bacteriophage took 4 weeks and the three application techniques produced a near-miraculous result. Over three days, all the prior 22 months of urogenital pain and urinary urgency disappeared and a sense of normal life started to rapidly return; but it was short-lived, on the 4th day an acute bladder-urethral infection ensued and a sample was sent to pathology. A return flight home was due in 3 days, too late to change the departure date.Medical tourism is essentially uninsurable.Remaining in Tbilisi likely meant the time and cost would again be spent unable to do anything, waiting for production of another bacteriophage. The treating Clinic promised that another bacteriophage would be produced and sent by courier, and so a very uncomfortable 33 hour trip back to New Zealand followed.

The new infection was identified as the “non-pathogenic” Staphylococcus haemolyticus shortly after leaving. Once the immediate-area Enterococcus had been removed by its bacteriophage, it appeared the new environment enabled the Staphylococcus to become virulently ascendant. This new infection not only quickly and aggressively occupied the same areas as the previous Enterococcus, but spread outside the urogenital system. The laboratory report included a list of 23 antibiotic sensitivities, with just one of the 4 that showed good sensitivity being available in New Zealand, but proving ineffective as single therapy as its drug notes indicated.phage

Seven long weeks followed, with no information from the Clinic on the E.T.A. of the new bacteriophage. It had become obvious that a “long-distance” patient had either gone to the bottom of the treatment priorities, or that other forces were at play. So, a return flight ensued, and upon arrival the Clinic announced that the Institute (apparently the only bacteriophage producer in Tbilisi) had a phage match and it would take the standard 2 weeks to produce. It was very tempting to think that the coming phage would be the total solution after a bad start but the former thoughts of “will phages work for me” had well and truly changed to “what’s going to happen with the next phage” and the coming days passed slowly.

The new bacteriophage was delivered and a repeat of the first bacteriophage reaction followed, except this time, the next ascendant infection appeared even more acutely in just 24 hours, so much so that antibiotics were used immediately to control it and a two week course halted any other progress. By now the summer break holidays were approaching and soon, behind closed doors, one of the Doctors for the first time broached the subject that resistant multi-pathogenic environments can be a problem to treat with phages, that the environment is easily unbalanced by the high specificity of a phage. Apparently, the “sometimes” use of antibiotics at the same time as the bacteriophage was started was specifically for this reason. I wasn’t convinced the increasingly virulent ascendant pathogens were unavoidable, I was getting a distinct impression that each phage was conferring some kind of virulence on other bacteria. Further, it appeared that the high phage specificity, single phage dosing, a variable concurrent antibiotic policy and a lack of awareness of the microbiology of the targeted area required a higher-level phage treatment protocol than the Clinic was offering. They were appearing at this point as little more than a matching agency for 3rd-party laboratory and phage production services.

This very competent Doctor formed a plan, the second bacteriophage** should be resumed, it would surely cause a repeat of the last infection and so all-important urinalysis would be done, and we would continue like before.. another bacteriophage. Airtickets were extended for an extra 2 weeks, giving nearly 4 in all, to accommodate this, with my distinct unease that phage treatment may never bring the resolution I sought.

And this is how the plan went; the organising Doctor went off for the Summer holidays, the Clinic’s Director (Managing Doctor) took over, a sample from a very virulent ensuing infection was sent off for pathology, however after waiting 5 days the Director declared it “an unusable sample”, and by now 4 days of injected and oral antibiotics getting the forced new infection back under control made getting another sample of no use. Further, the Director refused over the next few days to arrange an EPS which may have revealed a non-antibiotic-affected culprit, holding out until I had to meet my airline departure deadline. Now came the long trip back to New Zealand, uncomfortable in the knowledge that the clinic didn’t have the medical bacteriophage resilience required to engage with my condition. Further, in comparison to when I first went to Georgia, I now had a far more virulent unidentified infection and was antibiotic-dependant again, a return to a past I had hoped I had left for good.

If anyone has questions or observations you’d like a reply to, you can write to me here: nicois@gmail.com
**Where Bacteriophage is written in BOLD, Sam had initially used the word Autophage, a term that he came across in Georgia and which appears to be the way clinicians there refer to Bacteriophages used therapeutically.

About drhhnz

Microbiology, Evolution and Bacteriophages. Lecturer, Institute of Natural and Mathematical Sciences. Massey University. Superhero name: Microbiology Girl. Auckland, New Zealand · microbialevolution.massey.ac.nz Twitter: drhhnz
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