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 pseudonym.

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.

RB49 from Life in Our Phage World available here: http://2015phage.org/art.php

RB49 from Life in Our Phage World available here: http://2015phage.org/art.php

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-dependent again, a return to a past I had hoped I had left for good.  To read more from SamD, please continue directly to his post 2.

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.

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

  1. Hi ‘Sam’,

    Thank you very much for sharing your somewhat troubling story. Very sorry to hear what happened, fingers crossed something positive comes up soon! I just have one particular question, (thought I’d post on here so that other people could weigh in if needed), but how was your phage therapy administered? I read an interesting paper (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90351/) that mentioned several different ways of administering phage therapy – orally (before eating and after neutralising gastric acid), application of moist phage-containing dressings and direct application of phage suspension. And with the different session of phage therapy that you were part of, did these methods change at all or was it the same procedure each time?

    Looking forward to hearing part 2 of this blog.

    Thanks again,
    Courtney Davies (fellow phage enthusiast!)

    • drhhnz says:

      This is from SamD:

      Hello Courtney, the standard approach is oral, one to two phials of each phage (ea 10ml), morning and night, preceded by either a small amount of mineral water or a small amount of sodium bicarbonate or a mild branded antacid; at least 30 mins before eating. I took standard commercial phages, although not active on my cultured results, like this during the “autophage” (making an infection isolate-specific phage) production periods.
      As soon as a specific phage had been produced, it was directed to be taken by mouth, and urethral instillations; the latter method brought the fast negative responses as detailed in the post. For the usually intractable problem of these infections being mirrored in the prostate and unreachable (by antibiotics), rectal suppositories were supplied (efficacy undeterminable – no testing and premature discontinuance of phages).
      After the second ascendant infection, urethral instillations were removed from the treatment schedule, but it was too late by then; the previously indiscernible oral “autophage” doses evoked acute responses in the bladder after about an hour and none of the “autophages” (3 – Part 2) can be used. N.B. – this removed all previous doubts from my mind of the ability of phages to survive stomach acid! (preceded by no acid mediators).
      Feel free to ask anything more here, or email, Best wishes, Sam

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  5. Amadinae says:

    Hi Sam,
    Thank you for sharing your story.
    Even though urogenital infections tend to cause a lot of trouble before they are completely eliminated , your case is way beyond conventional understanding of what ‘chronic infection’ really look like.
    Meanwhile, can I ask you a few questions?
    1. Do you have any underlying conditions that might have affected the outcome of treatment?
    2. What particularly went wrong with the initial treatment with antibiotics?
    3. Were you given any of the broad spectrum antibiotics at the first time you were diagnosed with infection? (I mean 29 years ago)?

  6. SamD says:

    Hello Amadinae,
    Greetings, I haven’t checked this article for comments for a long time. Let’s see if you are being notified of new comments.
    1/ No underlying condition.
    2/ If drug treatment is quick and of a reasonably long period, with the correct antibiotics, the vast majority of potentially devastating, chronic cases are avoided. And here’s where I answer your question; there was just one treatment chance for me for that initial antibiotic script to be successful. If the drug is ineffective, the infection will surely colonise the prostate and surrounding tissues; once in the prostate it’s there to stay short of radical treatment methods.
    And the only way to remove the majority of chance is to swab the urethra, culture, do the sensitivities and get the sensitivity-proven script to the patient (me) later the next day.
    And that wasn’t done.
    I was given what I now refer to as “guesswork medicine” – a lottery.
    My own doctor was fastidious in such an approach as I later found out; his locum had acquired the habit of charging a fee for a 3 minute consultation and a guesswork prescription.
    3/ I don’t have the records any longer to tell me what was originally prescribed. My doctor came back from holiday, was furious about the low quality care and immediately changed the antibiotic as within a couple of days of a 10 day course all symptoms were back. As it was still primarily an acute infection he first easily got it cultured and a brilliant local Urologist went overboard trying to eradicate it, including three exploratory interventions under anaesthesia. They both agreed that the situation was very likely avoidable if initial antibiotic sensitivities had been established and used.

    From that point on, an new infection “seeded” from the prostate every few days after the last was cleared, and short of removing the prostate (at that time), nothing was done.

    Positive cultures are only achieved these days by my request, and they are only of use to show the changing face of sensitivities. Of 21 prescribable antibiotics, none show “S” now; a legacy of the portion of all the “guesswork” scripts/short period scripts/oral scripts. In Auckland, currently we have no available Doctor with a sole-specialisation of chronic urogenital infection. Treatment of chronic infections almost always requires longer than the maximum LabTests 12 hour culture, and.. no positive culture in 12 hours = no treatment. The urogenital field is served by a number of Urologists who primarily specialise in BPH and prostate cancer-related work; 2 have looked after me and they are brilliant.

    For the record, as it seems pertinent to the basis of your questions, in my long and certain experience, the critical need to culture and prescribe only targeted antibiotics is not followed by many medical practitioners, and the reluctance to do so is far far more prevalent now than 30 years ago, in spite of all the knowledge and data of antibiotic resistance and ensuing warnings. It should be mandatory that at least an attempt is made to isolate the offending bacteria (with a 72 hours min. culture), but it is not. I have a fairly clear understanding of why this is so, which cannot be written about here.

    If you get to see this comment, I trust it answers some of your questions. Sam

  7. Deborah Caswell says:

    I am currently at the Phage Therapy Center having arrived in Tbilisi on 1/11/17. There are many very sick people here and I am not seeing any miracles. I am not seeing any improvement in the sinus infection patients. I do not have a serious illness. I am a 58 year old female who has never smoked, had allergies (not even to poison ivy), a sinus infection or an ear infection before now. I caught a cold in April 2016 and was left with post nasal drip and chronic cough. I do not have a chronic cough all the time but I can feel the thick mucus going down the back of my throat all the time. Kaiser HMO, my healthcare provider, prescribed prednisone and antibiotics when the cough would get really bad. I have only taken antibiotics twice. I used the prednisone carefully. It would work temporarily but I wanted a permanent solution. I had never been sick in my life. When I walked into the Phage Therapy Center on 1/12/17, I knew immediately that they did not have the financial resources or expertise to do a good job on any serious illness. I was just hoping that I would have a simple and common enough case that they would have a bacteriophage that would work and I could get out of there as fast as possible. They have not cultured my sample yet. I do not trust them to culture it accurately. I will keep updating.

  8. Vee says:

    Deborah
    Please give us an update.
    Can you send me your email? I would like to contact you while you are there.
    Mail2vw at gmail dot com

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