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Thursday, October 23, 2008

Case report validating the persistent of Borrelia burdorferi after extensive antibiotic treatment

There has been a longstanding debate between the IDSA and ILADS regarding Lyme symptoms which persist after standard doses of antibiotics as defined by the IDSA. They take the position that standard therapy eradicates the organism. Furthermore, they take the stance that symptoms which persist after standard therapy should be called "post Lyme," not chronic Lyme, because the cause relates to an autoimmune process. ILADS posits that persistent Lyme symptoms after IDSA recommended treatment are due to persistence of the organism. The following case should be written up and submitted to a peered reviewed journal for publication since it clearly sheds much light on this debate.

A 51 year old woman presented to my clinic on April 1, 2008. At that time she complained of multiple symptoms which she related to tick borne illness. She was in good health until August 2006. At that time she reported occupational exposure to Ixodes ticks and EM rash. She was evaluated by and infectious disease specialist in September 2006. This physician noted that symptoms started 3 to 4 days prior to the initiation of antibiotic therapy. She had received 6 weeks of doxycyline. The dose had ranged from 200mg to 400mg per day. This physician recommended two more weeks of doxycycline and follow up care. She subsequently went to another physician who had experience treating Lyme and tick born infections. He treated her with 5 weeks of Rocephin. The Rocephin was stopped due to an allergic reaction. She was treated with long term continuous oral antibiotics. These included: Zithromax, Mepron, Flagyl and Bactrim.

When I first saw her it was noted that an MRI of the brain was positive for WMD.
She complained of memory loss, headaches, fevers, swollen glands, muscle and joint pains, fatigue and numbness and tingling of the extremities. She had severe cognitive deficits and was fully disabled. Her neuro exam showed cognitive processing delay and evidence of peripheral neuropathy. It was noted that Lyme serology had been negative.

She was started on antimicrobial therapy including: Zithromax, Amoxil, Flagyl and Plaquenil. On May 7, 2008 the Flagyl was stopped and the other meds continued. On May 9, 2007 she was still on the same antibiotics. On May 16, 2008 the dose of Amoxil was increased. On May 21 she continued to have disabling symptoms. Intravenous antibiotic therapy was recommended. The results of a second Lyme serology Western Blot from IgeneX showed seroconversion. Her Bb IgM bands were positive in positions: 18,23,31,34,41,58 and 66. She was positive by both CDC and IgeneX criteria. Her IgG bands were positive by IgeneX internal criteria.

IV antibiotics were not covered by her insurance company. Therapeutic doses of oral antibiotic combinations were administered continuously through July 2008. She continued to have disabling muti-system symptoms and clinical neuroborreliosis. The IV antibiotics were finally approved in August 20008. While awaiting this approval she received a single dose of Bicillin 2.4 million units on August 1, 2008. On August 3, 2008 she was started on IV Primaxin, 500mg every 8 hours. This second line drug was picked because of a previous adverse reaction to Rocephin. The Primaxin was augmented with oral antibiotics including Zithromax and Flagyl. She also was re-treated for Babesia with Mepron. She symptomatically improved significantly for the first time. The intravenous therapy was only approved for 8 weeks. After this she was still symptomatic and oral antibiotics were continued.

On October 14, 2008, while still on oral antibiotics, she came into the office complaining of swelling and pain in both knees. An arthrocentesis was performed and the fluid was sent for analysis.

This patient's synovial fluid was PCR positive for Borrelia burdorferi.

Here is a very ill patient with chronic Lyme symptoms. After receiving standard therapy as defined by the IDSA, she was treated with very aggressive long term antibiotic therapy, both oral and intravenous, in accordance with ILADS' principals.

After more than two years of continuous antibiotic therapy this patient clearly demonstrates persistence of Borrelia burdorferi, the agent responsible for Lyme disease, presenting in synovial fluid. It should also be noted that prolonged therapy in this patient was associated with marked clinical improvement over time.

These findings refute the hypothesis that persistent symptoms are due to an autoimmune process. In fact they demonstrate the ability of the organism to persist in the face of massive anti-microbial therapy.

These findings provide evidence based support for ILADS based protocols for the management of chronic Lyme disease.


Leslie said...

Wow! Please try to publish that case. It speaks volumes. Keep it coming....

dogdoc said...

Wish we could get a culure/ sensitivity on this one- oh but to be dealing with a "regular" bacteria. Nice to have PCR confirmation- does the lab have any other ideas when we don't have a swollen joint to tap? I mean besides CSF. Out of curiousity, has this patient ever been on a quinalone or a rifamycin? I wonder why we end up in this situation- did you see my musings in last comment of Lyme lab?

Lyme report: Montgomery County, MD said...

Was on Rifampin

Lyme report: Montgomery County, MD said...

DD: I got some high power folks interested in helping me write this case up. We are going to send fluid to other labs for PCR confirmation. She has a recurrent effusion. I am going to withdraw more fluid and try to get a culture. Clongen claims to have a very sensitive culture medium for Bb.

You are great at research. Could you do me a favor?
Could you put together a bibliograpy of published studies which demonstrate the persistence of Bb after antibiotic therapy(human trials).

The best confirmation would be to do an arthroscopy and send a piece of synovial lining for PCR and culture. I don't think the patient is up for this. The Lyme controversy would be easy to resolve if we knew what tissues to biopsy or culture. That's why this is such a great case. I was driving down the road, musing, before it hit me on the head how powerful the evidence in this case is!

You can email me. Call for address.

Love you

dogdoc said...

Careful where car thinking gets you (smile)- I just got off the road from dc contemplating the total irony of strategizing for a global war on a pandemic of neatly bioencased designer genes on an immunosuppressed playing field ripe for opportunists.
I think with current thinking, a histopath to show form of persistance would be valuable with PCR and culture. I would think in treated patients we should look to collagen rich tissues for histopath sources. The issue is practicality of biopsy from those sources. An errant thought however- in order to move onto my next hosts, I would need to be either floating in the bloodstream or hanging out in the subcutis near the microvasculature to be in the right place at the right time when my future tick came with a blood meal. I couldn't depend on just being near skin site of initial innoculation where we look typically now. I believe we have some specific immunostaining techniques for histopath so architecture of surrounding tissues could be preserved. Or in packed cells/ buffy coat layer for that manner. That's an ask the pathology experts one! However, we shall have to think on the antibiotic effects on location... hmmm, where do we usually look in animal studies post antibiotics? Usually the obvious spots- joints, heart, cns. I'll think on that one.
On bibleography, do you think we could start with Dr Phillips powerpoint from 2007 posted on ILADS sidebar and update from there? Come to think of it, I'll bet he has a current set as he just lectured last week. Do you think he might be willing to share? I think we'll be more thorough augmenting rather than reinventing the wheel. I would be glad to assist- I'm a little time short coming up for a week or so but you never know what you can squeeze in. I'll call for particulars on Monday. The office was on my list anyway.

lymie said...

Not sure it is all-inclusive, but there is a list of articles in the persistence file at this url:

Anonymous said...

More studies can be found at Lyme Net Europe:

bitten said...

This story is about me. I am up for the test. I want to do it or any other one that would be useful. You guys keep trying. I'll be a case study. No laughing but here is a (maybe dumb) idea from just an engineer. If the bacteria hides in tissues and skin why not make an incision on the leg or somewhere and squeeze blood from there or take a little slice and sew it up. Happens all the time when people get hurt. How about all those floaters that are in the eye? What are they? Let me know.

dogdoc said...

Bitten- sorry I just noticed this. Looks like doc missed it too. A good summary of common floaters with pictures is at spotsfloats.htm. In many people are just occasional benign shadows from filling defects in vitreous (jelly part of interior of eyeball) projected onto retina as light shines thru it. Thats what they told my hubby 15 years ago (severe neuro lyme, babs, ect)- oops. Can also be disruption of visual pathway on the neuro side anywhere from retina, to optic nerves which transmit visual signals from retina to the brain, or actually in the areas of the brain that interpret the visual data. Esp if you have other visual signs. My husbands mapped out at specialty neuroopthomologists on testing to be in brain. Hubby had before treatment floaters, pinpoint flashing white lights, ocular migraines with spinning prismatic shapes in vision, green discolored patches in vision, areas of blurred focus, dim patches in vision, decreased color brightness, ect. Basically CPU of vision in the brain has scrambled circuits in interpreting of visual signals from the sensors (retinas). Thats how my engineer husband thought of things best. Hope that helps. By the way, that wasn't a dumb idea- that is what we were talking about. We just talk in what sounds like riddles to others- docs have somehow gotten both a common and scientific set of terms that makes a almost a language. I'm not so careful when blogging to doc- I'll say zebras instead of rare differential diagnoses. He knows what I mean and its shorter and more infomal when we're just yapping. Sorry. It sounds like from the early samples Doc has sent off to Clongen labs that were not blogged about, we can get it in whole blood maybe better than we thought we could. Along with bartonellas and mycoplasmas and others. This would be a good thing if it bears out over more patients. I bet doc would like it sometimes if I'd stop working on it- I'm sure I drive him nuts sometimes (smile). This is my way to blow off steam and banter around ideas.

atomicdoc said...

Before totally discarding the IDSA "auto immune" thing, think about this interesting paper that I came across. (I was a auto immune nay sayer before I came across this )

In it, it is speculated that Syphillis and Lyme late stage symptoms are not due directly to the bacteria proliferation but rather a forced autoimmune type reaction from the protein fragements given off by the dying bacteria. The twist here is that with this model the bacteria can are quiesent and reactivate periodcally as part of some sort sequestered life cycle. During the motile time some are knocked out either be chemo agents or by the immune system, with the fragments being given off at that time.

With this model a few things would make sense. In late stage syphillis, no bacteria are found in the guma's. The guma's could be due to a "auto immune" reaction cause by some distant infection focus. In lyme there is a similar observation in that the bacteria populations seem to be totally out of wack with the degree of symptoms observed.

If the fragment - auto immune like model is valid then the this could account for the intensification of symptoms during antibiotic treatment since more frageemtns are generated.

So if the basic concept that the bacteria fragments act in any way like short term complete Freund's adjuvant then this could be possible. (just like the adjuvants they add to vacines)

The kicker here is that despite what IDSA says, there are many examples of treatment resistant quiesent bacterial infections and lyme is likely no different. Re-emergence of the bacteria then triggers a magnified response which abates as the protein source becomes depleated during the re-entry into quiesent phase. This might also account for the lymerix response, ie lyme symptoms but no live bacteria. Incidentally an adjuvant (I don;t remember which one, i think it was squalene) was added to lymerix to magnify the immune response, likely not a good thing if some of the protein fragements look like human tissue.

I'm not saying this concept is fact, rather it is not a black and white situation and there could be components of truth in both ILADS and IDSA positions.

On the persitent infection aspect, I seem to recall that there have been some publications on persistence by the "godfather" of Lyme as well as his "family" (A. Steere et. al) If you have not already finished with the write up it might be good to include this in the references.

Thats the thing about journals, you can never unwrite what you have written, You just hope that everyone forgot.