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Monday, January 30, 2017

Chronic Lyme disease: an approach to treatment

I will talk a little about treatment approaches.
No one knows the best way to treat chronic Lyme disease; and what works best for one patient may not work well for another.  In a sense, each patient is his/her own “experiment.”
Treatment of chronic Lyme (and associated infections) is based on:  A new paradigm regarding the role of tickborne infections and its connection to chronic illness. Scientific information; empiric evidence from the collective experience of a large cohort of physicians over many years; the clinical acumen of the treating physician; and, parallel models which can be drawn from Mainstream Medicine comprise the basis for treatment.
Tuberculosis on one level offers clues as to the management of chronic Lyme disease.  Lyme and TB both bacterial illnesses which are difficult to treat due to the presence of Persister organisms.  Experience with TB may offer clues as to how best treat Lyme, and  -- offer proof of concept regarding the “cocktail” approach used to treat Lyme.
Lyme persisters are thought to largely be comprised of round body forms and biofilms colonies. Let’s correct the record.  No L-forms have been found.   The Lyme spirochete is pleomorphic. This means it can change its form.  Bacteria do not form cysts. Round forms of the spirochete may be referred to as pleomorphic variants or round body forms.
Antipersister drugs:  Persisters and their appropriate therapy is mysterious.  The drug pyrazinamide (Z/Pza) is a key part of the therapy for tuberculosis. The drug was discovered in the 1920s and first used for TB in the early 1950s. It is an essential, highly effective antipersister drug for TB.
With today's science the drug would never have been discovered.  The drug was not initially tested in a test tube (in-vitro). The drug was first test in a mouse model (in-vivo) and was found to be highly effective.  The drug has no activity whatsoever in a test tube. The modern scientific approach would have screened out and discarded the drug forever.
Initial therapy for TB consists of 4 drugs given together in a “cocktail.”  There are many other examples of bacteria which are treated with combination therapy, for example H. pylori, but TB provides a good template.  TB infection may be systemic, but is generally limited to a single organ – the lung.
Late stage Lyme is always disseminated, infecting many organs. TB is generally treated for 6 months. It makes sense that Lyme may require long term as well.
In test tube experiments Zhang found eradication of Lyme bacteria required a cocktail of three powerful antibiotics.  This is also provides proof of concept.
I typically treat Lyme with a cocktail of 3 drugs, as tolerated.  Choices are based on the answers to certain questions:  Has the drug been shown to have good activity against the organism, even at low serum concentrations?  Does the drug offer synergy when combined with others? Does the drug have good tissue penetration and can it pass through the blood brain barrier (BBB)?  Does the drug also hit coinfections? How will that impact choices?  Does the proposed "cocktail kill spirochetes and persisters well? Are drug to drug interactions a concern? Should the drug be given by mouth or by IV, or even IM?  Are side effects tolerable?  On balance, do the benefits outweigh the risks?

Doxycycline: always first line -  most effective against spirochete form of Borrelia organisms, usually well tolerated; may be given by mouth or IV -  either way, good systemic adsorption and good penetration into brain. Kills Lyme better than minocycline. Draw back:  no effect on persister forms. That’s OK. That’s why we use a cocktail.  The bonus of hitting coinfections cannot be understated.
Second drug choice(s) Rifampin is a good choice. By a synergistic mechanism, confers antpersister properties to doxycycline; achieves good tissue and brain levels; it is an antipersister with a proven track record, used for TB and used to eradicate Strep bacteria carriage.  Drawback:  Highly active against Bartonella sp.  Herxheimer reactions can be intolerable.
Another choice could be Bactrim, effective only at higher doses, unlike doxycycline which can be effective at lower doses, also hits Bartonella sp. Herxheimer response less drastic than that seen with Rifampin. Still can be a no starter. Kills persisters and penetrates BBB.
Another option could be Tindamax.  Well tolerated, good blood and tissue levels and highly active against Lyme organisms. Sapi’s research says it is excellent against persisters. Zhang's research says it is only slightly better than Flagyl (which he surprisingly found has little or no activity against persisters.  All I can say is it works.
Another option could be Amoxicillin or Ceftin.  I typically use these drugs when doxycycline is not tolerated or not an option.  Amoxicillin does not penetrate the blood brain barrier unless given in high doses but may be an excellent choice because of low toxicity and it is hightly active against spirochete forms.  Ceftin is the only oral cephalorsporin said to penetrate the BBB; It also shows activity against all forms of Lyme (spirochetes and persisters).  Not my first choice because it may be too hard on the gut and I it s more likely than others on this list to cause C. diff. Good option when tolerated.
The worst offenders for C. diff are quinolones such as Levaquin.  Drugs of this class can also cause tendon rupture. They penetrate well into the brain but can cause odd brain side effects that are not Herxheimer responses. I recommend avoiding these drugs if possible and using low doses when necessary.

Biaxin and Zithromax may be good choices but are not usually first line.
Why use 3 drugs?  There is no scientific basis for this. Zhang's test tube results are a weak argument, at best.  I have used to use 2 agents in the past and have found 3 works better.  I don't use 4 because I worry about the increased risk of toxicity, and -- 3 works.
There is no consensus on how best to treat the disease.  This approach has evolved over years and may be quite different from recommendations seen elsewhere. In general, treatment is long-term: The length of therapy  may be much more important than specific choices of therapy.  Again, what works for one patient may not work well for another.   Coinfections need to be considered and may alter the clinician's approach to the patient dramatically, even at the start. The use of IV antibiotics or IM (penicillin) vs oral agents needs to be sorted out. There are many other drugs which may be considered, not discussed here.  The duration of therapy is unpredictable and different for every patient.
Continuous therapy vs pulsed therapy is a complex discussion, not covered here.
Drugs are never started all at once. They are gradually added incrementally, watching for toxicity and/or side effects.   



JCarl said...

Are you still using mild hyperbaric oxygen in your treatment protocols?

LYMEMJ said...

Better than Tindamax is Ivermectin; better than Levofloxacin is Moxifloxacin.
Ask Dr Sapi about Ivermectin, I shared a bottle with her ;)
Quinolones are not bad, the problem is the wrong dosing US Drs administer. The correct way is to start with a high dose, for ex 2 gr per day and if there is any muscle pain to lower the dose to 1.5 mg/day and so on until if necessary lower to 500 mgr per day, but never stopping treatment. US Drs start the opposite with a lower dose ramping it up until patient stops due to pain....
How come Doxy is still the treatment knowing it only kills 10% of the bacteria and the rest 90% goes into hiding, it is a "cyst inducer" please!!!!
Anthelmintics are a must, why if Lyme Disease is parasitic it is not treated as such? If Borrelia goes inside the white blood cells and inside the tissues it acts as a parasite, antibacterials are not going to do the job, new perspectives in the drugs of choice are a must!
Dr Jaller, I admire you for all you have done for the lyme community, deeply grateful forever!
Maria LymeDisease

Lyme report: Montgomery County, MD said...

Low pressure (mild) hyperbaric is very helpful. The vast majority of my patients who do HBOT on a regular basis get home units. Some are very cost effective.

Mine is significantly better because although it is in the portable chamber genre, I offer a pressure of 1.6, 2X that of home units.

I think that is close to the ideal pressure.

Lyme report: Montgomery County, MD said...

Lyme is not a worm or a protozoan. It is bacteria (spirochete). It does not live inside red blood cells. It may live inside other cells, like macrophages. Some drugs not designated as antibiotics may kill Lyme, e.g. artemisinin, Diflucan. I think quinolones are more dangerous than most antibiotics so they are not my first line choices at this time.

It is referred to as a parasite because it cannot make all the metabolites it needs, it steels them from the host. It cannot survive outside of a host. The term refers to its function, not is classification as a microorganism.

Tim said...

LymeMJ . . . "Quinolones are not bad"??? Seriously - you don't know what you are talking about. There are support groups online with thousands of members who's lives have been utterly destroyed by these drugs - these groups also include MD's and Pharmacists who had NO IDEA just how destructive these drugs are - until it happened to them personally. This issue is as criminally under acknowledged in the medical community - just like chronic Lyme is. There are books and a documentary film about this and a recent FDA hearing (NOv 2015) FINALLY acknowledged FQAD -Fluoroquinolone Associated Disability - which is sometimes permanent and progressive. This is not a few tendon injuries - this is a multi systemic debilitating syndrome affecting all connective tissue, neuropathy and neuromuscular weakness, and CNS (brain) damage . . . Russian Roulette.

Lyme report: Montgomery County, MD said...


Clyde Bowers said...
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concerned Mom said...

My son just recently got diagnosed about 3 weeks ago and tested positive on Western bot for IgG Bands 18, 23, 28, 30, 39, 41, 45, 58, 66 , he was non reactive for IgM 23, 39 and 41. His doctor put him on doxycycline for 4 weeks, so he another week. He just developed a yeast infection....didn't tell me to have him on a probiotic. very frustrating as he is telling me they do not test after 4 week treatment? So new to all this, I am feeling overwhelmed. Does having so many bband be reactive mean anything? His EKG was borderline abnormal and want to test him in June? any recommendations on what to tell or ask doctor would be great. It seems he is being very vague and we are trying to get appointment with LLMD. His doctor told me to stay off internet because chronic lyme doesn't exist. I have asked for records because his symptoms have been going on for some time-years. when i got them in it was back in feb 2014 for the first vist of nausua, headache, random vomitting and headaches. brought him in every year for same thing and now this year a lyme test was done. why is this test not done more regularly. I feel he probably has had this for 3 or more years and he doesnt seem to be worried. Once we find LLMD , i may be finding new doctor-unhappy and frustrated mom...