Monday, April 3, 2017

The whole world is on disability

Disabled, or just desperate? Rural Americans turn to disability as jobs dry up

Recent article Washington Post

Its rural America. The whole word is on disability.  The number of Americans surviving on government disability checks has surged to 17 million and the number keeps growing.   Pain clinics are overflowing.  The 39 year old man, pictured above, has recurring painful, swollen fingers and recurrent knee pain.  Is it really due to past use of a hammer and a distant fall ?

Baby boomers, middle aged, retired or pushing retirement age, are the first generation of American who feel worse than their parents did at the same age.  32% of their parents reported excellent health and only 13% of (my group) boomers claims the same.  My cohorts have more aches and pains and are two times more like to need a walker or other assistive device compared with their parents.

Boomer parents smoked and loaded up on butter and cholesterol with impunity. They didn't go to gyms or run. They still had a better quality of life.

There is an exception: Hawaii, the one state with no reported native cases of Lyme disease.

Boomer parents didn't have fibromyalgia or chronic fatigue syndrome.  Boomer  parents walked in the woods without a second thought.

Baby boomers had no idea the woods weren't safe. They had no idea that newly arrived, tiny, nearly invisible ticks could make them deathly ill.  They were into exercise, hiking, camping; the great outdoors.

The CDC admits there are 300,000 new cases of Lyme annually. This a low ball estimate: most cased go unrecognized. People are getting sicker, and in so many unexpected ways. How do you tie the epidemic of MS with arthritic joints (if you are mainstream)?

Primary care clinics are deluged with a new class of patients. An onslaught of chronic fatigue syndrome, fibromyalgia and psychiatric illness -- especially somatization disease. There is an epidemic of craziness. Doctors frequently cringe when certain names appear on their daily schedule. Published data state somatization disorders is found in a small (stats vary, not clear)  but increasing percentage of the general population. Somehow these dreaded patients are filling the rosters of doctor's appointment schedules. Its like a zombie apocalypse.

What of the patients. The miserable souls get stuffed with pills that just make them feel even worse. Cymbalta and Lyrica. The patients are bounced around to numerous specialist and subspecialist, all anxious to scoot them out their offices as quickly as possible. Do not pass go, do not collect 200 dollars. Finally the patients turn to OxyContin which takes the edge off their misery. Many of the miserable sit on the porches of their dilapidated houses, nursing one too many beers, washing down an Oxy or two.

The whole word is on disability.

Readers, you can make a change. Contact your local politicians, state delegates, etc. Tell them to stop the witch hunts and persecution of the few doctors who challenge the status quo.

Its like medical marijuana, which helps some Lyme patients. The system tried to stop it. The FDA and DEA are still furious.  Ultimately, public outcry was strong enough to find a path around the system.

Access to Lyme doctors should be a fundamental right, a civil right, a patient choice issue.

The CDC states that 54 million adults suffer with some form of arthritis, a leading cause of disability.

Fast Facts -- (CDC published material)

  • In the United States, 23% of all adults—over 54 million people—have arthritis.
  • By 2040, an estimated 26% of all adults—over 78 million people—will have arthritis.
  • Arthritis is more common among women (24%) than men (18%), and it affects all racial and ethnic groups.
  • Arthritis commonly occurs with other chronic diseases, like diabetes, heart disease, and obesity, and can make it harder for people to manage these conditions.

RESEARCH LETTER --- 2013 - Dr.Dana King, West VA.
ONLINE FIRST The Status of Baby Boomers’ Health in the United States: The Healthiest Generation?
From 1946 through 1964, 78 million children (“baby boomers”) were born in the United States. In 2010, baby boomers made up 26.1% of the word population.1 Medicine has improved significantly during baby boomers’ lifetimes. Although these advantages have led to a progressively increasing life expectancy, 2 previous studies have shown mixed results regarding whether baby boomers are healthier than prior generations.3,4 The present study examined the health status of aging baby boomers relative to the previous generation to provide a vitally important context for health workforce and policy planning in the coming years.
Methods. National Health and Nutrition Examination Survey (NHANES), including NHANESIII(1988-1994) (for previous generation) and the NHANES for 2007 to 2010 (for baby boomers), focusing on respondents  46 to 64y years during either period... Results. The demographic characteristics of the cohorts were very similar except for the proportions in each racial/ ethnic group, with greater proportions of non-Hispanic blacks(11.3%vs9.4%)and Hispanics (9.8%vs3.7%) in the 2007-2010 group compared with the1988-1994 group (P .001). The mean (SD) ages were 54.1 (0.03) years in the 2007-2010 group and 54.5(0.03) years in the1988 1994 group; there was no difference in sex between the 2 cohorts (49.1%male [2007-2010 group] vs 47.5% male [1988-1994 group]).
Overall health status was lower in baby boomers, with 13.2% reporting “excellent” health compared with 32% of individuals in the previous generation (P .001). Of the sampled baby boomers, compared with the previous generation, 6.9% vs 3.3% used a walking assist device (P .001)

Thursday, March 30, 2017

Lyme and Fake News

I have known this 54-year-old woman for more than 2 years.  When she presented to my office she was a mess.  She thought she had Lyme disease after watching the movie “The Punk Singer.” She was disabled at the time, having been diagnosed with fibromyalgia, by her rheumatologist and diagnosed with depression and ADHD by her psychiatrist. She was told she did not have Lyme disease because a test was negative. I have previously discussed a gazillion reasons Lyme tests are unreliable. The persisting ignorance of other physicians, despite laws passed in VA and MD that require doctors inform patients the test is not reliable, is untenable.  My patient essentially lives in the woods, her back yard abuts a large park and she typically sees 20 deer daily in her back yard daily.  She is disabled by an illness, which is certainly not fibromyalgia and had to sell her business.  Her profession was:  boarding and walking dogs. Her son suffers with a similar disorder and 5 dogs she cared for tested positive for Lyme disease.   A reader might wonder: “how can the doctors discount Lyme when the history is so compelling?”  The answer is simple: Her doctors will not, cannot consider such a thing, when it is firmly entrenched in their brain(s)/medical world view that the diagnosis does not exist. For these doctors, Lyme is "Fake News".
Welcome to my world of medicine. The world is flat, not round.
My colleagues have been indoctrinated to believe: Lyme is rare, easy to diagnose and easy to cure. In my version of reality Lyme can devastate, maim and kill; lab tests are inaccurate, especially the commonly used one; treatment can be very difficult and prolonged.
The majority opinion still rules the land.  Opinion is the operative word.  As is said, you are entitled to your own opinion, not your own facts.  These blogs, scientific literature, books and films  and thousands of patient's stories, clearly tell us that Lyme is real.  It is the other side that has been beguiled by Fake News.
When I met this patient, she was bedridden. She had gained 60 pounds. Thinking about getting out of bed was a chore. Showers were virtually impossible. She was frequently confused and found her memory was slipping away. Her previous eidetic (photographic) memory was gone. Conversing was a challenge. Words didn’t come out right.  She couldn’t fall asleep, and on the occasion she did, she woke up every 2-3 hours. Her entire body hurt, head to toe. She was very weak. She couldn't hold a cup of coffee. Even cutlery dropped from her hands.   Her body felt numb and odd electrical sensations frightened her, sharp and burning, and without warning in differing areas of her body.  Numerous other symptoms included: fevers, chills, night sweats, hearing loss, loss of vision, floaters, neck pain, severe air hunger, new GERD, frequent urination, joint pain and swelling, stiffness, headaches, disorientation, inability to read and write, depression, mood swings, easy tearing and recurrent generalized itchy rashes.
There is more to her story.
As a child she had recurring sinusitis, bronchitis and pneumonia. She was diagnosed with asthma and spent a lot of time in an “iron lung.”
She experiences a lot of hives and itching which seem to appear randomly. She described a condition called dermatographia, written words on her skin become red and persist for a long time.
Lab tests:  Tickborne infection panel: negative Lyme, positive Bartonella, all others negative.  Histamine and tryptase normal.  Celiac panel: deaminated gliadin IgA aby 7 (positive cut off 19).  Imunnoglobulins: IgG 792 (normal 700-1600), IgG subclasses 1 and 3 mildly low, Pneumoccocal 14 aby 9 strains not immune.
I diagnosed her with: Lyme disease, babesiosis, bartonellosis, gluten sensitivity, immune deficiency (CVID), chronic variable immunodeficiency syndrome.
She tested positive for Bartonella; on clinical grounds, Babesia was the big issue.
I diagnosed a form of mast cell activation disorder based on the history. Blood tests and urine tests are usually negative and the diagnosis is made clinically.
CVID was diagnosed by: history of chronic infection; low immunoglobulin level; poor immunity to Strep pneumonia strains (which didn’t change post Pneumovax, pneumonia vaccine).
Gluten sensitivity was a guess.  A gliadin IgA antibody greater than 3-4 makes me suspicious.  The celiac panel reports 4 values: Gliadin IgA, gliadin IgG, tTG IgA, tTG IgG. Most doctors only look at the tTG IgA.
Treatment:  Diet -- low histamine and no gluten. Mast cell stabilization agents. Antibiotics. Anti-malarials. IVIG.  
I don’t automatically tell patients to eliminate gluten. Most my patients tolerate it. A slight bump in any of the antibody levels seems to correlate with gluten intolerance.
Most patients do not have significant mast cell issues.  In this case, a typical history was given.
 Most patients do not have an immune deficiency issue provable based on current standards.  Patients with chronic Lyme all have dysfunctional immunity.  In this case the diagnosis was firmly based on lab tests and a lack of immune response to vaccine.  Generally getting IVIG covered is tough and otherwise cost prohibitive.
I always include treatment for Lyme at the start, rather than targeting only a coinfection such as Babesia.  Lyme forms persisters but does not gain resistance to antibiotics in the usual way. In other words, the same drugs will always work. I typically work up to cocktail of 3 drugs when starting an oral regimen, adding one at a time. With intravenous therapy, I use fewer antibiotics.  Many antibiotics interact with Mepron, decreasing efficacy of the latter.
Mepron is still first line therapy: I always start with 2 tsp twice daily, double the usual dose. If I am concerned about drug interactions I may start with artemisinin instead.  When prescribed properly, pulsed for 3 days each week, artemisinin can be very effective.  Herxheimer reactions often direct therapy based on patient tolerance.
Excessive mast cell activation is modulated with a mix of meds.  H1 and H2 histamine receptors are blocked with drugs like Xyzal and Pepcid. Leukotriens are blocked with drugs like Singulair.  Mast cells are inhibited with drugs like cromolyn, benzodiazepines and ketotifen. Diet is key.
IVIG is given either subcutaneously or intravenously.  For immune disorders a lower dose is approved, 0.6 gm/kg.  With neurological disorders a higher dose, typically 1 gm/kg is used.  For autoimmune neurological disorders such as PANS, a higher dose of 1.5 gm/kg is used.  These are typical starting does and may be adjusted. Usually treatment is given every 3-4 weeks.  Treatment may be long-term or indefinite.
She has done great. Improvement occurred right away with mast cell therapy and then IVIG.  Antimicrobials did their job over a period of months. Within a year, she was essentially in remission.  She had a minor relapse after stopping antibiotics, and this has cleared.
She has only one remaining symptoms.  The eidetic memory did not return. Now she only has a very good memory. 

The story, save a few details changed intentionally, accurately depicts the case.

New patients are welcomed here. 

Monday, February 27, 2017

Bicillin LA

 My patient today is a 53-year-old woman who I have known for several years.  She has been disabled with Lyme and tickborne disease for the last decade and a half.  When she came to my office a few years ago, things had taken a turn for the worse. When she came to my office for the first time she had a clear agenda. She wanted IV antibiotics, the only thing that works she said.
Her saga dates back to 1995, in Silver Spring, Maryland.  She remembers finding a tiny tick attached to her abdominal wall. She recalls that 2 weeks later a large circular rash appeared on her abdominal wall.  She recalls being barraged with symptoms soon thereafter. She experienced fevers and had trouble walking and talking. Her doctor at the time ordered an array of tests, which were negative and the physician offered no diagnosis or treatment.  An ID doctor offered nothing. A neurologist ruled out MS. Other doctors suggested her symptoms were psychosomatic and she was left to suffer, without answers or help.  

After a few years, she developed burning sensations, tremors, leg pain, weakness, muscle twitching and jerking and progressive joint pain. She developed migratory pains in her shoulders, knees, wrists, ankles, fingers and toes.  Brain symptoms were insidious.  Her thinking felt clouded. She starting getting lost. She experienced disoriented episodic confusion.  Other strange neurological symptoms seemed to mimic strokes or seizures she thought.

Finally, in 1998, she diagnosed herself.  She convinced an ID doctor to treat her.  With 6 weeks of IV antibiotics and she began to improve.  They were taken away and she crashed.  She garnered a glimmer of hope.  She began looking for help elsewhere and saw many doctors.  She ultimately found a New Jersey physician who aggressively treated her with IV antibiotics for 12 months.  She regained a quality of life, did OK for a while – a couple of years. Gradually symptoms reappeared.  She called the same doctor only to discover she was no longer in business, courtesy of the State Medical Board.
She found other doctors who were loath to prescribe IVs. Lot of doctors, lots of oral meds.  Her stomach was a mess and she was no better.  She recalls that she tested positive for Lyme, Babesia and RMSF.  She remembered a yellow paint-like medicine which made her sick and no better.

When we first met, she was desperate for help.  Mostly bedridden, getting out of bed and getting dressed was a heroic action.

A partial list of symptoms included:  exhaustion, fevers, chills, night sweats, insomnia, double vision, flashing lights, blurred vision, tinnitus, trouble speaking, trouble swallowing, swollen lymph nodes, rapid and irregular heartbeats, abdominal and pelvic pain, generalized muscle and joint pain (severe), back pain, stiffness, headache, migraine, vertigo, numbness and tingling, weakness, loss of balance, trouble walking with falls, brain fog, forgetfulness, confusion, disorientation, depression, anxiety and panic attacks.

She knew what she wanted: IV antibiotics. I wasn’t a hard sell.

Laboratory testing was positive for Bartonella antibodies.  A Lyme Western Blot at LabCorp was negative across the board.  A Stony Brook Western Blot revealed a single nonspecific IgG band (64) and 9 IgM bands: 18,25,28,31,37,41,58,64,93.
I found other abnormal laboratory values from the start.  She had a very low B12 level. A parietal cell antibody test was positive. Folic acid and vitamin D were also very low.

IV therapy didn’t work.  First there was a DVT and we had to pull the line. We tried therapy through a peripheral line and she had an adverse reaction to Rocephin. 
She became discouraged and fell off the radar.

Doing poorly, after some months, she came back to try something else:  intramuscular penicillin.  This has worked beautifully – as well as Rocephin worked, she states. All major symptoms are melting away and after a couple of months she is functioning quite well.  I give her the shots. We warm up the syringe to room temperature, and slowly inject, (deep IM, lateral aspect of iliac crest)– based on tolerance. The injection site is “rubbed in.”  She tells me the pain is relatively minor and doable, especially once weekly.

Bicillin LA is used.  It is a depot form of the drug and stays in the tissues for 2-4 weeks. I understand some patients are injecting 1.2 million units 2-3X per week.  I have found that 2.4 million units weekly works fine.  The larger volume of the higher dose is tolerated when injected slowly.

She is also treated with complementary oral drugs for Lyme and Babesia. We have found effective options which she tolerates.  She receives various supportive therapies.  And B12 injections are key.

I don’t know why the pernicious anemia (PA) diagnosis had been missed.  B12 deficiency can mimic many Lyme symptoms and B12 levels should routinely be checked.  PA is an autoimmune disorder. Autoimmune issues are prevalent amongst Lyme patients, for example, thyroid disorders. I can’t say I routinely see cases of PA, but I think the prevalence in my patient population is greater than the general population which is around 0.1%.
Bicillin LA is very expensive and insurance doesn’t cover it.  I checked on  A 10 pack goes for 2,700 dollars. The monthly out of packet cost is about 1,000 dollars which isn’t horrible for a Lyme treatment.  A brief google search finds several outfits advertising a fraction of the cost.

The history that 12 months of IV Rocephin in the past imparted temporary relief would seem to augur poorly for the future. But I optimistic that a better understanding of cocktail therapy and coinfection therapy is changing this trajectory.  

An aside – let me digress.
Like many of the sickest, her positive Western Blots show a predominance of IgM responses.  In his research, Dr. Aucott incidentally discovered that about 20-25% of the populace, genetically, appears to be incapable of mounting an IgG response and may show only a weak IgM response.  This finding was predictive of a poor long term disease.  ID doctors still call IgM only “false positive” backed by the IDSA/CDC emphatically insisting that all chronic Lyme patients have the touted 5/10 IgG responses.

“You are entitled to your own opinion, but not your own facts.”  The erroneous version of reality stems from peer reviewed literature. Of course, it does.  Virtually all academic peer reviewed studies use the 5/10 IgG criteria for acceptance into clinical studies.  The conclusion that all chronic Lyme patients have these findings is silly. These criteria are used for study inclusion only. There is no clear academic peer reviewed literature that supports the notion that the criteria can be reliably used for diagnosis. Opinion papers, not research papers make this claim frequently, by incorrectly citing literature that uses the study inclusion criteria.  The first of 4 off cited academic, NIH sponsored studies (Krupp), specifically states that he included seronegative patients in his study.
The incorrect syllogistic reasoning used by the experts goes something like this:  In Lyme studies all chronic Lyme patients have CDC criteria:  patients have chronic Lyme; therefore, all chronic Lyme patients must have positive CDC findings.  And “experts” say it’s true – by fiat.

My 16-year-old daughter sees the erroneous logic and conclusion in about 30 seconds.
Everything about this case is all too familiar and horrible. Thankfully, this survivor of an odyssey of insanity and cruelty is headed for happier times.

Friday, February 17, 2017

Bartonella Madness and PANS

There exists a pernicious conspiracy between Borrelia species and Bartonella species with the intention of making us humans mad.  (This as close as I will get to conspiracy theories and politics in this BLOG).

One young man may have PANS as well (pediatric autoimmune neurological syndrome).  The teenager in question developed OCD, correctible anorexia with rapid weight loss and an aversion to one family member, for no apparent reason. The patient has no explanation or insight into this unusual change in his personality.  He is somewhat irritable, angry and rageful with other family members but not out of control, and, he does reasonably well at school, interacting well with teachers and peers.
The diagnosis of PANDAS was made because a particular expert who blames Strep.  Evidence for Strep is scant. The ASO titer and anti-DNase B were minimally elevated (Strep antibodies).  Lyme antibodies and Bartonella antibodies are present. Everyone in the family has tickborne disease.
The Cunningham panel was essentially normal.  This test is frequently relied upon for the diagnosis of PANS/PANDAS.  I ordered a GAD 65 auto-antibody which was elevated. This is a nonspecific marker but it can be associated with autoimmune encephalopathy.  
The hallmark of PANDAS is that symptoms seem to come on overnight.  In other patients, this has been the case and I have characteristically seen tics, including Tourette’s and more typical OCD manifestations. In my experience, the Cunningham panel is reliably positive.  This   patient’s symptoms came on over a short period of time, but not overnight.  The Cunningham panel is comprised a group autoantibodies directed against the brain that can be measured in a peripheral blood test. The test is supported by peer reviewed literature.
In this patient, the SPECT scan was dramatically abnormal.  This tends to confirm the diagnosis of encephalopathy but does not impute a cause.  
The patient was treated with a single dose of IVig and there was no response. The treating physician recommended waiting 6 months before retreating.  (Not what I would do).
Encephalopathy in patients with Lyme/Bartonella may be multifactorial. There may be an inflammatory component as well as an autoimmune component.  And there may be something else, far less understood.
Mysteriously, brain infectious, may induce specific effects. For example, Bartonella reliably causes, anxiety, irritability, rage (Lyme rage) in many patients. Patients may also suffer with virtually every other conceivable psychiatric symptom.
One can explain this case without consideration of PANS, or any autoimmune encephalopathy. But there is the GAD antibody, suggesting something autoimmune is going on.
Dreaded steroids (overly maligned in my opinion) are very helpful in these cases. Steroids may be administered on a one-time basis. A response to a burst of steroids is predictive of response to IVig.
If neuropsychiatric symptoms do not budge with steroids, IVig will likely fail. Steroids did not help the patient in question. This is important. IVig is prohibitively expensive. And even though tertiary academic centers recommend its use, insurance companies will not cover the therapy for PANDAS/PANS. 
If there is a dramatic response to steroids IVig can be life saver. In my experience, IVig, like antibiotics, must be given on a regular, consistent basis over a long period of time. And PANS requires high doses, 1.5 – 2 gm/kg. I have a patient who developed acute symptoms in early childhood with no evidence of strep and with 10/10 IgG Lyme WB bands and with a positive Cunningham test, who is maintained, a decade later, on IVig every 4 weeks. She has done beautifully. When IVig was withdrawn a few years ago, OCD symptoms emerged immediately.
If Bartonella is suspected to be the major culprit, specific therapy is indicated.  Combinations such as Biaxin, Rifampin and doxycycline have been used by some. This is not my favored approach. Biaxin crosses the blood brain barrier poorly (brain the target).  I like Doxycycline and Rifampin, both pass the BBB well and are active against Bartonella species. I like to add a third drug in the sulfa class. These drugs are active against Bartonella species and cross the BBB well, especially at higher doses.
This approach is not always highly effective.
The addition of low pressure hyperbaric oxygen therapy, good for all encephalopathies, may be a great adjunct.
If this isn’t working, I will go with IV therapy, preferably gentamycin and others. In lieu of IV, I have had good luck giving gentamycin as a once daily intramuscular shot. Never alone.
I stay away from quinolones which are riskier and less effective in my experience.
Gentamycin can be given as a single daily dose and relatively low doses can be clinically effective. Ear and kidney toxicity are minimized with lower doses. Gentamycin, like rifampin, is never given as solo therapy, it must be given in a cocktail with other drugs.
With these steps, I have successfully treated many cases.
I was asked recently by another physician what I do when patients don't get better.  My answer is go back to the drawing board, reconsider the diagnosis and options. Try a different approach. Sometimes you have to get creative. This is all unchartered water.
It may be necessary to juggle: IVig, hyperbaric oxygen therapy, IV gentamycin and other IV drugs while covering Lyme and sometimes Babesia species. 
A word about doxycycline.  A little bit of knowledge is dangerous and it is easy for a lay person to misinterpret things read on the internet.  Doxycycline does not kill only a small percent of Lyme bacteria and doxycycline is not a “cyst generator.” 
Doxycycline remains one of the very best drugs.  It is highly active against rapidly growing spirochete forms of Borrelia – perhaps the most active of any known drug.  It gets into tissues well when taken orally, including the brain. And, it may be given IV.  As is the case with two drugs mentioned above, rifampin and gentamycin, I don’t order doxycycline as solo therapy. It is part of a cocktail. If you look at Zhang’s work on in vitro eradication of Borrelia burdorferi, doxycycline is always a key component of successful three drug regimens. Doxycycline is also a primary component of many anti-Bartonella cocktails.
I have good success treating patients with therapies that are rational and can be explained within the context of available scientific facts.  My BLOGs and medical approaches to tick borne illness, are also based on empirical experience garnered over many years of trial and error practice.

A word about Bartonella testing. This patient tested positive for B. henselae.  Commercial antibody testing is unreliable. There are another 15 or so species and subspecies that may be clinically relevant for which no such test exists.  We got lucky here. I always tell patients: positive results are helpful, negative results are not. Clinical diagnosis is required in most cases.

The presence of darkly colored parallel stretch marks are hugely helpful, as in this case, but this is not a reliable sign.

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.