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 goodrx.com.  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.

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.