C. Diff and doxycycline magic

C diff is a dread complication of antibiotic therapy. Clostridia difficile, an anaerobic bacterium may reside in gut as an innocent bystander, causing no trouble unless something happens.  We call this germ an opportunistic pathogen.  It causes disease only when favorable circumstances present.  The degree of illness varies.  It may present as diarrhea which resolves when antibiotics are stopped or a life threatening disease. 

Risk factors  for C diff are well known.  Antibiotics are at the top of the lists. Other risk factors include age (greater than 65), chronic medical illness, hospitalization and admission to long-term care facilities, including nursing homes. 

C diff patients may have diarrhea:  frequent, watery stools. There may be associated mucous and/or blood and stools may be fowl swelling.  Symptoms and signs of more serious infection include:  fever, elevated white blood cell count, abdominal pain, abdominal swelling and shock. 

In the past Flagyl and Vancomycin were effective therapy. A new drug, Dificid is approved for C. diff.  Drug resistance strains have started appearing, of great concern. 

Sometimes infection is like a runaway wildfire and very hard to stop.  Surgery may be required. Fecal transplants are sometimes used.  Fatal cases occur. 

We like to think probiotics ward off the disease, but this is far from certain.  Traditional probiotics may have some benefits, but limited.  Florastor or Saccharomyces boulardii may be slightly beneficial.

There is something else to consider before we discard long-term antibiotics. 

The choice of antibiotic makes an enormous difference. 

When first described, C diff was tied to clindamycin. Later it was learned that other or most antibiotics can cause C diff colitis. Sometimes it is writ that “any antibiotic” can cause C diff.  Maybe not.

There is a hierarchy of which antibiotics and classes of antibiotics are most likely to cause C diff.

Clindamycin is at the top. Quinolones including Cipro and Levaquin are a close second. Cephalosporins, including Ceftin are next. Penicillins like amoxicillin are on the next rung. These drugs are all considered high-risk.  The next group, medium-risk, includes Macrolides such as Biaxin and Zithromax and Sulfa drugs such as Bactrim. Low-risk drugs include tetracyclines, doxycycline and minocycline, rifamycin including rifampin and certain antiparasitic drugs including Flagyl. 

And this brings us to my next topic. Doxycycline: the magical drug. 

It turns out that studies show not only that doxycycline is a C diff low-risk drug, but doxycycline seems to reduce the incidence of acquiring C diff when compared to a control group taking no antibiotics.  In other words, doxycycline may protect against getting C diff. 

This is huge.

No wonder dermatologists prescribe doxycycline to armies of 15-year-olds with impunity. 

Rifampin may have a similar benefit, lowering the risk of C diff. 

 Although there is not data regarding Flagyl, claims to the contrary, it is likely the risk of Flagyl is very low since this is one of the traditional drugs used to treat C diff. 

The prejudice against doxycycline percolating up through internet sources is unfounded.

It stems from the fact that doxycycline is ineffective against Lyme persister forms, round forms and biofilm communities. Take another look.

Doxycycline is the most active drug against spirochete forms.  No one drug does a great job killing persister forms, except daptomycin which is not a realistic option.  Cocktail therapy always works best. There is one drug which shows up in every cocktail group proposed through Zang’s research, with on exception, that is doxycycline. In the other group minocycline was used instead. 

Doxycycline appears to have unique, broad synergy when combined with a host of other antibiotics from other classes. 

Lyme killing cocktails rely on synergy between or amongst chosen antimicrobial agents. The above data show possible advantages of cocktail combining doxycycline, rifampin and Flagyl (Tindamax) and/or artemisinin, in some form (in theory).  Informational purposes. I am not recommending any specific therapy.  

Test tube data are really important, especially at this stage of our understanding,. This data cannot be and should not be translated directly into clinical recommendations. Please. 

There are other factors the Zhang data cannot take into account.  Antibiotics in a test tube are judged based on concentration in a culture broth, a surrogate for serum concentration. It turns out that the ability of drugs to concentrate in tissue is extremely variable.  Tissue concentration of an antibiotic, for example doxycycline, are frequently many fold higher than serum level.

This might seem irrelevant because after all, doxycycline has no impact on non-spirochete forms. Right? 

Maybe not.  In the 2017 study round forms of Borrelia burgdorferi, Lyme bacteria were cultivated the effects of many agents tested.  A goal of the study was to test the effects of sulfa drugs. Sulfa drugs performed poorly.  Drugs were tested at three different concentrations: low, medium and high. Concentrations are reported in molar values and I have no idea how this compares to real life serum values. The data show that as serum concentration increase the ability of the drugs to kill the round, persister form increases. At higher concentration doxycycline starts to diverge from the control and show benefits comparable to other drugs and drug combinations (still poor), having an impact on round forms. 

 Other factors are: bioavailability, tolerability and toxicity, clinical factors outside the sphere of test tube studies. Clinically, these are all very important.

Doxycycline has unique bioavailability, nearly 100% when taken orally. It is not metabolized by either the liver or kidneys. It has very low toxicity and is often well tolerated. These factors are clinically very important. 

Then there is the other thing, when it comes to treating and/or preventing tickborne infections.

Only one drug can kill germs associated with:  ehrlichiosis, anaplasmosis, STARI associated Borrelia species, Rickettsia (including Rocky Mountain Spotted Fever), Mycoplasma, Chlamydia pneumonia, tularemia, brucellosis and prevent early bartonellosis and babesiosis. 

You guessed it:  Doxycycline. 

Sure, a lot of people don’t tolerate it well in the summer and a lot of people experience GI upset.

Minocycline may be second choice, although I can’t say it has all the same benefits.

Keep this is mind when amoxicillin is offered as the second choice drug after a tick bite.

A 24 year old male with brain fog and more

Dear readers:

Thank you for reading my Blog which is now in its 10th year.

I am trying something different:  talking rather than writing. I am more experienced with the latter.

For those who live nearby:

I will be giving a presentation in the conference room in the basement of my office building in Rockville, MD

15245 Shady Grove Road (North entrance) on June 26, 2018 -- one week from today, 6PM.
The talk will not be recorded.

I am planning on doing a series of talks over the ensuing months.

Last month I discussed an approach to patients suffering with fatigue, pain and cognitive symptoms.

This talk is something different.

I present the case of a 24 year old male complaining of brain fog.  Symptoms are added one at a time leading us in different directions as the case unfolds.

I am adding a brief talk (I just put together) called Lyme the Big Picture to precede the other.

I will be taking Q&A at the end.

We do have limited space.  If possible call my office and gives us a heads up.  Reservations not required.  There is no charge.

I will continue to write the blog as well.


Dr. Jaller

Choosing the right antibiotic

I want to discuss several factors to be considered when choosing antibiotics in the management of Lyme disease. 

There is a lot of confusion about the basic biology of the Lyme spirochete, Borrelia burgdorferi. A lot has been worked out but there is some confusion and misinformation on the internet. 

Lyme is primarily an extracellular bacterium and resides in spaces between the cells, extracellular matrix. Without question Lyme spirochetes are occasionally intracellular but this is not the pathogen’s primary modus operandi. Not primarily intracellular.

Lyme is pleomorphic – takes on various forms and has modes of persisting. It forms round forms sometimes called cysts and congregates within biofilms.  Does not form L-forms. Discussed elsewhere.

There are many classes of antibiotics. Antibiotics within a class share features, typically chemical structure and mode of action. I will mention a few examples. 

The macrolide story is interesting.  Zithromax and Biaxin are the two clinical agents of this class most used. On the face they sound similar. Both work by an intracellular mechanism inhibiting protein synthesis.  But clinically there are differences.  Biaxin is more effective against Lyme and Zithromax is more effective against other organisms, for example Babesia. 

Zithromax has a unique and well-known ability to concentrate inside cells many times the concentration in serum.  Because Lyme is primarily extracellular this quality is not a critical factor. Otherwise Zithromax would be much more effective than Biaxin. 

When evaluating the effectiveness of an antibiotic against a particular bacterium, test tube, in-vitro data is cited.  Numbers include:  MIC (minimal inhibitor concentration), MBC (minimal bactericidal concentration).  The time during which the antibiotic concentration exceeds the minimum kill level is called AUC, area under curve. These numbers estimate what may happen in humans taking the drugs. The numbers have limitations and can mislead.

Doxycycline is a favorite drug. It is extremely bioavailable and easily reaches a steady state in the blood stream. For this reason, many experts claim there is no reason to ever give the drug IV. Not true. There is evidence that tissue levels are much higher when the drug is given IV. Our target is tissues where the germ resides – not the blood. 

Antibiotics may be: bactericidal, kill the bacteria or bacteriostatic stop their growth.  In clinical practice there is no difference.

Antibiotics may interact with bacteria in diverse ways. In most cases a sustained blood level is preferred, example, B lactam drugs, amoxicillin and Ceftin.  In other cases, drugs are more effective when there is a distinct peak serum level, as in the case with gentamicin, used for Bartonella.

Lyme has persister forms and is difficult to eradicate at best. Strategies to eliminate persister forms have including antibiotic cocktails and pulsing. Doctors have various theories and preferences.

Questions to consider when choosing an antibiotic:

1)     What germ(s) are we targeting? What is the pathobiology of the germ? Big word. How does the pathogen make us sick? Where does the target germ reside? 

2)     Does the antibiotic reach the target(s)?

3)     Is the antibiotic bioavailable (get into blood stream)?

4)     Does the antibiotic offer the right “killing kinetics?”  This asks if there is a steady state versus a sharp peak and trough levels, as desired, based on the pharmacology of the antibiotic.

5)     Oral or intravenous therapy?

6)     Continuous or pulse therapy?

7) Single therapy or combination therapy and how to proceed?

There are many other factors and considerations. For example, when used in combination antibiotics may exhibit synergy, mechanism unknown.  Drug combinations may be toxic or cancel out the efficacy of the other.  For example, rifampin reduces the effective dose of Mepron by 50%.  

Figuring out how best to treat infections is complicated.  Standard therapies may be poorly explained and not be effective.  We may have to go a step or 10 further. But there should be a method to the madness.

Lyme on a dime

Treating Lyme disease can be expensive, incredibly so. 

I hear all the time about patients suffering with the disease who don’t seek help because they can’t afford it.   

Patients sometimes treat themselves with dubious advice from “the internet.”

Doctors sometimes distance themselves from patient costs.

We can do better than that.

You can get good care for your Lyme disease and keep the farm as well.

Rule one:  Be your own advocate

Rule two:  Know what you are getting into: is the practice allopathic, integrative, functional, naturopathic etc.

My practice is allopathic which is a little confusing.  Allopathic doctors follow Western Medicine.  My beliefs and practices run counter to mainstream medical practice which follows a sort or orthodoxy. In that sense I am an alternative practitioner. In the sense that I primarily rely on Western Medicine tools I am an allopath. 

I base my diagnosis and treatment on evidence and science.

Make sure you know what you are committing yourself too so you don't prematurely spend your entire Lyme budget. 

Supplements

Supplements can cost a fortune. Do you really need them?

I am not inherently opposed to supplements or nutraceuticals but think their use should be well conceived and limited. I don’t sell supplements because I see it as a conflict of interest. Whenever I research a supplement I become half convinced than that it is a life saver that I must take. The other half says: wait a minute. It is important to distinguish between hype and science. (I do take several supplements daily) I assume the reader has a limited healthcare budget.  Beware of the supplement trap. Vitamins, herbs and various nutritional supplements can quickly drain limited resources. A poor investment of Lyme dollars.

Labs

Do not order your own tests. 

Labs can cost an unnecessary fortune.

I my early days patients were diagnosed using this on formula describing sources of data used to make a diagnosis: patient history 85%, physical exam 10% and lab 5%. Today there is an overreliance on technology. The new formula reverses the numbers, diagnosis 85% lab.  When it comes to diagnosing Lyme and tickborne disease the old paradigm (history 85%) should be applied; one of our problems is that the new paradigm (85% lab) is leading to misdiagnosis.  Patients should have a comprehensive general examination by a qualified physician. Most patients have seen many.  Physicians frequently order expensive and experimental tests.  Many such tests will not be covered by commercial insurance.  As a rule, if results of a test will not change treatment, don’t have it done.   Some excellent labs participate with insurance plans and have reasonable fee schedules.  Testing for Lyme and coinfections is a necessity.  The Lyme Western Blot, a standard test, should be done at a specialty lab because there is a lot of room for human error with this complex test. And -- because the standard test is inadequate. I like MDL; they do an excellent job with a good test for a reasonable price and a lower rate charged to patients without insurance. Many automated tests can be adequately performed at commercial laboratories.  I order only antibody tests, not DNA/PCR tests. The latter are costly and miss most cases.  I limit initial testing. Here is what I typically order:  MDL: Lyme Western Blot, Anaplasma and Bartonella henselae antibody panels. LabCorp or Quest:  Babesia microti, Babesia duncani called WA1, Ehrlichia, Rickettsia antibody panels. If Babesia is suspected an in-office Giemsa stain may be ordered.

Don't waste limited Lyme dollars on dubious and/or unhelpful lab work.  A little homework might save a lot of money. 

Treatment 

In most cases generic options exist.

Coupons from sources such as GoodRx.com can save tons of money.  Lyme and coinfections are treated with antimicrobial “cocktails.”  There are many alternative options. 

For example, Babesia treatment with Mepron is notoriously expensive.  Much cheaper, alternative options which include herbs e.g. (artemisinin derived from artemisia, worm wood) exist.

There are many ways to treat Lyme and associated infections. There is no clear right way.  There is a best way: the way you can afford.

Even IV antibiotics can be inexpensive.

Generic Rocephin, the most commonly used IV antibiotic is surprisingly inexpensive through generic sources. 

I have discussed primarily saving money on supplements and testing.  The biggest budget buster is treatment.  I will not discuss treatment specifics here. This is where I save my patients the most money. 

  

Fibromyalgia, a perspective

Estimates of the number of cases of fibromyalgia – fibro (FMS) in the US are unclear.  Ten percent of the population suffers with chronic, generalized pain.  Half of the patients seen in pain clinics suffer with the FMS – fibromyalgia syndrome.   Estimates for the number of cases in the US range from 4- 6 million but the true number may be in the 10s of millions.  More than one million Americans suffer with CFS, chronic fatigue syndrome which may be indistinguishable from fibromyalgia. 

The annual incidence of Lyme disease is at least 300,000 (CDC figure). A significant percent of patients with acute Lyme develop chronic Lyme. 

The symptoms of fibromyalgia, CFS and Lyme and a few other syndromes are virtually identical.  

Patients with all these syndromes experience a disintegrating quality of life, becoming increasingly disabled, unable to work and to participate in normal life activities. 

Fibromyalgia, once considered controversial -- a “garbage can diagnosis” is now widely accepted as “real” and the medical community extends their apologies to those previously told it is all in your head.  

Lyme disease is where FMS was 1-2 decades ago, but more so. As you have likely learned, doctors are poorly informed about FMS and some of the old prejudice remains – doctors and lay people alike. I am sure you still hear it is not real.  The politics of Lyme keep its truths whirling and swirling and hidden, endlessly churning in the washing machine of Medicine, hidden (writ large).  

The standard line from most doctor is that Lyme doesn’t exist – at least in a form causing chronic fibro-like illness. 

These doctors are poorly informed.  The CDC accepts the notion that some patients, diagnosed with and treated for Lyme disease have persistent FMS-like symptoms. These authorities say this group of folks are suffering with Post Treatment Lyme Disease Syndrome (PTLDS). The premise is that – maybe germs persist, acknowledged grudgingly – scientific facts are stubborn things, but still, the authorities state unequivocally that additional antibiotics are not beneficial and may be harmful. 

The minority view, the one that treatment of persistent germs helps many patients is trampled on by the system. 

Lyme facts.

One half of the patients diagnosed with and treated for chronic Lyme disease have no recollection of a tick bite. 

The ticks that transmit Lyme are increasing in numbers annually as is the percent of ticks infected with tickborne pathogens.  A veritable menagerie of germs: Borrelia species, Babesia, Ehrlichia, Anaplasmosis, Rickettsia, Mycoplasma, Bartonella, viruses – sometimes deadly and others, along with new and emerging strains, substrains and species of tickborne germs have been identified which may cause acute and/or chronic disease. 

Most patient never had/have a bull’s eye rash. Symptoms may begin suddenly or come on gradually. A stress to the immune system, like a car accident, seemingly unrelated, as with FMS may trigger Lyme disease. 

Lyme patients usually have chronic pain – joint and muscle pain which changes locations and intensity over time in an unpredictable manner.  

Lyme patients have impaired sleep, profound fatigue, brain fog and cognitive dysfunction.

Lyme patients frequently experience low grade fevers, night sweats and other associated symptoms suggesting the presence of a troublesome co-infecting tickborne pathogen such as Babesia. 

If you have been diagnosed with fibro and you experience so many symptoms it makes your head spin and if your doctor, no longer listening to your symptoms insists “no disease causes all of those symptoms” and suggests you need to see a psychiatrist -- join the club.  This frustrating or maddening experience is common amongst many with Lyme. 

Community is an important word. The world of patients with fatigue/pain/brain fog is divided into camps and associated support groups. 

I am concerned about medical tribalism, a tendency to adhere to a community world view and to block out competing views and information. 

CFS.  Fibro.  POTS.  Mast cell activation disorders.  Chlamydia pneumonia. EBV. Chronic candidiasis etc.  Beware of a "theory of everything." No one has it all figured out. 

It is likely that a common threads runs through the groups.  I would never claim that Lyme is always the common denominator but it should be strongly considered in many cases. 

Some symptoms commonly seen in Lyme patients are: exhaustion, low grade fevers, feeling feverish without a fever, chills, night sweats, fragmented sleep, unable to stand, unable to exercise, change in vision, photosensitivity, ringing in the ears, sound sensitivity, (associated thyroid disorders), shortness of breath, “air hunger,” racing heart, chest pain, gastrointestinal dysfunction, altered menstruation, other hormone imbalance, urinary dysfunction, headache, migraines, depression, anxiety, mood disorders, irritability, anger, rage, social isolation, depersonalization, poor memory, confusion, ADD-like symptoms, numbness, tingling, weakness, neuropathy and others. 

Lyme patients suffer with depression and many other psychiatric symptoms.  Preexisting depression, anxiety and other psych symptoms may have been there already -- or not --but germs residing in the brain make psych symptoms or cause psych to occur symptoms de novo - never experienced before. 

More Lyme facts.

Patients may not recall a tick bite; tiny ticks, the  size of a poppy seed may be the stealthy culprits; the classical rash rarely appears; Lyme is increasing common in regions of the country where it was once rare; any outdoor activity, not only hiking, camping and gardening or picking berries but also sitting on a picnic blanket at the park place you at increased or high risk; blood tests are unreliable and doctors and clinics are generally ill informed about testing; only a doctor who is familiar with the disease and “believes” in the disease is likely to get the diagnosis right (my opinion and that of many others);  patients are frequently misdiagnosed with depression, CFS and fibromyalgia. 

The existence of fibromyalgia is unimpeachable. But it is a syndrome – a collection or constellation of symptoms reliably found in cohort of patients who share certain characteristics. 

Experts suggest the “pathophysiology,” that which is wrong with the nervous system and brain is understood.  The underlying cause of the syndrome is unknown.  A few FDA approved therapies are available. These meds may help, help a little, do nothing or make symptoms worse. 

If you have Lyme and associated infections specific and helpful therapies may be available. 

These are opinions of the author and should not be used to diagnose or treat any disease or syndrome.

I am available for consultation in my Rockville Maryland office.