Bartonella persisters and daptomycin: two for the price of one?

While Lyme persistence I denied for political reasons the persistence of other human zoonotic pathogens is recognized. 

I have seen two cases of brucellosis recently and Brucella is recognized as a persistent bacterium, perhaps impossible to eradicate, at least with currently used and/or recommended therapy.

B. abortus is one of several well-known human pathogens of the genus, the one which may be acquired via tick bites.

Brucellosis can be acquired by consumption of uncooked meat and raw milk. I don’t understand the fad of drinking unpasteurized milk, a potentially deadly fad.

Brucellosis may cause numerous untoward clinical syndromes many of which similar to those seen with chronic Lyme.

Bartonella, especially B. henselae is a well known tickborne pathogen also known to exhibit persistence. The bacteria, a fastidious (difficult to culture) gram negative rod is an obligate (facultative) intracellular gram-negative bacteria associated with well described clinical syndromes, discussed elsewhere. Spotty medical literature supports the notion that Bartonella infection is clinically persistent.

Biologically, Bartonella are the only bacteria which may reside in red blood cells. The only other RBC pathogens are malaria and babesia species. Specific biological features, a protected niche and the discovery of stationary forms provide an ample narrative of fact and biological plausibility for persistence. 

The primary home for these bacteria is not RBCs but the endothelial cells that line blood vessels. This is why bartonellosis causes well known vasculitis syndromes. 

Zhang, a prolific publisher, should now be a star at JHH published about Bartonella persisters in antibiotics April. Again, daptomycin is the star.   Daptomycin has the best activity against stationary (persister) forms. Only aminoglycosides, e.g gentamycin are competitive.  In my experience, gentamycin may eradicate clinical infection, but not consistently. Complex multidrug regimens are frequently recommended for Bartonellosis, perhaps this is unnecessary.

This study added to others vis-à-vis Lyme raises the clinical (preclinical) question. Should patients with chronic illness caused by Lyme and Bartonella be treated with combination IV therapy, Rocephin, Doxycycline and Daptomycin earlier rather than later in the course of treatment?

From an Evidenced Based Medicine approach this is anathema,  such therapies can only be recommended after randomized clinical trials, peer reviewed and published.

Such studies are perhaps decades away.  Currently the political divide make diagnosis of Lyme nearly impossible, let alone coinfections.

The preclinical approach allows for empiric use of the therapy without waiting for IDSA approval, which may or may not ever come.

This concept of applying preclinical data (translational medicine) is well developed and well used in the field of oncology. Of course, cancer is considered a serious disease (and Lyme isn’t?).

Those of us in the alternative universe of Lyme disease are accustomed to very long-term antibiotics, including IV ones.  In this world, the use of these 3 IV drugs sounds reasonable. In the other world we are no strangers to cocktail therapy and IV therapy.  In the IDSA/CDC world of doxy for 3 weeks even discussion of this idea is heresy or treasonous, if such things apply in medicine (apparently, they do).

Treating chronic Lyme through the other world approach is very complicated, lengthy and expensive. This sort of preclinical information should be considered in lengthy, informed consent discussions with patients.  

Lyme arthritis, peptidoglycans and political correctness

Medical science and other branches of science are biased and political.  A researcher, an investigator(s) has to walk on eggshells when their findings bump up against beliefs of mainstream beliefs espoused by the experts. They have to fall in line with political correctness if they hope to see their research published, and if they want to keep their jobs as academic researchers. .  

The research findings published in the PNAS, Proceedings of the National Academy of Science this month entitled Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis appears to be excellent science.

The research moves the ball forward in our understanding of chronic inflammation associated with Lyme disease. Political correctness and conformity with mainstream thinking corrupts the paper from the start seriously damaging the credibility of the authors.  Immediately the terms postinfectious Lyme arthritis and posttreatment Lyme disease are used and they poison the broth.

The preponderance of scientific evidence, overwhelming and mounting evidence supports the understanding that Lyme bacteria persist in the face of the standard antibiotic therapies discussed.

The finding that peptidoglycan (PPG), the crosslinking molecules which comprise cell walls in gram-negative and gram-positive bacteria are a major determinant of persistent Lyme arthritis is new information that moves the ball forward.

Borrelia spirochetes have a double outer membrane and lack PG cell walls. However, PG molecules are present internally, inside the outer membrane (cell envelope) providing support to the spirochetes.

The fragments of PG are call muropeptides.

We learn Bb, Lyme processes a unique PG structure. And we learn these fragments are highly immunogenic – incite an excessive immune response or cytokine response likely responsible for clinical manifestations of Lyme arthritis.

Perhaps the peptide fragments do cause an autoimmune response. Although the theory is discussed at length this is not what the research shows. Lyme related joint inflammation is directly caused by unique Lyme PGs.  


A variety of experiments, controlled experiments using a variety of bacteria with different PGs, a variety of clinical diagnoses, mice, humans, joint fluid and serum support the findings. The findings are based on a great deal of animal and human research.

Antibodies were developed against Lyme specific PGs. These antibodies could be the basis for a new, more accurate diagnostic test.

From recent research we know that Lyme biofilms and planktonic round forms cause more inflammation than spirochete forms. We know these are the most antibiotic tolerant forms or resistant forms.

The article at length discusses issues related to diminished bacterial recycling of PGs compared with gram negative bacteria.

Two theories are proffered as to how Lyme PG persists after “curative therapy” with a short course of doxycycline or Rocephin. The authors suggest that these mechanisms account for the persistence of symptoms lasting weeks or months.

But Lyme arthritis lasts for years. Biofilm forms are impervious to standard antibiotic therapies.

Somehow the authors suggest that immune suppressive therapy should be considered rather than additional antibiotics.

We have heard catchy phrases like “persistence of evidence or evidence of persistence." The issue has prevsiously be settled.

Good science can easily self-destruct with the unforced errors all for the sake of political correctness.

To bad.

Lyme, Alzheimer's, Enbrel -- new potential treatment

I have learned that most people want a simple sound bite answer or conclusion. The edges of medicine always operate in the grey and nuanced.

It has long been dogma in Lyme circles that immune suppressing drugs, e.g. Enbrel are very dangerous and should not be used.  The same is true with prednisone.

I have patients who get the occasional injection by their rheumatologist; joint pain gets better and they are no worse for the wear.

The drug is used for psoriasis amongst other many other conditions. The drug has serious side effects: its use should not be taken lightly.

A study suppressed by Pfizer, brought to light be the Washington Post, was based on insurance company data considering outcomes of  hundreds of thousands of patients and found those taking Enbrel had a 64% decrease in the incidence of Alzheimer's disease. 

Enbrel impairs the function of TNF alpha, a master cytokine responsible for trafficking immune cells.

Pfizer did not make the disclosure because: a generic version will be  available.  A shiny new, me-too drug promoted heavily by pharm reps costing obscene amounts of money will take its place. Doctors will be given shiny data, along with lunch, proving equivalency? with the old drug.

The myth that generics are poor (dangerous) and lack quality control may be resurrected.

Watch out for first year generic prices: cute trick. For the first year a single company is given a monopoly and only required to reduce the price by 20%.  "See, the generic is almost as cheap as the brand," the rep will inform a doctor. This is a bad pro big-pharma rule passed by Congress decades ago I'm sure) by the way. Cheap is a relative term.

The pharmaceutical giant, Pizer has excuses, reasons why it withheld the data, for example, they  claimed the data is wrong because of biological plausibility: the molecule is too large to cross the blood brain barrier.

Really? I care if the molecule gets into the brain; maybe it's an advantage.  The brain has its own immune system which needs to be tweaked lightly. Ask anyone who has had a brain Herxheimer reaction knows. The Cytokine storm which may make you crazy results from peripheral cytokine reactions/overproduction primarily.  And there is no data the molecule cannot get into the brain. Cytokines get in the brain.

Alzheimer's is in part motivated by inflammation. Other major factors are: production of amyloid beta protein (AB) (plaques and tangles), genetic factors and multiple external factors.

It is thought that AB protein is a naturally occurring antibiotic which responds to inflammation. Discussed elsewhere. Lyme resides in the brain along with many  bacteria, viruses, protozoans. It is true that spirochetes have been reported to aid in the transportation of AB into the brain.  Infection (or colonization) may be omnipresent and therefore not the whole story -- or the most critical piece.

The vast majority of my patients present with cognitive complaints. Many or most Lyme patients, at one time or another fit the criteria for a disorder call MCI, minimal cognitive impairment. The mainstream medical community considers this a pre-Alzheimer's condition, often.

What's a Lyme patient to do?

First off, if symptoms completely resolve with usual therapy do nothing.

If you are a patient who has had very aggressive therapy, e.g. months of IV antibiotics and cognitive symptoms persist, look up MCI and consider the following:

Get an AB PET. The tests measures metabolic activity in the brain and the presence of early AB protein deposition. IF the test is positive you are at very high risk for developing Alzheimer's.

Prednisone and Enbrel have largely been dangerous seen as because patients are misdiagnosed and not also treated for Lyme. Enbrel is likely tolerably safe, in many cases, considering benefit to risk ratio.

A lot of money has been spent searching for an Alzheimer's cure. To no avail. Nothing very promising in the literature.

I for one am very angry with Pfizer. I suppose it is typical behavior in the industry. We still need big pharma. Don't throw out the baby with bathwater. Hold them accountable. But, do not  conclude big pharma is corrupt therefore all drugs developed through the system are fruit of a poisoned tree and are therefore inherently untrustworthy and dangerous -- in addition to being immorally overpriced.

It's a bad syllogism. Drug companies are a very necessary evil.

Getting back to Enbrel Is this a silver bullet?.  More comment, biostatistics and analysis are required as well as prospective RCT medical studies. Since the drug will be generic soon big pharma will not finance the research. Fortunately, Alzheimer's, a burgeoning epidemic as our population ages, is well funded through private sources.

Ideal prospective studies, which will likely be done make observations moving forward starting with a baseline current population. The process is slow.

Retrospective, population studies, primarily manipulation of data already there will not take long. These studies are never as good as prospective studies but perhaps good enough.

If you want my  bottom line: don't run out and get Enbrel-- YET.

I am not endorsing the use of the drug for any medical condition, including Alzheimer's,
This site is for informational purposes only.  Medical care can only be delivered by a certified medical practioner who properly evaluates your particular issues. Please don't diagnose or treat yourself.