The Latest Research in Lyme Disease Treatment

Note: I will be using this page to catalog the most recent published science in Lyme Disease treatment. I will be updating as new research becomes available so check back often.
<<Skip to "New Drugs and New Drug Combinations" below for the latest on Lyme treatment. >>

In my previous post I give a detailed background on Borrelia Burgdorferi persister cells and why many researchers now feel the only way to eradicate Late Stage (disseminated) or persistent Lyme Disease (PTLDS) is through the use of multi-drug combinations like they do for Tuberculosis and Leprosy.

Treatment History of Borrelia Burgdorferi 

The following highlights are taken from Dr. Joseph Burrascano lecture at NorVect , 2014.

• The early treatment protocols for Lyme were based upon what was done for early syphilis. We know today that B. burgdorferi, the bacteria that causes Lyme Disease, are 100 times more drug resistant than T. palladium, the bacteria that causes syphilis. 

Dr. Burrascano, NorVect 2014

• Borrelia is a very slow growing bacteria. As we know from Tuberculosis, the slower growing the bacteria the longer it takes for antibiotics to kill it. 
• In humans, there is a distinct 4-week cycle of Lyme Disease activity that correspond to the bacterial growth phase, followed by a latent phase. (Patients will feel better during latent phase and worse during the growth phase.)
• Antibiotics will not kill bacteria that are not in a growth phase. This is why short treatment courses are prone to failure. 
• Borrelia causes immune dysfunction which prevents the adaptive immune system from being fully effective. In addition, Borrelia can live inside of cells allowing it to spread throughout the entire body. 

Dr. Burrascano, NorVect 2014

• Borrelia can shape shift from spiral shape, to cell-wall deficient,  to cystic forms and has the ability to form a protective biofilm. Each of theses 4 forms has a different antibiotic susceptibility.
• Bb can be sequestered deep in tissues and hidden within collagen bundles. Low doses and some medications may not penetrate deep tissues. 
• Bb can also survive within cells (intracellular) which serves as a form of protection and dissemination. 
• Bb produces a protective biofilm -- a hallmark of Chronic persistent infections
• In order to kill the bacteria will you need an antibiotic to kill each of the bacterial forms, as well as an agent that aids in the penetration of biofilm. 

Dr. Burrascano, NorVect 2014

Biofilm Basics 

Eva Sapi, PhD Professor of Biology at University of New Haven does a great job of explaining the biofilm associated with Borrelia bacteria in this 2014 NorVect Conference. Basically she estimates 90% of all bacteria live in biofilm. (You can watch Dr. Sapi's lecture here)

In February, 2014 the FDA held a forum on with representatives from the U.S. FDA, CDC and EPA presenting research on technologies to prevent biofilm. Biofilms are colonies of microorganisms that can form any where bacteria are present. For example biofilm can form on contact lenses,  inside water lines, on medical equipment, and around implanted medical devices that are inside the human body. (Link to FDA Presentation Here )

The NIH estimates that 60% of all human infections and 80% of refractory infections are attributable to biofilm colonies.  It is felt that biofilm-related infections are up to 1,000 times more resistant to antibiotics and currently pose a serious health threat.  This conference revealed many promising technologies and new antimicrobials that are under development.

The Rational for Long-Term Therapy for Borrelia Infection: 

Precedents For Prolonged Antibiotic Therapy: (Stricker, R.) 

Evidence for the Benefit of Longer Treatment Regimens for Disseminated Lyme Disease: (Johnson, L. and Stricker, R.)

New Drugs, and New Drug Combinations 

1. Utah Drug Research Company, Curza, Takes Aim at Lyme Disease (Sept 2015) 

Curza is entering phase two of clinical research on their newly designed antibiotic CZ-99. They'll soon be testing the drug on infected mice at the University of California, Davis. An initial clinical trial at the University of New Haven in Connecticut, found CZ-99 to be 60 percent more effective in treating Lyme disease than the traditional antibiotics used to treat the illness. [1]

"Curza has developed a novel class of antibiofilm antibiotics with the ability to disrupt established biofilms and kill the emerging bacteria.  These antibiofilm antibiotics are up to 200x more effective at killing biofilms than last line of defense antibiotics like Vancomycin." [2]

2. Researchers at Northeastern University Seeking Ways to Kill Persister Cells (Aug 2015)

Dr. Kim Lewis, director of the Antimicrobial Discovery Center at Northeastern University says that Lyme Disease may linger in 1-in-5 patients due to persister cells.  In Lewis's research paper published in the Journal of Antimicrobial Agents and Chemotherapy he determined that four pulse doses of Ceftriaxone killed persisters, eradicating all live bacteria in laboratory cultures.[3]

"Persisters are not antibiotic-resistant mutants,... Instead they are bacteria that have gone into a dormant state." Lewis says, "These are some of the most robust persisters we've seen," [4] 

3. Researchers at Johns Hopkins University Identify FDA Approved Drugs with Higher Activity Against Borrelia Bacteria. (June 2014) 

Dr's Ying Zhang, Paul Auwaerter, et el published a study in which they identified 27 drugs from a list of 165 FDA approved drug candidates with higher activity against Borrelia persister cells than doxycycline and amoxicillin. Among the drugs identified, daptomycin, clofazimine, carbomycin, sulfamethoxazole, and cefoperazone had the highest anti-persister activity. [5]

In this "Letter to the Editor" of Emerging Microbes & Infections,  Zhang, et al point out that as high as 20% or more of patients who are treated for Lyme with the standard 2-4 week course of monotherapy doxycycline, amoxicillin or cefuroxime will go on to develop chronic symptoms of Lyme disease. In the treatment of Tuberculosis this would be considered a treatment failure. The authors hypothesize that these continuing symptoms could be the result of persistent infection as it has been proven in various animal models. [6]

Johns Hopkins Bloomberg School of Public Health press release quotes Dr. Zhang here,

“There are a significant number of people who are sick and desperate for a cure for their Lyme disease symptoms months and even years after they have been told they are cured of the disease,” Zhang says. “The current drugs we use aren’t good enough for these persistent cases. This is why I have been getting so many calls and emails about our test and the drugs we have identified.” [7]

4. Massachusetts General Hospital, second annual Lyme disease conference titled (April 2016)

 "Lyme Disease and Other Tick-Borne Illnesses: Clincal Features, Emerging Pathogens and Avenues for New Research" Dr. Ying Zhang presented his latest research on drug combinations found to be most effective against Borrelia persisters. In his paper Dr. Zhang reveals 2 triple-drug combinations with the highest activity against persistent Borrelia burgdorferi. They are:

• Artemisinin/Cefoperazone/Doxycycline

• Sulfachlorpyridazine/Daptomycin/Doxycicline [8]

5. Dr. Richard Horowitz and Dr. Phyllis Freeman published the results of their Dapsone treatment trial at Hudson Valley Arts Center. (April 2016) 

They study found a significant amount of improvement in clinical symptoms for all 100 patients with few side effects. While the study implies a positive role in persister drugs for patients with chronic Lyme or PTLDS, it did not determine the optimal dosage or length of treatment. [9]

Phase two will be a joint effort between Dr. Horowitz and Dr. Eva Sapi from the University of New Haven and will involve combining Dapsone with other antibiotics and biofilm busters. He says on his Facebook page:

"So although the recent PLEASE study didn't find answers to help suffering Lyme patients, and told them that longer term antibiotics don't work, this study, based on recent research on persister bacteria from Johns Hopkins and Northeastern University, had positive results, giving us all hope." 

6. Dr. Richard Horowitz and Dr. Phyllis Freeman published their second paper on the use of mycobacterium drugs in a patient with Lyme, co-infections and autoimmune disease in the journal JSM Arthritis. 

The female patient in this study had a history of being treated with rheumatoid arthritis drugs for 20 years without relief. The authors diagnosed her with Lyme and multiple co-infecions. Dr. Horowitz describes her case on his Facebook page: 

"This patient had evidence of a severe autoimmune disease (Behcet's disease), whose fatigue, joint pain and multi systemic symptoms were unresponsive to almost 20 years of DMARD regimens. When we saw her, she had evidence of multiple tick-borne infections, including Lyme, Borrelia hermsii (relapsing fever), as well as Bartonella and tularemia, which relapsed on immunosuppressive therapy." 

She was initially placed on Dapsone, a mycobacterium drug outlined in their previous paper (above). The patient received some relief of her Lyme Disease symptoms but the ulcers and vasculitis associated with her Bechet's disease remained. She was then placed on pyrazinamide (another mycobacterium drug) in combination with plaque nil, minocycline and rifampin after which the patient received relief from her symptoms for the first time in 20 years. Later while on immunosuppressive arthritis drugs she relapsed with Bartonella and Tularemia. She was treated successfully with an intracellular combination of doxycycline, rifampin, Dapsone and quinolone. [10]

1. Utah drug research company, Curza, takes aim at Lyme Disease
2. Curza - Antibiofilm Antibiotics
3. Borrelia burgdorderi, the causative agent of Lyme disease, forms drug-tolerant persister cells.
4. Lyme Disease May Linger for 1 in 5 Because of "Persisters"
5. Identification of novel activity against Borrelia burgdorferi persisters using an FDA approved drug library.
6. Persister mechanisms in Borrelia burgdorferi: implications for improved intervention.
7. New Test Shows Promise in Identifying New Drugs to Treat Lyme Disease.
8. A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorderi Persisters from an FDA Drug Library.
9. The Use of Dapsone as a Novel "Persister" Drug in the Treatment of Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome.
10.  Are Mycobacterium Drugs Effective for Treatment Resistant Lyme Disease, Tick-Borne Co-Infections and Autoimmune Disease?