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The Lyme Disease Treatment Guide
lyme disease 101
germ control & more
Updated: 2/1/23
In this chapter, you will learn how to build a Lyme disease herbal or prescription antibiotic treatment. Later in this guide, I provide 10 sample herbal and prescription antibiotic treatment plans, including the dosing regimens I find effective.
The focus of this article is on Lyme germ treatment. For information about treating Lyme disease coinfections, see:
Before I describe the plan, be aware that chronic Lyme disease recovery requires more than antibiotics. I cannot emphasize this point strongly enough. Treating Borrelia, the Lyme germ, with antibiotics is complicated because limited research shows which treatment regimens work best. As a result, many Lyme-literate medical doctors (LLMDs), like myself, prescribe antibiotics based on theory and our collective observation. Theory and observation show us that combinations of antimicrobials work better than single agents alone. It is critical that a Lyme disease treatment regimen addresses the first 10 steps outlined in my Lyme disease treatment guidelines, The Ross Lyme Support Protocol. These steps are designed to revive health and to boost the immune system. Even a year or more into treatment, when a person is feeling better, these steps are essential to speed recovery by supporting the immune system.
Therefore, the plan that follows is not—and cannot be—a complete or comprehensive guide. Rather, it reflects how I organize the available knowledge and understanding about Lyme disease to subsequently create effective Lyme disease antibiotic treatments.
Before I describe herbal and prescription antibiotic approaches I find helpful treating Lyme in my Seattle practice, let’s talk about terms.
Outside of cells, Lyme infection has two different looks, or forms. One form is the spirochete and the other is a microscopic cyst. Spirochetes can morph into cysts and cysts into spirochetes. Cysts are sometimes referred to as round bodies. An effective treatment approach must address both forms.
Research first published in 2015 shows that Lyme has two different growth states. There is a growing phase of the germs and there is a persister phase. Think of the persisters as germs that are in hibernation. These persisters—hibernating phase germs—ignore regular standard antibiotics we traditionally used to treat Lyme.
Lyme can live outside of cells and inside of cells. Inside of cells, Lyme exists without a cell covering known as an L-form. Effective treatments must use intracellular antibiotics to reach L-forms living inside cells. Fortunately, intracellular antibiotics also reach Lyme outside of cells, too. As an example, penicillins (like amoxicillin) and cephalosporins (like cefuroxime) only work outside of cells. Macrolides (like clarithromycin) and tetracyclines (like doxycycline), work in the intracellular and extracellular spaces. Antibiotics that work on germs inside and outside of cells include the tetracyclines, macrolides, rifamycins, and azoles.
Furthermore, while herbal antibiotics may work inside of cells, it is not clear from research that they do. However, I have seen wonderful recoveries for many on herbal antibiotics, so I assume the ones I recommend in this article help with intracellular Lyme.
Lyme spirochetes and cysts can exist in growing phases and in persister phases. Some lab experiments suggest that the great majority exist in the growing phase; however, prolonged use of regular antibiotics may push a greater portion of the germs into the persister phase.
In this article, by antibiotics I mean prescription and herbal medicines that have antimicrobial effects against the Lyme germ. In my practice, I often mix herbal and prescription options together.
The following are four general rules I use to develop a Lyme disease antibiotic regimen:
Be aware the doses I provide below are for adults. Use these same prescriptions with children but at lower doses. For pediatric dosing, talk with your family physician or pediatrician. Tetracyclines can be used in children under eight, but there is a risk of tooth staining. This staining seems not to be an issue if they are used for a month or less.
Penicillins
Cephalosporins
Additional IV Antibiotics
Vancomycin, imipenem, and ertapenem (Ivanz) are possible alternatives if someone is allergic to ceftriaxone or cefotaxime.
Macrolides
Tetracyclines
Note: I work with the following anti-cyst agents based on the mechanism by which these antibiotics work and some scientific experiments. For the rifamycins, no laboratory experiments show these agents work against cysts. Clinically, I see great benefit in using the rifamycins as my anti-cyst agents, so I list them here.
Rifamycins
Azoles
Herbal
Based on my observations, these herbal combination options have as good of a chance as the prescription options. They appear to kill intracellular and extracellular Lyme, too, based on the clinical benefit I see in my medical practice.
Inside of cells, Lyme may live in cave-like structures called vacuoles. In these vacuoles, Lyme germs create a hostile acidic environment that can limit the effectiveness of various antibiotics. Quinine derivatives, like hydroxychloroquine (Plaquenil), can make the inside of cells more basic (less acidic), which can help the tetracyclines and macrolides mentioned above work better.
Treating persisters is a newer area in Lyme treatment. To help justify these various antimicrobial options, in this section I describe the experimental basis behind my recommendations. These options are ones I am using with various degrees of success in my Seattle practice. They all have either laboratory experiments or published human experiments supporting their use.
The following prescription and herbal medicine options have been shown in lab experiments to kill persisters, which I am incorporating into my treatments of Lyme and/or Bartonella.
Disulfiram is shown in lab experiments by Jayakumar Rajadas, PhD and colleagues at Stanford to treat Lyme persisters. Ying Zhang, MD and colleagues at Johns Hopkins found disulfiram does not work against Bartonella, however. Furthermore, Dr. Rajadas and Dr. Zhang both showed that disulfiram can treat growing Lyme, although it is only moderately effective. Disulfiram is a drug used to treat alcoholism that is being repurposed to treat Lyme.
Dr. Zhang and colleagues at Johns Hopkins University have shown methylene blue treats growing and persister states of Lyme. Methylene blue is approved to treat a problem called methemoglobinemia where methylene blue causes hemoglobin to release oxygen. Methylene blue is repurposed to treat Lyme and Bartonella.
Dr. Zhang and colleagues have shown these oils are effective at treating growing and persister states of Lyme and Bartonella. Of the various herbal options listed here, this is my go-to favorite based on the clinical benefits I see in my practice.
This herbal medicine is traditionally used to treat Babesia and malaria. In two different studies in 2021, however, Dr. Zhang and colleagues have shown Cryptolepsis is effective at treating growing and persister forms of Bartonella and Lyme.
This herbal medicine is traditionally used to treat Lyme and Bartonella as described in the various books by master herbalist Stephen Buhner. Dr. Zhang and colleagues have also shown that Japanese knotweed treats growing and persister states of Lyme and Bartonella.
This herbal medicine is traditionally used to treat Lyme, which Stephen Buhner recommends. Additionally, Dr. Zhang and colleagues have shown that it treats persister Lyme.
Here is a list of prescription medications shown in human experiments to help with persister Lyme.
Ken Liegner, MD published a case report of more than 70 people he treated with disulfiram as a solo agent. Based on his reports and based on my experience, this repurposed drug is effective at putting about 36 percent of people with Lyme into remission and may help a larger group to have symptom improvements. However, disulfiram is a very difficult drug to use. For more information on this read Disulfiram.
Historically, dapsone is used to treat Leprosy. Richard Horowitz, MD has promoted the use of dapsone-based regimens to treat both Lyme and Bartonella persisters. He researched both a 100 mg dapsone protocol and a 200 mg dapsone protocol. Similar to disulfiram, dapsone-based treatment is a harsh regimen with nearly 40 percent of people dropping out of treatment due to side effects. Based on Horowitz’ experiments and my use of the medication with my patients, I find improvements of 20 percent or so in those that can tolerate the treatment. A small percentage of patients can get into remission with this treatment.
I recommend disulfiram-only regimens to people who have taken extensive numbers of antibiotics for a year or more of treatment and remain ill. In this type of situation, it is possible that the antibiotics have pushed most of the remaining germs out of a growing state into a persister state.
Dr. Liegner’s research shows that when disulfiram is used as a solo antibiotic, 36 percent of people can enter a period of extended remission. Therefore, in people who have failed years of antibiotics, without an active co-infection, I recommend a trial of disulfiram alone. Disulfiram does not have any benefit for Bartonella and is a very weak anti-Babesia agent. Because of this, I only use disulfiram alone to treat Lyme when these other germs are not active.
In the examples below, I also show that disulfiram can be used in combination with other antibiotics to treat perister Lyme where the other antibiotics treat growing phase Lyme.
In my practice, I offer two persister-oriented regimens for those that have failed years of regular antibiotics. Both regimens have some published clinical evidence of benefit. One regimen I offer is a Horowitz dapsone-persister regimen. The other option I offer is a disulfiram-only regimen or a disulfiram-combination regimen. (See Lyme Disease Antibiotic Combination Examples below). You can read more details about how to take both regimens in:
In my experience, I find the prescription antibiotic combinations below work 85-90 percent of the time. The herbal combination options help 85-90 percent of the time. I find all these combinations more successful than the Andrographis combinations that some like herbalist Stephen Buhner and Bill Rawls, MD recommend. The Buhner/Rawls combination helps about 60-65 percent of the time in my clinical observations. To reach the success rates I describe here, it is essential to follow the first 10 steps of The Ross Lyme Support Protocol to support the immune system.
Key Points: Each combination
This is the second time I am making this point because it is very important. It is essential to your recovery that, at a minimum, your treatment addresses the steps outlined in my Lyme disease treatment guidelines, The Ross Lyme Support Protocol (Chapter 4). Even a year or more into your treatment, these 10 steps are essential to resuscitate and support the immune system.
Pulsing herbal antibiotics does not work well; therefore, I do not recommend it here. Clinically, continuous use of herbal antibiotics works best in most situations. The only time I pulse is for two months on and two months off when using regimens to address persister Lyme. For more information about this, see How to Treat Persister Lyme & Bartonella. Pay attention to the Burrascano-type regimen I mention.
Some prescription antibiotics can be given using pulse dosing. The idea is to start and stop the antibiotics. This allows the body to recover from the toxicity of some of the drugs while effectively killing the germ using high doses. Again, pulsing may also help with persister cells. As Lyme is a slow-growing germ, the spirochete form only requires two to three days for some antibiotics to work and then several days to recover and Lyme to start growing again. All the antibiotics mentioned in this article may be pulse-dosed except for azithromycin. One way to pulse is in a 4-day-on-and-3-day-off cycle. Many physicians have different ways of pulsing antibiotics.
In my experience, I find most oral antibiotic combinations to work about 85 percent of the time, while IV equivalent treatments work about 90 percent of the time. Thus, the majority of people with chronic Lyme do not require IV antibiotics.
I find either benzathine penicillin G (Bicillin LA) 1.2 million units given 3-4 times a week or high dose oral amoxicillin 500 mg 3-4 pills given 3 times a day is nearly as effective as IV antibiotic regimens. These treatment regimens deliver effective drug levels that penetrate tissues and the brain.
Continue treatment with antibiotics until you are well. For some, this may mean they achieve complete recovery; for others, it may not. At the beginning of treatment for someone with chronic Lyme, it is difficult to predict what the length and degree of recovery will be. For more information about this, see When Will I Start to Feel Better? (Lyme, Babesia, & Bartonella Timelines).
Generally, I suggest rotating a prescription antibiotic every six months to prevent resistance to that antibiotic. However, I find herbal antibiotics work well for a year or more without changing the herbs. Lyme does not easily develop herbal antibiotic resistance.
It is time to stop a full treatment when someone is either symptom-free for two months or the improvements have plateaued for four months after adjusting the regimen. On average, it can take two years to recover for someone with chronic Lyme. This is an average. Some are on the six-month program, while others may require years.
Follow the steps in Can’t Get Better? Do This to see what else to address if antibiotics are not working, or if you are at a plateau.
For some with chronic Lyme disease, a cure does not occur. Refer to Finished? And How to Prevent Relapse for a discussion of this.
About 90 percent of the time when antibiotics are started or changed during a treatment, a person will initially worsen. This is often due to a Herxheimer die-off reaction. Refer to Herxheimer Die-off Reaction: Inflammation Run Amok for a discussion of this and practical steps you can take to prevent or treat it.
The ideas and recommendations on this website and in this article are for informational purposes only. For more information about this, review the sitewide Terms & Conditions.
Marty Ross, MD is a passionate Lyme disease educator and clinical expert. He helps Lyme sufferers and their physicians see what really works based on his review of the science and extensive real-world experience. Dr. Ross is licensed to practice medicine in Washington State (License: MD00033296) where he has treated thousands of Lyme disease patients in his Seattle practice.
Marty Ross, MD is a graduate of Indiana University School of Medicine and Georgetown University Family Medicine Residency. He is a member of the International Lyme and Associated Disease Society (ILADS), The Institute for Functional Medicine, and The American Academy of Anti-Aging Medicine (A4M).
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