A Lyme Disease Antibiotic Guide

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Herbal and Prescription Antibiotics for Lyme Image from Marty Ross MD

Herbal & Prescription Lyme Disease Antibiotics

In this article, you will learn how to build a Lyme disease herbal or prescription antibiotic treatment. Later, in this guide I provide 11 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 Kills Bartonella: A Brief Guide, Kills Babesia: A Brief GuideKills Anaplasma and Ehrlichia: A Brief Guide and Target Viruses, Mycoplasma, & Chlamydia in Lyme? Maybe Not.

Before I describe these plans, you should 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 me, prescribe antibiotics based on theory in addition to our collective observation, which is that combinations of antimicrobials work better than single agents alone. It is critical that a Lyme disease treatment regimen addresses the first ten 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, what 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.

Marty Ross MD Presents a Video Version of This Guide

 
 
 
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I. Lyme Disease Antibiotics Overview

The following are four rules to develop a Lyme disease antibiotic regimen.

Rule 1. Combine antibiotics to treat all forms of the germ.

Borrelia exists in two separate forms. These forms are the spirochete and a cell-wall deficient form that goes by a few names, including “round body,” “L-form,” and “cyst.” In this article, I refer to the non-spirochete form as the cyst. The spirochete is the form many know from pictures; it looks like a spiral or a coiled snake.

Under stress, Borrelia changes itself from one form to another. For instance, when the spirochete is exposed to doxycycline, it can convert to a more treatment-resistant cyst form of the germ. At any given time, it is likely that a person with chronic Lyme disease has Borrelia existing in both forms. To get rid of Lyme germs, all forms must be treated at the same time.

Rule 2. Combine antibiotics to treat Lyme living outside and inside of cells.

Most physicians think Lyme lives outside of cells in tissues that hold cells and body structures together, or even on nerve coverings. However, Miklossy shows that Lyme lives inside cells and outside of cells. (6) To recover from Lyme, it is necessary to treat Lyme germs living inside cells and outside of cells at the same time. Antibiotics that work inside 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.

Rule 3. Combine antibiotics that work in different ways to attack the germ from different angles.

Families of antibiotics work differently. For instance, the penicillins and cephalosporins work to weaken the outer covering of the spirochete, while the tetracyclines and the macrolides limit the ability of the spirochete to grow by blocking protein production.

Rule 4. Use no more than three herbal or prescription antibiotic products at a time.

As much as possible, follow this rule to limit toxicity and adverse interactions.

Special Considerations

See “Section IV. Special Considerations” below for information about:

  • Pulse Dosing
  • IV versus Oral Antibiotics
  • IV Equivalent Treatments
  • Treatment Length
  • Remission
  • Herxheimer Die-off Reactions

II.  Families of Lyme Disease Antibiotics

(Note: This is not a comprehensive list of all antibiotics that can be used. For information about Alinia see the IV. Special Considerations section below.)

Penicillins.

  • Types: Benzathine penicillin G (Bicillin LA), amoxicillin, amoxicillin/clavulanic acid (Augmentin).
  • Germ Forms Treated: The spirochete and possibly the cyst.
  • Location: Outside of cells.
  • Mechanism: Works by limiting the growth of the cell wall matrix. This results in the covering of the spirochete breaking down. Eventually due to pressure inside, the germ bursts through its weakened cell wall and dies. It is not clear how penicillins treat cysts, but Eva Sapi’s lab research shows that amoxicillin does. (7)
  • Available As: Prescription medicine.

Cephalosporins.

  • Types: Ceftriaxone (Rocephin) 2gm, ceftazidime (Zinacef), cefuroxime (Ceftin), cefdinir (Omnicef)
  • Germ Forms Treated: The spirochete and possibly cyst.
  • Location: Outside of cells.
  • Mechanism: Same as penicillins.
  • Available As: Prescription medicine.

Tetracyclines.

  • Types: Doxycycline, minocycline, tetracycline
  • Germ Forms Treated: The spirochete.
  • Location: Inside and outside of cells.
  • Mechanism: Blocks protein production at a part of the cell called the 30s ribosome. Ribosomes are located inside of cells where they use genetic programming and amino acids to produce proteins. When protein production is blocked, germ growth is limited, leading to eventual death.
  • Available As: Prescription medicine.

Macrolides.

  • Types: Azithromycin (Zithromax), clarithromycin (Biaxin), clarithromycin extended release (Biaxin XL)
  • Germ Forms Treated: The spirochete.
  • Location: Inside and outside of cells.
  • Mechanism: Blocks protein production at a part of the cell called the 50s ribosome. Ribosomes are located inside of cells where they use genetic programming and amino acids to produce proteins. When protein production is blocked, germ growth is limited, leading to eventual death.
  • Available As: Prescription medicine.

Azoles.

  • Types: Metronidazole (Flagyl), tinidazole (Tindamax)
  • Germ Forms Treated: Spirochete and cyst.
  • Location: Inside and outside of cells.
  • Mechanism: Impairs bacterial enzymes and destabilizes DNA.
  • Available As: Prescription medicine.

Rifamycins.

  • Types: Rifampin, rifabutin
  • Germ Forms Treated: Spirochete and cyst.
  • Location: Inside and outside of cells.
  • Mechanism: Prevents production of RNA from the cell DNA. Without RNA, the bacteria cannot make protein. When protein production is blocked, germ growth is limited, leading to eventual death.
  • Available As: Prescription medicine.

Sulfa Antibiotics.

Quinine Derivatives.

  • Types: Hydroxychloroquine (Plaquenil)
  • Germ Forms Treated: None. Conflicting research shows could kill cyst or promote cyst growth.
  • Location: Inside of cells.
  • Other Action: Improves effectiveness of macrolides and tetracyclines.
  • Mechanism: Lowers acid levels inside of cell vacuoles where germs can live. Lowering acid levels can help antibiotics work better.
  • Available As: Prescription medicine.

Grapefruit Seed Extract.

  • Types: Various supplement brands
  • Germ Forms Treated: Supports killing of cyst.
  • Location: Unclear from research.
  • Mechanism: Unclear.
  • Available As: Natural medicine.

Herbal Combination: Option 1.

  • Types: Otoba Bark Extract (Otoba parvifolia) used with Cat’s Claw (Uncaria tomentosa). See Otoba Bark Extract and Cat’s Claw Tinctures (Chapter 10) for more information.
  • Germ Forms Treated: Supports killing of spirochete and cyst.
  • Location: Unclear from research.
  • Mechanism: Unclear.
  • Available As: Natural medicine.

Herbal Combination: Option 2.

  • Types: A combination called Biocidin LSF composed of bilberry extract (25% anthocyanosides), noni, milk thistle, echinacea (purpurea and angustifolia), goldenseal, shiitake, white willow (bark), garlic, grape seed extract (minimum 90 percent polyphenols), black walnut (hull and leaf), raspberry, fumitory, gentian, tea tree oil, galbanum oil, lavender oil (plant and flower), oregano oil (plant and flower). See Biocidin: A Potent Antimicrobial & Biofilm Breaker for more information about these herbs used in combination.
  • Germ Forms Treated: Supports killing of spirochete and cyst.
  • Location: Lyme living inside and outside of cells.
  • Mechanism: Echinacea, goldenseal, gentian, and shiitake mushroom found in Biocidin are bacteriostatic and may limit the ability of Lyme to grow. Volatile oils like lavender, oregano, and tea tree are bactericidal and may kill germs outright. Bilberry, black walnut, garlic, gentian, grape seed, olive leaf, and shiitake mushrooms are also bactericidal.
  • Available As: Natural medicine.

III. Lyme Disease Antibiotic Combination Examples

Persister Lyme

Recent research shows Lyme can form persisters. These are forms of spirochetes and cysts that slow their metabolism way down. In this hibernation state, they can ignore the antibiotics sent to kill them.

Note, as I write this article in August 2019, it is too early to tell if the new focus on treating persisters in Lyme will or will not help most people. As such, I think it is best to use one of the combinations below for a minimum of six or more months to see if it will work before trying a persister regimen.

For the most recent advances in treating persister Lyme see the following articles:

The Lyme Disease Antibiotic Herbal and Prescription Combinations

The following is a very limited list of antibiotic herbal and prescription combinations. There are many possible combinations, but these are combinations I have tried and find very effective.

In my experience, I find the prescription antibiotic combinations below work 85 to 90 percent of the time. The combination of otoba bark and cat's claw also help 85 to 90 percent of the time. The Biocidin LSF helps around 70 to 75 percent of the time. I find all these combinations more successful than the Andrographis/Japanese knotweed/cat’s claw combinations that some like herbalist Stephen Harrod Buhner and Bill Rawls, MD, recommend. The Buhner/Rawls combination helps about 60 to 65 percent of the time in my clinical observations. To reach the success rates I describe here, it is essential to follow the first ten steps of The Ross Lyme Support Protocol to support the immune system.

Key Points: Each combination

  • treats or supports killing of all Lyme germ forms,
  • attacks the germ from different angles through different mechanisms of action, and
  • can work inside and outside of cells.

Macrolide plus Azole

Clarithromycin (Biaxin) 500 mg 1 pill 2 times a day and tinidazole 500 mg 1 pill 2 or 3 times a day.

Key Point

  • Tinidazole can remove biofilms that block the immune system and antibiotics. (See Biofilms: Lyme Disease Gated Communities (treatlyme.net) for more information about biofilms and treatments.)

Macrolide plus Quinine Derivative plus Azole

Azithromycin (Zithromax) 500 mg 1 pill 1 time a day, hydroxychloroquine (Plaquenil) 200 mg 1 pill 2 times a day, and metronidazole (Flagyl) 500 mg 1 pill 2 or 3 times a day.

Key Points:

  • Since azithromycin is not as effective as other macrolides like clarithromycin, hydroxychloroquine is used to increase the effectiveness.
  • Tinidazole could be substituted for the metronidazole because it may remove biofilms more effectively.

Macrolide plus Grapefruit Seed Extract

Clarithromycin (Biaxin) 500 mg 1 pill 2 times a day and grapefruit seed extract 250 mg 1 pill 2 times a day.

Key Point:

  • Grapefruit seed extract is better tolerated than both tinidazole and metronidazole and supports killing of Lyme cysts.

Tetracycline plus Macrolide plus Grapefruit Seed Extract

Doxycycline 100 mg 2 pills 2 times a day, clarithromycin (Biaxin) 500 mg 1 pill 2 times a day, and grapefruit seed extract 250 mg 1 pill 2 times a day.

Key Point:

  • Tetracyclines and macrolides both block protein production by binding to the protein production apparatus in germs called ribosomes. But they each bind to a different part of the ribosome improving the blockade of protein production.

Penicillin plus Azole

Amoxicillin 500 mg 4 pills 3 times a day plus tinidazole (Tindamax) 500 mg 1 pill 2 or 3 times a day for 4 days on and 3 days off in 7-day cycles.

Key Points:

  • This is a very high dose of Amoxicillin, which is four times stronger than physicians prescribe for other infections like ear infections. I consider this dose to be nearly as effective as IV antibiotics. (See IV Equivalent Treatments below in this article.)
  • This is a pulse dose regimen of the tinidazole. It may be more effective than continuous regimens. (See Pulse Dosing below.)

Cephalosporin plus Tetracycline plus Azole

Cefuroxime (Ceftin) 500 mg 2 pills 2 times a day, minocycline 100 mg 1 pill 2 times a day, and Flagyl 500 mg 2 to 3 times a day for 2 weeks on and 2 weeks off on 4-week cycles.

Key Point:

  • Some experts suggest that a tetracycline or macrolide in combination with a cephalosporin or penicillin could limit effectiveness. In theory, cephalosporins and penicillins work best with rapid germ growth. However, the tetracyclines and macrolides also limit germ growth. So, in theory the minocycline in this combination should cancel the effect of the Cefuroxime. I understand the theory, but in some I find this to be a very effective combination.

Herbal Combination 1

Otoba Bark Extract plus Cat’s Claw. Start at 5 drops of each 2 times a day and increase every other day by 1 drop per dose until taking 30 drops of each 2 times a day. If increasing the dosages makes a person feel worse, they should not increase until the worsening improves. Take without food (i.e., do not take beginning 30 minutes before food through 2 hours after food, but you may take it with medicines and supplements).

Key Points:

  • I find this combination to be as effective as oral prescription antibiotic combinations. It works successfully as a support in a Lyme treatment about 85 to 90 percent of the time.
  • In addition to treating all three forms of the germ, this combination supports the removal of biofilms.

Herbal Combination 2

Biocidin LSF. Start at 1 pump under the tongue 1 time a day. Every 2 days, increase by 1 pump first as 1 pump 2 times a day, then 1 pump 3 times a day, and eventually to 2 pumps 3 times a day. If a person gets worse due to a Herxheimer die-off reaction (see Part IV of this article), they should not increase the pumps until it passes. For sensitive people, place 1 pump in 5 ounces of water. Start with 1 ounce, from the 5-ounce mix, 1 time a day. Increase by 1 ounce a day increasing gradually at first to 1 ounce 3 times a day. Eventually, as tolerated, work up to 10 ounces (2 pumps) 3 times a day.

Key Points:

  • I find this combination works successfully about 70 to 75 percent of the time as a standalone medicine. I use it as an herbal alternative if the otoba bark and cat’s claw combination do not work. I prefer this combination to the andrographis/Japanese knotweed/cat’s claw combinations recommended by Buhner and Rawls.
  • In addition to supporting the treatment of all three forms of the germ, herbs in this combination remove biofilms. Component herbs block efflux pumps Lyme uses to remove herbal and prescription antibiotics from its inside.
  • This product is useful in prescription antibiotic combinations because its herbal components support the removal of biofilms and block efflux pumps Lyme uses to get rid of antibiotics.

Tetracycline with Rifamycin

Minocycline 100 mg 1 pill 2 times a day plus rifampin 300 mg 2 pills 1 time a day.

Key Point:

  • This is also an effective regimen for treating a Bartonella co-infection. Co-infections are other germs passed on during a tick bite. If someone has a co-infection, when possible I choose antibiotic combinations that simultaneously treat Lyme germs and the co-infection germs.

IV Antibiotic Regimen: Cephalosporin and Azole

Ceftriaxone (Rocephin) 2 gm IV 2 times a day for 4 days on and 3 days off, plus tinidazole 500 mg taken orally 1 pill 2-3 times a day for 4 days on and 3 days off in 7-day cycles.

Key Points:

  • Various antibiotics can be used as IV. I use this one most commonly because it is the easiest to administer and one of the lowest cost IV regimens. The ceftriaxone is given in a syringe and injected over 10 minutes. This is also a pulse dose regimen (see below under Special Considerations). Ceftriaxone could be given daily instead as 2 gm IV 1 time a day.
  • I have found various pulse dose regimens of tinidazole to work. These include 2 weeks on and 2 weeks off or in the regimen seen here.

IV Antibiotic Regimen: Macrolide and Grapefruit Seed Extract

Azithromycin 500 mg IV plus grapefruit seed extract 250 mg orally 2 times a day.

Key Point:

  • Azithromycin works quite well as an IV antibiotic but is much weaker in oral form.

IV. Special Considerations for Lyme Disease Antibiotics

Antibiotics Alone Are Unlikely to Get You Well.

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 address the steps outlined in my Lyme disease treatment guidelines: The Ross Lyme Support Protocol. Even a year or more into your treatment, these ten steps are essential to resuscitate and support the immune system.

Pulse Dosing.

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. What Works? 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 effectivly 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.

IV Versus Oral Antibiotics.

In my experience, I find most oral antibiotic combinations to work around 85 percent of the time, while IV equivalent treatments work around 90 percent of the time. Thus, the majority of people with chronic Lyme do not require IV antibiotics.

IV Equivalent Treatments.

I find either benzathine penicillin G (Bicillin LA) 1.2 million units given 3 to 4 times a week or high dose oral amoxicillin 500 mg 3-4 pills 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.

Treatment Length.

Continue treatment with antibiotics until you are well. For some, this may mean 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 Getting Healthy: Will I? When? How Do I?

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 making adjustments in 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.

Remission.

For some with chronic Lyme disease, a cure does not occur. Refer to Finished? And How to Prevent Relapse for a discussion of this.

Herxheimer Die-off Reaction.

About 90% 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.

Alinia.

This is an antiparasite medication that some are using to treat Lyme disease. Because of its cost (nearly $1500/month), lack of scientific support, and limited help in treatment, I think it could be used as a treatment of later or last resort. For more information see Alinia: When & Why in Lyme Disease Treatment.

Disclaimer

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. 

References

View Citations

  1. Buhner SH. Healing Lyme: Natural Healing of Lyme Borreliosis and the Coinfections Chlamydia and Spotted Fever Rickettsioses. 2nd ed. Silver City, NM: Raven Press; 2015.
  2. Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guidelines recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti-Infect Ther. 2014;12:1103–1135. doi: 10.1586/14787210.2014.940900.
  3. Datar A, Kaur N, Patel S, Luecke D, Sapi E. In vitro effectiveness of samento and banderol herbal extracts on the different morphological forms of Borrelia burgdorferi. Townsend Lett. 2010;7: 1–4.
  4. Gilbert L. Analysis of the activity of Biocidin compounds against Borrelia. Unpublished presentation of research conducted by Dr. Gilbert’s lab in Finland provided through personal communication from Rachel Fresco LAc PhD. 2016.
  5. Goc A, Rath M. The anti-Borreliae efficacy of phytochemicals and micronutrients: an update. Ther Adv Infect Dis. 2016;3(3-4):75–82. doi:10.1177/2049936116655502.
  6. Miklossy J, Kasas S, Zurn AD, McCall S, Yu S, McGeer PL. Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis. J Neuroinflammation. 2008;5:40.
  7. Sapi E, Kaur N, Ananwu S, Luecke DF, Luecke DF, Datar A, Patel S, Rossi M, Stricker RB. Evaluation of in-vitro antibiotic susceptibility of different morphological forms of Borrelia burgdorferi. Infect Drug Resist. 2011;4:97–11.

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About the Author

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 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) and The Institute for Functional Medicine.

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