How to Treat Persister Lyme & Bartonella

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Persister Lyme in a Lyme disease treatment image from Marty Ross MD

Updated: 2/1/23

I provide a large part of the information in this article in A Lyme Disease Antibiotic Guide and in Kills Bartonella: A Brief Guide. I am including this information as a stand-alone article on persisters for those looking for information just on this topic and additional persister treatment options from those I lay out in the Lyme and Bartonella articles.

About Persister Lyme & Bartonella

Lyme and Bartonella are hard to treat for many reasons. One reason is persister Lyme and Bartonella germs ignore standard antibiotics. Based on numerous laboratory experiments since 2015, the Lyme germ is shown to have a growth state, as well as a hibernating, non-growing state. These hibernators are called persisters. They do not respond to regular prescription antibiotics, although they do seem to respond to many herbal antibiotics that we use.

More recently, experiments starting in late 2019 from Ying Zhang, MD and colleagues show that Bartonella also has persister forms.

Lyme Terminology 101

Lyme has three different forms—or ways the germ looks. Two of these forms include the spirochete (which looks like a corkscrew) and the microscopic cyst form. These germ forms can exist in a growing state or in a persister state. The third form is an intracellular form of the germ called an L-form. There is no data I am aware of about whether or not this exists in a persister state.

Research published in 2015 by Kim Lewis, PhD and colleagues at Northeastern University in Boston suggest about 10 percent of spirochetes and cysts—when exposed to antibiotics in the lab—go into the persister state. In their experiments, if the researchers stopped the antibiotics and let the germs wake back up into a growth state, the antibiotics kill the germs again. He did this four times, which killed all germs. Therefore, his experiments showed that persisters exist and that one way to treat them is to pulse (start and stop) antibiotics.

Bartonella Terminology 101

Bartonella does not have spirochetes and cysts. It does have growing and persister states like Lyme, however.

Lab Investigations & More Lab Investigations

These persisters could explain why many with Lyme do not recover with regular antibiotics. Regular antibiotics in various laboratory experiments do not treat persisters. These regular antibiotics include common antibiotics like amoxicillin, doxycycline, azithromycin, clarithromycin, tinidazole, rifampin, cefuroxime, among others.

Researchers are doing a lot of laboratory work trying to figure out what will kill persister forms of Lyme and/or Bartonella. Keep in mind, a human is different from a lab. So, what seems to work in a lab may or may not work in a human.

What the Lab Experiments Show

The following are prescription and herbal medicine options shown in lab experiments to kill persisters that I am incorporating into my treatments of Lyme and/or Bartonella.

  • Disulfiram.  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. For more information about disulfiram, see Disulfiram.
  • Methylene Blue. 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.
  • Cefuroxime plus Clarithromycin plus Nitazoxanide. Dr. Zhang’s petri dish experiments from 2020 show this is a very effective combination at killing and preventing regrowth of persister Lyme. The drugs in this combination also can treat growing Lyme, too. I just recently learned about this combination as I write this in May of 2022. This combination shows promise. One problem is that nitazoxanide (Alinia) is very expensive. Usually, insurance will not pay for it as a Lyme disease treatment.
  • Liposomal Oregano, Cinnamon, and Clove Oils. Dr. Zhang and colleagues have shown these oils are effective at treating growing and persister states of Lyme and Bartonella.
  • Cryptolepis. 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.
  • Japanese Knotweed. 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.
  • Cat’s Claw. 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.
  • Azlocillin. Dr. Rajadas and colleagues have shown this penicillin is effective at treating growing and persister states of Lyme in lab experiments. One big problem, however, is that Azlocillin is not currently produced by any pharmaceutical company.

What Human Experiments and Case Reports Show

  • Disulfiram. 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. Nonetheless, it is a very difficult drug to use. For more information on this, read Disulfiram.
  • Dapsone. Richard Horowitz, MD has promoted the use of dapsone-based regimens to treat both Lyme and Bartonella persisters. Historically, dapsone is used to treat leprosy. Dr. Horowitz researched both a 100 mg dapsone protocol and a 200 mg dapsone protocol using patients in his practice. This regimen is also 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 who can tolerate the treatment. A small percentage of patients can get into remission with this treatment. For more information about dapsone-based regimens, see Dapsone for Lyme Persisters. A Miracle Antibiotic?

Long-Pulse Regimens Based on Burrascano

Before leaving clinical practice in the early 2010s, Lyme treatment pioneer Joseph Burrascano, MD was treating patients by stopping antibiotics for long periods of time, allowing the patient to get sick. Then he would restart the antibiotics for a couple of months or so, long enough to see improvements and for Herxheimer reactions to disappear.

Burrascano hypothesized that after a period of prolonged antibiotic treatment Lyme ignored the antibiotics and stopped growing but did not die. During the off period, he let people get sick as a sign the germ was fully back into a growth state where antibiotics could kill it more effectively. Generally, his approach worked out to about two months off antibiotics and then two months on. He suggested the sicker a person let himself or herself become, the greater chance the antibiotics would work. He claims a cure with this method after four starting-and-stopping cycles.

When Burrascano came up with this idea, the work of Lewis and colleagues at Northeastern was not complete. Yet, Burrascano’s idea is supported by Lewis’ research that Lyme develops hibernating persister cells that stop responding to antibiotics. When antibiotics are stopped, they wake back up again and respond.

My Treatment Recommendations

Lyme & Bartonella Persisters

Here is how I am currently incorporating persister treatments into my Lyme and Bartonella regimens.

Lyme Persisters Without Bartonella Infection

I find that disulfiram gives the best chance of improvement out of these options, but it is very hard to tolerate for many people. I consider the dapsone-based treatment option to offer a slightly better chance of improvement compared to the herbal options below.


See Disulfiram for information about how to dose and use disulfiram.

  • Disulfiram-only. Try a Disulfiram-only regimen if you have been treated for a year or more for Lyme with standard prescription antibiotic treatments and have not gotten better. Disulfiram could help Babesia, but is not effective against Bartonella. So be sure to have cleared those two coinfections before trying a disulfiram-only regimen.
  • Disulfiram With Growing-State Antibiotics. If you have improved on disulfiram, but relapse when you stop it, add antibiotics that target growing Lyme, too. You may have relapsed because disulfiram may not treat growing Lyme. For information about antibiotics to treat growing spirochetes and cysts see, A Lyme Disease Antibiotic Guide.
  • Just Beginning Treatment. If you are new to treating Lyme disease, I do not recommend starting with a disulfiram treatment due to how difficult a treatment can be and the fact it is only moderately effective at treating growing forms of Lyme.

Lyme and/or Bartonella Persisters

The following options work for both Lyme and for Bartonella. The disulfiram options discussed above only work for Lyme.

Dapsone-Based Antibiotic Protocol

See Dapsone for Lyme Persisters. A Miracle Antibiotic? for information about how to build a dapsone-based regimen including dapsone and the other required antibiotics and supplements. I tend to offer this type of treatment at six months or more into a chronic Lyme disease treatment or Bartonella treatment if a person is not improving. I also try this type of regimen if someone has first tried a disulfiram regimen (for Lyme only) and it does not work.

Herbal Lyme and Bartonella Persister Options

At the beginning of treatment, or after one to two months of treatment after a person is no longer having Herxheimer reactions from their growing Lyme and/or Bartonella regimen, I am adding one or two of the following herbs. I usually start with the liposomal cinnamon, clove, and oregano oil and/or the cryptolepis. Another option if you cannot take one of these is to substitute it for Japanese knotweed.

What to Use for Growing Bartonella or Lyme

Growing Lyme and Bartonella regimens could include Cat’s Claw, Otoba, Sida acuta, Japanese knotweed and/or houttuynia tinctures, cefuroxime, clarithromycin, azithromycin, grapefruit seed extract, tinidazole, rifampin, bactrim, or metronidazole. See A Lyme Disease Antibiotic Guide and/or Kills Bartonella: A Brief Guide for more information specific to the germ you are trying to kill.

What to Use for Persister Bartonella or Lyme

Herbal Medicines

  • Liposomal Cinnamon, Clove, and Oregano Oil. Take one pill two times a day. I prefer the Doctor Inspired Formulations product called Liposomal Cinnamon Clove & Oregano Essentials.* This is my go-to herbal option. I include it in most of my Lyme and Bartonella treatments.
  • Cryptolepis Tincture. Work up to 5 ml (1 tsp) 3 times a day over 3 weeks by starting at 5 ml 1 time a day, then 5 ml 2 times a day, then 5 ml 3 times a day.
  • Japanese Knotweed. Work up to 1.25 ml (¼ tsp) to 2.5 ml (½ tsp) 3 times a day over a 3-week period of time.

Methylene Blue

I add Methylene Blue to the herbal options above if one or two of the herbal medicine options is not helping. Methylene Blue must be compounded. Be aware methylene blue costs nearly $350 a month. It also turns urine and stool blue and is very hard to scrub off porcelain toilets. Your clinician will need to order a glucose 6 phosphate dehydrogenase (G6PD) blood test. If this red blood cell antioxidant is low, then you should not take methylene blue. With low G6PD there is a risk that your red blood cells will break apart.

I find the herbal options have as good of a chance of helping.

  • Methylene Blue 50 mg 1 pill 2 times a day.

One Last Lyme Option - Burrascano Long Pulse

I use several antibiotic combinations like those mentioned in A Lyme Disease Antibiotic Guide. I use them for two months off, then two months on. Sometimes I use them for one month on or one month off. This approach helps about 10-20 percent of the time with various degrees of improvements. Unlike Burrascano, I do not believe these cure people. However, several of my patients who remained quite ill from Lyme infection after taking antibiotics got very well on this approach.


The ideas and recommendations on this website and in this article are for informational purposes only. For more information about this, see the sitewide Terms & Conditions.

* These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.


View Citations

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  7. Horowitz R, Freeman, PR. The use of dapsone as a novel “persister” drug in the treatment of chronic Lyme disease/post treatment Lyme disease syndrome. J Clin Exp Dermatol Res. 2016;7(3):1000345. doi:10.4172/2155-9554.1000345 (View)
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  9. Liegner KB. Disulfiram (tetraethylthiuram disulfide) in the treatment of Lyme disease and Babesiosis: Report of experience in three cases. Antibiotics (Basel). 2019;8(2):72. doi:10.3390/antibiotics8020072 (View)
  10. Ma X, Leone J, Schweig S, Zhang Y. Botanical medicines with activity against stationary phase Bartonella henselae. Infect Microb Dis. 2021;3(3):158-167. doi:10.1097/IM9.0000000000000069 (View)
  11. Pothineni VR, Wagh D, Babar MM, et al. Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening. Drug Des Devel Ther. 2016;10:1307–1322. doi:10.2147/DDDT.S101486 (View)
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  13. Potula H-HSK, Shahryari J, Inayathullah M, Malkovskiy AV, Kim K-M, Rajadas J. Repurposing disulfiram (tetraethylthiuram disulfide) as a potential drug candidate against Borrelia burgdorferi in vitro and in vivo. Antibiotics (Basel). 2020;9(9):633. doi:10.3390/antibiotics9090633 (View)
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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 (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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