Dapsone for Lyme Persisters. A Miracle Antibiotic?

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Dapsone for a Lyme disease treatment image from Marty Ross MD

Dapsone for Lyme Persisters

Dapsone, a Leprosy drug, can help some with treatment resistant Lyme due to persister cells. In 2016, Horowitz and Freeman published research on 100 patients. The study showed 59 percent of people had improvements with Dapsone of 100 mg or less. However, my experience with dapsone is mixed. While it helps some, it is also a very difficult medicine for many to take.

More recently, Dr. Horowitz has been using dapsone at a higher dose of 200 mg. He claims success getting people into remission at this dose.

In this article I review:

  • my experience with this novel medicine,
  • a specific antibiotic protocol that includes dapsone for Lyme persisters as both a lower dose regimen and a high dose regimen,
  • how to decrease side effects and Herxheimer reactions on dapsone,
  • the risks of using dapsone, and
  • the chances for treatment success using a dapsone regimen.

Marty Ross MD on Dapsone for Persister Lyme Treatment

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Persisters in Lyme

Lyme disease is difficult to treat. While a majority of people do get better following the standard one to two months of antibiotics recommended by the CDC and the IDSA in acute Lyme, many do not. If Lyme treatment starts more than a month or so after the acute infection, it appears harder to treat.

There are a number of reasons Lyme is difficult to treat. One idea that is getting a lot of current attention is Lyme, like tuberculosis and leprosy, can develop persister cells. Persisters in Lyme are composed of the spirochetes, cysts, and biofilm communities that grow very slowly or not at all. These persisters essentially go into hibernation where they ignore the antibiotics a person takes. Faster-growing Lyme is much easier to treat, but persisters evade the immune system and the antibiotics we send to poison them.

This article is about dapsone for treating persisters. Adding dapsone is one way to address persisters, but there are a number of persister and treatment resistant Lyme approaches. Read more in How to Treat Persister Lyme. What Works?

Why Dapsone?

Dapsone is an antibiotic used to treat slow-growing persister bacteria. Because of this, it is regularly used to treat leprosy and a form of skin inflammation called dermatitis herpetiformis. It can also kill malaria. Therefore, it could help treat those with a Babesia coinfection. Finally, dapsone can lower inflammation in Lupus. So, it could control inflammation in Lyme.

Warning: Dapsone is a Harsh Drug

Dapsone in Lyme is a hard medicine to take. In fact, in my Seattle practice I see 30 percent of patients do not tolerate this medicine and have to stop taking it. At the November 2017 International Lyme and Associated Diseases conference in Boston, Richard Horowitz MD, the pioneer of the dapsone approach, spoke of similar findings in his practice during his conference presentation.

  1. Check G6PD Levels Before You Start. Do not use dapsone if you have low Glucose-6-phosphate dehydrogenase (G6PD) deficiency. This condition mostly affects men. If a person has G6PD deficiency and they take dapsone, it could cause hemolysis (the tearing apart of the red blood cells). Before starting this medication, your physician should measure a G6PD blood test.
  2. Dapsone Blocks Folate Metabolism. Dapsone works by blocking folate metabolism in germs, but it also blocks folate metabolism in red blood cells leading to severe anemia. To prevent this consider taking up to 65 mg of folate a day (15 mg as 5-MTHF and 50 mg as prescription Leucovorin) while you are on this medication at a 100 mg dose. If you use the newer 200 mg dose, you may need to take up to 120 mg of folate a day. 
  3. Dapsone Suppresses the Bone Marrow. Red blood cells are manufactured in the bone marrow. Dapsone makes it harder for the bone marrow to make red blood cells. Although this is a separate method from folate metabolism interference, it also can lead to anemia. If anemia is a problem, lowering the dapsone dose can help.
  4. Dapsone in Lyme Causes Severe Herxheimer Reactions. I have seen some severe Herxheimer reactions using dapsone. As a result, I started all of my dapsone treatments at low doses and raised them slowly.
  5. Dapsone can Cause an Allergic Rash. About 5 percent of people who are allergic to sulfa antibiotics like Bactrim, may develop a rash on Dapsone. This usually can be managed using anti-histamine approaches. Most with sulfa allergies can take Dapsone. 
  6. Dapsone can Cause Methemoglobinemia. In methemoglobinemia, the oxygen carrying protein in red blood cells does not release oxygen into the tissues. This can cause some people to look blue. If this happens taking up to 2000 mg a day of liposomal glutathione can help. Taking the prescription methylene blue 50 mg two times a day reverses the situation. If you use the higher 200 mg dose of dapsone, there is a greater chance this situation could happen. 
  7. Dapsone Has Many Side Effects. The list of dapsone side effects reads like a list of Herxheimer reactions. It can cause fever, muscle pain, headache, fatigue, dizziness, nausea, and joint pains. In addition, it can cause neuropathy, severe allergic reactions, and other problems.

Because of these problems, dapsone in Lyme is not suitable for everyone.

When to Use Dapsone in Lyme

So, when is the right time to use dapsone in a Lyme treatment?

  1. Try a persister regimen, like dapsone, for any person who has tried various oral herbal and prescription antibiotic regimens for Lyme over the course of a year or more and did not have good improvements. Before doing so, I try various approaches to move the treatment forward that I outline in Can't Get Better? Do This.
  2. Use dapsone as an alternative to a trial of IV antibiotics.
  3. Finally, consider dapsone for a person who has tried IV antibiotics, but who did not have good improvements.
  4. As I mention above, a person must have a normal G6PD level to try dapsone.
  5. Before proceeding with dapsone, review the other persister regimens. Read more about these in How to Treat Persister Lyme. What Works?

The Lower Dose Dapsone Lyme Persister Regimen

This lower dose dapsone regimen is based on the research I mentioned above that Horowitz published in 2016.

  1. Dapsone 25 mg. Start 1 pill every other day for 1 week, then increase to 1 pill daily for a week, then to 2 pills every other day, alternating with 1 pill every other day for a week, then to 2 pills every day. 50 mg is the minimum effective dose. If a person can tolerate this for a week, then continue increasing slowly up to 100 mg a day.
  2. Cefuroxime 500 mg 1 pill 2 times a day. Use this to treat the cell wall of the persister spirochetes and for growing forms of the spirochetes. (This antibiotic is optional, while the others in this regimen are essential)
  3. Rifampin 300 mg 2 pills 1 time a day. Use this to treat intracellular Lyme and to treat cyst forms of the germ. If rifampin is not tolerated, a second choice for cyst Lyme is grapefruit seed extract 250 mg 1 pill 2 times a day.
  4. Minocycline 100 mg 1 pill 2 times a day or Doxycycline 100 mg 1 pill 2 times a day or Biaxin 500 mg 1 pill 2 times a day or Zithromax 500 mg 1 pill 1 time a day. These antibiotics block protein production to treat intracellular Lyme. In this regimen these drugs are interchangeable.
  5. Liposomal Curcumin 500 mg 1 pill 3 times a day. Use this as a nutritional support because it may limit Herxheimer die-off reactions. If a Herx is bad, then increase to 2 pills 3 times a day. Liposomal Curcumin, which is microscopically wrapped in fat to increase absorption is better than regular curcumin.
  6. Liposomal Glutathione 400 to 500 mg take 2 times a day. As a nutritional support this also may limit Herxheimer reactions and help with detoxification. Read more in Glutathione: The Great Fixer (treatlyme.net). For methemoglobinemia, increase the daily dose up to 2000 mg divided into two daily doses.
  7. Folate. Combine two forms of folate to reach 65 mg if needed. Use 5 MTHF 5 mg 3 pills 1 time a day. This is a methylated folate that may overcome the blockage of folate metabolism caused by dapsone. If you develop anemia at this dose then, add prescription Leucovorin 25mg 1 or 2 pills a day. Leucovorin is a form of folate called folinic acid. 

The High Dose Dapsone Lyme Persister Regimen

Dr. Horowitz discovered by accident that taking 200 mg a day of Dapsone for 2 months can put many people into extended remission, and may even cure them of Lyme. One of his patients took double the usual dose of Dapsone by accident and had great improvments. Horowitz claims he is seeing others who can tolerate taking Dapsone at 200 mg a day go into remission. 

The high dose Dapsone regimen is the same as the lower dose persister regimen above with the following changes. 

  1. Dapsone 100 mg 1 pill 2 times a day. Work the dose up to 200 mg a day following the increase schedule above.
  2. Liposomal Glutathione 400 to 500 mg. Take 800 mg to 1000 mg two times a day. This dose helps limit herxheimer reactions. It also prevents and helps manage methemoglobinemia.
  3. Methylene Blue 50 mg 1 pill two times a day. If you develop blue lips or blue skin color changes. This reverses methemoglobinemia.
  4. Folate. Combine two forms of folate to reach 115 mg if needed. Use 5 MTHF 5 mg 3 pills 1 time a day. This is a methylated folate that may overcome the blockage of folate metabolism caused by dapsone. If you develop anemia at this dose then, add prescription Leucovorin 25mg 3 or 4 pills a day. Leucovorin is a form of folate called folinic acid.
  5. Liposomal Curcumin 500 mg, Minocycline 100 mg or Zithromax 500 mg or Biaxin 500 mg or Doxycyline 100 mg, Rifampin 300 mg, Cefuroxime 500 mg. Take all of these as recommended in the Lower Dose Dapsone regimen above. 

Additional Notes

It is critical when doing this regimen to take the three nutritional support supplements I list above. The curcumin and glutathione may dramatically improve the problems with Herxheimer reactions and the 5 MTHF (folate) decreases the chances of anemia.

For a sensitive person who may have increased side effects and Herxheimer reactions in this regimen, do not use the Cefuroxime until the second or third month of the regimen. At times, it is not necessary to use the Cefuroxime at all based on the improvements. It is necessary in the beginning months on this regimen to test blood for anemia, kidney, and liver function monthly. Try the Lower Dose Dapsone regimen for a minimum of six months before deciding if it helps a person or not. If it is helping, keep using it as long as a person is improving. If you choose the Higher Dose Dapsone regimen, stay at the 200 mg dose of dapsone for two months. 

Does Dapsone for Lyme Persisters Work?

I have seen some wonderful improvements on the Lower Dose Dapsone regimen. My best situation is a nurse who did years of IV antibiotics with minimal improvements before transferring her care to my Seattle practice. On a ten-point scale, she had energy of six to seven. After using dapsone for a few months, she returned to work as a nurse, experienced improved energy levels to nine out of ten, and reported normal thinking. On average, however, people have improvements of 10 to 20 percent. And as I noted earlier, about 30 percent of patients cannot tolerate the dapsone at all due to side effects. Like Horowitz, I saw improvements in about 59 percent of my patients.

My experiences seem similar to those reported by Horowitz in his study of 100 patients using a dapsone regimen. This regimen does offer hope and a path to improved health for many. I am encouraged by the work of Horowitz and others like Zhang who are researching ways to treat Lyme persisters.


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.


View Citations

  1. Horowitz RI, Freeman PR. Precision medicine: retrospective chart review and data analysis of 200 patients on dapsone combination therapy for chronic Lyme disease/post-treatment Lyme disease syndrome: part 1. Int J Gen Med. 2019;12:101-119. Published 2019 Feb 18. doi:10.2147/IJGM.S193608 (View)
  2. Feng J, Auwaerter PG, Zhang Y. Drug combinations against Borrelia burgdorferi persisters in vitro: eradication achieved by using daptomycin, cefoperazone and doxycycline. PLoS One. 2015;10(3):e0117207. Published 2015 Mar 25. doi:10.1371/journal.pone.0117207 (View)
  3. Sharma B, Brown AV, Matluck NE, Hu LT, Lewis K. Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells. Antimicrob Agents Chemother. 2015;59(8):4616-4624. doi:10.1128/AAC.00864-15 (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) and The Institute for Functional Medicine.

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