How to Treat Persister Lyme. What Works?

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

Persister Lyme

Lyme disease is hard to treat. While a majority of people with acute Lyme do get better following the standard 1 to 2 months of antibiotics recommended by The US Centers for Disease Control and Prevention and The Infectious Diseases Society of America, many do not. And 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 hard 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 forms 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.

In this article I review a number of ways I treat persister Lyme. These treatment approaches are based on the ground breaking research of 

  • Lewis and colleagues at Northeastern University in Boston published in 2015 showing Lyme develops persisters,
  • the growing work of Ying Zhang MD figuring out combinations of antibiotics to treat persisters working out of his lab at John's Hopkins University in Baltimore, and
  • the clinical research of Richard Horowitz MD out of his practice in New York State.

And one of my older approaches, using a very long pulse regimen, comes from the clinical experience of Lyme treatment pioneer, Joseph Burrascano MD.

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The Northeastern University Studies

In 2015, Lewis and colleagues showed Lyme developed persister cells when exposed to ongoing antibiotics. More importantly their bench science studies showed that once antibiotics are stopped, the germs moves out of persister hibernation back into a growth phase that responds to antibiotics again. In Lewis' experiments starting and stopping antibiotics four times killed all forms of Lyme. Another key finding is Lyme does not develop antibiotic resistance by starting and stopping antibiotics. Most bacteria learn resistance to an antibiotic through genetic mechanisms when antibiotics are started and stopped, but this does not happen in Lyme. So a persister cell or state is not the same as drug resistance. In a slowed growth persister state, Lyme just simply ignores the antibiotics.

Zhang Studies

Ying Zhang MD comes to the world of Lyme from the world of tuberculosis research. Like Lyme, tuberculosis develops persister cells too. In tuberculosis, multiple drug regimens work best to target persistence. Zhang is bringing that idea to the world of his Lyme persister research. He has done a number of experiments finding different antibiotic combinations that can treat persister Lyme. The problem with most of his work, is that most of the combinations of antibiotics he has found effective are not accessible to the average person. Either the drug combinations he found effective are very costly, certain medications are only available for certain diseases, or the drugs are not available in the USA.

For instance, one of the promising combinations is Daptomycin, Cefoperazone, and Doxycyline. The Daptomycin is approved for skin infections in IV form and is very expensive. It is unlikely any insurance company would pay for it in a Lyme treatment based on Zhang's lab experiments. And the Cefoperazone is not available in the States.

There is one combination that Zhang proposes that is available. It includes Cefuroxime, doxycyline, and Bactrim DS. In the combination

  • Cefuroxime blocks the repair of Lyme spirochete cell walls in growing and persister Lyme,
  • Bactrim likely damages the DNA of persister spirochetes and cysts,  and
  • Doxycycline blocks protein production in persister forms.

Horowitz Studies

Horowitz used various combinations of antibiotics and a leprosy antibiotic called Dapsone to treat persister Lyme. Leprosy, like Lyme has persister cells. His study of 100 patients in his practice showed 59% of those that took Dapsone who had difficulty improving on other treatments, had improvements. Read more about the ins and outs of Dapsone treatment and the chances of it helping in Dapsone for Lyme Persisters. Miracle Drug?


Before leaving clinical practice in the early 2010s, Burrascano 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 go away.

Burrascano thought after a period of time Lyme ignored the antibiotics and stopped growing. He let people get sick during the off period 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 2 months off antibiotics and then 2 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 4 starting and stopping cycles. Each cycle included about 2 months off and then 2 months on antibiotics.

When Burrasano came up with this idea, the work of Lewis and his colleagues at Northeastern was not done. And yet his idea is supported by Lewis' research that Lyme develops slow growing persister cells that stop responding to antibiotics. And that when antibiotics are stopped they wake back up again and respond.

So What Works for Lyme Persisters?

In my practice I use three different Lyme persister regimens. If one does not work after 6-8 months, then I try the next one. I

  • explain the 3 options to my patients and let them choose,
  • reserve these regimens for people who are over a year or more into treatment, for which nothing else has helped, or who are still very ill with limited improvements, and
  • try the approaches outlined in the chapter Can't Get Better? Do This.

 Option 1. A Horowitz Dapsone Approach

To see this full approach, including the steps I take to prevent side effects and limit Herxheimer reactions read my full article: Dapsone for Lyme Persisters. Miracle Drug?. This approach helps 59% of people to get various degrees of improvement. But it is a very harsh treatment at times. Because of this 30% of people have to stop taking the medication. And yet I have seen some wonderful improvements on this regimen.

Option 2. A Zhang Approach

I work with the three drug combo mentioned above. To this I add grapefruit seed extract for better Lyme cyst coverage. I find this combination helps 50% of the time with various degrees of improvements. I have not seen someone get very well on this regimen like I have seen with a Horowitz protocol or a Burrascano approach mentioned below. But I have only offered this approach for a year, so it is too early to tell.

  • Cefuroxime 500mg1 pill 2 times a day
  • Doxycycline 100mg1 pill 2 times a day
  • Bactrim DS1 pill 2 times a day
  • Grapefruit Seed Extract 250mg1 pill 2 times a day. this is a supplement.

Option 3. A Burrascano Protocol

I use a number of antibiotic combinations like those mentioned in A Lyme Disease Antibiotic Guide. I use them for two months off then two months on. Sometimes I will use them for 1 month on or 1 month off. I see this approach help about 50% of the time with various degrees of improvements. Unlike Burrascano, I do not believe these cure people. However I have seen a number of my patients who remained quite well after antibiotics get very well on this approach.

New Ideas

As I mentioned above, Ying Zhang MD continues experiments to identify drugs and supplements to treat persister Lyme.

He has identified the malaria and babesia herbal antibiotic called artemesinin as an agent that can disrupt the Lyme cell membrane. And some of his latest work shows that oregano oil can treat persisters. I am only recently adding these to my Lyme persister treatments. I will report back in the future on the success of these.


1. Horowitz, Richard & Freeman, Phyllis R.. (2016). The Use of Dapsone as a Novel “Persister” Drug in the Treatment of Chronic Lyme Disease/Post Treatment Lyme Disease Syndrome. Journal of Clinical and Experimental Dermatology Research. 07. 10.4172/2155-9554.1000345.

2. Feng J, Auwaerter PG, Zhang Y (2015). Drug Combinations against Borrelia burgdorferi Persisters In Vitro: Eradication Achieved by Using Daptomycin, Cefoperazone and Doxycycline. PLoS ONE 10(3): e0117207.

3. Sharma B, Brown AV, Matluck NE, Hu LT, Lewis K. (2015). Borrelia burgdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells. Antimicrob Agents Chemother 59:4616–4624. doi:10.1128/AAC.00864-15

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