A newly published study by the American Society for Microbiology may fundamentally change the way we view and treat chronic Lyme disease. While it has been well known that Borrelia burgdorferi (Lyme disease) has multiple methods to become resistant to antibiotics, this study demonstrates that it may not be an actual resistance (which is seen in many other bacteria), at all. Rather, this study demonstrates that Lyme has the ability to transform into a metabolically inactive form, called a persister cell. The metabolically inactive persister cells are essentially in a state of suspended animation. This lack of metabolic activity makes them totally resistant to any antibiotic at any dose and also any combination of antibiotics. This is in contrast to other methods that bacteria use to become resistant that can be overcome by using larger doses of antibiotics, different antibiotics or a combination of antibiotics. None of these strategies have any effect upon the persister cells. Upon regrowth back to the normal active form, which occurs when the antibiotic is removed, the persister cells have no antibiotic resistance. Such new knowledge may change the way Lyme disease is viewed and treated.
Is there any good news? Thankfully and hopefully, yes. This study showed that Lyme was rapidly killed, essentially equally with different antibiotics and independent of the dose. Again, once they transformed into persister cells, nothing worked. But if they were left alone and allowed to grow without any antibiotics, they reverted back to the standard form. This form was susceptible to antibiotics and was quickly killed. A small percentage again went into persister cell forms and became totally resistant but when they were left alone without antibiotics, they then reverted to standard form and became susceptible to the antibiotics. They found that four cycles essentially eradiated the infection. While real-life is, no doubt, more complex than what happens in a test tube, this may truly be a game changer.
It is truly unbelievable that standard infectious disease doctors refuse to acknowledge the thousands of studies demonstrating the existence of chronic Lyme disease in epidemic proportions. Based on the best available medical evidence, Lyme literate doctors generally use high doses of oral and IV antibiotics for long-periods of time. We, and many other such doctors, have used numerous combinations of antibiotics and antiparasitics in an attempt to counter the Lyme bacteria's mechanisms of resistance. While this has proven to be more effective and to generate fewer side-effects than continuous long-term dosing, we have all worried that allowing too much time off of antibiotics would allow the Lyme to "regain a foot-hold" and ground gained would be lost. This study shows, however, that the key to successful long-term treatment may be allowing sufficient time off of antibiotics to allow the reconversion back to the standard form, then to "surprise" this relatively more defenseless form of Lyme. This strategy is then used over and over. Based on this study, a more appropriate dosing schedule may be five days on and five days off.
Interestingly, I myself had been taking one or two days of antibiotics every week or two as a precaution against a Lyme relapse, as I simply found that I feel better when I did this, even though such dosing is against standard infectious disease principles because it could theoretically contribute to the formation of resistant strains. This study shows that the key may not be the length of treatment, the antibiotic dose or the combination of antibiotics used, but rather the time off the antibiotics.
Another part of the study found the antibiotic mitomycin C, which is used as a chemotherapy agent against gastrointestinal cancer (potentially caused by an infectious agent), completely eradicated all persister cells with a single low dose. While this treatment still needs to be confirmed in clinical studies and is not without significant potential side-effects, such results should give the sickest of Lyme disease patients who have not responded to aggressive therapies a new found hope. A clinical therapeutic trial in a subset of the most ill, treatment resistant patients may be a reasonable approach.
Reference:
Sharma B, Brown AV, Matluck NE, et al. Borrelia bugdorferi, the causative agent of Lyme disease, forms drug-tolerant persister cells. Antimicrob. Agents Chemother 2015
