Identification of Additional Anti-Persister Activity against Borrelia burgdorferi from an FDA Drug Library

Sept, 2015

Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA

Abstract

 

Lyme disease is a leading vector-borne disease in the United States. Although the majority of Lyme patients can be cured with standard 2–4 week antibiotic treatment, 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, persisting organisms not killed by current Lyme antibiotics may be involved. In our previous study, we screened an FDA drug library and reported 27 top hits that showed high activity againstBorrelia persisters. In this study, we present the results of an additional 113 active hits that have higher activity against the stationary phase B. burgdorferi than the currently used Lyme antibiotics. Many antimicrobial agents (antibiotics, antivirals, antifungals, anthelmintics or antiparasitics) used for treating other infections were found to have better activity than the current Lyme antibiotics. These include antibacterials such as rifamycins (3-formal-rifamycin, rifaximin, rifamycin SV), thiostrepton, quinolone drugs (sarafloxacin, clinafloxacin, tosufloxacin), and cell wall inhibitors carbenicillin, tazobactam, aztreonam; antifungal agents such as fluconazole, mepartricin, bifonazole, climbazole, oxiconazole, nystatin; antiviral agents zanamivir, nevirapine, tilorone; antimalarial agents artemisinin, methylene blue, and quidaldine blue; antihelmintic and antiparasitic agents toltrazuril, tartar emetic, potassium antimonyl tartrate trihydrate, oxantel, closantel, hycanthone, pyrimethamine, and tetramisole. Interestingly, drugs used for treating other non-infectious conditions including verteporfin, oltipraz, pyroglutamic acid, pidolic acid, and dextrorphan tartrate, that act on the glutathione/γ-glutamyl pathway involved in protection against free radical damage, and also the antidepressant drug indatraline, were found to have high activity against stationary phase B. burgdorferi. Among the active hits, agents that affect cell membranes, energy production, and reactive oxygen species production are more active against the B. burgdorferi persisters than the commonly used antibiotics that inhibit macromolecule biosynthesis. Future studies are needed to evaluate and optimize the promising active hits in drug combination studies in vitro and also in vivo in animal models. These studies may have implications for developing more effective treatments of Lyme disease.

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  1. I was bitten by a tick in a wooded area in the middle of the state of Virginia, USA. This was in 1999. Four days passed from the time I was in the tick infested area to the time I discovered the tick on my body. I removed it immediately and threw it down the toilet bowl, a very stupid thing to do. Within 24 to 36 hours I developed a bull’s eye rash and went to my local general practitioner. Although the tick bite came from the US, the initial treatment I received was in Germany. The doctor gave me 2 weeks of Amoxycillin immediately and this was before my body had a chance to build any antibodies, at least this is my theory. He refused to give me any more antibiotics when I went back to him with persistent Lyme like symtoms. His refusal began a 17 year struggle trying to find a doctor willing to give me antibiotics long enough to kill all the Lyme bacteria in my body. I repeatedly test negative on all blood tests whether taken in the US or in Germany. The only so-called marker I have is a very low CD-57 NK blood cell level. Sometimes I can go a very long time without antibiotics but the symptoms always seem to return, sooner or later. I have never had a treatment with a combination of antibiotics taken at the same time. The primary symptoms are a peculiar kind of headache, mental fog and problems with my eyes. There is also some joint pain. In fact, in July 2014, I was diagnosed with bone marrow edema in my right knee. I got this diagnosis after an MRI. I had no injury to my knee prior to receiving this diagnosis. Thank God, I found a doctor who was willing to prescribe one month of antibiotics for me and, within a week, all the bone marrow edema and the pain associated with it went away. The orthopedist I saw could not believe the miracle healing that took place in my knee so quickly after having such a diagnosis. Today a doctor has put me on 500 mg Cefuroxim 2x daily. I will go back to him in 2 weeks and we will discuss whether to continue longer with this medicine or try another one. I know nothing about Rifampicin and, because I have never tried it before, could it possibly be an antibiotic for someone like me to try? I could be so much worse off with this Lyme problem but the big thing for me is the limited quality of life that comes when the symptoms re-appear and, of course, the constant worries. Do you have any advice for me? Does anyone know a Lyme doctor in Germany to recommend to me? They really don’t believe in long term antibiotic treatment in this country, unfortunately. I hope I haven’t written too much or too long but I did it in the hopes of learning some new information or recommendations. Thank you!

    • Contact ILADS.org They can give you a list of US doctors, and European ones who may prescribe longer courses of antibiotics if warranted. You did not say where you are now, the US or Germany.

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