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» LymeNet Flash » Questions and Discussion » Medical Questions » New Study Shows Eradication of Chronic Lyme ie Persisters

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Author Topic: New Study Shows Eradication of Chronic Lyme ie Persisters
Bugg
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http://commonhealth.wbur.org/2015/06/lyme-disease-bacteria-persister-pulse
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hiker53
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In a way this is what Dr. B did (who made the guidelines). Give ceftin for awhile. Then stop and let symptoms come back and give it again. DO this until symptoms do not come back.

So, hopefully this pulse method will work.

--------------------
Hiker53

"God is light. In Him there is no
darkness." 1John 1:5

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marcholland81
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Would be interesting if we would have details to dosage and pulsing schedule.
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marcholland81
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ok, someone purchased the article:

"I purchased the article from the referenced journal Antimicrobial Agents and Chemotherapy. From how I interpret it the test (ref pages 30 forward) they used in test tubes were 5 days on, 3 days off. Cycle 4 times. They tried tests with Amoxicillin, Ceftriaxone, Doxycycline and others. From the last figure in the paper comparing Ceftriaxone and Amoxicillin it looks like Amoxicillin removed the bacteria from detection in the 4th round."

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Bugg
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Thank u so much for buying the article. The pulsing method may be different when applied to humans as the administration and delivery and processing of the drug through the blood, brain, liver, kidneys etc is different than direct administration in a Petri dish. Does the article talk about a potential dosing schedule for humans?
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marcholland81
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I didn't buy it although I'm considering it.
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marcholland81
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ok, bought it. Here some quotations:

Amoxicillin (6 µg/ml, 100X MIC) and ceftriaxone (3 µg/ml, 300X MIC) at clinically
achievable levels killed the majority of cells in the first day, after which a slow phase of
death followed for the next 6 days

As the concentration of amoxicillin and ceftriaxone increased, the fraction of surviving cells remained largely unchanged

Thus, B. burgdorferi forms persisters capable of surviving very high concentrations of antibiotics, which exceed what is clinically achievable.

In B. burgdorferi, we observe a very different picture – both amoxicillin and ceftriaxone kill stationary cells fairly well, yet the fraction of persisters continues to increase.

Both gemifloxacin and spectinomycin were ineffective in killing B. burgdorferi at tested
concentrations

However, ADEP4 did not have significant activity against B. burgdorferi (not shown), which may be due to poor penetration.

Daptomycin was highly bactericidal against B. burgdorferi, but a remaining subpopulation of persisters survived.

Vancomycin effectively killed growing cells of B. burgdorferi, but not persisters, and was comparable to ceftriaxone.

teixobactin is considerably smaller than vancomycin (1.8 kDa), but it did not exhibit
good activity in killing B. burgdorferi

Mitomycin C eradicated a late exponential culture of B. burgdorferi within 24 hours, with no detectable persisters remaining

Based on our results, the level of persisters is lowest during early exponential growth

Persisters were substantially diminished after four rounds of killing with amoxicillin, and were eradicated below the limit of detection after four rounds of killing with ceftriaxone

Based on the genome, B. burgdorferi lacks recFOR. In E. coli, both RecBC and RecFOR are required for repair of DNA damage caused by mitomycin C, an anticancer drug. Mitomycin C at a low, clinically achievable dose (8X MIC), eradicated B. burgdorferi persisters in both exponential and stationary cultures within 24 hours.

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Bugg
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Thank you so much for buying this article.. It appears ceftriaxone which many lyme patients including myself have taken is effective against persisters. We just need to understand the length of time between pulsing it .
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Rhiagel
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That's too bad about teixobactin, which was a newly discovered abx. OTOH, that chemo drug could be the 1-time cure, if one could withstand the side effects. From another article summarizing the study,

In addi­tion to iden­ti­fying the pres­ence of these per­sister cells, Lewis’ team also pre­sented two methods for wiping out the infection—both of which were suc­cessful in lab tests. One involved an anti-​​cancer agent called Mit­o­mycin C, which com­pletely erad­i­cated all cul­tures of the bac­terium in one fell swoop. How­ever, Lewis stressed that, given Mit­o­mycin C’s tox­i­city, it isn’t a rec­om­mended option for treating Lyme dis­ease, though his team’s find­ings are useful to helping to better under­stand the disease.

http://www.northeastern.edu/news/2015/06/researchers-discovery-may-explain-difficulty-in-treating-lyme-disease/

Regarding pulsing, that may be the way to go. My son was treated with 5+ years of mostly continuous oral abx without a herx. His new LLMD put him on doxy et al M-W-F and he has had 5 herxes in the last few months.
----------------------------------------------------------------------

marcholland81, your summary of the article is great, but does it specifically mention the timing of the rounds, e.g., 1 dose and then wait three weeks, another 1 dose and then wait another 3 weeks, etc.?

The article in the OP says, "His research team attacked some Borrelia with antibiotics and then waited…and waited…a very long time in the world of bacteria — three weeks. They found that with time, regular cells were killed but persisters remained completely intact." It's unclear if that 3 week waiting period is the one that was successful with ceftriaxone over 4 rounds or if they tweaked it to another waiting time period between rounds.

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marcholland81
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@rhiagel

No, they only mention:

"The surviving persisters were allowed to resuscitate for a short period of time in fresh media, and then exposed to antibiotic again for a second round of killing."

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Rhiagel
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Thanks, marcholland81. That's what I thought.

It seems that they are keeping the time periods underwraps until they test it in animals and then humans.

"But I think, for now, we should proceed a little bit conservatively, and let Dr. Lewis finish his work — because he is going on to animal studies to verify that concept.”

The last part is a bit discouraging for those of us looking for a possible quick fix.

"How soon might his findings affect clinical practices? Lewis says that because a clinical study in humans would not be held up by the need for approval of any new drugs, it may be possible to formulate better drug regimens within a couple of years."

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marcholland81
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I also am quite pessimistic about finding a cure soon although I think mr. Zhang and Lewis made some good progress last year thanks to the funding of organisations like lyme research alliance.
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CherylSue
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Ceftin (cefuroxime axetel is the generic) has always been a life saver for me.

I was off abx for 3 months, and restarted again after symptoms started coming back.

Should I let it Lyme totally come back before I resume abx?

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