Pulsing - what do we know? and what do we think is going on?

thought i would start a post on this as it seems pulsing anti-biotics is common with many LLMD's these days

despite this there seems relatively little science available on the subject - apart from a couple of test tube type experiments.

so I thought a discussion to try to outline what we know and hopefully shine some light on:

1, separating what is known as facts from some mere theories or Lyme urban legend on the topic
2, what organisms it might be expected to work best for
3, which antibiotics suit pulsing / and which do not ( if there is any distinction)
4, what about herbs - if taking herbs and pulsing abx should these herbs be pulsed also (depending on which theories we are following you could make arguments for continuous use or pulsing the herbs too)
5, when pulsing strategies are typically applied
6, other benefits of pulsing strategies - eg easier tolerated, lower cost, etc

Post Edited (Garzie) : 6/6/2021 2:48:47 PM (GMT-6)

“ in fact most common lyme and even bart abx are now pulsed by many LLMDs - “

I didn’t think many llmds pulse?

I don’t think Dr H or SP or MR pulse - or I mistaken?

Here's what Dr. MR has to say:

https://www.treatlyme.net/guide/lyme-pulse-antibiotics

RainyCloud said...
Here's what Dr. MR has to say:

https://www.treatlyme.net/guide/lyme-pulse-antibiotics

thanks Rainy - that's a different MR article than the one I read - but right on target

the first time i had seen short pulse - vs long pulse durations explained

he is clearly in the camp of DO NOT TREAT BABS/BART WITH PUSING

but i know others like Dr J and Dr SP do treat Bart with pulse approaches

still on part 1,

Dr SP comments in one of his videos that for Lyme - if we know these antibiotics do not kill 100% of spirochetes in the test tube - and we give them to a patient who has Lyme and they don't get fully well either - he sees no sense in just continuing giving the same antibiotics continuously - given that in the lab experiments the bacteria, once in their low energy persister state, seem to be able to continue to survive in that state indefinitely - and even if you add more antibiotics/ higher doses.

RainyCloud said...
Garzie does he mention what the solution to that problem is? Different antibiotics or maybe disulfiram?

Hi Rainy

he sees pulsing conventional antibiotics - Doxy, tetracycline ( often his preferred primary abx) , Azithromycin as the solution to persister cells - together with some other things like some herbs and supplements ( eg i have heard him talk about liposomal oregano oil and liposomal artemisinin)

as far as i can tell from his videos
he doesn't use disulfiram - i think due to his concerns over tolerability/ extreme herx reactions
he doesn't use MB - over concerns around toxicity / possible carcinogenic effects in one rat study

from what i can tell from his overall tone and reasoning style Dr SP is rather research oriented - basing his approach as far as possible on medical studies and attempting to do a risk / benefit calculation in each patient - keeping pretty close to the first rule they teach in med school - 1st do no harm.

2, what organisms might it be expected to work best for.

the research quoted was only done on lyme - not co-infections.
the two features of the lyme spirochetes that it relies on are :

i, that lyme spirochetes are very slow growing - it replicates once every 30 days approximately.
This means that if you stop antibiotics its not going to suddenly run riot and make you sicker than you were before - it grows slowly - so you have time to take a break - and then anfter a while start again - and you will still bring numbers down.

ii, it forms persister cells - and in lyme at least - forming these persister cells seems to have a high metabolic cost to the organism - such that, if it is forced to do so repeatedly, eventually it becomes unviable or dies. obviously if a microbe does not form persister cells the use of anti-persister treatments is somewhat irrelevant

the theory is being extrapolated to use pulsing in other infections - like bartonella etc - and here the case is much less clear.

bartonella does form persister cells - but its reproductive time is from a few hours to around 1 day - so in theory - there is much less time to play with. as if an organism can double every day - after 2 weeks off an initial population would be over 8,000 times larger.

i don't have the reproductive times of other co infections - but i believe they are similarly short - from a few hours to a few days.

perhaps this is why we see some short duration pulsing regimes - eg where bart or mycoplasma or chlamydia species are suspected - ie to try to counter the faster reproductive times - but if so i have not seen it discussed as the hypothesis or explicit justification for them.

that said Dr SP does use it for bartonella patients on 2weeks on 2weeks off schedules so there is a lot of different interpretations by different LLMD's

Babesia - i have not seen LLMDs propose pulsing for Babesia - except perhaps for artemisinin or its derivatives - but i believe this is more to to with the drug pharma-dynamics than the biology of the infectious organism. in fact i think relatively little is known about how or where Babesia can survive in the body long term. it is known to do so because its known for relapsing years later after initial infections - but how it does this seems mysterious.

so in summary -

-pulsing is typically used for lyme
-less so - but perhaps useful for some bacterial co-infections - but on shorter cycles
-less often used for piroplast infections ( Babesia and similar )

again - of anyone finds anything substantially different in their own research please chime in - i am just relaying what i have found but its not necessarily the whole story or the only picture

yeah - i thought he might Girlie.

Did he ever explain his reasoning for doing so ?

Babesia has a higher rate of resistance and pulsing can lower that.

One thing to consider when talking about antibiotics is their Volume of Distribution. Our cells are made of varying degrees of fats (lipids) and some antibiotics can penetrate some areas that others can't. It is based off of the drug's lipophilicity, or how much it loves fats (fat soluble). For instance, Azithromycin has more lipophilicity as Clarithromycin. This means that Azithromycin is readily absorbed into our tissues and doesn't maintain high blood levels very long. Clarithromycin stays in the blood longer and keeps higher blood levels.

Antibiotics either kill a pathogen or they don't. This can get tricky because of the way certain antibiotics work, some are bacteriostatic which means they stop or slow the growth of the pathogen and the immune system can kill it or it could be bactericidal where the antibiotic kills the bacteria. And then there are the resistant ones. It can be a situation where the antibiotic kills some of them but can't kill the rest. A persister or "L" form of Borrelia is an example. But Borrelia has other methods to stay alive, like burying itself into the extracellular matrix. Blood levels of antibiotics are often low in these areas and that is where exercise or movement of the joints can vastly improve bactericidal activity. Situations where biofilms are present is where pulsing really shines. Pathogens in the biofilm communities are constantly shed and pulsing is effective at eliminating them while not completely destroying as much normal flora.

I think when you take a break from the abx, the bacteria come out of the biofilms/cysts and then you can hit them again.

Garzie said...
thank you for teh contributions Georgia

Couple of points i would love you to expand upon if you can

ref Babesia and its higher rate of resistance - by that do you mean Babesia is thought to develop resistance in any given patient more easily - or that it is generally more likely to already be resistant in the wild. how does pulsing lower that rate?

Similarly on pulsing and biofilms - how does pulsing help kill more of these vs continuous abx.

I spent almost an hour looking at many dozens of articles to answer your questions and I just can't give you a good answer. I just don't know. Babesiosis, like malaria, are caused by pathogens that we just can't seem to handle. What we try doesn't work for everyone. I'm not sure if pulsing lowers the rate of resistance, but it does have better effects on the body compared to continuous dose of medications. Constant dosing like IV's over time just wreak havoc on our system.

As for biofilms, constant dosing is an overkill because the antibiotics kill what they can kill and there aren't any more pathogens floating around. The biofilm pathogens are released every so often so pulsing has less effect on our system but still kills the pathogens. What I have noticed is that the amount of cholesterol I eat plays a role in my pathogens (presumably some form of babesia) survival. I found research to back this up. I can kill my pathogens by eating less cholesterol. The price I pay to do this is way too high. If you ever see me wigging out, you'll know I stopped eating a lot of fats. My detox pathways just can't handle that burden.

Georgia Hunter said...

I spent almost an hour looking at many dozens of articles to answer your questions and I just can't give you a good answer. .

thanks for trying Georgia - it is appreciated

ref diet -interestingly, my responses seem to be the other way around - if i avoid starches and sugars my function goes up very significantly - to do so i get pretty much all my calories from fat and protein - which includes beef, lamb, and eggs as well as coconut oil, olive oil, butter. This seems to be helping over the long term as my progress only started after switching to this approach.

the second paper is more of an in depth investigation into the mechanisms and characteristic of the persister mechanism in borrelia burgdorferi.

their goal seems to be able to model the behaviour mathematically - but that is less relevant to our discussion

what is relevant is their in-depth work on the persister behaviour of the spirochetes

they demonstrate a few things that are pertinent to this discussion

1, when a population of bb is growing more slowly - it is more likely to form persister cells
this can be due to lack of available nutrients ( which is what happens in older cultures in the lab) or due to other stressors on the organism - eg oxygen, temperature etc - basically the organism is preprogramed to have this persister behaviour - and the more signs its getting that its environment is getting less favourable - the more likely it is to transition into persister cells.

2, when dosed with the doxycycline in moderate doses - not all spirochetes are killed - even if you pulse this dose 4 times - each time waiting for them to regrow and then hitting them again. the first time you dose them - you wipe out the majority and they come back a bit slower - but after that they just keep coming back at the same rate and in the same numbers - it doesn't wear them down

3, if you can load enough even bacteriostatic drugs in - like doxy - it will kill all of them - at least in a test tube - but i think we knew that already - these doses are however difficult to attain in all tissues in the human patient. they also quote studies showing clinical isolates have widely varying susceptibility to many antibiotics - surprisingly wide.

4, the persister mechanism in BB is referred to as stochastic - by which they mean it is randomly distributed in the population - even if the population is genetically identical. we should think of this as a pre-programmed variability that the bacteria have evolved to have in response to certain conditions.
however, even if you just keep selecting the persister and regrowing them- they do not keep developing more antibiotic tolerance or even more likelihood of becoming persister cells when you treat them again.

5, BB seems to be more prone to produce persisters than many other studied bacteria - this is theorised to be because of its lifecycle - it needs to service very long periods inside a tick - eg when a tick over winters - and this low metabolic state of persister cells allows it to stop using energy and nutrients and become dormant - yet sense when conditions change and are suitable for it to grow again. it is further hypothesised that in humans - when bb infects them it often finds its way into sites that are poorly served with blood flow and nutrients and this in itself may cause sub populations of persisters to form.

so in summary whenever you have a population of bb - some are always primed to go into a low energy state where they are no longer growing and very hard to kill. the older that culture and the higher the density of bacteria - the more likely they are to form persister. ie if they are already slowing in growth then they are harder to eradicate

so whilst this study did show pulsing with moderate doses of Doxy did not kill all of them - it does seem to suggest that if you an hit them hard when they are growing the fastest then you will tend to kill more of them / get less persisters formed ( this kind of supports the pulsing approach )