Re: Pulsed doses

[Guest guest]

Re: Pulsing to minimize herx-

I'm recalling Wheldon's comments (at least I think it

was his, could have been Stratton's) on how duo

therapy ie with two antibiotics that work on

inhibiting different proteins in replication are both

complimentary and lower the risk of developing

resistance. Pulsing a monotherapy antibiotic has more

likelihood that those bacteria which are not prevented

from replicating will develop resistance.

That being said, Wheldon has noted in his regime for

Cpn for multiple sclerosis, that folks with high

bacterial load have to start slowly and may be on low

dose monotherapy, building that up over three months

until the herx is manageable before adding the second

antibiotic. That happened, by happenstance, for me: I

was on tetracycline for 3 months with a big initial

herx and then a slower and steadier herx before I

discovered his protocol. Adding the second antibiotic

brought another wave of herx, and daily waves about

1-2 hours after taking the abx doses. On this regime

it is the abx which are constant, and the flagyl which

is pulsed. This way you can take as long a course as

is needed without building up resistance and manage

the different phases of the organism, and the impact

of flagyl toxicity, by the pulsed doses.

I think the pulsing thing is all relative to how heavy

your initial load of organisms is. If your load is

very high, the herx can be life-threatening. We all

need to find our pace, but it seems to me that the

goal is a constant enough dose for a long enough time

of the right agents to kill all forms of the beast.

There may be some benefit in pulsing with a dual abx

rather than a single one. We would need a

bacteriologist to know this for sure.

My two cents,

Jim

[Guest guest]

<jimk192002@y...> wrote:

> Re: Pulsing to minimize herx-

> I'm recalling Wheldon's comments (at least I think it

> was his, could have been Stratton's) on how duo

> therapy ie with two antibiotics that work on

> inhibiting different proteins in replication are both

> complimentary and lower the risk of developing

> resistance. Pulsing a monotherapy antibiotic has more

> likelihood that those bacteria which are not prevented

> from replicating will develop resistance.

Doxy and zith dont inhibit different proteins - they both inhibit

ribosomes, which produce all of the bacterias proteins. They inhibit

them by binding to them and ruining their shape, and the 2 drugs bind

at different spots on the ribosome.

You are right on about resistance. Its occurance is natural, but very

rare. No single trait will give a bacterium strong resistance to both

doxy and zith - and a bacterium that is resistant to doxy is no

likelier to be resistant to zith just because it is resistant to doxy.

Therefore, in a population of bacteria, if each individual has a 1/100

chance of being resistant to doxy and a 1/200 chance of being

resistant to zith, then each individual has a (1/100)*(1/200) =

1/200,000 chance of being resistant to both drugs. Thus, each drug

tends to protect against the emergence of a population of individuals

resistant to the other drug. In reality the frequency of resistant

individuals in a generally-suceptible population, for a given drug, is

much less than 1/100. If I recall correctly, I think it might be more

like 1/10,000,000 at *most*. But then, there are quite alot of

bacteria in an infection.

With our kind of diseases, the big problem is that the drugs

apparantly just dont kill the bacteria nearly as potently as we would

reasonably expect - and no one knows why (WHY?? WHY?? WHY????

AAAAAAAAAIIIIIEEEEEEEEEEEEEEeeeee... oh - excuse me... where am I? -

ah yes). Hence, for us, the potentially synergistic lethality of some

drug combos is at least as important as their resistance-suppression.

The mathematics of this is comparable to the mathematics of

resistance. But its a significantly more complicated business for

various reasons. For one example, ribosome-inhibiting drugs may not be

as great as they could be as a combination partner for cell-wall

inhibiting drugs like penicillin. Bacteria are much more vulnerable to

penicillin when they are dividing, which they do less often when faced

with ribosome-inhibiting drugs. In practice, this little kink doesnt

turn out to be such a big deal necessarily - it depends on who you

talk to and what you think about various things. Certainly, the combo

of anti-wall and anti-ribosome drugs is used widely.