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Maybe I missed the point of your post -- I skimmed the article

instead of looking at the refs, but it sure sounds like we all ought

to be taking rifampin. Er, so why aren't we?

- Kate

On Aug 8, 2006, at 1:33 PM, wrote:

> For several older papers on " intracellular protection " - all distinct

> from the 4-5 I have cited before - see refs 1-6 here:

>

> http://www.pubmedcentral.nih.gov/pagerender.fcgi?

> artid=302442 & pageindex=1

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> Maybe I missed the point of your post -- I skimmed the article

> instead of looking at the refs, but it sure sounds like we all ought

> to be taking rifampin. Er, so why aren't we?

>

> - Kate

Actually, while its unfotunately inactive on spirochetes, my thinking

so far is that rifampin is probably not something I'm going to pass up

a trial of. (More later on this, probably much later.) I have not used

it yet.

(By the way, the usual belief is, it should not be used alone, nor in

an on-and-off pattern - there may well be other important directives /

contraindications as well, especially if one has a liver history.)

I dont think the Mandell paper's conclusion is necessarily right, if I

remember it correctly. What it says about that particular B-lactam

having poor cellular penetration, may be true. But in many

intracellular protection situations observed in vitro (in other

papers), various bacteria (including staph) have survived even tho the

cellular/extracellular ratio of the drug being used is well above one

(tho not necessarily as high as rifampins C/E ratio). So, poor host

cell penetration by the drug cant universally be the origin of

protection within host cells. Either there is no univeral origin or the

universal origin is something else.

However, because intracellular protection is not absolute, in some

infections the difference between a C/E ratio of one and a C/E ratio of

ten might still (conceivably) be a significant determinant of what

happens with a given therapy. So could certain other phenomena that

also dont look to be the universal origin of intracellular protection -

for example, the variation in power that some drugs undergo as a

function of pH.

Everything I'm discussing is pretty theoretical of course; in most

cases we dont know if these intracellular protection phenomena extend

beyond a day or so, as Barb underlined recently. One possible exception

is the continuous culture-with-abx experiment on chlamydiae by I

believe Hammerschlag et all, in which the chlamydia were cut to a few

percent after a protracted period, but were far from eradicated.

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Useless drug IMO. Shoemaker didn't win too many fans with his choice

of rifampin and bactrim. I actually found rifampin to build

resistance extremely quickly to your sinus bugs.

tony

>

>

> > Maybe I missed the point of your post -- I skimmed the article

> > instead of looking at the refs, but it sure sounds like we all

ought

> > to be taking rifampin. Er, so why aren't we?

> >

> > - Kate

>

> Actually, while its unfotunately inactive on spirochetes, my

thinking

> so far is that rifampin is probably not something I'm going to pass

up

> a trial of. (More later on this, probably much later.) I have not

used

> it yet.

>

> (By the way, the usual belief is, it should not be used alone, nor

in

> an on-and-off pattern - there may well be other important

directives /

> contraindications as well, especially if one has a liver history.)

>

> I dont think the Mandell paper's conclusion is necessarily right,

if I

> remember it correctly. What it says about that particular B-lactam

> having poor cellular penetration, may be true. But in many

> intracellular protection situations observed in vitro (in other

> papers), various bacteria (including staph) have survived even tho

the

> cellular/extracellular ratio of the drug being used is well above

one

> (tho not necessarily as high as rifampins C/E ratio). So, poor host

> cell penetration by the drug cant universally be the origin of

> protection within host cells. Either there is no univeral origin or

the

> universal origin is something else.

>

> However, because intracellular protection is not absolute, in some

> infections the difference between a C/E ratio of one and a C/E

ratio of

> ten might still (conceivably) be a significant determinant of what

> happens with a given therapy. So could certain other phenomena that

> also dont look to be the universal origin of intracellular

protection -

> for example, the variation in power that some drugs undergo as a

> function of pH.

>

> Everything I'm discussing is pretty theoretical of course; in most

> cases we dont know if these intracellular protection phenomena

extend

> beyond a day or so, as Barb underlined recently. One possible

exception

> is the continuous culture-with-abx experiment on chlamydiae by I

> believe Hammerschlag et all, in which the chlamydia were cut to a

few

> percent after a protracted period, but were far from eradicated.

>

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