Re: Whipple bacillus perfectly abx-sensitive in culture

[Guest guest]

,

Been looking into Whipple's for a while now and it looks like bactrim or even just sulfamethoxazole alone is the only drug which has been consistently found active with easily attainable and tolerable MIC MICs of sulfamethoxazole is in the range 0.5-1 mg/L.

Nelly

[infections] Whipple bacillus perfectly abx-sensitive in culture

Didnt even know this lil piece of crap had been cultured; I think thats rather recent.Havent read this full text but it is definitely quite sensitive to clinical concentrations of a number of drugs.THerapy of the human infection is usually multi-year and I have some vague info regarding a significant number of incomplete cures (tho no hard data). Therefore this looks like another probable multi-drug vitro/vivo sensitivity paradox. Collect em all.====================================================The active compounds in axenic medium were doxycycline, macrolide compounds, penicillin G, streptomycin, rifampicin, chloramphenicol, thiamphenicol, teicoplanin, vancomycin, amoxicillin, gentamicin, aztreonam, levofloxacin and ceftriaxone, with MICs in the range 0.06-1 mg/L. Cefalothin was less active, with MICs in the range 2-4 mg/L. We found that co-trimoxazole was active with MICs in the range 0.5-1 mg/L, and sulfamethoxazole alone was active with MICs in the range 0.5-1 mg/L. PMID: 15650004

[Guest guest]

Do you mean sulfameth is the only one effective in vivo? Cause it

looks like lots of these in vitro MICs below, for various drugs, are

tolerable. I will have to scope the full text to be certain.

Cmax for sulfameth is 40-60 mg/L and half life is 8h, so it should be

brutalizing the little guys, long generation time or no.

IMO no lyme-shaded glasses are required to make out a connection

here - whatevers happening is probably the same thing, and the only

known mechanism for pan-drug insensitivity is drug efflux by the

bacteria, tho I cant make it into a tight model so far.

> ,

>

> Been looking into Whipple's for a while now and it looks like

bactrim or even just sulfamethoxazole alone is the only drug which

has been consistently found active with easily attainable and

tolerable MIC MICs of sulfamethoxazole is in the range

> 0.5-1 mg/L.

>

> Nelly

> [infections] Whipple bacillus perfectly

abx-sensitive in culture

>

>

> Didnt even know this lil piece of crap had been cultured; I think

> thats rather recent.

>

> Havent read this full text but it is definitely quite sensitive

to

> clinical concentrations of a number of drugs.

>

> THerapy of the human infection is usually multi-year and I have

some

> vague info regarding a significant number of incomplete cures

(tho no

> hard data). Therefore this looks like another probable multi-drug

> vitro/vivo sensitivity paradox. Collect em all.

>

>

> ====================================================

>

> The active compounds in axenic medium were doxycycline, macrolide

> compounds, penicillin G, streptomycin, rifampicin,

chloramphenicol,

> thiamphenicol, teicoplanin, vancomycin, amoxicillin, gentamicin,

> aztreonam, levofloxacin and ceftriaxone, with MICs in the range

0.06-

> 1 mg/L. Cefalothin was less active, with MICs in the range 2-4

mg/L.

> We found that co-trimoxazole was active with MICs in the range

0.5-1

> mg/L, and sulfamethoxazole alone was active with MICs in the

range

> 0.5-1 mg/L.

> PMID: 15650004

>

>

>

>

>

[Guest guest]

,

I can't find the actual bits where bactrim (co-trimoxazole= sulfamethoxazole + trimethoprim) has been shown to be the best abx against Whipple's but bactrim has been the abx most commonly given for it.

But your are right other abx like cyclines, macrolides and aminoglycosides appear to also be useful.

The study I posted said that it was the sulfamethoxazole part of the bactrim that was effective against Whipple's not the trimethoprim.

Other studies say best to start with IV penicillin + streptomycin for a couple of weeks followed by a couple of years of bactrim.

Recently the Marseilles Rickettsia mob (Raoult et al) have trialed doxy + plaquenil and have reported good results (they had trialed the same regimen on C.burnetii and had found treatment duration could be halved from 3 years of doxy to 18 months when adding plaquenil) so they are putting Whipple's to the same test.

If you're interested, I have lots of stuff on it, but you can also find it all from medline, quite a few free full-text articles.

I think Whipple's is a very interesting case, and I think some of us with "chronic Lyme" should all look at it much more closely, and we could also shove a few Whipple's studies under our doctors' noses when they claim that a few weeks of abx is a cure all.

Nelly

[infections] Whipple bacillus perfectly abx-sensitive in culture> > > Didnt even know this lil piece of crap had been cultured; I think > thats rather recent.> > Havent read this full text but it is definitely quite sensitive to > clinical concentrations of a number of drugs.> > THerapy of the human infection is usually multi-year and I have some > vague info regarding a significant number of incomplete cures (tho no > hard data). Therefore this looks like another probable multi-drug > vitro/vivo sensitivity paradox. Collect em all.> > > ====================================================> > The active compounds in axenic medium were doxycycline, macrolide > compounds, penicillin G, streptomycin, rifampicin, chloramphenicol, > thiamphenicol, teicoplanin, vancomycin, amoxicillin, gentamicin, > aztreonam, levofloxacin and ceftriaxone, with MICs in the range 0.06-> 1 mg/L. Cefalothin was less active, with MICs in the range 2-4 mg/L. > We found that co-trimoxazole was active with MICs in the range 0.5-1 > mg/L, and sulfamethoxazole alone was active with MICs in the range > 0.5-1 mg/L. > PMID: 15650004> > > > >

[Guest guest]

This is the Raoult paper Nelly; it sounds like youve read it.

" In vivo, co-trimoxazole is not always effective for the treatment

of Whipple's disease and an 30% failure or relapse rate has been

reported even after a 1 year course of treatment.2 The failures and

relapses frequently reported could be due firstly to a lack of

bactericidal activity of sulfamethoxazole at low pH where the

bacteria lives.16 Indeed, we have previously demonstrated that only

the association of doxycycline with hydroxychloroquine was able to

kill the intracellular bacteria.7 Secondly, relapses could be due to

the acquisition of resistance against sulfamethoxazole during the

course of the treatment, especially by mutation in the DHPS encoding

gene. There is one report of acquisition of resistance to co-

trimoxazole after long and repeated treatment using this

antibiotic.20 Finally, failure and relapses could be due to an

inadequate concentration of antibiotic at the site of infection

(cardiac valve or cerebrospinal fluid). "

====================================================

Note that the highest intracellular/extracellular activity ratio is

100, for ceftriaxone, which aligns with Klempners work " Fibroblasts

protect the lyme spirochete from ceftriaxone in vitro. "

IMportant to note is that according to these authors the whipple

bacillus resides in acidic endosomes in vivo.

Table 2. MICs (mg/L) of antibiotics for T. whipplei strains (Twist,

Endo-5, Slow2) obtained in axenic medium [ie alone in medium], as

compared with the results previously obtained in cells [ie in cell

culture],7 as determined using Light Cycler assay

Antibiotics Extracellular (E) Intracellular (I) Ratio I/E

---------------------------------------------------------------------

-----------

Penicillin G 0.25–0.5 0.5–1 2

Amoxicillin 0.06–0.25 0.5–1 4–8

Teicoplanin 0.25–0.5 0.25–0.5 1

Vancomycin 1–2 10 5

Imipenem 0.5–1 0.5–10 1–10

Aztreonam 0.5–1 10–20 20

Cefalothin 2–4 10–20 5

Ceftriaxone 0.06–0.25 10 100

Gentamicin 0.06 4–8 100

Streptomycin 0.5 0.5–1 1–2

Rifampicin 0.25–0.5 0.5–2 2–4

Erythromycin 0.06–1 1–2 2–16

Clarithromycin 0.06–0.25 2 8

Telithromycin 0.06–0.25 0.25–0.5 2–4

Doxycycline 0.25–0.5 1–2 4

Thiamphenicol 0.25–0.5 0.25–1 1–2

Chloramphenicol 0.5–1 1–2 2

Levofloxacin 0.25 0.5 2

Ofloxacin 2–4 4 1

Ciprofloxacin 4 4 1

[Guest guest]

" In vivo, co-trimoxazole is not always effective for the treatment of

Whipple's disease and an 30% failure or relapse rate has been reported

even after a 1 year course of treatment "

" The aim of the present study was to evaluate the antibiotic

susceptibility of the three strains in axenic medium [ie pure culture]

and to compare the results with intracellular activity [ie within-host-

cell cultures]. We believe that in vivo discrepancies reported in the

treatment of Whipple's disease may be partly explained by a difference

in susceptibility of the bacteria extracellularly and intracellularly.

This has previously been shown for other facultative intracellular

bacteria such as Bartonella and Brucella.15 "

" Partly, " yes, sort of, but the data (see last post) do not really

support this as being the major phenomenon here. The vivo/vitro

descrepancy reflected by the theraputic failures has to be due to

something else...

[Guest guest]

,

yes, I have been reading Raoult's papers on Whipple's but i don't have the last one, not the full-text, do you have access to it?

I have one of my abx/infection induced monster headaches so I won't be able to read or communicate for a few hours/days?

I am glad to see you are taking an interest in Whipple's, I know there are things to be learnt from the studies on the treatment of it, but as I am nearly always skimming over things diagonally and as fast as I can because of eye pain, I never really get down to the nitty-gritty details and it is very frustrating for me as I cannot be as accurate as I would like to be (often I just get things wrong because I have to take so many short cuts).

Read on, , and let's see what I am capable of to-morrow (it is 7 pm here).

Nelly

[infections] Re: Whipple bacillus perfectly abx-sensitive in culture

This is the Raoult paper Nelly; it sounds like youve read it."In vivo, co-trimoxazole is not always effective for the treatment of Whipple's disease and an 30% failure or relapse rate has been reported even after a 1 year course of treatment.2 The failures and relapses frequently reported could be due firstly to a lack of bactericidal activity of sulfamethoxazole at low pH where the bacteria lives.16 Indeed, we have previously demonstrated that only the association of doxycycline with hydroxychloroquine was able to kill the intracellular bacteria.7 Secondly, relapses could be due to the acquisition of resistance against sulfamethoxazole during the course of the treatment, especially by mutation in the DHPS encoding gene. There is one report of acquisition of resistance to co-trimoxazole after long and repeated treatment using this antibiotic.20 Finally, failure and relapses could be due to an inadequate concentration of antibiotic at the site of infection (cardiac valve or cerebrospinal fluid)." ====================================================Note that the highest intracellular/extracellular activity ratio is 100, for ceftriaxone, which aligns with Klempners work "Fibroblasts protect the lyme spirochete from ceftriaxone in vitro."IMportant to note is that according to these authors the whipple bacillus resides in acidic endosomes in vivo.Table 2. MICs (mg/L) of antibiotics for T. whipplei strains (Twist, Endo-5, Slow2) obtained in axenic medium [ie alone in medium], as compared with the results previously obtained in cells [ie in cell culture],7 as determined using Light Cycler assayAntibiotics Extracellular (E) Intracellular (I) Ratio I/E --------------------------------------------------------------------------------Penicillin G 0.25–0.5 0.5–1 2 Amoxicillin 0.06–0.25 0.5–1 4–8 Teicoplanin 0.25–0.5 0.25–0.5 1 Vancomycin 1–2 10 5 Imipenem 0.5–1 0.5–10 1–10 Aztreonam 0.5–1 10–20 20 Cefalothin 2–4 10–20 5 Ceftriaxone 0.06–0.25 10 100 Gentamicin 0.06 4–8 100 Streptomycin 0.5 0.5–1 1–2 Rifampicin 0.25–0.5 0.5–2 2–4 Erythromycin 0.06–1 1–2 2–16 Clarithromycin 0.06–0.25 2 8 Telithromycin 0.06–0.25 0.25–0.5 2–4 Doxycycline 0.25–0.5 1–2 4 Thiamphenicol 0.25–0.5 0.25–1 1–2 Chloramphenicol 0.5–1 1–2 2 Levofloxacin 0.25 0.5 2 Ofloxacin 2–4 4 1 Ciprofloxacin 4 4 1

[Guest guest]

Nelly, have you ever tried pseudophedrine along with an anti-

inflammatory like ibuprofen or acetomenephin for your headaches?

This always worked for me in the past, although I stopped doing the

pseudophedrine regularly because it caused heart palpitations that

made me nervous (and I can't take any ibuprofen/aspirin type

products at all any more). Unfortunately, the migraine meds like

Immitrex (tryptophan) also have heart risks in a small percentage of

users, and it became less and less effective besides, whereas the

pseudophedrine continues to work (with the side effect of keeping me

awake all night).

Pseudophedrine, and the tryptophans are vasoconstrictors, in part.

Apparently some of us get headaches due to swelling of the blood

vessels around the brain and in the head/sinus regions. If you

reduce that temporary swelling the headache goes away. It's worked

for me this way, but if you have any heart issues, you should

proceed with caution. I do know though that you don't really care if

you live or die when you've got one of these monster headaches, so

you have to weigh the risk. Most people don't have this heart

reaction, so it could be irrelevant in your case.

Also, I always keep some magnesium on hand, in case the heart starts

acting up.

I wouldn't recommend this as a regular treatment, but for occasional

episodes, you might want to consider it. I still resort to it once

in a while in an emergency. I've also wanted to try a nasal spray

version of the pseudophedrine, rather than a tablet, thinking

perhaps this would have less impact on the heart. I'm down to only

one migraine a month now, which is tied to my period, but I remember

well what a nightmare migraines are.

penny

" Nelly Pointis " wrote:

>

> I have one of my abx/infection induced monster headaches so I

won't be able to read or communicate for a few hours/days?

[Guest guest]

I've been interested in whipple's as well. Do you know why they

suggest penicillin, then the bactrim? Maybe I could attempt bactrim

again, after I do the penicillin for a while.

When I took bactrim, I started having hallucinations. More like

psychedelic visuals when I closed my eyes. Not so bad for my artist

side, but scary as they were increasing in frequency, and I didn't

want to risk having them happen when my eyes were open. They stopped

when I stopped the bactrim.

Are there any other reports of hallucinations in people being

treated with Bactrim? Or explanations?

I'm feeling very good about the penicillin and that it's killing at

least some of my bugs. Funny, haven't had penicillin since I was a

kid.

penny

> > ,

> >

> > Been looking into Whipple's for a while now and it looks like

> bactrim or even just sulfamethoxazole alone is the only drug

which

> has been consistently found active with easily attainable and

> tolerable MIC MICs of sulfamethoxazole is in the range

> > 0.5-1 mg/L.

> >

> > Nelly

> > [infections] Whipple bacillus

perfectly

> abx-sensitive in culture

> >

> >

> > Didnt even know this lil piece of crap had been cultured; I

think

> > thats rather recent.

> >

> > Havent read this full text but it is definitely quite

sensitive

> to

> > clinical concentrations of a number of drugs.

> >

> > THerapy of the human infection is usually multi-year and I

have

> some

> > vague info regarding a significant number of incomplete

cures

> (tho no

> > hard data). Therefore this looks like another probable multi-

drug

> > vitro/vivo sensitivity paradox. Collect em all.

> >

> >

> > ====================================================

> >

> > The active compounds in axenic medium were doxycycline,

macrolide

> > compounds, penicillin G, streptomycin, rifampicin,

> chloramphenicol,

> > thiamphenicol, teicoplanin, vancomycin, amoxicillin,

gentamicin,

> > aztreonam, levofloxacin and ceftriaxone, with MICs in the

range

> 0.06-

> > 1 mg/L. Cefalothin was less active, with MICs in the range 2-

4

> mg/L.

> > We found that co-trimoxazole was active with MICs in the

range

> 0.5-1

> > mg/L, and sulfamethoxazole alone was active with MICs in the

> range

> > 0.5-1 mg/L.

> > PMID: 15650004

> >

> >

> >

> >

> >

[Guest guest]

Yeah, Nelly, I definitely know the panicky search phase, when you're

in too much pain to even know what you're taking, and all you want

is to curl up in the dark somewhere and hope you don't throw up,

because that just makes your head pound even more.

Funny, but I've also found that codeine helps, when I'm desperate,

or really don't want to be awake all night with the pain. I can

never take codeine more than one day or it starts messing with my

head badly, but sometimes when I'm desperate it has the same effect

as you noticed, where the headache gradually subsides after a couple

of hours. None of the other narcotics do that for me.

Too bad about the pseudophedrine. That's what I was afraid of. For

me, the trade off is worth it. Like you said, I wouldn't care if I

died anyway, so dealing with the heart effects at that point seems

like a minor trade off. :-)

I read an interesting site one time, where the guy believes that

depending on which side of the head the headache is on, you need

either potassium or magnesium. I was out of town and at lunch once

with some people and a migraine started coming on. Of course I lost

my appetite, but tried to blend in, so ordered the only thing that

sounded tolerable, potato skins. Amazingly the headache went away.

Potassium and Magnesium both affect the heart, and with this recent

news that 80% of migraine sufferers are being cured when they have a

tiny hole between the two chambers of the heart repaired. Have you

read about this? Very simple procedure, easy to test for, etc. I'm

going to get tested for it. Migraine sufferers are at risk for

stroke as I'm sure you know, and this is how this surgery was first

discovered, --as a procedure for people who'd had strokes, then as a

preventative for strokes. Now as a cure for migraines.

penny

" Nelly Pointis " <janel@p...> wrote:

> Penny,

>

> Thanks for trying to help me with THE HEADACHES, I see you have

been there as well!:

>