Re: CROHNS AND PEUDOMONAS - Clofazimine

[Guest guest]

> was it any particular combo of triple abx or did it vary?

Rifabutin (450 mg/d), clarithromycin (750 mg/d) and clofazimine (2

mg/kg/d).

All I know on rifabutin is its pretty similar to rifampin

structurally, but small structural differences can be criticially

important. Clarithromycin has been (circa 1995?) discovered and

hailed as particularly effective in human MAC infection, even tho it

is not outstanding against MAC in vitro.

Clofazimine apparantly has no known antimicrobic mechanism. This is

news to me.

" Clofazimine has been in clinical use for almost 40 years, but little

is known of its mechanism of action. The primary indication for

clofazimine is multibacillary leprosy, but it is useful in several

infectious and noninfectious [uMMM... MAYBE WE SHOULD SAY

IDIOPATHIC?] diseases, such as typical myocobacterial infections,

rhinoscleroma, pyoderma gangrenosum, necrobiosis lipoidica, severe

acne, pustular psoriasis, and discoid lupus erythematosus. Postulated

mechanisms of action include intercalation of clofazimine with

bacterial DNA and increasing levels of cellular phospholipase A2.

Clinical experience, possible mechanisms of action, and side effects

of clofazimine are summarized. [PMID: 7829710] "

Borodys success with it thus becomes interesting to me personally, as

its conceivably a sign the drug could have some sort of special

charecteristics with respect to other of our diseases of interest. If

anyone spots clofazimine making some smooth moves out there in the

literature or the world, please let it be known.

" Gram-positive bacteria were found to be generally susceptible to

these agents, whereas gram-negative organisms were uniformly

resistant. [PMID: 1482140] "

However, chlamydiae, borreliae, and T pallidum are atypical " gram-

negatives " that might or might not be resistant (unless they were

spoecifically shown to be in the full text of this paper, or

elsewhere). Any drug resistance enjoyed uniquely by gram-negatives is

usually due to impermeability to molecules over ~600-700 Da, which is

not a feature of these atypicals. Its a little surprising, then, to

see that clof weighs in at only 473 Da:

http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?

CARD=APRD00278.txt

Maybe its not a permeation issue after all, in which case atypicals

might well not be suceptible to it.

This group has been knocking off some of the postulated mechanisms of

action:

Bopape MC, Steel HC, Cockeran R, Matlola NM, Fourie PB, R.

Related Articles, Links

Antimicrobial activity of clofazimine is not dependent on

mycobacterial C-type phospholipases.

J Antimicrob Chemother. 2004 Jun;53(6):971-4. Epub 2004 Apr 29.

PMID: 15117926 [PubMed - indexed for MEDLINE]

Cholo MC, Boshoff HI, Steel HC, Cockeran R, Matlola NM, Downing KJ,

Mizrahi V, R. Related Articles, Links

Effects of clofazimine on potassium uptake by a Trk-deletion mutant

of Mycobacterium tuberculosis.

J Antimicrob Chemother. 2006 Jan;57(1):79-84. Epub 2005 Nov 12.

PMID: 16286358 [PubMed - indexed for MEDLINE]

[Guest guest]

> Clarithromycin has been (circa 1995?) discovered and

> hailed as particularly effective in human MAC infection, even tho it

> is not outstanding against MAC in vitro.

Here by MAC I meant pulmonary MAC and AIDS-associated systemic MAC.

Didnt mean to include MAP, tho obviously Borodys study suggests

clarithromycin may be pretty great for MAP - if in fact MAP causes

Crohns.

There is a whole advocacy group for MAP as a cause of Crohns. I know

there is alot of controversy about that, but I dont know the science.

[Guest guest]

We are riddled with infections that keep coming out... wave after

wave of therapy keeps revealing wave after wave of infection.The

trick is to keep the infection going down- you sort of gain a

millimeter a month with these persisting infections if you keep the

pressure on them.

I think one of your article's recently summarised a persistant staph

areus infection.Some drugs are possably just able to break the

infections out of there deep tissue or fat homes..

>

>

> > was it any particular combo of triple abx or did it vary?

>

> Rifabutin (450 mg/d), clarithromycin (750 mg/d) and clofazimine (2

> mg/kg/d).

>

> All I know on rifabutin is its pretty similar to rifampin

> structurally, but small structural differences can be criticially

> important. Clarithromycin has been (circa 1995?) discovered and

> hailed as particularly effective in human MAC infection, even tho

it

> is not outstanding against MAC in vitro.

>

> Clofazimine apparantly has no known antimicrobic mechanism. This is

> news to me.

>

> " Clofazimine has been in clinical use for almost 40 years, but

little

> is known of its mechanism of action. The primary indication for

> clofazimine is multibacillary leprosy, but it is useful in several

> infectious and noninfectious [uMMM... MAYBE WE SHOULD SAY

> IDIOPATHIC?] diseases, such as typical myocobacterial infections,

> rhinoscleroma, pyoderma gangrenosum, necrobiosis lipoidica, severe

> acne, pustular psoriasis, and discoid lupus erythematosus.

Postulated

> mechanisms of action include intercalation of clofazimine with

> bacterial DNA and increasing levels of cellular phospholipase A2.

> Clinical experience, possible mechanisms of action, and side

effects

> of clofazimine are summarized. [PMID: 7829710] "

>

>

> Borodys success with it thus becomes interesting to me personally,

as

> its conceivably a sign the drug could have some sort of special

> charecteristics with respect to other of our diseases of interest.

If

> anyone spots clofazimine making some smooth moves out there in the

> literature or the world, please let it be known.

>

> " Gram-positive bacteria were found to be generally susceptible to

> these agents, whereas gram-negative organisms were uniformly

> resistant. [PMID: 1482140] "

>

> However, chlamydiae, borreliae, and T pallidum are atypical " gram-

> negatives " that might or might not be resistant (unless they were

> spoecifically shown to be in the full text of this paper, or

> elsewhere). Any drug resistance enjoyed uniquely by gram-negatives

is

> usually due to impermeability to molecules over ~600-700 Da, which

is

> not a feature of these atypicals. Its a little surprising, then, to

> see that clof weighs in at only 473 Da:

>

> http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?

> CARD=APRD00278.txt

>

> Maybe its not a permeation issue after all, in which case atypicals

> might well not be suceptible to it.

>

> This group has been knocking off some of the postulated mechanisms

of

> action:

>

>

> Bopape MC, Steel HC, Cockeran R, Matlola NM, Fourie PB, R.

> Related Articles, Links

> Antimicrobial activity of clofazimine is not dependent on

> mycobacterial C-type phospholipases.

> J Antimicrob Chemother. 2004 Jun;53(6):971-4. Epub 2004 Apr 29.

> PMID: 15117926 [PubMed - indexed for MEDLINE]

>

> Cholo MC, Boshoff HI, Steel HC, Cockeran R, Matlola NM, Downing KJ,

> Mizrahi V, R. Related Articles, Links

> Effects of clofazimine on potassium uptake by a Trk-deletion

mutant

> of Mycobacterium tuberculosis.

> J Antimicrob Chemother. 2006 Jan;57(1):79-84. Epub 2005 Nov 12.

> PMID: 16286358 [PubMed - indexed for MEDLINE]

>