Fw: [InfectionAndInflammation] To - Cipro/Flagyl and drug resistance

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Donna in NC

(don't post but have been a member since the original group was conceived)

[infectionAndInflammation] Cipro/Flagyl and drug resistance

Penny and all

I, too, am very concerned about drug resistance. I have two

points to make on this that I have never heard discussed before,

but that I think are critical. . First, the newer generation

quinolones are vastly superior to Cipro. Second, Flagyl should

not be used at low doses.

Many months ago when I was trying to figure out if all this talk

about bacteria and herxing were relevant to me I tested Cipro for

its effects on me. Two consecutive days of Cipro (500 mg/day)

rendered me bed-ridden for almost 3 days with very severe

meningitis-like symptoms. So I know the power of Cipro.

However, I wish now that I had used the newer quinolones (e.g.,

moxifloxacin and gatifloxacin) instead of Cipro, for the following

reasons.

This landmark paper:

Zhao X, Xu C, Domagala J, Drlica K.

DNA topoisomerase targets of the fluoroquinolones: a strategy

for avoiding bacterial resistance.

Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13991-6.

PMID: 9391140

http://tinyurl.com/52coe

says,

" Compounds containing a C8-methoxyl group were particularly

lethal, and incubation of wild-type cultures on agar containing

C8-methoxyl fluoroquinolones produced no resistant mutant,

whereas thousands arose during comparable treatment with

control compounds lacking the C8 substituent. "

Cipro lacks this critical C8 moiety.

They describe the ability of the newer quinolones to bind two

different topoisomerases. This in itself helps reduce the

likelihood that bacteria will become resistant. However, if prior

use of Cipro (which only binds one of the topoisomerases)

results in resistance to Cipro, then the bacteria have a better

chance of becoming resistant to the newer quinolones (they

would then only have to overcome sensitivity to one of the

topoisomerases). That is, Cipro is a stepping-stone for the

attainment of resistance to the newer quinolones. The reverse,

however, is not true because the newer quinolones give the

bacteria far less opportunities for the development of resistance

in the first place.

What is even more important than the dual targeting of the newer

quinolones, is the ability of the C8-methoxyl group to induce

lethal DNA strand breakage. Apparently all quinolones " freeze "

the bacterial topoisomerase onto the DNA. These

topoisomerases can induce a cleavage of the DNA. The older

quinolones (e.g., Cipro) apparently keep the topoisomerases

" frozen " for much longer than the newer ones. This may give the

bacteria time to re-ligate the broken ends. By contrast, the

C8-methoxyl group is conjectured to induce the release of the

topoisomerases, thereby enhancing the likelihood that the two

free ends of the DNA will be liberated and diffuse away from

each other. This is typically a catastrophic event for the bacteria.

(I'm recounting the ideas of this paper as I remember it, but

since it's been awhile since I've read this paper you'll want to

read the full-text yourself).

Flagyl is the other antibiotic that I believe is being misused.

Some people believe that Flagyl is a quinolone. It's not. It is a

nitroimidazole. Here is a good PDF that describes the

mechanism of action of nitroimidazoles

http://www.ub.rug.nl/eldoc/dis/medicine/e.j.van.der.wouden/c8.pd

f

One of the consequences of Flagyl's mechanism of action is that

if the DNA damage is not extensive enough, the bacterium will

survive and will be a mutant. Low doses of Flagyl therefore

increase the genetic diversity of the bacterial population that

infects you. That is, low doses can increase the likelihood that

the bacterial population will be represented by members that are

resistant to antibiotics-and not just to Flagyl. This is not just a

theoretical possibility. This paper says,

http://tinyurl.com/62tz2

" that levels of Mtz that partially inhibit growth stimulate forward

mutation to rifampin resistance. " That is, non-lethal doses of

flagyl were shown in this paper to induce rifampin-resistance.

Rifampin and Flagyl are unrelated. This is why the misuse of

flagyl may be catastrophic for your long-term goals.

This issue is stated right in Pfizer's product insert:

www.pfizer.com/download/uspi_flagyl.pdf

which says, " Skipping doses or not completing the full course of

therapy may..increase the likelihood that bacteria will develop

resistance and will not be treatable by Flagyl OR OTHER

ANTIBACTERIAL DRUGS in the future. " (I've added the capital

letters).

Flagyl is a fantastic drug if you're going after, say, lyme cysts.

But, in my opinion, it must be used at high doses. The folks at

lymenet often encourage starting out with extremely low doses,

in order to avoid intolerable herxing. This may be long-term

therapy-suicide. If you can't handle the herx from high dose

Flagyl, then it may be better to post-pone its use, say, until cysts

get older and less viable or perhaps following the use of HCQ. I

realize for Lyme there aren't a lot of good options for cysts, but I

think people should consider very carefully how they address

this issue, and at least be aware of the risks inherent to

low-dose Flagyl. (All of this applies to tinidazole as well).

And it probably goes without saying, but I'll say it anyway. Your

pathogens don't know why you're taking the ABX. If you are

prescribed Cipro or Flagyl for something other than your A-CID

pathogens, those A-CID pathogens will be subjected to the

influence of these drugs just the same. And the reverse is true

as well. If you use antibiotics for your A-CID and do so

inappropriately, you may find that when your H. pylori, say,

becomes a problem for you in the future, that your prior misuse

of ABX has rendered them resistant.

Matt

>

> Unfortunately, if you don't have your organisms tested, taking

any

> of these abx can just make your bugs more resistant. When I

first

> had mine i.d.'d, they were resistant to 12 of the first 14 abx

> tested (and I had avoided abx most of my life).

>

> It's possible that some abx may be more effective for a good

segment

> of the population, but unless we're lucky, this kind of guess

work

> just perpetuates our illness, can make it worse, and even

convinces

> many people that abx treatment doesn't work at all. Throw the

> nebulous " herx " misconception into the mix, and we're in real

> trouble.

>

> I've seen a number of ENTs who don't have the first clue about

the

> antibiotic resistance that these organisms develop and how

that

> keeps us sick, and unresponsive to treatment. I saw one of the

head

> guys at UCSD Medical, and he ONLY prescribes Amoxicillin

(and

> surgery or course) because " amoxicillin works for him " . Okay,

this

> is a teaching hospital and this is what med students are being

> taught???? We're in the darkest of dark ages here, obviously.

>

> I'm ecstatic that I've just recently discovered (after how many

> years?) an ENT who DOES do nasal swabs, who DOES work

with

> infectious disease docs and prescribes the APPROPRIATE

antibiotic

> depending on the organisms a person tests postive for.

INCLUDING

> STAPH!!!! (Probably the most overlooked, yet debiliating and

> resistant organism alive). She also completely understands

that

> these ongoing but hidden sinus infections create CFS, FMS,

> arthritis, etc. Hallelujah!

>

> This is what Tony's always going on about. Why is it so hard to

find

> docs to perform these simple tests that used to be standard

> procedure in doctors' offices across the country in the 1950s

before

> commercial labs took over? Before abx prescriptions became

> ridiculous and ineffective and underprescribed, based on

nothing but

> text books, thereby creating super resistant bugs?

>

> The other thing Tony's always trying to say, but I think gets lost

> in translation, is that we need to watch the trends of our blood

> work and how they change when we are undergoing some

specific

> treatment. It doesn't matter if they're in " normal ranges " . Most

> pwc's bloodwork is " normal " . The key is, what is the TREND?

For

> instance, if we're on heparin, or one of the anti-coagulants, or

> even whey protein, how does our blood work (say a simple INR

test)

> reflect that treatment?

>

> I'm with Tony. I'm not sure why we have this sort of haphazard

> approach. Are our doctors just terrified of facing these growing,

> resistant, infections head-on? Do they have their heads buried

in

> the sand? Why are we using guesswork, or other people's

results to

> determine if a treatment is having an effect on us or not when

there

> are simple tests (not expensive or complex tests) that can give

us

> strong indicators of what really IS going on?

>

> Someone needs to write a book maybe, because somehow,

we need to

> start demanding answers to these questions.

>

> For me personally, the best " cfs " antibiotics I've taken, in terms

> of relieving my fatigue, have been cipro, ceftin, and Ketek. I've

> had minor improvements with other abx, like doxy, and zero

response

> to MANY others, and adverse reactions to a few, but these 3

have

> been " MY " big guns. I've been off abx for several weeks, but the

> effects of the Ketek (and the Tibetan medicine) are still lasting.

> Still no jaw pain, and I'm not completely dysfunctional

considering

> I've been extremely busy for the last several weeks. This is a

major

> improvement.

>

> I think the Benicar has helped substantially as well in that the

> reduction of inflammation seems to be having a positive

overall

> health effect. I do believe that a combo of ARBs and ABX may

be the

> answer we've been looking for. But it doesn't have to be as

limited

> or as restrictive as that outlined at marshallprotocol.com. (yet

> another one-size-fits all approach.) I'm going to resume the

Ketek,

> and maybe revisit Ceftin, now that my life is getting back to

normal.

>

> By the way, I like Ken's creative abbreviations. I guess I'm on

the

> AAPS (abx/arb/protocol with supplementation :-).

>

> penny

>

>

>