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1 16th September 10:02
ms
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Default Long-Term Use of Azithromycin as anti-inflammatory?


In the following Medscape article, long-term use of the macrolide antibiotic
azithromycin ("Zithromax") has been shown to have benefit in cystic
fibrosis, in children and adults, with little negative side effects. Not
used for its antibacterial properties, but for its anti-inflammatory
properties, which it has been found to have.

Has this also been prescribed in such a manner for chronic sinusitis? I
wonder if it could be helpful?

Finding a safe anti-inflammatory medication is a problem--as long-term usage
of oral corticosteroids has harmful effects, and there are also negative
effects from long-term NSAID usage.

I would guess that the azithromycin would lose its antibacterial effect if
used regularly over a long period, as the bacteria would develop resistance
to it. But if it remains effective as an anti-inflammatory, with little
negative side effects--could be a good thing, no?

(Of course--one negative for people without health insurance--could get very
expensive to use long term. With health insurance--would depend if the plan
would cover it long term like that.)

Anyone reading has prescribed or been prescribed azithromycin long-term as
an anti-inflammatory?

http://www.medscape.com/viewarticle/503819_3 (scroll down to see part
about this med)

quote of part of article---------


Azithromycin
Azithromycin is a macrolide commonly used for its antibacterial activity in
both children and adults. It is approved for treatment of acute otitis media
and community-acquired pneumonia in patients older than 6 months and for
treatment of pharyngitis or tonsillitis in those aged 2 years or older.[77]
Azithromycin has a long tissue half-life and ac***ulates in the sputum and
lungs of treated patients.[78] The potential role of azithro-mycin in cystic
fibrosis is extrapolated from experience with diffuse panbronchiolitis, a
respiratory disease similar to cystic fibrosis. In patients with diffuse
panbronchiolitis, long-term erythromycin therapy improved both symptoms and
survival.[79, 80]

Azithromycin has been evaluated as a treatment option for patients with
cystic fibrosis for its antiinflammatory properties.[81] The precise
mechanism through which azithromycin exerts these effects has not been
elucidated (Figure 2).[82-99] Antimicrobial classes typically used in the
treatment of acute cystic fibrosis exacerbations, such as third-generation
cephalosporins, amino-glycosides, and fluoroquinolones, do not appear to
exert any significant direct antiinflammatory action and have not been
included in this review.[100]


Figure 2. (click image to zoom) Proposed antiinflammatory mechanisms
of macrolide antibiotics. The precise mechanism by which azithromycin
mitigates inflammation is unknown, but it affects neutrophils through
mediation of apoptosis, migration, chemotactic activity, and phagocytic
function. Azithromycin is an indirect antioxidant and may prevent lung
damage through this function. Therapy with this agent has inhibited
production of nitric oxide, prostaglandin E2, and proinflammatory cytokines
interleukin (IL)-8, IL-1?, and tumor necrosis factor (TNF)-?. Azithromycin
may also downregulate growth-related oncogene-? as well as soluble vascular
cell adhesion molecule (SVCAM)-1. Reduced sputum viscoelasticity and
improved mucociliary and cough transportability of airway secretions has
been noted. Antagonism of the virulence of Pseudomonas aeruginosa has been
proposed as a mechanism, an effect mediated through a decrease in airway
adherence, inhibition of production of various exoproducts, and interference
with Pseudomonas mucoid-alginate biofilm formation. In addition, it may
affect Pseudomonas aeruginosa's viability directly despite subinhibitory
minimum inhibitory concentrations. Restoration of the cystic fibrosis
transmembrane conductance regulator (CFTR) chloride channel is an additional
possible mechanism. X = mitigation of adverse effect.[82-89]


Treatment with either erythromycin or clarithromycin has not been beneficial
in cystic fibrosis.[101] Six trials have evaluated the effects of
azithromycin in children and adults with cystic fibrosis ( Table
2 ).[102-107] Of the three randomized, placebo-controlled trials conducted,
two involved patients younger than 18 years.[106, 107] Although a benefit
with azithromycin was observed in both of these studies, the more recent one
provides the most compelling evidence of the****utic improvement.[107]

In a randomized, double-blind, placebo-controlled study involving 60 adults
with cystic fibrosis, treatment with azithromycin led to an improvement in
total quality of life (p=0.035), a reduction in antibiotic therapy
associated with acute respiratory exacerbations (p < 0.037), and a slowed
rate of decline in predicted FEV1 (p=0.047) and FVC (p=0.001).[105] This
benefit was observed despite baseline patient characteristics indicating the
treatment group had less lung function than the placebo group (mean FEV1
50.9% vs 62.3%, mean FVC 67.3% vs 77.5%). The treatment group also was
shorter, on average, and weighed less than the placebo group. However,
outcome changes in lung function were small, indicating maintenance rather
than improvement.

In the first trial involving patients younger than 18 years with cystic
fibrosis, pulmonary function was only modestly affected after a 6-month
course of azithromycin.[106] This study-a 15-month, prospective, randomized,
double-blind, placebo-controlled, crossover trial-included 41 children (18
boys, 23 girls) aged 8-18 years, with a median FEV1 of 61% (range 33-80%). A
history of chronic P. aeruginosa colonization was not a specific entry
criterion. Exclusion criteria were liver disease, hearing impairment,
Burkholderia cepacia colonization, previous organ transplantation, treatment
with macrolide antibiotics or oral corticosteroids for more than 14 days, or
treatment with dornase alfa begun within 2 months of enrollment.

Azithromycin dosage was based on weight; patients weighing 40 kg or less
received 250 mg once/day; those weighing more than 40 kg received 500 mg
once/day. A clinically significant change in the primary outcome measure,
FEV1, and the secondary outcome measures, FVC and FEF25-75, was defined as a
change of more or less than 13%, 13%, and 20%, respectively. At every time
point during treatment, mean FEV1, mean FVC, and mean FEF25-75 were higher
in the azithromycin-treated patients than in the placebo patients. However,
the median relative difference in predicted FEV1 between azithromycin and
placebo was only 5.4% (p > 0.05). Improvement in FEV1 greater than 13% was
noted in 13 of 41 patients, whereas deterioration of more than 13% was
observed in five (p=0.059). The median relative difference in predicted FVC
and FEF25-75 between the two groups was 3.9% and 11.4%, respectively (p >
0.05). The results of this study suggest that azithromycin treatment in
children and adolescents may exert clinically important beneficial effects
on pulmonary function in approximately 33% of patients but may result in
worsening lung function in approximately 10-20% of patients.
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2 16th September 10:02
jeff
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Default Long-Term Use of Azithromycin as anti-inflammatory?


You are comparing apples and oranges. Chronic sinusitis is different in
important ways from the chronic infections in cystic fibrosis.

You can go to scholar.google.com or http://www.pubmed.gov and do your own search
using keywords like azithromycin and chronic sinusitis.

And there may be long-term problems from using azithromycin, as well.
Considering the long-term problems of having cystic fibrosis vs. the risks
from using azithromycin chronically, the benefits of azythromycin may
outweigh the risks, while in chronic sinusitis, they may not.

It sounds like you need to find out what is causing your chronic sinusitis
rather than treat the inflammation.

Jeff
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3 16th September 10:02
ms
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Default Long-Term Use of Azithromycin as anti-inflammatory?


f


Yes, they are two different diseases. But there are some connections. I have
read they have found a similar gene connected to both diseases. Both involve
chronic inflammation involving respiratory airways. But yes, not the same
disease. I didn't imply they were. Just that on reading an article how a
particular medication is used to control chronic inflammation in one
disease, one wonders whether it could also be helpful for other chronic
inflammatory diseases. Perhaps arthritis as well. I don't know, just wondering.


Well, I obviously did do some searching, which brought me to the article I
posted from Medscape. (I forget which search terms I used, which brought me
to that article.) Yes, I could do a search for the terms azithromycin and .
I would probably come across results listing azithromycin as one of the
antibiotics used in treating sinusitis. Not likely to find one on use as a
long-term anti-inflammatory in chronic sinusitis, but I guess it's possible.
Again, I was just speculating on a possible use, not positing that it is
already used that way.

Of course. All medications have side effects, and the doctor needs to weigh
the benefits vs. risks in prescribing them. As I wrote though,
anti-inflammatories in particular have serious problems with side effects,
even the OTC ones. Would you consider long-term use of azythromycin to be
more risky than long-term use of prednisone, for example? Or even long-term
high dosages of ibuprofen? Yes, of course, risks and benefits always have to
be weighed, when considering medications.

I've been doing that all my life. Sure I would prefer to cure it (by finding
out the "cause", and changing that), than deal with symptoms. But
unfortunately, there is no easy answer, as of yet certainly no cure. (Do you
have chronic sinusitis, or do you treat it frequently as an ENT or
allergist?) It is a far more serious and widespread disease than many people
realize.
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4 16th September 10:02
woody long
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Default Long-Term Use of Azithromycin as anti-inflammatory?


For long term use I would rate azithromycin as roughly 10x more harmful
than prednisone (depending on the dose of each), with prednisone being
again 10x more harmful than the maximum recommended dose of ibuprofen.

Unlike the others, ibuprofen will not worsen your underlying disease
(although it may cause other problems)

Worst of all would be prednisone and azithromycin simultaneously -
probably > 10x more dangerous than either one alone.

Woody
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5 16th September 10:02
woody long
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Default Long-Term Use of Azithromycin as anti-inflammatory?


For long term use I would rate azithromycin as roughly 10x more harmful
than prednisone (depending on the dose of each), with prednisone being
again 10x more harmful than the maximum recommended dose of ibuprofen.

Unlike the others, ibuprofen will not worsen your underlying disease
(although it may cause other problems)

Worst of all would be prednisone and azithromycin simultaneously -
probably > 10x more dangerous than either one alone.

Woody
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6 16th September 10:02
sbharris[atsign]ix.netcom.com
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Default Long-Term Use of Azithromycin as anti-inflammatory?


And why is that?
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7 16th September 10:02
ms
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Default Long-Term Use of Azithromycin as anti-inflammatory?


He (Woody Long) does not reply, as to why he makes such a statement. I
suspect he just made up those figures with no basis for them, with his
statement about each being ten times more harmful than the next. (Quite
convenient in our decimal system, no, that everything is "ten times more
harmful"?)

Long term oral steroid usage, and long term high dosage NSAIDS usage, will
have definite serious side effects to anyone so using them. It is possible
that some people might have severe reactions to azithromycin, but I don't
think most people do,

Well, Woody, if there is a basis for your statements, please elaborate.

Thank you.
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8 16th September 10:03
woody long
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Default Long-Term Use of Azithromycin as anti-inflammatory?


Notice I qualified my statement with "roughly" and "depending on the dose"


After only 10 days "C. albicans-colonized mice treated with each
macrolide had highly significant increase in colony counts of C.
albicans in their stools compared to C. albicans-colonized mice treated
with saline only"

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12058726&query_hl=1

The increase in colony count will vary by individual but lets say it
doubles after 10 days. Since organisms tend to grow exponentially,
after 1 year (say 360 days) of continuous uninterrupted use, the fungal
colony count could be as much as 2^36 higher or 68719476736.

This will make your underlying disease worse.

http://www.medicineatmichigan.org/magazine/2004/fall/huron/huron01.asp

And while you may not notice a modest 2 fold fungal colony count
increase you are very likely to notice a 68719476736-fold increase.

Therefore, I would not touch the stuff if I were you, but I realize you
will probably ignore this advice regardless.

If you do decide to take it long term, best of luck to you, and please
report back as to how sick you are or are not after 1 year of use. Woody
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9 16th September 10:03
ms
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Default Long-Term Use of Azithromycin as anti-inflammatory?


Are you saying that use of azithromycin increases fungi in the body? Would
you say that is true for all antibiotics in general? All macrolides?


I wouldn't be in the position to make such a decision. This medication is
not available OTC, I cannot just decide to start taking it long-term. After
reading about it being prescribed long-term as an anti-inflammatory for
cystic fibrosis, I was only speculating whether it might be useful as an
anti-inflammatory for other conditions as well.

When you write "I would not touch the stuff", are you saying that you never
take an antibiotic, or that you would never take azithromycin, or any
macrolides, not even short-term?
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10 16th September 10:03
woody long
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Default Long-Term Use of Azithromycin as anti-inflammatory?


Yes it seems all antibiotics have the potential to increase fungi in
the body. However, it appears that some have a greater potential than
others (e.g macrolides appear to be worse than penicillin)

I would take an antibiotic (including a macrolide) short term, if I
needed it, like for a gunshot wound in the leg that got infected with
flesh eating bacteria, syphilis, anthrax, or something like that. I
would take the best antibiotic for whatever type of infection I had.
Usually only a short course of a few weeks or less is needed even for
very severe infections, when such infections are actually caused by
bacteria.

What I would not do is take an antibiotic for something not imminently
life threatening, or use it as an anti-inflammatory.

The fact that antibiotics act as anti-inflammatory is interesting
because it means that just because you take it and feel better, you
CANNOT assume that bacteria were contributing to your symptoms.

Woody
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