Just curious to know whose done pretty good on this since i started iv actually kept dropping so as for increasing my fev it hasnt done that..just wandering if i should stop taking it..whats everyones experience with it? Has it helped you?..has your fev increased or decreased?
Zithromycin Mon wed and fri
- Thread starter carly23
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athletixbc
New member
I have been on this regimen since 2003, and while I can't say it has increased my FEV1, I have had virtually no issues with staph infections while taking it. I believe it helped keep my FEV1 stable for several years until I became colonized with b. cepatia.
rubyroselee
New member
I've been on Zithro for a few years now. I have not had an increase in FEV, but they have remained stable.
M
MiddleAgedLady
Guest
they told me it was to help reduce sinus infections but i seemed to keep getting them until I got on Cayston which clears them up immediately for me. I still take the Zithro.
imported_Momto2
New member
I did not experience any positives from taking zithromax, but I did have worsening of my GERD and other stomach issues. I did not notice any negative change in my lungs when I stopped taking it. But, everyone is different!
JennyCoulon
New member
My oldest who is 12 just started on this about 6 months ago. He has had other coughing/asthma issues going on that we are now trying to treat with Tobi and Cipro so I haven't really been able to see if it has. I am excited to see as I have heard from many people that this works.
petitesouris
New member
When I started Zithro, I did notice a reduction in the severity and rapid onset of my infections. However, I also experienced some side effects; Most notably, my heart would race and beat irregularly, often skipping beats. It was very scary. I didn't associate it with the Zithro until I saw something about this "dangerous, sometimes fatal side effect" on my evening news. I know we're not supposed to just stop taking meds, but the report was really effective, and I stopped immediately. I haven't had any heart problems since, so I think it was the Zithro.
To sum, I think it can be a very effective drug, just watch out for weird side effects while on it.
To sum, I think it can be a very effective drug, just watch out for weird side effects while on it.
G
Gorf
Guest
Its hard to tell if it helps but I am on it the same way.
Incomudrox
New member
Azithromycin is not used to increase FEV1. Azithromycin, even though it is an antibiotic is not used as an antibiotic in Cystic Fibrosis patients. Azithromycin is used in CF patients because it inhibits the genetics of Pseudomonas that allow the bacteria to talk to each-other.
This is known as Quorum sensing. Another example is bugs such as ants also use this to talk. Azithromycin prevents this in the bacteria known and Pseudomonas which you probably have. So in closing, if the bacteria can not talk to each other they do not reproduce as much because they don't know how big their populations is because they can not talk.
Azithromycin can cause INCREASED heart rate. I stopped taking it and my heart rate dropped 20-30BPM.
This is known as Quorum sensing. Another example is bugs such as ants also use this to talk. Azithromycin prevents this in the bacteria known and Pseudomonas which you probably have. So in closing, if the bacteria can not talk to each other they do not reproduce as much because they don't know how big their populations is because they can not talk.
Azithromycin can cause INCREASED heart rate. I stopped taking it and my heart rate dropped 20-30BPM.
Interesting! Thankyou for the response incromudox...oh i didnt email you back but im starting pulmonary rehab in a week this is the best thing for me!! If i want numbers improving an away from oxygen 
Im always having pseudomonas issues in the nose and chest..so im wanderig if its even worth staying on..an yea i bet my heart rate would drop..thanks everyone for your inputs <img src="i/expressions/face-icon-small-smile.gif" border="0">
Im always having pseudomonas issues in the nose and chest..so im wanderig if its even worth staying on..an yea i bet my heart rate would drop..thanks everyone for your inputs <img src="i/expressions/face-icon-small-smile.gif" border="0">
musclemania70
New member
I heard that it was used as an anti-inflammatory agent in CF patients. ?
Incomudrox, where did you read about azithromycin affecting p.a.'s quorum sensing? I've never heard of that before. My boyfriend takes it 3x/day to reduce lung inflammation. That's the only reason why his CF doc prescribed for. He has P.A. exacerbation (his p.a. is the mucoid type), and azithromycin didn't had any effect on P.A's quorum sensing.
Incomudrox
New member
<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/</a>
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<h1 class="content-title">Azithromycin Inhibits Quorum Sensing in<em>Pseudomonas aeruginosa</em></h1>
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<div class="contrib-group fm-author"><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20Tateda%2BK[auth]">Kazuhiro Tateda</a>,<sup>1</sup><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20Comte%2BR[auth]">Rachel Comte</a>,<sup>2</sup><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20Pechere%2BJC[auth]">Jean-Claude Pechere</a>,<sup>2</sup><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20K%26%23x000f6%3Bhler%2BT[auth]">Thilo Köhler</a>,<sup>2</sup><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20Yamaguchi%2BK[auth]">Keizo Yamaguchi</a>,<sup>1</sup>and<a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20Van%20Delden%2BC[auth]">Christian Van Delden</a><sup>2,</sup><sup>*</sup>
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<h2 id="__abstractid4738360title" class="head no_bottom_margin ui-helper-clearfix">ABSTRACT</h2>
<p id="__p2">We report that 2 μg of azithromycin/ml inhibits the quorum-sensing circuitry of<em>Pseudomonas aeruginosa</em>strain PAO1. Addition of synthetic autoinducers partially restored the expression of the trancriptional activator-encoding genes<em>lasR</em>and<em>rhlR</em>but not that of the autoinducer synthase-encoding gene<em>lasI</em>. We propose that azithromycin interferes with the synthesis of autoinducers, by an unknown mechanism, leading to a reduction of virulence factor production.
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<p id="__p3"><em>Pseudomonas aeruginosa</em>is a major bacterial pathogen in patients suffering from cystic fibrosis (CF) or diffuse panbronchiolitis (DPB) (<a id="__tag_112604784" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8016786" data-jigconfig="destSelector: "#body-link-popper-B7", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">7</a>). Macrolides, such as azithromycin, are normally not included in the antipseudomonal therapeutic arsenal because of the absence of bactericidal or bacteriostatic activity. However, several studies have highlighted the benefit of long-term macrolide treatment in patients suffering from DPB or CF (<a id="__tag_112604781" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8553295" data-jigconfig="destSelector: "#body-link-popper-B5", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">5</a>,<a id="__tag_112604788" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9482305" data-jigconfig="destSelector: "#body-link-popper-B10", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">10</a>). The mechanisms by which macrolides affect the outcome of chronic infections with<em>P. aeruginosa</em>could include an anti-inflammatory activity and/or a modulation of the production of bacterial virulence factors (<a id="__tag_112604772" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9301978" data-jigconfig="destSelector: "#body-link-popper-B9", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">9</a>). Macrolides inhibit the production of bacterial exoproteases; however, whether this is independent of a decrease in bacterial growth and total protein production is controversial (<a id="__tag_112604783" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8203850" data-jigconfig="destSelector: "#body-link-popper-B13", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">13</a>,<a id="__tag_112604790" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8392997" data-jigconfig="destSelector: "#body-link-popper-B14", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">14</a>,<a id="__tag_112604794" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8214925" data-jigconfig="destSelector: "#body-link-popper-B19", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">19</a>,<a class="cite-reflink bibr popnode jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/#B24" data-jigconfig="destSelector: "#body-link-popper-B24", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">24</a>,<a id="__tag_112604774" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8891128" data-jigconfig="destSelector: "#body-link-popper-B25", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">25</a>).
<p id="__p4">In<em>P. aeruginosa</em>, the<em>las</em>and<em>rhl</em>quorum-sensing systems regulate the production of several extracellular virulence factors, including elastase and rhamnolipid (<a id="__tag_112604775" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9866731" data-jigconfig="destSelector: "#body-link-popper-B27", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">27</a>). Each system is composed of a gene encoding a transcriptional activator,<em>lasR</em>and<em>rhlR</em>, and a gene encoding an autoinducer synthase,<em>lasI</em>and<em>rhlI</em>, required for the synthesis of the autoinducer molecules 3-oxo-C<sub>12</sub>-homoserine lactone (3-oxo-C<sub>12</sub>-HSL) (<a id="__tag_112604780" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8278364" data-jigconfig="destSelector: "#body-link-popper-B15", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">15</a>) and C<sub>4</sub>-HSL (<a id="__tag_112604789" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/7878006" data-jigconfig="destSelector: "#body-link-popper-B16", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">16</a>), respectively. The importance of quorum sensing in the pathogenesis of chronic infections is unknown.<em>P. aeruginosa</em>isolates from CF patients produce autoinducers (<a id="__tag_112604791" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/10713433" data-jigconfig="destSelector: "#body-link-popper-B6", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">6</a>), and autoinducer production by CF sputum has been associated with<em>P. aeruginosa</em>biofilms (<a id="__tag_112604796" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/11048725" data-jigconfig="destSelector: "#body-link-popper-B22", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">22</a>). Autoinducers have also been found in lung tissue of mice infected with<em>P. aeruginosa</em>(<a id="__tag_112604778" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/11021924" data-jigconfig="destSelector: "#body-link-popper-B29", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">29</a>). A reduction of autoinducer production by 50 μg of erythromycin/ml has been suggested (<a id="__tag_112604795" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/10473921" data-jigconfig="destSelector: "#body-link-popper-B23", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">23</a>). However, the<em>Chromobacterium violaceum</em>bioassay used could only measure the C<sub>4</sub>-HSL autoinducer (<a id="__tag_112604800" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9421896" data-jigconfig="destSelector: "#body-link-popper-B11", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">11</a>).
<p id="__p5">We wondered whether azithromycin interferes with the quorum-sensing circuitry. To differentiate the inhibition of virulence factor production from a nonspecific effect, we optimized our experimental conditions so that at the onset of stationary phase, when quorum sensing is active, growth was not notably affected. Figure<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/"><span>?<span class="figpopup-sensitive-area">Figure1A<span>1</a>A shows growth curves of wild-type PAO1 (<a id="__tag_112604769" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/111024" data-jigconfig="destSelector: "#body-link-popper-B8", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">8</a>) in the presence of increasing concentrations of azithromycin. Exponential growth was slightly affected in the presence of 2 μg of azithromycin/ml, but no effect on the stationary growth phase was observed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of total protein extracts of cells grown either in the absence or the presence of 2 μg of azithromycin/ml did not reveal major differences (data not shown). We next determined the effect of 2 μg of azithromycin/ml on elastase and rhamnolipid production in strain PAO1. Elastase production was monitored using elastin Congo red assays (<a id="__tag_112604785" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9294432" data-jigconfig="destSelector: "#body-link-popper-B17", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">17</a>). In accordance with previous reports (<a id="__tag_112604770" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8203850" data-jigconfig="destSelector: "#body-link-popper-B13", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">13</a>,<a id="__tag_112604793" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8392997" data-jigconfig="destSelector: "#body-link-popper-B14", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">14</a>), azithromycin inhibited the production of elastase (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/"><span>?<span class="figpopup-sensitive-area">(Fig.1B).<span>1</a>B). To determine the effect of azithromycin on rhamnolipid production, we used an azithromycin gradient incorporated into M9-based agar plates (<a class="cite-reflink bibr popnode jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/#B21" data-jigconfig="destSelector: "#body-link-popper-B21", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">21</a>). The production of rhamnolipids progressively decreased with increasing azithromycin concentrations without a parallel drop in growth (data not shown). To reveal a possible effect on<em>rhlAB</em>transcription, we measured β-galactosidase (β-Gal) activity (<a class="cite-reflink bibr popnode jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/#B12" data-jigconfig="destSelector: "#body-link-popper-B12", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">12</a>) using the<em>rhlA′-lacZ</em>reporter fusion pECP60 (<a id="__tag_112604777" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9150205" data-jigconfig="destSelector: "#body-link-popper-B18", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">18</a>). The expression of<em>rhlAB</em>was strongly inhibited by the macrolide (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/"><span>?<span class="figpopup-sensitive-area">(Fig.1C),<span>1</a>C), thus confirming the results from the plate assays. Interestingly, no inhibition of virulence factor production was observed when the antibiotic was omitted in the overnight preculture, suggesting that prolonged exposure to the antibiotic is required. Subsequently, we determined the effect of azithromycin on the expression of the two transcriptional activator genes,<em>lasR</em>and<em>rhlR</em>, using the reporter fusions pPCS1001(<em>lasR′-lacZ</em>) (<a id="__tag_112604773" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9150205" data-jigconfig="destSelector: "#body-link-popper-B18", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">18</a>) and pPCS1002(<em>rhlR′-lacZ</em>) (<a id="__tag_112604787" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9150205" data-jigconfig="destSelector: "#body-link-popper-B18", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">18</a>). Azithromycin reduced the expression of both reporter fusions (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/"><span>?<span class="figpopup-sensitive-area">(Fig.2A).<span>2</a>A). We further investigated whether the macrolide also affects the expression of the two autoinducer synthase genes,<em>lasI</em>and<em>rhlI</em>, by using the reporter fusions pPCS223(<em>lasI′-lacZ</em>) (<a id="__tag_112604792" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9712807" data-jigconfig="destSelector: "#body-link-popper-B28", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">28</a>) and pLPRI(<em>rhlI′-lacZ</em>) (<a id="__tag_112604768" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9712807" data-jigconfig="destSelector: "#body-link-popper-B28", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">28</a>). Azithromycin reduced the transcription of<em>lasI</em>by 80% and of<em>rhlI</em>by 50% (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/"><span>?<span class="figpopup-sensitive-area">(Fig.2B).<span>2</a>B). To ensure that this inhibition was effectively associated with a decreased production of the 3-oxo-C<sub>12</sub>-HSL and C<sub>4</sub>-HSL signaling molecules, we extracted these two autoinducers from bacterial supernatants and measured their respective concentrations using specific bioassays (<a id="__tag_112604779" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9294432" data-jigconfig="destSelector: "#body-link-popper-B17", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">17</a>,<a id="__tag_112604797" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/7836299" data-jigconfig="destSelector: "#body-link-popper-B20", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">20</a>). In the presence of the macrolide, the concentrations of 3-oxo-C<sub>12</sub>-HSL and C<sub>4</sub>-HSL were reduced by 94 and 72%, respectively (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F3/"><span>?<span class="figpopup-sensitive-area">(Fig.3A).<span>3</a>A). We also measured the effect of azithromycin on the expression of the<em>xcpR</em>gene, which codes for a structural protein belonging to the type II secretion pathway (<a id="__tag_112604798" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/7934833" data-jigconfig="destSelector: "#body-link-popper-B1", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">1</a>,<a id="__tag_112604776" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/1588814" data-jigconfig="destSelector: "#body-link-popper-B2", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">2</a>), by using the transcriptional reporter fusion pMPR(<em>xcpR′-lacZ</em>) (<a id="__tag_112604771" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9218766" data-jigconfig="destSelector: "#body-link-popper-B3", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">3</a>). The transcription of<em>xcpR</em>was not affected by azithromycin (2,741 ± 37 Miller units versus 2,760 ± 25 Miller units, respectively; mean of three experiments ± standard deviation [SD], measured at an optical density at 660 nm of 4.8). These results seem to be in contradiction with a previous report suggesting that<em>xcpR</em>transcription is positively regulated by the<em>las</em>system (<a id="__tag_112604765" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9218766" data-jigconfig="destSelector: "#body-link-popper-B3", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">3</a>). This apparent discrepancy could be explained by dissimilar experimental conditions and the use of different laboratory strains. Another explanation could be the compensation by other, already previously suspected (<a id="__tag_112604767" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9218766" data-jigconfig="destSelector: "#body-link-popper-B3", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">3</a>), regulatory pathways maintaining<em>xcpR</em>expression despite the inhibition of the<em>las</em>quorum-sensing system by azithromycin. Since the expression of both<em>lasR</em>and<em>rhlR</em>genes is dependent on the presence of adequate autoinducer levels, we measured their transcription in the presence of exogenous synthetic 3-oxo-C<sub>12</sub>-HSL and C<sub>4</sub>-HSL, each provided at concentrations of 10 μM. The addition of both autoinducers completely restored the expression of<em>rhlR</em>and almost completely restored the expression of<em>lasR</em>(5,500 ± 600 Miller units in the absence of azithromycin versus 4,600 ± 300 Miller units in the presence of azithromycin and exogenous autoinducers) (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/"><span>?<span class="figpopup-sensitive-area">(Fig.2A).<span>2</a>A). In contrast, the addition of exogenous autoinducers could not restore the expression of the<em>lasI</em>autoinducer synthase gene (20% of initial value in the presence of azithromycin and 16% in the presence of both azithromycin and exogenous autoinducers; data not shown). The addition of exogenous autoinducers also partially restored the production of elastase and almost completely restored the expression of<em>rhlAB</em>(Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F3/"><span>?<span class="figpopup-sensitive-area">(Fig.3B).<span>3</a>B). These results suggest that azithromycin might reduce the production of quorum-sensing-dependent virulence factors by inhibiting the synthesis of the autoinducer molecules.
<div id="F1" class="fig iconblock ten_col whole_rhythm clearfix"><a class="img_link icnblk_img figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/" target="figure"><img class="small-thumb" title="FIG. 1" src="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/bin/ac06108631ab.gif" alt="FIG. 1" /><img class="small-thumb" title="FIG. 1" src="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/bin/ac061086301c.gif" alt="FIG. 1" /></a>
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<h4><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/" target="figure">FIG. 1</a></h4>
<span>Effect of azithromycin on growth and elastase and rhamnolipid production. (A) Bacterial strains were grown in Luria-Bertani (LB) medium in the absence (squares) or in the presence (circles, 2 μg/ml; upside triangles, 3 μg/ml; downside<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/">(more ...)</a>
<div id="F2" class="fig iconblock ten_col whole_rhythm clearfix"><a class="img_link icnblk_img figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/" target="figure"><img class="small-thumb" title="FIG. 2" src="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/bin/ac0610863002.gif" alt="FIG. 2" /></a>
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<h4><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/" target="figure">FIG. 2</a></h4>
<span>Azithromycin affects transcription of quorum-sensing genes. The expression of the transcriptional activator and the autoinducer synthase genes was measured by β-Gal determinations in strain PAO1 cultures grown for 10 h in the absence (azithromycin<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/">(more ...)</a>
<div id="F3" class="fig iconblock ten_col whole_rhythm clearfix"><a class="img_link icnblk_img figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F3/" target="figure"><img class="small-thumb" title="FIG. 3" src="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/bin/ac0610863003.gif" alt="FIG. 3" /></a>
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<h4><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F3/" target="figure">FIG. 3</a></h4>
<span>Autoinducers are reduced in the presence of azithromycin and partially restore<em>rhlAB</em>expression and elastase production. (A) Strain PAO1 cultures were grown for 12 h in Luria-Bertanimedium, either in the absence (azithromycin &minus<img src="i/expressions/face-icon-small-wink.gif" border="0"> or presence (azithromycin<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F3/">(more ...)</a>
<p id="__p6">How does azithromycin interfere with the transcription of genes belonging to the quorum-sensing circuitry? The absence of a reduction of<em>xcpR</em>transcription suggests that, in our experimental conditions, azithromycin does not inhibit the transcription of genes in a nonspecific manner. Azithromycin inhibits protein synthesis at the ribosomal level, and therefore a direct effect on gene transcription seems unlikely. The necessity of a prolonged exposure to azithromycin suggests an indirect effect on the quorum-sensing circuitry. As the expression of<em>lasI</em>could not be complemented by exogenous autoinducers, we hypothesize that azithromycin might interfere with the translation of a so-far-unidentified protein important for the transcription of the autoinducer synthase. A reduced level of autoinducer could explain the observed effects on the quorum-sensing circuitry.
<p id="__p7">Chronic infections by<em>P. aeruginosa</em>lead to serious deterioration of lung function in DPB and CF patients. The recent reports showing improvement in DPB and CF patients treated with macrolides have been encouraging (<a id="__tag_112604786" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8553295" data-jigconfig="destSelector: "#body-link-popper-B5", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">5</a>,<a id="__tag_112604799" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9482305" data-jigconfig="destSelector: "#body-link-popper-B10", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">10</a>). Our data show a clear inhibition of the quorum-sensing circuitry of<em>P. aeruginosa</em>by azithromycin. Most of the quorum-sensing-regulated virulence factors cause tissue damage. Moreover, the 3-oxo-C<sub>12</sub>-HSL autoinducer has some immunomodulatory activity (<a id="__tag_112604782" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9423836" data-jigconfig="destSelector: "#body-link-popper-B26", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">26</a>) and stimulates the production of interleukin-8 by respiratory epithelial cells (<a id="__tag_112604766" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/7593606" data-jigconfig="destSelector: "#body-link-popper-B4", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">4</a>). Therefore, this autoinducer might itself be responsible for a chronic inflammatory response. Administration of macrolides to reduce autoinducer synthesis might therefore partially prevent the tissue damage.
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<p id="__p11">We gratefully acknowledge B. H. Iglewski for providing plasmids and synthetic autoinducers. This work was supported by a Pfizer grant (to K.T.), a research grant from the Programme Commun de Recherche en Genie Biomedical Geneve-Lausanne 1999–2002 (to C.V.D.), and research grants 3231-051940.97 and 3200-052189.97 from the Swiss National Research Foundation (to C.V.D.).
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<h1 class="content-title">Azithromycin Inhibits Quorum Sensing in<em>Pseudomonas aeruginosa</em></h1>
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<div class="contrib-group fm-author"><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20Tateda%2BK[auth]">Kazuhiro Tateda</a>,<sup>1</sup><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20Comte%2BR[auth]">Rachel Comte</a>,<sup>2</sup><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20Pechere%2BJC[auth]">Jean-Claude Pechere</a>,<sup>2</sup><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20K%26%23x000f6%3Bhler%2BT[auth]">Thilo Köhler</a>,<sup>2</sup><a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20Yamaguchi%2BK[auth]">Keizo Yamaguchi</a>,<sup>1</sup>and<a href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=PubMed&term=%20Van%20Delden%2BC[auth]">Christian Van Delden</a><sup>2,</sup><sup>*</sup>
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<h2 id="__abstractid4738360title" class="head no_bottom_margin ui-helper-clearfix">ABSTRACT</h2>
<p id="__p2">We report that 2 μg of azithromycin/ml inhibits the quorum-sensing circuitry of<em>Pseudomonas aeruginosa</em>strain PAO1. Addition of synthetic autoinducers partially restored the expression of the trancriptional activator-encoding genes<em>lasR</em>and<em>rhlR</em>but not that of the autoinducer synthase-encoding gene<em>lasI</em>. We propose that azithromycin interferes with the synthesis of autoinducers, by an unknown mechanism, leading to a reduction of virulence factor production.
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<p id="__p3"><em>Pseudomonas aeruginosa</em>is a major bacterial pathogen in patients suffering from cystic fibrosis (CF) or diffuse panbronchiolitis (DPB) (<a id="__tag_112604784" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8016786" data-jigconfig="destSelector: "#body-link-popper-B7", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">7</a>). Macrolides, such as azithromycin, are normally not included in the antipseudomonal therapeutic arsenal because of the absence of bactericidal or bacteriostatic activity. However, several studies have highlighted the benefit of long-term macrolide treatment in patients suffering from DPB or CF (<a id="__tag_112604781" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8553295" data-jigconfig="destSelector: "#body-link-popper-B5", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">5</a>,<a id="__tag_112604788" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9482305" data-jigconfig="destSelector: "#body-link-popper-B10", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">10</a>). The mechanisms by which macrolides affect the outcome of chronic infections with<em>P. aeruginosa</em>could include an anti-inflammatory activity and/or a modulation of the production of bacterial virulence factors (<a id="__tag_112604772" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9301978" data-jigconfig="destSelector: "#body-link-popper-B9", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">9</a>). Macrolides inhibit the production of bacterial exoproteases; however, whether this is independent of a decrease in bacterial growth and total protein production is controversial (<a id="__tag_112604783" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8203850" data-jigconfig="destSelector: "#body-link-popper-B13", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">13</a>,<a id="__tag_112604790" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8392997" data-jigconfig="destSelector: "#body-link-popper-B14", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">14</a>,<a id="__tag_112604794" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8214925" data-jigconfig="destSelector: "#body-link-popper-B19", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">19</a>,<a class="cite-reflink bibr popnode jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/#B24" data-jigconfig="destSelector: "#body-link-popper-B24", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">24</a>,<a id="__tag_112604774" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8891128" data-jigconfig="destSelector: "#body-link-popper-B25", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">25</a>).
<p id="__p4">In<em>P. aeruginosa</em>, the<em>las</em>and<em>rhl</em>quorum-sensing systems regulate the production of several extracellular virulence factors, including elastase and rhamnolipid (<a id="__tag_112604775" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9866731" data-jigconfig="destSelector: "#body-link-popper-B27", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">27</a>). Each system is composed of a gene encoding a transcriptional activator,<em>lasR</em>and<em>rhlR</em>, and a gene encoding an autoinducer synthase,<em>lasI</em>and<em>rhlI</em>, required for the synthesis of the autoinducer molecules 3-oxo-C<sub>12</sub>-homoserine lactone (3-oxo-C<sub>12</sub>-HSL) (<a id="__tag_112604780" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8278364" data-jigconfig="destSelector: "#body-link-popper-B15", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">15</a>) and C<sub>4</sub>-HSL (<a id="__tag_112604789" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/7878006" data-jigconfig="destSelector: "#body-link-popper-B16", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">16</a>), respectively. The importance of quorum sensing in the pathogenesis of chronic infections is unknown.<em>P. aeruginosa</em>isolates from CF patients produce autoinducers (<a id="__tag_112604791" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/10713433" data-jigconfig="destSelector: "#body-link-popper-B6", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">6</a>), and autoinducer production by CF sputum has been associated with<em>P. aeruginosa</em>biofilms (<a id="__tag_112604796" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/11048725" data-jigconfig="destSelector: "#body-link-popper-B22", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">22</a>). Autoinducers have also been found in lung tissue of mice infected with<em>P. aeruginosa</em>(<a id="__tag_112604778" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/11021924" data-jigconfig="destSelector: "#body-link-popper-B29", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">29</a>). A reduction of autoinducer production by 50 μg of erythromycin/ml has been suggested (<a id="__tag_112604795" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/10473921" data-jigconfig="destSelector: "#body-link-popper-B23", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">23</a>). However, the<em>Chromobacterium violaceum</em>bioassay used could only measure the C<sub>4</sub>-HSL autoinducer (<a id="__tag_112604800" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9421896" data-jigconfig="destSelector: "#body-link-popper-B11", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">11</a>).
<p id="__p5">We wondered whether azithromycin interferes with the quorum-sensing circuitry. To differentiate the inhibition of virulence factor production from a nonspecific effect, we optimized our experimental conditions so that at the onset of stationary phase, when quorum sensing is active, growth was not notably affected. Figure<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/"><span>?<span class="figpopup-sensitive-area">Figure1A<span>1</a>A shows growth curves of wild-type PAO1 (<a id="__tag_112604769" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/111024" data-jigconfig="destSelector: "#body-link-popper-B8", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">8</a>) in the presence of increasing concentrations of azithromycin. Exponential growth was slightly affected in the presence of 2 μg of azithromycin/ml, but no effect on the stationary growth phase was observed. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of total protein extracts of cells grown either in the absence or the presence of 2 μg of azithromycin/ml did not reveal major differences (data not shown). We next determined the effect of 2 μg of azithromycin/ml on elastase and rhamnolipid production in strain PAO1. Elastase production was monitored using elastin Congo red assays (<a id="__tag_112604785" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9294432" data-jigconfig="destSelector: "#body-link-popper-B17", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">17</a>). In accordance with previous reports (<a id="__tag_112604770" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8203850" data-jigconfig="destSelector: "#body-link-popper-B13", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">13</a>,<a id="__tag_112604793" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8392997" data-jigconfig="destSelector: "#body-link-popper-B14", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">14</a>), azithromycin inhibited the production of elastase (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/"><span>?<span class="figpopup-sensitive-area">(Fig.1B).<span>1</a>B). To determine the effect of azithromycin on rhamnolipid production, we used an azithromycin gradient incorporated into M9-based agar plates (<a class="cite-reflink bibr popnode jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/#B21" data-jigconfig="destSelector: "#body-link-popper-B21", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">21</a>). The production of rhamnolipids progressively decreased with increasing azithromycin concentrations without a parallel drop in growth (data not shown). To reveal a possible effect on<em>rhlAB</em>transcription, we measured β-galactosidase (β-Gal) activity (<a class="cite-reflink bibr popnode jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/#B12" data-jigconfig="destSelector: "#body-link-popper-B12", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">12</a>) using the<em>rhlA′-lacZ</em>reporter fusion pECP60 (<a id="__tag_112604777" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9150205" data-jigconfig="destSelector: "#body-link-popper-B18", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">18</a>). The expression of<em>rhlAB</em>was strongly inhibited by the macrolide (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/"><span>?<span class="figpopup-sensitive-area">(Fig.1C),<span>1</a>C), thus confirming the results from the plate assays. Interestingly, no inhibition of virulence factor production was observed when the antibiotic was omitted in the overnight preculture, suggesting that prolonged exposure to the antibiotic is required. Subsequently, we determined the effect of azithromycin on the expression of the two transcriptional activator genes,<em>lasR</em>and<em>rhlR</em>, using the reporter fusions pPCS1001(<em>lasR′-lacZ</em>) (<a id="__tag_112604773" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9150205" data-jigconfig="destSelector: "#body-link-popper-B18", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">18</a>) and pPCS1002(<em>rhlR′-lacZ</em>) (<a id="__tag_112604787" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9150205" data-jigconfig="destSelector: "#body-link-popper-B18", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">18</a>). Azithromycin reduced the expression of both reporter fusions (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/"><span>?<span class="figpopup-sensitive-area">(Fig.2A).<span>2</a>A). We further investigated whether the macrolide also affects the expression of the two autoinducer synthase genes,<em>lasI</em>and<em>rhlI</em>, by using the reporter fusions pPCS223(<em>lasI′-lacZ</em>) (<a id="__tag_112604792" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9712807" data-jigconfig="destSelector: "#body-link-popper-B28", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">28</a>) and pLPRI(<em>rhlI′-lacZ</em>) (<a id="__tag_112604768" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9712807" data-jigconfig="destSelector: "#body-link-popper-B28", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">28</a>). Azithromycin reduced the transcription of<em>lasI</em>by 80% and of<em>rhlI</em>by 50% (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/"><span>?<span class="figpopup-sensitive-area">(Fig.2B).<span>2</a>B). To ensure that this inhibition was effectively associated with a decreased production of the 3-oxo-C<sub>12</sub>-HSL and C<sub>4</sub>-HSL signaling molecules, we extracted these two autoinducers from bacterial supernatants and measured their respective concentrations using specific bioassays (<a id="__tag_112604779" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9294432" data-jigconfig="destSelector: "#body-link-popper-B17", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">17</a>,<a id="__tag_112604797" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/7836299" data-jigconfig="destSelector: "#body-link-popper-B20", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">20</a>). In the presence of the macrolide, the concentrations of 3-oxo-C<sub>12</sub>-HSL and C<sub>4</sub>-HSL were reduced by 94 and 72%, respectively (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F3/"><span>?<span class="figpopup-sensitive-area">(Fig.3A).<span>3</a>A). We also measured the effect of azithromycin on the expression of the<em>xcpR</em>gene, which codes for a structural protein belonging to the type II secretion pathway (<a id="__tag_112604798" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/7934833" data-jigconfig="destSelector: "#body-link-popper-B1", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">1</a>,<a id="__tag_112604776" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/1588814" data-jigconfig="destSelector: "#body-link-popper-B2", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">2</a>), by using the transcriptional reporter fusion pMPR(<em>xcpR′-lacZ</em>) (<a id="__tag_112604771" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9218766" data-jigconfig="destSelector: "#body-link-popper-B3", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">3</a>). The transcription of<em>xcpR</em>was not affected by azithromycin (2,741 ± 37 Miller units versus 2,760 ± 25 Miller units, respectively; mean of three experiments ± standard deviation [SD], measured at an optical density at 660 nm of 4.8). These results seem to be in contradiction with a previous report suggesting that<em>xcpR</em>transcription is positively regulated by the<em>las</em>system (<a id="__tag_112604765" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9218766" data-jigconfig="destSelector: "#body-link-popper-B3", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">3</a>). This apparent discrepancy could be explained by dissimilar experimental conditions and the use of different laboratory strains. Another explanation could be the compensation by other, already previously suspected (<a id="__tag_112604767" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9218766" data-jigconfig="destSelector: "#body-link-popper-B3", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">3</a>), regulatory pathways maintaining<em>xcpR</em>expression despite the inhibition of the<em>las</em>quorum-sensing system by azithromycin. Since the expression of both<em>lasR</em>and<em>rhlR</em>genes is dependent on the presence of adequate autoinducer levels, we measured their transcription in the presence of exogenous synthetic 3-oxo-C<sub>12</sub>-HSL and C<sub>4</sub>-HSL, each provided at concentrations of 10 μM. The addition of both autoinducers completely restored the expression of<em>rhlR</em>and almost completely restored the expression of<em>lasR</em>(5,500 ± 600 Miller units in the absence of azithromycin versus 4,600 ± 300 Miller units in the presence of azithromycin and exogenous autoinducers) (Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/"><span>?<span class="figpopup-sensitive-area">(Fig.2A).<span>2</a>A). In contrast, the addition of exogenous autoinducers could not restore the expression of the<em>lasI</em>autoinducer synthase gene (20% of initial value in the presence of azithromycin and 16% in the presence of both azithromycin and exogenous autoinducers; data not shown). The addition of exogenous autoinducers also partially restored the production of elastase and almost completely restored the expression of<em>rhlAB</em>(Fig.<a class="fig-table-link fig figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F3/"><span>?<span class="figpopup-sensitive-area">(Fig.3B).<span>3</a>B). These results suggest that azithromycin might reduce the production of quorum-sensing-dependent virulence factors by inhibiting the synthesis of the autoinducer molecules.
<div id="F1" class="fig iconblock ten_col whole_rhythm clearfix"><a class="img_link icnblk_img figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/" target="figure"><img class="small-thumb" title="FIG. 1" src="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/bin/ac06108631ab.gif" alt="FIG. 1" /><img class="small-thumb" title="FIG. 1" src="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/bin/ac061086301c.gif" alt="FIG. 1" /></a>
<div class="icnblk_cntnt">
<h4><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/" target="figure">FIG. 1</a></h4>
<span>Effect of azithromycin on growth and elastase and rhamnolipid production. (A) Bacterial strains were grown in Luria-Bertani (LB) medium in the absence (squares) or in the presence (circles, 2 μg/ml; upside triangles, 3 μg/ml; downside<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F1/">(more ...)</a>
<div id="F2" class="fig iconblock ten_col whole_rhythm clearfix"><a class="img_link icnblk_img figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/" target="figure"><img class="small-thumb" title="FIG. 2" src="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/bin/ac0610863002.gif" alt="FIG. 2" /></a>
<div class="icnblk_cntnt">
<h4><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/" target="figure">FIG. 2</a></h4>
<span>Azithromycin affects transcription of quorum-sensing genes. The expression of the transcriptional activator and the autoinducer synthase genes was measured by β-Gal determinations in strain PAO1 cultures grown for 10 h in the absence (azithromycin<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F2/">(more ...)</a>
<div id="F3" class="fig iconblock ten_col whole_rhythm clearfix"><a class="img_link icnblk_img figpopup" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F3/" target="figure"><img class="small-thumb" title="FIG. 3" src="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/bin/ac0610863003.gif" alt="FIG. 3" /></a>
<div class="icnblk_cntnt">
<h4><a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F3/" target="figure">FIG. 3</a></h4>
<span>Autoinducers are reduced in the presence of azithromycin and partially restore<em>rhlAB</em>expression and elastase production. (A) Strain PAO1 cultures were grown for 12 h in Luria-Bertanimedium, either in the absence (azithromycin &minus<img src="i/expressions/face-icon-small-wink.gif" border="0"> or presence (azithromycin<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/figure/F3/">(more ...)</a>
<p id="__p6">How does azithromycin interfere with the transcription of genes belonging to the quorum-sensing circuitry? The absence of a reduction of<em>xcpR</em>transcription suggests that, in our experimental conditions, azithromycin does not inhibit the transcription of genes in a nonspecific manner. Azithromycin inhibits protein synthesis at the ribosomal level, and therefore a direct effect on gene transcription seems unlikely. The necessity of a prolonged exposure to azithromycin suggests an indirect effect on the quorum-sensing circuitry. As the expression of<em>lasI</em>could not be complemented by exogenous autoinducers, we hypothesize that azithromycin might interfere with the translation of a so-far-unidentified protein important for the transcription of the autoinducer synthase. A reduced level of autoinducer could explain the observed effects on the quorum-sensing circuitry.
<p id="__p7">Chronic infections by<em>P. aeruginosa</em>lead to serious deterioration of lung function in DPB and CF patients. The recent reports showing improvement in DPB and CF patients treated with macrolides have been encouraging (<a id="__tag_112604786" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/8553295" data-jigconfig="destSelector: "#body-link-popper-B5", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">5</a>,<a id="__tag_112604799" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9482305" data-jigconfig="destSelector: "#body-link-popper-B10", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">10</a>). Our data show a clear inhibition of the quorum-sensing circuitry of<em>P. aeruginosa</em>by azithromycin. Most of the quorum-sensing-regulated virulence factors cause tissue damage. Moreover, the 3-oxo-C<sub>12</sub>-HSL autoinducer has some immunomodulatory activity (<a id="__tag_112604782" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/9423836" data-jigconfig="destSelector: "#body-link-popper-B26", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">26</a>) and stimulates the production of interleukin-8 by respiratory epithelial cells (<a id="__tag_112604766" class="cite-reflink bibr popnode tag_hotlink tag_tooltip jig-ncbipopper" href="http://www.ncbi.nlm.nih.gov/pubmed/7593606" data-jigconfig="destSelector: "#body-link-popper-B4", isTriggerElementCloseClick: false, hasArrow: true, width: "30em", adjustFit: "autoAdjust", triggerPosition: "center right"">4</a>). Therefore, this autoinducer might itself be responsible for a chronic inflammatory response. Administration of macrolides to reduce autoinducer synthesis might therefore partially prevent the tissue damage.
<div id="__ackid4740826" class="sec">
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<h2 id="__ackid4740826title" class="head no_bottom_margin ui-helper-clearfix">ACKNOWLEDGMENTS</h2>
<div class="sec">
<p id="__p11">We gratefully acknowledge B. H. Iglewski for providing plasmids and synthetic autoinducers. This work was supported by a Pfizer grant (to K.T.), a research grant from the Programme Commun de Recherche en Genie Biomedical Geneve-Lausanne 1999–2002 (to C.V.D.), and research grants 3231-051940.97 and 3200-052189.97 from the Swiss National Research Foundation (to C.V.D.).
<a href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90577/"></a>
Incomudrox
New member
<div class="FTQUOTE"><begin quote><em>Originally posted by: <strong>musclemania70</strong></em> I heard that it was used as an anti-inflammatory agent in CF patients. ?</end quote>
Yes and this is what the CFF categorizes it under on their site. Reason being is its easier to understand anti-inflammitory than the concept and mechanisms behind quorum sensing. The anti-inflammitory effect is sometimes a result in our case of quorum sensing. When the bacteria are blind they can't cause as much trouble thus inflammation is reduced. Azithroycin also encourages air-way epithelial cell apoptosis and is key in formation of new airway epithelium.
<a href="http://www.ncbi.nlm.nih.gov/pubmed/16737992">http://www.ncbi.nlm.nih.gov/pubmed/16737992</a>
<h1>Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages.</h1>
<div class="auths"><a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Hodge%20S%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Hodge S</a>,<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Hodge%20G%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Hodge G</a>,<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Brozyna%20S%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Brozyna S</a>,<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Jersmann%20H%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Jersmann H</a>,<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Holmes%20M%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Holmes M</a>,<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Reynolds%20PN%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Reynolds PN</a>.
<div class="aff">
<h3 class="label">Source</h3>
Dept of Thoracic Medicine, Royal Adelaide Hospital and Lung Research Laboratory, Hanson Institute, Adelaide, Australia. sandy.hodge@imvs.sa.gov.au
<div class="abstr">
<h3>Abstract</h3>
Chronic obstructive pulmonary disease (COPD) is associated with increased apoptosis and defective phagocytosis in the airway. As uncleared cells can undergo secondary necrosis and perpetuate inflammation, strategies to improve clearance would have therapeutic significance. There is evidence that the 15-member macrolide antibiotic azithromycin has anti-inflammatory properties. Its effects may be increased in the lung due to its ability to reach high concentrations in alveolar macrophages (AMs). The present study investigated the effects of low-dose (500 ng x mL(-1)) azithromycin on the phagocytosis of apoptotic bronchial epithelial cells and neutrophils by AMs. Flow cytometry was applied to measure phagocytosis and receptors involved in AM recognition of apoptotic cells. Cytokines were investigated using cytometric bead array. Baseline phagocytosis was reduced in COPD subjects compared with controls. Azithromycin significantly improved the phagocytosis of epithelial cells or neutrophils by AMs from COPD subjects by 68 and 38%, respectively, often up to levels comparable with controls. The increase in phagocytosis was partially inhibited by phosphatidylserine, implicating the phosphatidylserine pathway in the pro-phagocytic effects of azithromycin. Azithromycin had no effect on other recognition molecules (granulocyte-macrophage colony-stimulating factor, CD44, CD31, CD36, CD91, alphavbeta3 integrin). At higher doses, azithromycin decreased levels of pro-inflammatory cytokines. Thus, low-dose azithromycin therapy could provide an adjunct therapeutic option in chronic obstructive pulmonary disease.
Yes and this is what the CFF categorizes it under on their site. Reason being is its easier to understand anti-inflammitory than the concept and mechanisms behind quorum sensing. The anti-inflammitory effect is sometimes a result in our case of quorum sensing. When the bacteria are blind they can't cause as much trouble thus inflammation is reduced. Azithroycin also encourages air-way epithelial cell apoptosis and is key in formation of new airway epithelium.
<a href="http://www.ncbi.nlm.nih.gov/pubmed/16737992">http://www.ncbi.nlm.nih.gov/pubmed/16737992</a>
<h1>Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages.</h1>
<div class="auths"><a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Hodge%20S%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Hodge S</a>,<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Hodge%20G%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Hodge G</a>,<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Brozyna%20S%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Brozyna S</a>,<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Jersmann%20H%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Jersmann H</a>,<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Holmes%20M%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Holmes M</a>,<a href="http://www.ncbi.nlm.nih.gov/pubmed?term=Reynolds%20PN%5BAuthor%5D&cauthor=true&cauthor_uid=16737992">Reynolds PN</a>.
<div class="aff">
<h3 class="label">Source</h3>
Dept of Thoracic Medicine, Royal Adelaide Hospital and Lung Research Laboratory, Hanson Institute, Adelaide, Australia. sandy.hodge@imvs.sa.gov.au
<div class="abstr">
<h3>Abstract</h3>
Chronic obstructive pulmonary disease (COPD) is associated with increased apoptosis and defective phagocytosis in the airway. As uncleared cells can undergo secondary necrosis and perpetuate inflammation, strategies to improve clearance would have therapeutic significance. There is evidence that the 15-member macrolide antibiotic azithromycin has anti-inflammatory properties. Its effects may be increased in the lung due to its ability to reach high concentrations in alveolar macrophages (AMs). The present study investigated the effects of low-dose (500 ng x mL(-1)) azithromycin on the phagocytosis of apoptotic bronchial epithelial cells and neutrophils by AMs. Flow cytometry was applied to measure phagocytosis and receptors involved in AM recognition of apoptotic cells. Cytokines were investigated using cytometric bead array. Baseline phagocytosis was reduced in COPD subjects compared with controls. Azithromycin significantly improved the phagocytosis of epithelial cells or neutrophils by AMs from COPD subjects by 68 and 38%, respectively, often up to levels comparable with controls. The increase in phagocytosis was partially inhibited by phosphatidylserine, implicating the phosphatidylserine pathway in the pro-phagocytic effects of azithromycin. Azithromycin had no effect on other recognition molecules (granulocyte-macrophage colony-stimulating factor, CD44, CD31, CD36, CD91, alphavbeta3 integrin). At higher doses, azithromycin decreased levels of pro-inflammatory cytokines. Thus, low-dose azithromycin therapy could provide an adjunct therapeutic option in chronic obstructive pulmonary disease.
Incomudrox
New member
It is something you need to talk to your doctor about and weigh the pros and cons.
A
alegris
Guest
Carly23:
I would keep taking it even though you're not seeing an increase in lung function. I've been on it for maybe a little more than a year and while I haven't noticed an increase in FEV1, it has made a positive difference in my health overall.
First of all, it takes away my cough. Almost completely (unless I'm doing treatments) which is amazing. Even my co-workers have commented on it asking why I don't cough anymore.
I find it makes it easier to maintain my lung function and not be such a disaster if I skip a treatment. I used to neb hypertonic saline once a day but now due to reduced mucus production I've decreased that to every second day. I was finding that doing it every day I wasn't coughing anything up and the saline was irritating my lungs.
I also have asthma and I find it has helped reduce my wheezing. I'm not sure if that's from the reduced mucus production or reduced coughing overall?
It has helped reduce my sinus headaches to a bearable level. I still get them but not nearly so severe.
And all of these things combined have helped my overall morale and energy levels. It's shocking how quickly all the little things add up. So while azithromycin probably won't drastically affect your lung function, it might make it easier to maintain your health and improve how you're feeling.
I would keep taking it even though you're not seeing an increase in lung function. I've been on it for maybe a little more than a year and while I haven't noticed an increase in FEV1, it has made a positive difference in my health overall.
First of all, it takes away my cough. Almost completely (unless I'm doing treatments) which is amazing. Even my co-workers have commented on it asking why I don't cough anymore.
I find it makes it easier to maintain my lung function and not be such a disaster if I skip a treatment. I used to neb hypertonic saline once a day but now due to reduced mucus production I've decreased that to every second day. I was finding that doing it every day I wasn't coughing anything up and the saline was irritating my lungs.
I also have asthma and I find it has helped reduce my wheezing. I'm not sure if that's from the reduced mucus production or reduced coughing overall?
It has helped reduce my sinus headaches to a bearable level. I still get them but not nearly so severe.
And all of these things combined have helped my overall morale and energy levels. It's shocking how quickly all the little things add up. So while azithromycin probably won't drastically affect your lung function, it might make it easier to maintain your health and improve how you're feeling.
I've been taking it for a few months now and it has had a possitive effect on me. Unlike most though I don't take any antibiotics on a regular basis. Dr had to convince me that bacteria couldn't build up a resistance in order to get me to take it. I also take Mucinex and Ibuprofen as a way to reduce inflamation and clear out my lungs. Those 3 things, along w/ Vest, Pulmozyme, and 7%HTS have made a gradual improvement at least in how I feel.
I took it for a few years but I've stopped because I haven't noticed any positive effect from it. Also, my doctor constantly tells me taking antibiotics for an extended period is bad, but it's not bad with zithro because I take it for inflammation. Well, I know that, and the doctor knows that, but does my body know that? For instance, if you eat products with high fructose corn syrup everyday, regardless of why you eat it, it's still taxing on your body. And I'd rather not constantly put a drug in my body that has no noticeable effect, neither in the way I feel or on PFTs.