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<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
</div>
<div class="form-field recaptcha ">
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
</div>
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="send">
Send email
</button>
<button class="action-panel-cancel"
aria-label="Close 'Email citations' panel"
ref="linksrc=close_email_panel"
aria-controls="email-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="email"
data-ga-label="cancel">
Cancel
</button>
</div>
<input type="hidden" name="email-search-details" value="" />
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
</form>
</div>
</div>
<div id="collections-action-panel"
class="collections-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-collections-open-panel-enabled="false"
data-collections-open-panel-url-hash="#open-collections-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to Collections
</h3>
<form id="collections-action-panel-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-myncbi-max-collection-name-length="100"
data-add-to-collection-max-amount="1000"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
<input type="hidden" name="csrfmiddlewaretoken" value="4H9KC8KydrAG2QR3R2MV1jjvCHSmxM0vluTPfYdUN2naWhXTulpXvrP9aLAyqnyP">
<div class="choice-group" role="radiogroup">
<ul class="radio-group-items">
<li>
<input type="radio"
id="collections-action-panel-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_new">
<label for="collections-action-panel-new">Create a new collection</label>
</li>
<li>
<input type="radio"
id="collections-action-panel-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="collections_radio_existing">
<label for="collections-action-panel-existing">Add to an existing collection</label>
</li>
</ul>
</div>
<div class="controls-wrapper">
<div class="action-panel-control-wrap new-collections-controls">
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label>
<input
type="text"
name="add-to-new-collection"
id="collections-action-panel-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="save_share"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection">
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div>
</div>
<div class="action-panel-control-wrap existing-collections-controls">
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
Choose a collection:
</label>
<select id="collections-action-panel-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="save_share"
data-ga-action="select_collection"
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
</select>
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br>
<a href="#">Please try again</a>
</div>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="add">
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to Collections' panel"
ref="linksrc=close_collections_panel"
aria-controls="collections-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="collections"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="bibliography-action-panel"
class="bibliography-action-panel action-panel in-progress-dots-panel"
aria-hidden="true"
data-bibliography-open-panel-enabled="false"
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
<div class="inner-wrap">
<h3 class="action-panel-heading">
Add to My Bibliography
</h3>
<form id="bibliography-action-panel-form"
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-add-to-bibliography-max-amount="100"
data-add-to-bibliography-batch-size="10"
data-bibliography-delegates-url="/list-bibliography-delegates/"
data-add-to-bibliography-url="/add-to-bibliography/"
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
<input type="hidden" name="csrfmiddlewaretoken" value="4H9KC8KydrAG2QR3R2MV1jjvCHSmxM0vluTPfYdUN2naWhXTulpXvrP9aLAyqnyP">
<div class="action-panel-control-wrap bibliographies-controls">
<div class="choice-group">
<ul class="bibliographies-action-add radio-group-items">
<li>
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
<label for="my-bibliography">My Bibliography</label>
</li>
</ul>
</div>
</div>
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your delegates due to an error<br>
<a href="#">Please try again</a>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
data-pinger-ignore>
Add
</button>
<button class="action-panel-cancel"
aria-label="Close 'Add to bibliography' panel"
ref="linksrc=close_bibliography_panel"
aria-controls="bibliography-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="mybib"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
data-saved-search-open-panel-enabled="false"
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your saved search
</h2>
<form id="saved-search-action-panel-form"
class="saved-search-action-panel-form action-panel-content action-form"
data-create-saved-search-url="/create-saved-search/"
data-try-search-terms-url="/try-search-term/"
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
<input type="hidden" name="csrfmiddlewaretoken" value="4H9KC8KydrAG2QR3R2MV1jjvCHSmxM0vluTPfYdUN2naWhXTulpXvrP9aLAyqnyP">
<div class="action-panel-control-wrap">
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
Name of saved search:
</label>
<input maxlength="200"
type="text"
name="saved-search-name"
id="saved-search-name"
class="saved-search-name"
value=""
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
Search terms:
</label>
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
</div>
<div class="test-search-term-wrap">
<a href="#" class="try-search-term">Test search terms</a>
</div>
<div class="choice-group action-panel-extra-margin-top">
<span class="action-panel-label" id="fieldset-label">
Would you like email updates of new search results?
</span>
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
<ul class="radio-group-items">
<li>
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
</li>
<li>
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
<label for="saved-search-alert-no" class="action-panel-label">No</label>
</li>
</ul>
</fieldset>
</div>
<div class="alert-schedule-wrap">
<div class="action-panel-control-wrap">
<label class="action-panel-label">
Email:
</label>
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
</div>
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="saved-search-frequency" class="action-panel-label">
Frequency:
</label>
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
<option value="monthly">Monthly</option>
<option value="weekly">Weekly</option>
<option value="daily">Daily</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-monthly-additional">
<label for="saved-search-monthly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
<option value="Sunday">The first Sunday</option>
<option value="Monday">The first Monday</option>
<option value="Tuesday">The first Tuesday</option>
<option value="Wednesday">The first Wednesday</option>
<option value="Thursday">The first Thursday</option>
<option value="Friday">The first Friday</option>
<option value="Saturday">The first Saturday</option>
<option value="day">The first day</option>
<option value="weekday">The first weekday</option>
</select>
</div>
<div class="action-panel-control-wrap saved-search-weekly-additional">
<label for="saved-search-weekly-on-day" class="action-panel-label">
Which day?
</label>
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
<option value="Sunday">Sunday</option>
<option value="Monday">Monday</option>
<option value="Tuesday">Tuesday</option>
<option value="Wednesday">Wednesday</option>
<option value="Thursday">Thursday</option>
<option value="Friday">Friday</option>
<option value="Saturday">Saturday</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-report" class="action-panel-label">
Report format:
</label>
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
<option value="DocSum">Summary</option>
<option value="DocSumText">Summary (text)</option>
<option value="Abstract">Abstract</option>
<option value="AbstractText">Abstract (text)</option>
<option value="MEDLINE">PubMed</option>
</select>
</div>
<div class="action-panel-control-wrap">
<label for="saved-search-amount" class="action-panel-label">
Send at most:
</label>
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
<option value="1">1 item</option>
<option value="5" selected>5 items</option>
<option value="10">10 items</option>
<option value="20">20 items</option>
<option value="50">50 items</option>
<option value="100">100 items</option>
<option value="200">200 items</option>
</select>
</div>
<div>
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
Send even when there aren't any new results
</label>
</div>
<div class="action-panel-control-wrap option-text-in-email-wrap">
<label for="saved-search-email-text" class="action-panel-label">
Optional text in email:
</label>
<textarea name="saved-search-email-text"
id="saved-search-email-text"
class="saved-search-email-text"></textarea>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Saving..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Save
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your saved search' panel"
ref="linksrc=close_saved_search_panel"
aria-controls="saved-search-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Create a file for external citation management software
</h2>
<form id="citation-manager-action-panel-form"
class="action-panel-content action-form"
action="/results-export-ids/"
data-by-search-action="/results-export-search-data/"
data-by-ids-action="/results-export-ids/"
method="post"
data-by-search-method="post"
data-by-ids-method="post">
<input type="hidden" name="csrfmiddlewaretoken" value="4H9KC8KydrAG2QR3R2MV1jjvCHSmxM0vluTPfYdUN2naWhXTulpXvrP9aLAyqnyP">
<input name="results-format" type="hidden" value="pubmed"/>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Sending..."
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="save">
Create file
</button>
<button class="action-panel-cancel"
aria-label="Close 'Send citations to citation manager' panel"
ref="linksrc=close_citation_manager_panel"
aria-controls="citation-manager-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="citation_manager"
data-ga-label="cancel">
Cancel
</button>
</div>
</form>
</div>
</div>
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
<div class="inner-wrap">
<h2 class="action-panel-heading">
Your RSS Feed
</h2>
<form id="rss-action-panel-form"
class="rss-action-panel-form action-panel-content action-form"
data-create-rss-feed-url="/create-rss-feed-url/"
data-search-form-term-value="">
<input type="hidden" name="csrfmiddlewaretoken" value="4H9KC8KydrAG2QR3R2MV1jjvCHSmxM0vluTPfYdUN2naWhXTulpXvrP9aLAyqnyP">
<div class="action-panel-control-wrap">
<label for="rss-name" class="action-panel-label required-field-asterisk">
Name of RSS Feed:
</label>
<input maxlength="200"
placeholder="Name"
type="text"
name="rss-name"
id="rss-name"
class="rss-name"
value=''
required
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/">
</div>
<div class="rss-limit-wrap">
<div class="action-panel-control-wrap action-panel-extra-margin-top">
<label for="rss-limit" class="action-panel-label">
Number of items displayed:
</label>
<select id="rss-limit" class="no-border-panel-selector rss-limit">
<option value="5">5</option>
<option value="10">10</option>
<option value="15" selected="selected">15</option>
<option value="20">20</option>
<option value="50">50</option>
<option value="100">100</option>
</select>
</div>
</div>
<div class="action-panel-actions">
<button class="action-panel-submit"
type="submit"
data-loading-label="Creating..."
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="save">
Create RSS
</button>
<button class="action-panel-cancel"
aria-label="Close 'Your RSS' panel"
ref="linksrc=close_rss_panel"
aria-controls="rss-action-panel"
aria-expanded="false"
data-ga-category="save_share"
data-ga-action="alert"
data-ga-label="cancel">
Cancel
</button>
</div>
<div class="action-panel-control-wrap rss-link-copy-wrap">
<label for="rss-link" class="usa-sr-only">RSS Link</label>
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
<button
type="button"
disabled
class="rss-link-copy-button disabled"
data-ga-category="save_share"
data-ga-action="rss"
data-ga-label="copy">
Copy
</button>
</div>
</form>
</div>
</div>
</div>
</div>
<div class="article-page" id="article-page" data-article-pmid="38023412">
<aside class="page-sidebar">
<div class="inner-wrap">
<div class="full-text-links">
<div class="full-view">
<h3 class="title">
Full text links
</h3>
<div class="full-text-links-list">
<a class="link-item
dialog-focus"
href="https://dx.doi.org/10.2147/IDR.S427232"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=False&amp;PrId=7093&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=38023412&amp;db=pubmed&amp;nlmid=101550216"
title="See full text options at Dove Medical Press"
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data-ga-action="Dove Medical Press"
data-ga-label="38023412"
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.dovepress.com-img-dpfree.png" alt="Dove Medical Press full text link"><span class="text">
Dove Medical Press
</span></a><a class="link-item
pmc
"
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/38023412/"
target="_blank"
rel="noopener"
ref="linksrc=fulltextorjournal_fulltext&amp;is_pmc=True&amp;PrId=3494&amp;itool=Abstract-def&amp;log$=linkouticon&amp;uid=38023412&amp;db=pubmed&amp;nlmid=101550216"
title="Free full text at PubMed Central"
data-ga-category="full_text"
data-ga-action="PMC"
data-ga-label="38023412"
><span class="text">
Free PMC article
</span></a>
</div>
</div>
<div class="short-view">
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
Full text links
</a>
</div>
</div>
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
aria-label="Open dialog with citation text in different styles"
data-ga-category="save_share"
data-ga-action="cite"
data-ga-label="open"
data-all-citations-url="/38023412/citations/"
data-citation-style="nlm"
data-pubmed-format-link="/38023412/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="38023412" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
aria-label="Save article in MyNCBI collections."
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_button"
data-collections-open-dialog-enabled="false"
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F38023412%2F%23open-collections-dialog"
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
class="dialog collections-dialog"
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
data-existing-collections-url="/list-existing-collections/"
data-add-to-existing-collection-url="/add-to-existing-collection/"
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
data-myncbi-max-collection-name-length="100"
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="4H9KC8KydrAG2QR3R2MV1jjvCHSmxM0vluTPfYdUN2naWhXTulpXvrP9aLAyqnyP"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
id="collections-action-dialog-new"
class="collections-new"
name="collections"
value="new"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
id="collections-action-dialog-existing"
class="collections-existing"
name="collections"
value="existing"
checked="true"
data-ga-category="collections_button"
data-ga-action="click"
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
Name your collection:
</label><input
type="text"
name="add-to-new-collection"
id="collections-action-dialog-add-to-new"
class="collections-action-add-to-new"
pattern="[^&quot;&amp;=&lt;&gt;\/]*" title="The following characters are not allowed in the Name field: &quot;&amp;=&lt;&gt;/"
maxlength="100"
data-ga-category="collections_button"
data-ga-action="create_collection"
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
Name must be less than 100 characters
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
Choose a collection:
</label><select id="collections-action-dialog-add-to-existing"
class="action-panel-selector collections-action-add-to-existing"
data-ga-category="collections_button"
data-ga-action="select_collection"
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
type="submit"
data-loading-label="Adding..."
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Combination of AS101 and Mefloquine Inhibits Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> in vitro and in vivo
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Combination of AS101 and Mefloquine Inhibits Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> in vitro and in vivo
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data-ga-label="Hao Tang">Hao Tang</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, People&#x27;s Republic of China." href="#short-view-affiliation-5" ref="linksrc=author_aff">
5
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6
</a></sup><span class="comma">,&nbsp;</span></span><span class="authors-list-item "><a class="full-name"
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1
</a><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Anhui Public Health Clinical Center, Hefei, People&#x27;s Republic of China." href="#short-view-affiliation-7" ref="linksrc=author_aff">
7
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data-ga-label="Yuanhong Xu">Yuanhong Xu</a><sup class="affiliation-links"><span class="author-sup-separator">&nbsp;</span><a class="affiliation-link" title="Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, People&#x27;s Republic of China." href="#short-view-affiliation-1" ref="linksrc=author_aff">
1
</a></sup></span>
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<div class="affiliations">
<h3 class="title">
Affiliations
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<li data-affiliation-id="short-view-affiliation-1"
id="short-view-affiliation-1"
><sup class="key">1</sup> Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, People&#x27;s Republic of China.</li>
<li data-affiliation-id="short-view-affiliation-2"
id="short-view-affiliation-2"
><sup class="key">2</sup> Provincial Laboratories of Pathogen Biology and Zoonoses, Anhui Medical University, Hefei, People&#x27;s Republic of China.</li>
<li data-affiliation-id="short-view-affiliation-3"
id="short-view-affiliation-3"
><sup class="key">3</sup> Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, People&#x27;s Republic of China.</li>
<li data-affiliation-id="short-view-affiliation-4"
id="short-view-affiliation-4"
><sup class="key">4</sup> Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, People&#x27;s Republic of China.</li>
<li data-affiliation-id="short-view-affiliation-5"
id="short-view-affiliation-5"
><sup class="key">5</sup> Department of Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, People&#x27;s Republic of China.</li>
<li data-affiliation-id="short-view-affiliation-6"
id="short-view-affiliation-6"
><sup class="key">6</sup> Department of Clinical Laboratory, the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, People&#x27;s Republic of China.</li>
<li data-affiliation-id="short-view-affiliation-7"
id="short-view-affiliation-7"
><sup class="key">7</sup> Anhui Public Health Clinical Center, Hefei, People&#x27;s Republic of China.</li>
</ul>
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<h2 class="title">
Abstract
</h2>
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id="eng-abstract">
<p>
<strong class="sub-title">
Background:
</strong>
In recent years, carbapenem-resistant <i>Pseudomonas aeruginosa</i> (CRPA) has spread around the world, leading to a high mortality and close attention of medical community. In this study, we aim to find a new strategy of treatment for CRPA infections.
</p>
<p>
<strong class="sub-title">
Methods:
</strong>
Eight strains of CRPA were collected, and PCR detected the multi-locus sequence typing (MLST). The antimicrobial susceptibility test was conducted using the VITEK@2 compact system. The minimum inhibitory concentration (MIC) for AS101 and mefloquine was determined using the broth dilution method. Antibacterial activity was tested in vitro and in vivo through the chessboard assay, time killing assay, and a mouse model. The mechanism of AS101 combined with mefloquine against CRPA was assessed through the biofilm formation inhibition assay, electron microscopy, and detection of reactive oxygen species (ROS).
</p>
<p>
<strong class="sub-title">
Results:
</strong>
The results demonstrated that all tested CRPA strains exhibited multidrug resistance. Moreover, our investigation revealed a substantial synergistic antibacterial effect of AS101-mefloquine in vitro. The assay for inhibiting biofilm formation indicated that AS101-mefloquine effectively suppressed the biofilm formation of CRPA-5 and CRPA-6. Furthermore, AS101-mefloquine were observed to disrupt the bacterial cell wall and enhance the permeability of the cell membrane. This effect was achieved by stimulating the production of ROS, which in turn hindered the growth of CRPA-3. To evaluate the therapeutic potential, a murine model of CRPA-3 peritoneal infection was established. Notably, AS101-mefloquine administration resulted in a significant reduction in bacterial load within the liver, kidney, and spleen of mice after 72 hours of treatment.
</p>
<p>
<strong class="sub-title">
Conclusion:
</strong>
The present study showed that the combination of AS101 and mefloquine yielded a notable synergistic bacteriostatic effect both in vitro and in vivo, suggesting a potential clinical application of this combination in the treatment of CRPA.
</p>
</div>
<p>
<strong class="sub-title">
Keywords:
</strong>
AS101; Pseudomonas aeruginosa; biofilm; carbapenem resistance; mefloquine; synergy.
</p>
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© 2023 Li et al.
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Conflict of interest statement
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The authors have no competing interests to declare for this work.</p>
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<div class="figures" id="figures">
<h2 class="title">
Figures
</h2>
<div class="figures-list" id="slides-container"
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<figure class="figure-item "
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itemprop="contentUrl"
aria-describedby="figure-caption-0"
role="button"
data-image-width="748"
data-image-height="1655"
data-image-alt="Figure 1"
data-pmc-id="PMC10664714"
data-figure-id="f0001">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-0"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/ccd9c408fbf6/IDR-16-7271-g0001.gif"
alt="Figure 1" />
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<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 1 </p>
</strong>
<div class="figure-caption-contents"><p> Time killing curves of AS101… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 1 </p>
</strong>
<div class="figure-caption-contents"><p> Time killing curves of AS101 and mefloquine acting alone or jointly on eight… </p></div>
</div>
<figcaption id="figure-caption-0" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 1
</strong>
<div class="figure-caption-contents">Time killing curves of AS101 and mefloquine acting alone or jointly on eight CRPA strains.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="1"
data-label-slug="figure-2">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/092e1019a2cb/IDR-16-7271-g0002.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-1"
role="button"
data-image-width="745"
data-image-height="574"
data-image-alt="Figure 2"
data-pmc-id="PMC10664714"
data-figure-id="f0002">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-1"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/7f40f81289a8/IDR-16-7271-g0002.gif"
alt="Figure 2" />
</a>
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> AS101 and mefloquine used separately… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 2 </p>
</strong>
<div class="figure-caption-contents"><p> AS101 and mefloquine used separately or jointly on the inhibition of biofilm formation… </p></div>
</div>
<figcaption id="figure-caption-1" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 2
</strong>
<div class="figure-caption-contents">AS101 and mefloquine used separately or jointly on the inhibition of biofilm formation of CRPA. Bars of different colors represented different treatment groups. The data were analyzed by Students <i>t</i> test; ns, no statistical significance; *<i>P</i> &lt; 0.05; **<i>P</i> &lt; 0.01; ***<i>P</i> &lt; 0.001. The experiment was conducted three times. Data was expressed in mean±standard deviation; OD595, optical density at 595 nm.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="2"
data-label-slug="figure-3">
<a class="figure-link"
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itemprop="contentUrl"
aria-describedby="figure-caption-2"
role="button"
data-image-width="790"
data-image-height="601"
data-image-alt="Figure 3"
data-pmc-id="PMC10664714"
data-figure-id="f0003">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-2"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/3da60c92fa9c/IDR-16-7271-g0003.gif"
alt="Figure 3" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="790">
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> SEM images of CRPA-3 processed… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 3 </p>
</strong>
<div class="figure-caption-contents"><p> SEM images of CRPA-3 processed by AS101 and mefloquine. ( <b> A </b> ) BHI… </p></div>
</div>
<figcaption id="figure-caption-2" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 3
</strong>
<div class="figure-caption-contents">SEM images of CRPA-3 processed by AS101 and mefloquine. (<b>A</b>) BHI blank control at 15 000x magnetization (<b>B</b>) Mefloquine at 15 000x magnetization (<b>C</b>) AS101 at 15 000x magnetization (<b>D</b>) MefloquineAS101 combination at 15 000x magnetization. The red arrows indicate the holes in the bacterial cell wall.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="3"
data-label-slug="figure-4">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/84c6cbf8718c/IDR-16-7271-g0004.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-3"
role="button"
data-image-width="749"
data-image-height="757"
data-image-alt="Figure 4"
data-pmc-id="PMC10664714"
data-figure-id="f0004">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-3"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/a9c8e561db84/IDR-16-7271-g0004.gif"
alt="Figure 4" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="749">
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><p> TEM images of CRPA-3 processed… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 4 </p>
</strong>
<div class="figure-caption-contents"><p> TEM images of CRPA-3 processed with AS101 and mefloquine. ( <b> A </b> ) BHI… </p></div>
</div>
<figcaption id="figure-caption-3" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 4
</strong>
<div class="figure-caption-contents">TEM images of CRPA-3 processed with AS101 and mefloquine. (<b>A</b>) BHI blank control at 22 000x magnetization (<b>B</b>) Mefloquine at 22 000x magnetization (<b>C</b>) AS101 at 22 000x magnetization (<b>D</b>) MefloquineAS101 combination at 22 000x magnetization. The red arrows indicate cell wall ruptured.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="4"
data-label-slug="figure-5">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/de8ac879a8d8/IDR-16-7271-g0005.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-4"
role="button"
data-image-width="790"
data-image-height="788"
data-image-alt="Figure 5"
data-pmc-id="PMC10664714"
data-figure-id="f0005">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-4"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/94787c87d313/IDR-16-7271-g0005.gif"
alt="Figure 5" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="790">
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<div class="figure-caption figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="caption" aria-hidden="true">
<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 5 </p>
</strong>
<div class="figure-caption-contents"><p> The flow cytometry picture of… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 5 </p>
</strong>
<div class="figure-caption-contents"><p> The flow cytometry picture of cell membrane permeability of CRPA-3 treated with AS101… </p></div>
</div>
<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 5
</strong>
<div class="figure-caption-contents">The flow cytometry picture of cell membrane permeability of CRPA-3 treated with AS101 and mefloquine. Compared with the control group (<b>A</b>) and the monotherapy group (<b>B</b> and <b>C</b>), the bacterial particles generally moved to the right after the combination of AS101 and mefloquine (<b>D</b>), that was, the fluorescence intensity increased and the permeability of cell membrane increased.</div>
</figcaption>
</figure>
<figure class="figure-item "
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="5"
data-label-slug="figure-6">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/702c71f3a49e/IDR-16-7271-g0006.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-5"
role="button"
data-image-width="710"
data-image-height="916"
data-image-alt="Figure 6"
data-pmc-id="PMC10664714"
data-figure-id="f0006">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-5"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/25c671a639ff/IDR-16-7271-g0006.gif"
alt="Figure 6" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="710">
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<div class="caption-wrap">
<strong class="figure-label">
<p> Figure 6 </p>
</strong>
<div class="figure-caption-contents"><p> The statistical results of cell… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 6 </p>
</strong>
<div class="figure-caption-contents"><p> The statistical results of cell membrane permeability of the CRPA-3 under the action… </p></div>
</div>
<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
<strong class="figure-label">
Figure 6
</strong>
<div class="figure-caption-contents">The statistical results of cell membrane permeability of the CRPA-3 under the action of AS101 and mefloquine by flow cytometry. Compared with the control group and the monotherapy group, the fluorescence intensity after the combination of AS101 and mefloquine was significantly increased. The data were analyzed by Students <i>t</i> test; ns, no statistical significance; **<i>P</i> &lt; 0.01; ***<i>P</i> &lt; 0.001. The experiment was conducted three times. Data was expressed in mean ± standard deviation.</div>
</figcaption>
</figure>
<figure class="figure-item tail"
itemscope itemtype="http://schema.org/ImageObject"
itemprop="associatedMedia"
data-slide-index="6"
data-label-slug="figure-7">
<a class="figure-link"
href="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/a8789e97c53f/IDR-16-7271-g0007.jpg"
itemprop="contentUrl"
aria-describedby="figure-caption-6"
role="button"
data-image-width="710"
data-image-height="845"
data-image-alt="Figure 7"
data-pmc-id="PMC10664714"
data-figure-id="f0007">
<img class="figure-thumb" itemprop="thumbnail"
id="article-image-6"
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9252/10664714/59452f6e2ddf/IDR-16-7271-g0007.gif"
alt="Figure 7" />
</a>
<meta itemprop="width" itemtype="http://schema.org/ImageObject" content="710">
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<strong class="figure-label">
<p> Figure 7 </p>
</strong>
<div class="figure-caption-contents"><p> ROS production after the CRPA-3… </p></div>
</div>
</div>
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
<strong class="figure-label">
<p> Figure 7 </p>
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<div class="figure-caption-contents"><p> ROS production after the CRPA-3 treated with AS101 and mefloquine. Compared with the… </p></div>
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Figure 7
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<div class="figure-caption-contents">ROS production after the CRPA-3 treated with AS101 and mefloquine. Compared with the control group and the monotherapy group, the combined use of AS101 and mefloquine significantly increased ROS. The data were analyzed by Students <i>t</i> test; ***<i>P</i> &lt; 0.001. The experiment was conducted three times. Data was expressed in mean ± standard deviation.</div>
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<div class="figure-caption-contents"><p> Log <sub> 10 </sub> changes of liver,… </p></div>
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<div class="figure-caption-contents"><p> Log <sub> 10 </sub> changes of liver, kidney and spleen of CRPA-3 infected mice after… </p></div>
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<div class="figure-caption-contents">Log<sub>10</sub> changes of liver, kidney and spleen of CRPA-3 infected mice after 72 h of treatment with placebo (1 x PBS), single drug (mefloquine 10 mg/kg/day, AS101 3.33 mg/kg/day) or combination (mefloquine 10 mg/kg/day + AS101 3.33 mg/kg/day). The data were analyzed by Students <i>t</i>-test; *<i>P</i> &lt; 0.05; **<i>P</i> &lt; 0.01; ***<i>P</i> &lt; 0.001. Three mice in each group. Data was expressed in mean ± standard deviation.</div>
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