{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:46:19Z","timestamp":1793321179727,"version":"4.5.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    has emerged as a major clinical and public health threat owing to the increasing prevalence of healthcare-associated infections caused by multidrug-resistant or extensively drug-resistant strains. However, increasing antibiotic resistance and the absence of clinically effective antimicrobial agents make combination therapy an urgent need. This study investigated the anti-microbial activity of SPR741, a polymyxin B derivative, in combination with macrolide antibiotics (erythromycin and clarithromycin), against extensively drug-resistant and pandrug-resistant\n                    <jats:italic>K. pneumoniae.<\/jats:italic>\n                    Monotherapy, double, and triple combination therapies were performed to identify the most effective treatment combination using\n                    <jats:italic>in vitro<\/jats:italic>\n                    checkerboard, time-killing kinetics. Furthermore, we evaluated the biofilm eradication and persister cell-killing activity of these combinations using laser confocal microscopy and colony forming unit counting. In addition, a neutropenic mouse thigh infection model was used to assess the therapeutic efficacy and toxicity of the triple antibiotic combination against pandrug-resistant\n                    <jats:italic>K. pneumoniae in vivo<\/jats:italic>\n                    . Our results suggested that SPR741 combined with macrolides exhibited strong synergistic antibacterial activity against extensively drug-resistant and pandrug-resistant\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    . These antibiotic combinations could also effectively eradicate highly resistant bacterial biofilms and persister cells\n                    <jats:italic>in vitro<\/jats:italic>\n                    and demonstrate considerable efficacy and low toxicity\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In summary, our findings indicated that SPR741, in combination with macrolide antibiotics (double or triple combination), has the potential to serve as a novel treatment option against drug-resistant\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    -related infections.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2022.858606","type":"journal-article","created":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T02:09:58Z","timestamp":1647569398000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["SPR741, Double- or Triple-Combined With Erythromycin and Clarithromycin, Combats Drug-Resistant Klebsiella pneumoniae, Its Biofilms, and Persister Cells"],"prefix":"10.3389","volume":"12","author":[{"given":"Pengfei","family":"She","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanlan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zubair","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02064","article-title":"Clarithromycin Enhances the Antibacterial Activity and Wound Healing Capacity in Type 2 Diabetes Mellitus by Increasing LL-37 Load on Neutrophil Extracellular Traps","volume":"9","author":"Arampatzioglou","year":"2018","journal-title":"Front. 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