Cefiderocol Retains Antibiofilm Activity in Multidrug-Resistant Gram-Negative Pathogens
Cefiderocol is a siderophore cephalosporin with potent antibacterial activity against a broad range of Gram-negative pathogens, including multidrug-resistant strains. Siderophore antibiotics bind ferric iron and utilize iron transporters to cross the cell membrane. In the biofilm setting, where anti...
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| Veröffentlicht in: | Antimicrobial agents and chemotherapy 2021-01, Vol.65 (2) |
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| creator | Pybus, Christine A Felder-Scott, Christina Obuekwe, Victor Greenberg, David E |
| description | Cefiderocol is a siderophore cephalosporin with potent antibacterial activity against a broad range of Gram-negative pathogens, including multidrug-resistant strains. Siderophore antibiotics bind ferric iron and utilize iron transporters to cross the cell membrane. In the biofilm setting, where antibiotic resistance is high but iron scavenging is important, cefiderocol may have advantageous antimicrobial properties. In this study, we compared the antimicrobial activity of cefiderocol to that of seven commonly used antibiotics in well-characterized multidrug-resistant pathogens and then determined their efficacy in the biofilm setting. MIC
values for cefiderocol were consistently lower than those of other antibiotics (ceftolozane-tazobactam, ceftazidime-avibactam, ceftazidime, piperacillin-tazobactam, imipenem, and tobramycin) in all strains tested. Cefiderocol treatment displayed a reduction in the levels of
biofilm (93%,
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| doi_str_mv | 10.1128/AAC.01194-20 |
| format | Article |
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values for cefiderocol were consistently lower than those of other antibiotics (ceftolozane-tazobactam, ceftazidime-avibactam, ceftazidime, piperacillin-tazobactam, imipenem, and tobramycin) in all strains tested. Cefiderocol treatment displayed a reduction in the levels of
biofilm (93%,
< 0.0001) superior to that seen with the other antibiotics (49% to 82%). Cefiderocol was generally as effective as or superior to the other antibiotics, depending on the pathogen-antibiotic combination, in reducing biofilm in other pathogens. There was a trend toward greater biofilm reduction seen with increased antibiotic dose or with increased frequency of antibiotic treatment. We conclude that cefiderocol effectively reduces biofilm and is a potent inhibitor of planktonic growth across a range of Gram-negative medically important pathogens.</description><identifier>ISSN: 0066-4804</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AAC.01194-20</identifier><identifier>PMID: 33199383</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Anti-Bacterial Agents - pharmacology ; Anti-Bacterial Agents - therapeutic use ; Biofilms ; Cefiderocol ; Cephalosporins - pharmacology ; Drug Resistance, Multiple, Bacterial ; Gram-Negative Bacteria ; Gram-Negative Bacterial Infections - drug therapy ; Humans ; Mechanisms of Action: Physiological Effects ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa</subject><ispartof>Antimicrobial agents and chemotherapy, 2021-01, Vol.65 (2)</ispartof><rights>Copyright © 2021 Pybus et al.</rights><rights>Copyright © 2021 Pybus et al. 2021 Pybus et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a418t-7aa2369d5db8fad8e998ae308a8baaa8def43d32b4092f135798864754924cad3</citedby><cites>FETCH-LOGICAL-a418t-7aa2369d5db8fad8e998ae308a8baaa8def43d32b4092f135798864754924cad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849010/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849010/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33199383$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pybus, Christine A</creatorcontrib><creatorcontrib>Felder-Scott, Christina</creatorcontrib><creatorcontrib>Obuekwe, Victor</creatorcontrib><creatorcontrib>Greenberg, David E</creatorcontrib><title>Cefiderocol Retains Antibiofilm Activity in Multidrug-Resistant Gram-Negative Pathogens</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><description>Cefiderocol is a siderophore cephalosporin with potent antibacterial activity against a broad range of Gram-negative pathogens, including multidrug-resistant strains. Siderophore antibiotics bind ferric iron and utilize iron transporters to cross the cell membrane. In the biofilm setting, where antibiotic resistance is high but iron scavenging is important, cefiderocol may have advantageous antimicrobial properties. In this study, we compared the antimicrobial activity of cefiderocol to that of seven commonly used antibiotics in well-characterized multidrug-resistant pathogens and then determined their efficacy in the biofilm setting. MIC
values for cefiderocol were consistently lower than those of other antibiotics (ceftolozane-tazobactam, ceftazidime-avibactam, ceftazidime, piperacillin-tazobactam, imipenem, and tobramycin) in all strains tested. Cefiderocol treatment displayed a reduction in the levels of
biofilm (93%,
< 0.0001) superior to that seen with the other antibiotics (49% to 82%). Cefiderocol was generally as effective as or superior to the other antibiotics, depending on the pathogen-antibiotic combination, in reducing biofilm in other pathogens. There was a trend toward greater biofilm reduction seen with increased antibiotic dose or with increased frequency of antibiotic treatment. We conclude that cefiderocol effectively reduces biofilm and is a potent inhibitor of planktonic growth across a range of Gram-negative medically important pathogens.</description><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Biofilms</subject><subject>Cefiderocol</subject><subject>Cephalosporins - pharmacology</subject><subject>Drug Resistance, Multiple, Bacterial</subject><subject>Gram-Negative Bacteria</subject><subject>Gram-Negative Bacterial Infections - drug therapy</subject><subject>Humans</subject><subject>Mechanisms of Action: Physiological Effects</subject><subject>Microbial Sensitivity Tests</subject><subject>Pseudomonas aeruginosa</subject><issn>0066-4804</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9LHTEQx0NR6tP21nPZYwVX82v3JZfC8mhVUFukpccwu5l9RnYTTbKC_72rT8UePA3DfPgMM19CvjB6yBhXR02zOqSMaVly-oEsGNWqrCtdb5EFpXVdSkXlDtlN6ZrOfaXpR7IjBNNaKLEg_1bYO4sxdGEoLjGD86lofHatC70bxqLpsrtz-b5wvjifhuxsnNblJSaXMvhcHEcYywtcw4xh8RvyVVijT5_Idg9Dws_PdY_8_fnjz-qkPPt1fLpqzkqQTOVyCcBFrW1lW9WDVai1AhRUgWoBQFnspbCCt5Jq3jNRLbVStVxWUnPZgRV75PvGezO1I9oOfY4wmJvoRoj3JoAz_0-8uzLrcGeWSmrK6Cz49iyI4XbClM3oUofDAB7DlAyXNRPzs2oxowcbtIshpYj96xpGzWMWZs7CPGVh-KN5f4NDGrm5DlP08yfeY7--PeNV_BKUeACh0pLX</recordid><startdate>20210120</startdate><enddate>20210120</enddate><creator>Pybus, Christine A</creator><creator>Felder-Scott, Christina</creator><creator>Obuekwe, Victor</creator><creator>Greenberg, David E</creator><general>American Society for Microbiology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210120</creationdate><title>Cefiderocol Retains Antibiofilm Activity in Multidrug-Resistant Gram-Negative Pathogens</title><author>Pybus, Christine A ; Felder-Scott, Christina ; Obuekwe, Victor ; Greenberg, David E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a418t-7aa2369d5db8fad8e998ae308a8baaa8def43d32b4092f135798864754924cad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Biofilms</topic><topic>Cefiderocol</topic><topic>Cephalosporins - pharmacology</topic><topic>Drug Resistance, Multiple, Bacterial</topic><topic>Gram-Negative Bacteria</topic><topic>Gram-Negative Bacterial Infections - drug therapy</topic><topic>Humans</topic><topic>Mechanisms of Action: Physiological Effects</topic><topic>Microbial Sensitivity Tests</topic><topic>Pseudomonas aeruginosa</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pybus, Christine A</creatorcontrib><creatorcontrib>Felder-Scott, Christina</creatorcontrib><creatorcontrib>Obuekwe, Victor</creatorcontrib><creatorcontrib>Greenberg, David E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antimicrobial agents and chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pybus, Christine A</au><au>Felder-Scott, Christina</au><au>Obuekwe, Victor</au><au>Greenberg, David E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cefiderocol Retains Antibiofilm Activity in Multidrug-Resistant Gram-Negative Pathogens</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2021-01-20</date><risdate>2021</risdate><volume>65</volume><issue>2</issue><issn>0066-4804</issn><eissn>1098-6596</eissn><abstract>Cefiderocol is a siderophore cephalosporin with potent antibacterial activity against a broad range of Gram-negative pathogens, including multidrug-resistant strains. Siderophore antibiotics bind ferric iron and utilize iron transporters to cross the cell membrane. In the biofilm setting, where antibiotic resistance is high but iron scavenging is important, cefiderocol may have advantageous antimicrobial properties. In this study, we compared the antimicrobial activity of cefiderocol to that of seven commonly used antibiotics in well-characterized multidrug-resistant pathogens and then determined their efficacy in the biofilm setting. MIC
values for cefiderocol were consistently lower than those of other antibiotics (ceftolozane-tazobactam, ceftazidime-avibactam, ceftazidime, piperacillin-tazobactam, imipenem, and tobramycin) in all strains tested. Cefiderocol treatment displayed a reduction in the levels of
biofilm (93%,
< 0.0001) superior to that seen with the other antibiotics (49% to 82%). Cefiderocol was generally as effective as or superior to the other antibiotics, depending on the pathogen-antibiotic combination, in reducing biofilm in other pathogens. There was a trend toward greater biofilm reduction seen with increased antibiotic dose or with increased frequency of antibiotic treatment. We conclude that cefiderocol effectively reduces biofilm and is a potent inhibitor of planktonic growth across a range of Gram-negative medically important pathogens.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>33199383</pmid><doi>10.1128/AAC.01194-20</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Anti-Bacterial Agents - pharmacology Anti-Bacterial Agents - therapeutic use Biofilms Cefiderocol Cephalosporins - pharmacology Drug Resistance, Multiple, Bacterial Gram-Negative Bacteria Gram-Negative Bacterial Infections - drug therapy Humans Mechanisms of Action: Physiological Effects Microbial Sensitivity Tests Pseudomonas aeruginosa |
| title | Cefiderocol Retains Antibiofilm Activity in Multidrug-Resistant Gram-Negative Pathogens |
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