Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy
Intravenous colistimethate sodium (CMS) is used to treat infections with multiresistant Gram-negative bacteria. Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear. In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill p...
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| Veröffentlicht in: | Antimicrobial agents and chemotherapy 2019-02, Vol.63 (2) |
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| container_title | Antimicrobial agents and chemotherapy |
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| creator | Leuppi-Taegtmeyer, Anne B Decosterd, Laurent Osthoff, Michael Mueller, Nicolas J Buclin, Thierry Corti, Natascia |
| description | Intravenous colistimethate sodium (CMS) is used to treat infections with multiresistant Gram-negative bacteria. Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear. In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill patients requiring CRRT (8 underwent continuous venovenous hemodialysis [CVVHD]; median blood flow, 100 ml/min). Intensive sampling was performed on treatment days 1, 3, and 5 after an intravenous CMS loading dose of 9 million international units (MU) (6 MU if body weight was |
| doi_str_mv | 10.1128/AAC.01957-18 |
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Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear. In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill patients requiring CRRT (8 underwent continuous venovenous hemodialysis [CVVHD]; median blood flow, 100 ml/min). Intensive sampling was performed on treatment days 1, 3, and 5 after an intravenous CMS loading dose of 9 million international units (MU) (6 MU if body weight was <60 kg) with a consecutive 3-MU (respectively, 2 MU) maintenance dose at 8 h. CMS and colistin concentrations were determined by liquid chromatography with mass spectroscopy. A model-based population pharmacokinetic analysis incorporating CRRT settings was applied to the observations. Sequential model building indicated a monocompartmental distribution for both CMS and colistin, with interindividual variability in both volume and clearance. Hematocrit was shown to affect the efficacy of drug transfer across the filter. CRRT clearance accounted for, on average, 41% of total CMS and 28% of total colistin clearance, confirming enhanced elimination of colistin compared to normal renal function. Target colistin steady-state trough concentrations of at least 2.5 mg/liter were achieved in all patients receiving 3 MU at 8 h. In conclusion, a loading dose of 9 MU followed after 8 h by a maintenance dose of 3 MU every 8 h independent of body weight is expected to achieve therapeutic colistin concentrations in patients undergoing CVVHD using low blood flows. Colistin therapeutic drug monitoring might help to further ensure optimal dosing in individual patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02081560.).</description><identifier>ISSN: 0066-4804</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AAC.01957-18</identifier><identifier>PMID: 30478168</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Adult ; Aged ; Anti-Bacterial Agents ; Anti-Bacterial Agents - pharmacokinetics ; Anti-Bacterial Agents - therapeutic use ; Chromatography, Liquid ; Colistin ; Colistin - analogs & derivatives ; Colistin - pharmacokinetics ; Colistin - therapeutic use ; Continuous Renal Replacement Therapy ; Continuous Renal Replacement Therapy - methods ; Escherichia coli - drug effects ; Escherichia coli Infections ; Escherichia coli Infections - drug therapy ; Escherichia coli Infections - mortality ; Female ; Humans ; Male ; Mass Spectrometry ; Middle Aged ; Pharmacology ; Prospective Studies ; Pseudomonas aeruginosa - drug effects ; Pseudomonas Infections ; Pseudomonas Infections - drug therapy ; Pseudomonas Infections - mortality</subject><ispartof>Antimicrobial agents and chemotherapy, 2019-02, Vol.63 (2)</ispartof><rights>Copyright © 2019 American Society for Microbiology.</rights><rights>Copyright © 2019 American Society for Microbiology. 2019 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a418t-47dd9b99e80ac848742d225bb3120ee062621fadbd50ce5e192fe44e36c22b093</citedby><cites>FETCH-LOGICAL-a418t-47dd9b99e80ac848742d225bb3120ee062621fadbd50ce5e192fe44e36c22b093</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/PMC6355613/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355613/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30478168$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leuppi-Taegtmeyer, Anne B</creatorcontrib><creatorcontrib>Decosterd, Laurent</creatorcontrib><creatorcontrib>Osthoff, Michael</creatorcontrib><creatorcontrib>Mueller, Nicolas J</creatorcontrib><creatorcontrib>Buclin, Thierry</creatorcontrib><creatorcontrib>Corti, Natascia</creatorcontrib><title>Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><description>Intravenous colistimethate sodium (CMS) is used to treat infections with multiresistant Gram-negative bacteria. Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear. In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill patients requiring CRRT (8 underwent continuous venovenous hemodialysis [CVVHD]; median blood flow, 100 ml/min). Intensive sampling was performed on treatment days 1, 3, and 5 after an intravenous CMS loading dose of 9 million international units (MU) (6 MU if body weight was <60 kg) with a consecutive 3-MU (respectively, 2 MU) maintenance dose at 8 h. CMS and colistin concentrations were determined by liquid chromatography with mass spectroscopy. A model-based population pharmacokinetic analysis incorporating CRRT settings was applied to the observations. Sequential model building indicated a monocompartmental distribution for both CMS and colistin, with interindividual variability in both volume and clearance. Hematocrit was shown to affect the efficacy of drug transfer across the filter. CRRT clearance accounted for, on average, 41% of total CMS and 28% of total colistin clearance, confirming enhanced elimination of colistin compared to normal renal function. Target colistin steady-state trough concentrations of at least 2.5 mg/liter were achieved in all patients receiving 3 MU at 8 h. In conclusion, a loading dose of 9 MU followed after 8 h by a maintenance dose of 3 MU every 8 h independent of body weight is expected to achieve therapeutic colistin concentrations in patients undergoing CVVHD using low blood flows. Colistin therapeutic drug monitoring might help to further ensure optimal dosing in individual patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02081560.).</description><subject>Adult</subject><subject>Aged</subject><subject>Anti-Bacterial Agents</subject><subject>Anti-Bacterial Agents - pharmacokinetics</subject><subject>Anti-Bacterial Agents - therapeutic use</subject><subject>Chromatography, Liquid</subject><subject>Colistin</subject><subject>Colistin - analogs & derivatives</subject><subject>Colistin - pharmacokinetics</subject><subject>Colistin - therapeutic use</subject><subject>Continuous Renal Replacement Therapy</subject><subject>Continuous Renal Replacement Therapy - methods</subject><subject>Escherichia coli - drug effects</subject><subject>Escherichia coli Infections</subject><subject>Escherichia coli Infections - drug therapy</subject><subject>Escherichia coli Infections - mortality</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Middle Aged</subject><subject>Pharmacology</subject><subject>Prospective Studies</subject><subject>Pseudomonas aeruginosa - drug effects</subject><subject>Pseudomonas Infections</subject><subject>Pseudomonas Infections - drug therapy</subject><subject>Pseudomonas Infections - mortality</subject><issn>0066-4804</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcFvFCEUxonR2LV682w4atKpwDAsXEw2Y6smVTdtPRNmeOtSZ2CEwWT_I_9MaXfb6MEL8PL9-F7e-xB6SckppUy-Xa3aU0JVs6yofIQWlChZiUaJx2hBiBAVl4QfoWcp3ZBSN4o8RUc14UtJhVyg35_zMLse_AwRr8OUBzO74PF6a-Jo-vDDeSg6vpqz3eGwwW0YXJrdCPPWzICvgnV5xMbbe8Xj9yGBxSbh8v4Sis2AL8GX8zz7_s69COvSp3RNuJRt8OVfDjkdwEuYBtPDWAB8vYVopt1z9GRjhgQvDvcx-nZ-dt1-rC6-fvjUri4qw6mcK760VnVKgSSml1wuObOMNV1XU0YAiGCC0Y2xnW1IDw1QxTbAOdSiZ6wjqj5G7_a-U-5GsLebiWbQU3SjiTsdjNP_Kt5t9ffwS4u6aQSti8Hrg0EMPzOkWY8u9TAMxkOZUDNaS8EVk7SgJ3u0jyGlCJuHNpTo23B1CVffhaupLPibPW7SyPRNyLHsKv2PffX3GA_G98nXfwBQgbDI</recordid><startdate>20190201</startdate><enddate>20190201</enddate><creator>Leuppi-Taegtmeyer, Anne B</creator><creator>Decosterd, Laurent</creator><creator>Osthoff, Michael</creator><creator>Mueller, Nicolas J</creator><creator>Buclin, Thierry</creator><creator>Corti, Natascia</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>20190201</creationdate><title>Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy</title><author>Leuppi-Taegtmeyer, Anne B ; Decosterd, Laurent ; Osthoff, Michael ; Mueller, Nicolas J ; Buclin, Thierry ; Corti, Natascia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a418t-47dd9b99e80ac848742d225bb3120ee062621fadbd50ce5e192fe44e36c22b093</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Anti-Bacterial Agents</topic><topic>Anti-Bacterial Agents - pharmacokinetics</topic><topic>Anti-Bacterial Agents - therapeutic use</topic><topic>Chromatography, Liquid</topic><topic>Colistin</topic><topic>Colistin - analogs & derivatives</topic><topic>Colistin - pharmacokinetics</topic><topic>Colistin - therapeutic use</topic><topic>Continuous Renal Replacement Therapy</topic><topic>Continuous Renal Replacement Therapy - methods</topic><topic>Escherichia coli - drug effects</topic><topic>Escherichia coli Infections</topic><topic>Escherichia coli Infections - drug therapy</topic><topic>Escherichia coli Infections - mortality</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Middle Aged</topic><topic>Pharmacology</topic><topic>Prospective Studies</topic><topic>Pseudomonas aeruginosa - drug effects</topic><topic>Pseudomonas Infections</topic><topic>Pseudomonas Infections - drug therapy</topic><topic>Pseudomonas Infections - mortality</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leuppi-Taegtmeyer, Anne B</creatorcontrib><creatorcontrib>Decosterd, Laurent</creatorcontrib><creatorcontrib>Osthoff, Michael</creatorcontrib><creatorcontrib>Mueller, Nicolas J</creatorcontrib><creatorcontrib>Buclin, Thierry</creatorcontrib><creatorcontrib>Corti, Natascia</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>Leuppi-Taegtmeyer, Anne B</au><au>Decosterd, Laurent</au><au>Osthoff, Michael</au><au>Mueller, Nicolas J</au><au>Buclin, Thierry</au><au>Corti, Natascia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2019-02-01</date><risdate>2019</risdate><volume>63</volume><issue>2</issue><issn>0066-4804</issn><eissn>1098-6596</eissn><abstract>Intravenous colistimethate sodium (CMS) is used to treat infections with multiresistant Gram-negative bacteria. Optimal dosing in patients undergoing continuous renal replacement therapy (CRRT) is unclear. In a prospective study, we determined CMS and colistin pharmacokinetics in 10 critically ill patients requiring CRRT (8 underwent continuous venovenous hemodialysis [CVVHD]; median blood flow, 100 ml/min). Intensive sampling was performed on treatment days 1, 3, and 5 after an intravenous CMS loading dose of 9 million international units (MU) (6 MU if body weight was <60 kg) with a consecutive 3-MU (respectively, 2 MU) maintenance dose at 8 h. CMS and colistin concentrations were determined by liquid chromatography with mass spectroscopy. A model-based population pharmacokinetic analysis incorporating CRRT settings was applied to the observations. Sequential model building indicated a monocompartmental distribution for both CMS and colistin, with interindividual variability in both volume and clearance. Hematocrit was shown to affect the efficacy of drug transfer across the filter. CRRT clearance accounted for, on average, 41% of total CMS and 28% of total colistin clearance, confirming enhanced elimination of colistin compared to normal renal function. Target colistin steady-state trough concentrations of at least 2.5 mg/liter were achieved in all patients receiving 3 MU at 8 h. In conclusion, a loading dose of 9 MU followed after 8 h by a maintenance dose of 3 MU every 8 h independent of body weight is expected to achieve therapeutic colistin concentrations in patients undergoing CVVHD using low blood flows. Colistin therapeutic drug monitoring might help to further ensure optimal dosing in individual patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02081560.).</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>30478168</pmid><doi>10.1128/AAC.01957-18</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Anti-Bacterial Agents Anti-Bacterial Agents - pharmacokinetics Anti-Bacterial Agents - therapeutic use Chromatography, Liquid Colistin Colistin - analogs & derivatives Colistin - pharmacokinetics Colistin - therapeutic use Continuous Renal Replacement Therapy Continuous Renal Replacement Therapy - methods Escherichia coli - drug effects Escherichia coli Infections Escherichia coli Infections - drug therapy Escherichia coli Infections - mortality Female Humans Male Mass Spectrometry Middle Aged Pharmacology Prospective Studies Pseudomonas aeruginosa - drug effects Pseudomonas Infections Pseudomonas Infections - drug therapy Pseudomonas Infections - mortality |
| title | Multicenter Population Pharmacokinetic Study of Colistimethate Sodium and Colistin Dosed as in Normal Renal Function in Patients on Continuous Renal Replacement Therapy |
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