Insufficient plasma concentrations of empiric anti‐pseudomonal beta‐lactam antibiotics in critically ill patients with suspected sepsis
Aim To determine if empirical anti‐pseudomonal beta‐lactam antibiotic (BLA) dosing achieves adequate drug exposure in septic patients. Method A single‐centre, prospective pharmacokinetic study was conducted in Intensive Care Unit (ICU) patients with sepsis, receiving empirical therapy with piperacil...
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| Veröffentlicht in: | Journal of pharmacy practice and research 2020-08, Vol.50 (4), p.345-350 |
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| container_title | Journal of pharmacy practice and research |
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| creator | Pai Mangalore, Rekha Padiglione, Alexander A. Martin, Emma‐Leah Schneider, Hans G. F. Ngo‐Thai, Lam Lan McGloughlin, Steven A. Peleg, Anton Y. Udy, Andrew A. |
| description | Aim
To determine if empirical anti‐pseudomonal beta‐lactam antibiotic (BLA) dosing achieves adequate drug exposure in septic patients.
Method
A single‐centre, prospective pharmacokinetic study was conducted in Intensive Care Unit (ICU) patients with sepsis, receiving empirical therapy with piperacillin/tazobactam or meropenem. The pharmacokinetic/pharmacodynamic (PK/PD) targets were free BLA concentrations above the MIC at the mid‐point (Concentration A, 50%f T > MIC) and end of the dosing interval (Concentration B, 100% fT > MIC). Sub‐therapeutic concentrations were defined as concentration A |
| doi_str_mv | 10.1002/jppr.1639 |
| format | Article |
| fullrecord | <record><control><sourceid>wiley_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1002_jppr_1639</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>JPPR1639</sourcerecordid><originalsourceid>FETCH-LOGICAL-c2199-c4b2985109d6ac9cc388c00e38518133318a633734d58567d6ae025fba73e7393</originalsourceid><addsrcrecordid>eNp1kL1OwzAUhS0EEqUw8AZeGdLacZzEI6r4KapEhUBiixzHEa6cxPJ1VWVjZ-EZeRLclpXp3nv03SOdg9A1JTNKSDrfOOdnNGfiBE1SwnmSMsZP0YRmGU8EK97P0QXAJqKcl_kEfS172LatUUb3ATsroZNYDb2Kp5fBDD3gocW6c8YbhWUfzM_ntwO9bYZu6KXFtQ4ySlaqILsDUJshGAXY9Fh5E1dp7YiNtdhFx2gMeGfCB4YtOK2CbjBoBwYu0VkrLeirvzlFb_d3r4vHZPX8sFzcrhKVUiESldWpKDklosmlEkqxslSEaBa1kjLGaClzxgqWNbzkeREpHeO2tSyYLphgU3Rz9FV-APC6rZw3nfRjRUm1b7Hat1jtW4zs_MjujNXj_2D1tF6_HD5-ATKNeoY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Insufficient plasma concentrations of empiric anti‐pseudomonal beta‐lactam antibiotics in critically ill patients with suspected sepsis</title><source>Wiley Online Library Journals Frontfile Complete</source><creator>Pai Mangalore, Rekha ; Padiglione, Alexander A. ; Martin, Emma‐Leah ; Schneider, Hans G. F. ; Ngo‐Thai, Lam Lan ; McGloughlin, Steven A. ; Peleg, Anton Y. ; Udy, Andrew A.</creator><creatorcontrib>Pai Mangalore, Rekha ; Padiglione, Alexander A. ; Martin, Emma‐Leah ; Schneider, Hans G. F. ; Ngo‐Thai, Lam Lan ; McGloughlin, Steven A. ; Peleg, Anton Y. ; Udy, Andrew A.</creatorcontrib><description>Aim
To determine if empirical anti‐pseudomonal beta‐lactam antibiotic (BLA) dosing achieves adequate drug exposure in septic patients.
Method
A single‐centre, prospective pharmacokinetic study was conducted in Intensive Care Unit (ICU) patients with sepsis, receiving empirical therapy with piperacillin/tazobactam or meropenem. The pharmacokinetic/pharmacodynamic (PK/PD) targets were free BLA concentrations above the MIC at the mid‐point (Concentration A, 50%f T > MIC) and end of the dosing interval (Concentration B, 100% fT > MIC). Sub‐therapeutic concentrations were defined as concentration A < MIC, and sub‐optimal as concentration B < MIC. The MIC breakpoint for Pseudomonas aeruginosa, as defined by The European Committee on Antimicrobial Susceptibility Testing (EUCAST) (available from <http://www.eucast.org/clinical_breakpoints>) was used.
Results
Of the 37 eligible patients, 20 were receiving piperacillin/tazobactam (TZP), and 17 meropenem (MEM). PK data were available for 36 patients (concentration A) and 34 patients (concentration B). The median measured plasma concentrations (mg/L) were: piperacillin for doses 4 g 8‐hourly and 4 g 6‐hourly – concentration A 53.9 [14.38–123.71] and 36.44 [13.38–107.45], concentration B 8.01 [2.57–71.08] and 27.31 [3.32–59.76], MEM for doses 1 g 8‐hourly and 2 g 8‐hourly – concentration A 12.49 [7.35–23.63] and 30.5, concentration B 7.47 [2.97–11.33] and 9.31. 27.8% (10 of 36) of patients had sub‐therapeutic concentrations (concentration A) and 50% (17 of 34) had sub‐optimal concentrations (concentration B).
Conclusion
Our study confirms that sub‐therapeutic unbound plasma anti‐pseudomonal BLA concentrations are common in critically ill septic patients and underscores the urgent need for future trials exploring the efficacy of BLA therapeutic drug monitoring in these patients.</description><identifier>ISSN: 1445-937X</identifier><identifier>EISSN: 2055-2335</identifier><identifier>DOI: 10.1002/jppr.1639</identifier><language>eng</language><subject>beta‐lactam antibiotics ; critically ill ; ICU ; pharmacodynamics ; pharmacokinetics ; sepsis ; TDM</subject><ispartof>Journal of pharmacy practice and research, 2020-08, Vol.50 (4), p.345-350</ispartof><rights>2020 The Society of Hospital Pharmacists of Australia</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2199-c4b2985109d6ac9cc388c00e38518133318a633734d58567d6ae025fba73e7393</citedby><cites>FETCH-LOGICAL-c2199-c4b2985109d6ac9cc388c00e38518133318a633734d58567d6ae025fba73e7393</cites><orcidid>0000-0002-8447-6836</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjppr.1639$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjppr.1639$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Pai Mangalore, Rekha</creatorcontrib><creatorcontrib>Padiglione, Alexander A.</creatorcontrib><creatorcontrib>Martin, Emma‐Leah</creatorcontrib><creatorcontrib>Schneider, Hans G. F.</creatorcontrib><creatorcontrib>Ngo‐Thai, Lam Lan</creatorcontrib><creatorcontrib>McGloughlin, Steven A.</creatorcontrib><creatorcontrib>Peleg, Anton Y.</creatorcontrib><creatorcontrib>Udy, Andrew A.</creatorcontrib><title>Insufficient plasma concentrations of empiric anti‐pseudomonal beta‐lactam antibiotics in critically ill patients with suspected sepsis</title><title>Journal of pharmacy practice and research</title><description>Aim
To determine if empirical anti‐pseudomonal beta‐lactam antibiotic (BLA) dosing achieves adequate drug exposure in septic patients.
Method
A single‐centre, prospective pharmacokinetic study was conducted in Intensive Care Unit (ICU) patients with sepsis, receiving empirical therapy with piperacillin/tazobactam or meropenem. The pharmacokinetic/pharmacodynamic (PK/PD) targets were free BLA concentrations above the MIC at the mid‐point (Concentration A, 50%f T > MIC) and end of the dosing interval (Concentration B, 100% fT > MIC). Sub‐therapeutic concentrations were defined as concentration A < MIC, and sub‐optimal as concentration B < MIC. The MIC breakpoint for Pseudomonas aeruginosa, as defined by The European Committee on Antimicrobial Susceptibility Testing (EUCAST) (available from <http://www.eucast.org/clinical_breakpoints>) was used.
Results
Of the 37 eligible patients, 20 were receiving piperacillin/tazobactam (TZP), and 17 meropenem (MEM). PK data were available for 36 patients (concentration A) and 34 patients (concentration B). The median measured plasma concentrations (mg/L) were: piperacillin for doses 4 g 8‐hourly and 4 g 6‐hourly – concentration A 53.9 [14.38–123.71] and 36.44 [13.38–107.45], concentration B 8.01 [2.57–71.08] and 27.31 [3.32–59.76], MEM for doses 1 g 8‐hourly and 2 g 8‐hourly – concentration A 12.49 [7.35–23.63] and 30.5, concentration B 7.47 [2.97–11.33] and 9.31. 27.8% (10 of 36) of patients had sub‐therapeutic concentrations (concentration A) and 50% (17 of 34) had sub‐optimal concentrations (concentration B).
Conclusion
Our study confirms that sub‐therapeutic unbound plasma anti‐pseudomonal BLA concentrations are common in critically ill septic patients and underscores the urgent need for future trials exploring the efficacy of BLA therapeutic drug monitoring in these patients.</description><subject>beta‐lactam antibiotics</subject><subject>critically ill</subject><subject>ICU</subject><subject>pharmacodynamics</subject><subject>pharmacokinetics</subject><subject>sepsis</subject><subject>TDM</subject><issn>1445-937X</issn><issn>2055-2335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp1kL1OwzAUhS0EEqUw8AZeGdLacZzEI6r4KapEhUBiixzHEa6cxPJ1VWVjZ-EZeRLclpXp3nv03SOdg9A1JTNKSDrfOOdnNGfiBE1SwnmSMsZP0YRmGU8EK97P0QXAJqKcl_kEfS172LatUUb3ATsroZNYDb2Kp5fBDD3gocW6c8YbhWUfzM_ntwO9bYZu6KXFtQ4ySlaqILsDUJshGAXY9Fh5E1dp7YiNtdhFx2gMeGfCB4YtOK2CbjBoBwYu0VkrLeirvzlFb_d3r4vHZPX8sFzcrhKVUiESldWpKDklosmlEkqxslSEaBa1kjLGaClzxgqWNbzkeREpHeO2tSyYLphgU3Rz9FV-APC6rZw3nfRjRUm1b7Hat1jtW4zs_MjujNXj_2D1tF6_HD5-ATKNeoY</recordid><startdate>202008</startdate><enddate>202008</enddate><creator>Pai Mangalore, Rekha</creator><creator>Padiglione, Alexander A.</creator><creator>Martin, Emma‐Leah</creator><creator>Schneider, Hans G. F.</creator><creator>Ngo‐Thai, Lam Lan</creator><creator>McGloughlin, Steven A.</creator><creator>Peleg, Anton Y.</creator><creator>Udy, Andrew A.</creator><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-8447-6836</orcidid></search><sort><creationdate>202008</creationdate><title>Insufficient plasma concentrations of empiric anti‐pseudomonal beta‐lactam antibiotics in critically ill patients with suspected sepsis</title><author>Pai Mangalore, Rekha ; Padiglione, Alexander A. ; Martin, Emma‐Leah ; Schneider, Hans G. F. ; Ngo‐Thai, Lam Lan ; McGloughlin, Steven A. ; Peleg, Anton Y. ; Udy, Andrew A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2199-c4b2985109d6ac9cc388c00e38518133318a633734d58567d6ae025fba73e7393</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>beta‐lactam antibiotics</topic><topic>critically ill</topic><topic>ICU</topic><topic>pharmacodynamics</topic><topic>pharmacokinetics</topic><topic>sepsis</topic><topic>TDM</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pai Mangalore, Rekha</creatorcontrib><creatorcontrib>Padiglione, Alexander A.</creatorcontrib><creatorcontrib>Martin, Emma‐Leah</creatorcontrib><creatorcontrib>Schneider, Hans G. F.</creatorcontrib><creatorcontrib>Ngo‐Thai, Lam Lan</creatorcontrib><creatorcontrib>McGloughlin, Steven A.</creatorcontrib><creatorcontrib>Peleg, Anton Y.</creatorcontrib><creatorcontrib>Udy, Andrew A.</creatorcontrib><collection>CrossRef</collection><jtitle>Journal of pharmacy practice and research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pai Mangalore, Rekha</au><au>Padiglione, Alexander A.</au><au>Martin, Emma‐Leah</au><au>Schneider, Hans G. F.</au><au>Ngo‐Thai, Lam Lan</au><au>McGloughlin, Steven A.</au><au>Peleg, Anton Y.</au><au>Udy, Andrew A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Insufficient plasma concentrations of empiric anti‐pseudomonal beta‐lactam antibiotics in critically ill patients with suspected sepsis</atitle><jtitle>Journal of pharmacy practice and research</jtitle><date>2020-08</date><risdate>2020</risdate><volume>50</volume><issue>4</issue><spage>345</spage><epage>350</epage><pages>345-350</pages><issn>1445-937X</issn><eissn>2055-2335</eissn><abstract>Aim
To determine if empirical anti‐pseudomonal beta‐lactam antibiotic (BLA) dosing achieves adequate drug exposure in septic patients.
Method
A single‐centre, prospective pharmacokinetic study was conducted in Intensive Care Unit (ICU) patients with sepsis, receiving empirical therapy with piperacillin/tazobactam or meropenem. The pharmacokinetic/pharmacodynamic (PK/PD) targets were free BLA concentrations above the MIC at the mid‐point (Concentration A, 50%f T > MIC) and end of the dosing interval (Concentration B, 100% fT > MIC). Sub‐therapeutic concentrations were defined as concentration A < MIC, and sub‐optimal as concentration B < MIC. The MIC breakpoint for Pseudomonas aeruginosa, as defined by The European Committee on Antimicrobial Susceptibility Testing (EUCAST) (available from <http://www.eucast.org/clinical_breakpoints>) was used.
Results
Of the 37 eligible patients, 20 were receiving piperacillin/tazobactam (TZP), and 17 meropenem (MEM). PK data were available for 36 patients (concentration A) and 34 patients (concentration B). The median measured plasma concentrations (mg/L) were: piperacillin for doses 4 g 8‐hourly and 4 g 6‐hourly – concentration A 53.9 [14.38–123.71] and 36.44 [13.38–107.45], concentration B 8.01 [2.57–71.08] and 27.31 [3.32–59.76], MEM for doses 1 g 8‐hourly and 2 g 8‐hourly – concentration A 12.49 [7.35–23.63] and 30.5, concentration B 7.47 [2.97–11.33] and 9.31. 27.8% (10 of 36) of patients had sub‐therapeutic concentrations (concentration A) and 50% (17 of 34) had sub‐optimal concentrations (concentration B).
Conclusion
Our study confirms that sub‐therapeutic unbound plasma anti‐pseudomonal BLA concentrations are common in critically ill septic patients and underscores the urgent need for future trials exploring the efficacy of BLA therapeutic drug monitoring in these patients.</abstract><doi>10.1002/jppr.1639</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-8447-6836</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | beta‐lactam antibiotics critically ill ICU pharmacodynamics pharmacokinetics sepsis TDM |
| title | Insufficient plasma concentrations of empiric anti‐pseudomonal beta‐lactam antibiotics in critically ill patients with suspected sepsis |
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