S13 Antibiotic penetration into the infected pleural space; a PK/PD study
Introduction and ObjectivesPleural infection is a serious clinical condition with an average hospital length of stay of 13 days. Current standard of care defaults to hospital admission for drainage of the infected fluid and intravenous antibiotics. The standard empirical antibiotic choice varies nat...
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description | Introduction and ObjectivesPleural infection is a serious clinical condition with an average hospital length of stay of 13 days. Current standard of care defaults to hospital admission for drainage of the infected fluid and intravenous antibiotics. The standard empirical antibiotic choice varies nationally but the ability of these antibiotics to reach the pleura is poorly understood. Previous pharmacokinetics and pharmacodynamics (PK/PD) literature on the penetrance of antibiotics into pleural fluid is extrapolated from non-infected effusions (e.g. malignant effusions) or animal models.The Pleural Antibiotic Concentrations informing Treatment (PACT) study is a single centre PK/PD study that aims to assess the concentration of antibiotics within the infected pleural space to improve the evidence base around antimicrobial choice, route and duration of therapy.MethodsPatients with parapneumonic effusions/empyema planned for pleural drainage were prospectively recruited. Serial pleural fluid samples were collected timed with routine antibiotic administration and paired with synchronous serum sampling. Pleural fluid and serum antibiotic concentrations were measured using a validated high performance liquid chromatography (HPLC) method at the National Antimicrobial Reference Laboratory (Bristol UK).ResultsThis study is ongoing, further results on a wider range of antimicrobials will be available for the conference.At the time of writing, 18 patients had been recruited (15 CPPE, 3 empyema) with over 150 paired serum/fluid samples collected. Ten different antibiotics have been assayed although the majority of timepoints relate to Amoxicillin/Co-amoxiclav (n=36), Metronidazole (n=28) and Piperacillin-Tazobactam (n=22) at this time, see figure 1.Abstract S13 Figure 1Amoxicillin, Metronidazole and Tazocin (Tazobactam) levels in serum and pleural fluid post intravenous administrationFor these antibiotics the peak concentration and area under the curve within the pleural space was equivalent to serum levels. Importantly, across the dosing schedule the pleural antibiotic levels never fell below the minimum inhibitory concentrations (MICs) for bacteria known to cause pleural infection even when given orally. The pleural levels for penicillins persisted beyond the dosing schedule (8 hours) and were not affected by pleural pH or fibrinolytics.ConclusionsFor 3 commonly used antibiotics (Amoxicillin, Metronidazole, Piperacillin-Tazobactam) the pleural fluid concentration of |
doi_str_mv | 10.1136/thorax-2021-BTSabstracts.19 |
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fullrecord | <record><control><sourceid>proquest_bmj_j</sourceid><recordid>TN_cdi_proquest_journals_2594960535</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2594960535</sourcerecordid><originalsourceid>FETCH-LOGICAL-b1299-22639bc1abd3d799bb1166e22e272d586bc91239b5511c0d8c60ee031038b6883</originalsourceid><addsrcrecordid>eNpNkM1KAzEUhYMoWKvvEOg67b3JTCbBVa2_tGChdT0kmZROqTPjJAO6c-OL-iROqaCrcxYf58BHyAhhjCjkJG7r1rwzDhzZzXplbIitcTGMUZ-QASZSMcG1PCUDgASYFJk8Jxch7ABAIWYDMl-h-P78mlaxtGUdS0cbX_l-JZZ1Rcsq1jRufV823kVf0Gbvu9bsaWiM89fU0OV8srylIXbFxyU525h98Fe_OSQv93fr2SNbPD88zaYLZpFrzTiXQluHxhaiyLS2FlFKz7nnGS9SJa3TyHskTREdFMpJ8B4EglBWKiWGZHTcbdr6rfMh5ru6a6v-MuepTrSEVKQ9lR0p-7r7AxDyg7n8aC4_mMv_m8tRix_P72ae</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2594960535</pqid></control><display><type>article</type><title>S13 Antibiotic penetration into the infected pleural space; a PK/PD study</title><source>Alma/SFX Local Collection</source><creator>Arnold, DT ; Read, L ; Noel, A ; Hamilton, FW ; MacGowan, A ; Bayliss, M ; Maskell, NA</creator><creatorcontrib>Arnold, DT ; Read, L ; Noel, A ; Hamilton, FW ; MacGowan, A ; Bayliss, M ; Maskell, NA</creatorcontrib><description>Introduction and ObjectivesPleural infection is a serious clinical condition with an average hospital length of stay of 13 days. Current standard of care defaults to hospital admission for drainage of the infected fluid and intravenous antibiotics. The standard empirical antibiotic choice varies nationally but the ability of these antibiotics to reach the pleura is poorly understood. Previous pharmacokinetics and pharmacodynamics (PK/PD) literature on the penetrance of antibiotics into pleural fluid is extrapolated from non-infected effusions (e.g. malignant effusions) or animal models.The Pleural Antibiotic Concentrations informing Treatment (PACT) study is a single centre PK/PD study that aims to assess the concentration of antibiotics within the infected pleural space to improve the evidence base around antimicrobial choice, route and duration of therapy.MethodsPatients with parapneumonic effusions/empyema planned for pleural drainage were prospectively recruited. Serial pleural fluid samples were collected timed with routine antibiotic administration and paired with synchronous serum sampling. Pleural fluid and serum antibiotic concentrations were measured using a validated high performance liquid chromatography (HPLC) method at the National Antimicrobial Reference Laboratory (Bristol UK).ResultsThis study is ongoing, further results on a wider range of antimicrobials will be available for the conference.At the time of writing, 18 patients had been recruited (15 CPPE, 3 empyema) with over 150 paired serum/fluid samples collected. Ten different antibiotics have been assayed although the majority of timepoints relate to Amoxicillin/Co-amoxiclav (n=36), Metronidazole (n=28) and Piperacillin-Tazobactam (n=22) at this time, see figure 1.Abstract S13 Figure 1Amoxicillin, Metronidazole and Tazocin (Tazobactam) levels in serum and pleural fluid post intravenous administrationFor these antibiotics the peak concentration and area under the curve within the pleural space was equivalent to serum levels. Importantly, across the dosing schedule the pleural antibiotic levels never fell below the minimum inhibitory concentrations (MICs) for bacteria known to cause pleural infection even when given orally. The pleural levels for penicillins persisted beyond the dosing schedule (8 hours) and were not affected by pleural pH or fibrinolytics.ConclusionsFor 3 commonly used antibiotics (Amoxicillin, Metronidazole, Piperacillin-Tazobactam) the pleural fluid concentration of antibiotic remined well above the usual MICs of causative bacteria. Penetrance and persistence of antibiotics make twice-daily or oral administration a possibility in pleural infection.</description><identifier>ISSN: 0040-6376</identifier><identifier>EISSN: 1468-3296</identifier><identifier>DOI: 10.1136/thorax-2021-BTSabstracts.19</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Thoracic Society</publisher><subject>Antibiotics ; Infections ; Probing the pleural space</subject><ispartof>Thorax, 2021-11, Vol.76 (Suppl 2), p.A13-A13</ispartof><rights>Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.</rights><rights>2021 Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids></links><search><creatorcontrib>Arnold, DT</creatorcontrib><creatorcontrib>Read, L</creatorcontrib><creatorcontrib>Noel, A</creatorcontrib><creatorcontrib>Hamilton, FW</creatorcontrib><creatorcontrib>MacGowan, A</creatorcontrib><creatorcontrib>Bayliss, M</creatorcontrib><creatorcontrib>Maskell, NA</creatorcontrib><title>S13 Antibiotic penetration into the infected pleural space; a PK/PD study</title><title>Thorax</title><addtitle>Thorax</addtitle><description>Introduction and ObjectivesPleural infection is a serious clinical condition with an average hospital length of stay of 13 days. Current standard of care defaults to hospital admission for drainage of the infected fluid and intravenous antibiotics. The standard empirical antibiotic choice varies nationally but the ability of these antibiotics to reach the pleura is poorly understood. Previous pharmacokinetics and pharmacodynamics (PK/PD) literature on the penetrance of antibiotics into pleural fluid is extrapolated from non-infected effusions (e.g. malignant effusions) or animal models.The Pleural Antibiotic Concentrations informing Treatment (PACT) study is a single centre PK/PD study that aims to assess the concentration of antibiotics within the infected pleural space to improve the evidence base around antimicrobial choice, route and duration of therapy.MethodsPatients with parapneumonic effusions/empyema planned for pleural drainage were prospectively recruited. Serial pleural fluid samples were collected timed with routine antibiotic administration and paired with synchronous serum sampling. Pleural fluid and serum antibiotic concentrations were measured using a validated high performance liquid chromatography (HPLC) method at the National Antimicrobial Reference Laboratory (Bristol UK).ResultsThis study is ongoing, further results on a wider range of antimicrobials will be available for the conference.At the time of writing, 18 patients had been recruited (15 CPPE, 3 empyema) with over 150 paired serum/fluid samples collected. Ten different antibiotics have been assayed although the majority of timepoints relate to Amoxicillin/Co-amoxiclav (n=36), Metronidazole (n=28) and Piperacillin-Tazobactam (n=22) at this time, see figure 1.Abstract S13 Figure 1Amoxicillin, Metronidazole and Tazocin (Tazobactam) levels in serum and pleural fluid post intravenous administrationFor these antibiotics the peak concentration and area under the curve within the pleural space was equivalent to serum levels. Importantly, across the dosing schedule the pleural antibiotic levels never fell below the minimum inhibitory concentrations (MICs) for bacteria known to cause pleural infection even when given orally. The pleural levels for penicillins persisted beyond the dosing schedule (8 hours) and were not affected by pleural pH or fibrinolytics.ConclusionsFor 3 commonly used antibiotics (Amoxicillin, Metronidazole, Piperacillin-Tazobactam) the pleural fluid concentration of antibiotic remined well above the usual MICs of causative bacteria. Penetrance and persistence of antibiotics make twice-daily or oral administration a possibility in pleural infection.</description><subject>Antibiotics</subject><subject>Infections</subject><subject>Probing the pleural space</subject><issn>0040-6376</issn><issn>1468-3296</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpNkM1KAzEUhYMoWKvvEOg67b3JTCbBVa2_tGChdT0kmZROqTPjJAO6c-OL-iROqaCrcxYf58BHyAhhjCjkJG7r1rwzDhzZzXplbIitcTGMUZ-QASZSMcG1PCUDgASYFJk8Jxch7ABAIWYDMl-h-P78mlaxtGUdS0cbX_l-JZZ1Rcsq1jRufV823kVf0Gbvu9bsaWiM89fU0OV8srylIXbFxyU525h98Fe_OSQv93fr2SNbPD88zaYLZpFrzTiXQluHxhaiyLS2FlFKz7nnGS9SJa3TyHskTREdFMpJ8B4EglBWKiWGZHTcbdr6rfMh5ru6a6v-MuepTrSEVKQ9lR0p-7r7AxDyg7n8aC4_mMv_m8tRix_P72ae</recordid><startdate>20211108</startdate><enddate>20211108</enddate><creator>Arnold, DT</creator><creator>Read, L</creator><creator>Noel, A</creator><creator>Hamilton, FW</creator><creator>MacGowan, A</creator><creator>Bayliss, M</creator><creator>Maskell, NA</creator><general>BMJ Publishing Group Ltd and British Thoracic Society</general><general>BMJ Publishing Group LTD</general><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20211108</creationdate><title>S13 Antibiotic penetration into the infected pleural space; a PK/PD study</title><author>Arnold, DT ; Read, L ; Noel, A ; Hamilton, FW ; MacGowan, A ; Bayliss, M ; Maskell, NA</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b1299-22639bc1abd3d799bb1166e22e272d586bc91239b5511c0d8c60ee031038b6883</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibiotics</topic><topic>Infections</topic><topic>Probing the pleural space</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arnold, DT</creatorcontrib><creatorcontrib>Read, L</creatorcontrib><creatorcontrib>Noel, A</creatorcontrib><creatorcontrib>Hamilton, FW</creatorcontrib><creatorcontrib>MacGowan, A</creatorcontrib><creatorcontrib>Bayliss, M</creatorcontrib><creatorcontrib>Maskell, NA</creatorcontrib><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Thorax</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Arnold, DT</au><au>Read, L</au><au>Noel, A</au><au>Hamilton, FW</au><au>MacGowan, A</au><au>Bayliss, M</au><au>Maskell, NA</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>S13 Antibiotic penetration into the infected pleural space; a PK/PD study</atitle><jtitle>Thorax</jtitle><stitle>Thorax</stitle><date>2021-11-08</date><risdate>2021</risdate><volume>76</volume><issue>Suppl 2</issue><spage>A13</spage><epage>A13</epage><pages>A13-A13</pages><issn>0040-6376</issn><eissn>1468-3296</eissn><abstract>Introduction and ObjectivesPleural infection is a serious clinical condition with an average hospital length of stay of 13 days. Current standard of care defaults to hospital admission for drainage of the infected fluid and intravenous antibiotics. The standard empirical antibiotic choice varies nationally but the ability of these antibiotics to reach the pleura is poorly understood. Previous pharmacokinetics and pharmacodynamics (PK/PD) literature on the penetrance of antibiotics into pleural fluid is extrapolated from non-infected effusions (e.g. malignant effusions) or animal models.The Pleural Antibiotic Concentrations informing Treatment (PACT) study is a single centre PK/PD study that aims to assess the concentration of antibiotics within the infected pleural space to improve the evidence base around antimicrobial choice, route and duration of therapy.MethodsPatients with parapneumonic effusions/empyema planned for pleural drainage were prospectively recruited. Serial pleural fluid samples were collected timed with routine antibiotic administration and paired with synchronous serum sampling. Pleural fluid and serum antibiotic concentrations were measured using a validated high performance liquid chromatography (HPLC) method at the National Antimicrobial Reference Laboratory (Bristol UK).ResultsThis study is ongoing, further results on a wider range of antimicrobials will be available for the conference.At the time of writing, 18 patients had been recruited (15 CPPE, 3 empyema) with over 150 paired serum/fluid samples collected. Ten different antibiotics have been assayed although the majority of timepoints relate to Amoxicillin/Co-amoxiclav (n=36), Metronidazole (n=28) and Piperacillin-Tazobactam (n=22) at this time, see figure 1.Abstract S13 Figure 1Amoxicillin, Metronidazole and Tazocin (Tazobactam) levels in serum and pleural fluid post intravenous administrationFor these antibiotics the peak concentration and area under the curve within the pleural space was equivalent to serum levels. Importantly, across the dosing schedule the pleural antibiotic levels never fell below the minimum inhibitory concentrations (MICs) for bacteria known to cause pleural infection even when given orally. The pleural levels for penicillins persisted beyond the dosing schedule (8 hours) and were not affected by pleural pH or fibrinolytics.ConclusionsFor 3 commonly used antibiotics (Amoxicillin, Metronidazole, Piperacillin-Tazobactam) the pleural fluid concentration of antibiotic remined well above the usual MICs of causative bacteria. Penetrance and persistence of antibiotics make twice-daily or oral administration a possibility in pleural infection.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Thoracic Society</pub><doi>10.1136/thorax-2021-BTSabstracts.19</doi><oa>free_for_read</oa></addata></record> |
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title | S13 Antibiotic penetration into the infected pleural space; a PK/PD study |
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