Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients.
Identifieur interne : 001093 ( PubMed/Corpus ); précédent : 001092; suivant : 001094Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients.
Auteurs : Abdulaziz S. Alobaid ; Steven C. Wallis ; Paul Jarrett ; Therese Starr ; Janine Stuart ; Melissa Lassig-Smith ; Jenny Lisette Ord Ez Mejia ; Michael S. Roberts ; Claire Roger ; Andrew A. Udy ; Jeffrey Lipman ; Jason A. RobertsSource :
- Antimicrobial agents and chemotherapy [ 1098-6596 ] ; 2017.
English descriptors
- KwdEn :
- Adult, Aged, Anti-Bacterial Agents (blood), Anti-Bacterial Agents (pharmacokinetics), Bacterial Infections (blood), Bacterial Infections (complications), Bacterial Infections (drug therapy), Bacterial Infections (microbiology), Biological Availability, Body Mass Index, Creatinine (blood), Critical Illness, Drug Administration Schedule, Drug Dosage Calculations, Female, Humans, Infusions, Intravenous, Linear Models, Male, Microbial Sensitivity Tests, Middle Aged, Monte Carlo Method, Obesity, Morbid (blood), Obesity, Morbid (complications), Obesity, Morbid (drug therapy), Obesity, Morbid (microbiology), Penicillanic Acid (analogs & derivatives), Penicillanic Acid (blood), Penicillanic Acid (pharmacokinetics), Piperacillin (blood), Piperacillin (pharmacokinetics).
- MESH :
- chemical , analogs & derivatives : Penicillanic Acid.
- chemical , blood : Anti-Bacterial Agents, Creatinine, Penicillanic Acid, Piperacillin.
- chemical , pharmacokinetics : Anti-Bacterial Agents, Penicillanic Acid, Piperacillin.
- blood : Bacterial Infections, Obesity, Morbid.
- complications : Bacterial Infections, Obesity, Morbid.
- drug therapy : Bacterial Infections, Obesity, Morbid.
- microbiology : Bacterial Infections, Obesity, Morbid.
- Adult, Aged, Biological Availability, Body Mass Index, Critical Illness, Drug Administration Schedule, Drug Dosage Calculations, Female, Humans, Infusions, Intravenous, Linear Models, Male, Microbial Sensitivity Tests, Middle Aged, Monte Carlo Method.
Abstract
The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m(2), respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h(-1), and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h(-1) A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.
DOI: 10.1128/AAC.01276-16
PubMed: 28052849
Links to Exploration step
pubmed:28052849Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients.</title><author><name sortKey="Alobaid, Abdulaziz S" sort="Alobaid, Abdulaziz S" uniqKey="Alobaid A" first="Abdulaziz S" last="Alobaid">Abdulaziz S. Alobaid</name><affiliation><nlm:affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Wallis, Steven C" sort="Wallis, Steven C" uniqKey="Wallis S" first="Steven C" last="Wallis">Steven C. Wallis</name><affiliation><nlm:affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Jarrett, Paul" sort="Jarrett, Paul" uniqKey="Jarrett P" first="Paul" last="Jarrett">Paul Jarrett</name><affiliation><nlm:affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Starr, Therese" sort="Starr, Therese" uniqKey="Starr T" first="Therese" last="Starr">Therese Starr</name><affiliation><nlm:affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Stuart, Janine" sort="Stuart, Janine" uniqKey="Stuart J" first="Janine" last="Stuart">Janine Stuart</name><affiliation><nlm:affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Lassig Smith, Melissa" sort="Lassig Smith, Melissa" uniqKey="Lassig Smith M" first="Melissa" last="Lassig-Smith">Melissa Lassig-Smith</name><affiliation><nlm:affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Mejia, Jenny Lisette Ord Ez" sort="Mejia, Jenny Lisette Ord Ez" uniqKey="Mejia J" first="Jenny Lisette Ord Ez" last="Mejia">Jenny Lisette Ord Ez Mejia</name><affiliation><nlm:affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Roberts, Michael S" sort="Roberts, Michael S" uniqKey="Roberts M" first="Michael S" last="Roberts">Michael S. 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Alobaid</name><affiliation><nlm:affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Wallis, Steven C" sort="Wallis, Steven C" uniqKey="Wallis S" first="Steven C" last="Wallis">Steven C. Wallis</name><affiliation><nlm:affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Jarrett, Paul" sort="Jarrett, Paul" uniqKey="Jarrett P" first="Paul" last="Jarrett">Paul Jarrett</name><affiliation><nlm:affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Starr, Therese" sort="Starr, Therese" uniqKey="Starr T" first="Therese" last="Starr">Therese Starr</name><affiliation><nlm:affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Stuart, Janine" sort="Stuart, Janine" uniqKey="Stuart J" first="Janine" last="Stuart">Janine Stuart</name><affiliation><nlm:affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Lassig Smith, Melissa" sort="Lassig Smith, Melissa" uniqKey="Lassig Smith M" first="Melissa" last="Lassig-Smith">Melissa Lassig-Smith</name><affiliation><nlm:affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Mejia, Jenny Lisette Ord Ez" sort="Mejia, Jenny Lisette Ord Ez" uniqKey="Mejia J" first="Jenny Lisette Ord Ez" last="Mejia">Jenny Lisette Ord Ez Mejia</name><affiliation><nlm:affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Roberts, Michael S" sort="Roberts, Michael S" uniqKey="Roberts M" first="Michael S" last="Roberts">Michael S. Roberts</name><affiliation><nlm:affiliation>Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Roger, Claire" sort="Roger, Claire" uniqKey="Roger C" first="Claire" last="Roger">Claire Roger</name><affiliation><nlm:affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Udy, Andrew A" sort="Udy, Andrew A" uniqKey="Udy A" first="Andrew A" last="Udy">Andrew A. Udy</name><affiliation><nlm:affiliation>Department of Intensive Care and Hyperbaric Medicine, The Alfred, Prahran, Melbourne, Victoria, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Lipman, Jeffrey" sort="Lipman, Jeffrey" uniqKey="Lipman J" first="Jeffrey" last="Lipman">Jeffrey Lipman</name><affiliation><nlm:affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Roberts, Jason A" sort="Roberts, Jason A" uniqKey="Roberts J" first="Jason A" last="Roberts">Jason A. Roberts</name><affiliation><nlm:affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia j.roberts2@uq.edu.au.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Antimicrobial agents and chemotherapy</title><idno type="eISSN">1098-6596</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Anti-Bacterial Agents (blood)</term><term>Anti-Bacterial Agents (pharmacokinetics)</term><term>Bacterial Infections (blood)</term><term>Bacterial Infections (complications)</term><term>Bacterial Infections (drug therapy)</term><term>Bacterial Infections (microbiology)</term><term>Biological Availability</term><term>Body Mass Index</term><term>Creatinine (blood)</term><term>Critical Illness</term><term>Drug Administration Schedule</term><term>Drug Dosage Calculations</term><term>Female</term><term>Humans</term><term>Infusions, Intravenous</term><term>Linear Models</term><term>Male</term><term>Microbial Sensitivity Tests</term><term>Middle Aged</term><term>Monte Carlo Method</term><term>Obesity, Morbid (blood)</term><term>Obesity, Morbid (complications)</term><term>Obesity, Morbid (drug therapy)</term><term>Obesity, Morbid (microbiology)</term><term>Penicillanic Acid (analogs & derivatives)</term><term>Penicillanic Acid (blood)</term><term>Penicillanic Acid (pharmacokinetics)</term><term>Piperacillin (blood)</term><term>Piperacillin (pharmacokinetics)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Penicillanic Acid</term></keywords><keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Creatinine</term><term>Penicillanic Acid</term><term>Piperacillin</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Penicillanic Acid</term><term>Piperacillin</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Bacterial Infections</term><term>Obesity, Morbid</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Bacterial Infections</term><term>Obesity, Morbid</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Bacterial Infections</term><term>Obesity, Morbid</term></keywords><keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Bacterial Infections</term><term>Obesity, Morbid</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Biological Availability</term><term>Body Mass Index</term><term>Critical Illness</term><term>Drug Administration Schedule</term><term>Drug Dosage Calculations</term><term>Female</term><term>Humans</term><term>Infusions, Intravenous</term><term>Linear Models</term><term>Male</term><term>Microbial Sensitivity Tests</term><term>Middle Aged</term><term>Monte Carlo Method</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m(2), respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h(-1), and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h(-1) A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">28052849</PMID><DateCreated><Year>2017</Year><Month>01</Month><Day>05</Day></DateCreated><DateCompleted><Year>2017</Year><Month>09</Month><Day>20</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>20</Day></DateRevised><Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1098-6596</ISSN><JournalIssue CitedMedium="Internet"><Volume>61</Volume><Issue>3</Issue><PubDate><Year>2017</Year><Month>Mar</Month></PubDate></JournalIssue><Title>Antimicrobial agents and chemotherapy</Title><ISOAbbreviation>Antimicrob. Agents Chemother.</ISOAbbreviation></Journal><ArticleTitle>Population Pharmacokinetics of Piperacillin in Nonobese, Obese, and Morbidly Obese Critically Ill Patients.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">e01276-16</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1128/AAC.01276-16</ELocationID><Abstract><AbstractText>The treatment of infections in critically ill obese and morbidly obese patients is challenging because of the combined physiological changes that result from obesity and critical illness. The aim of this study was to describe the population pharmacokinetics of piperacillin in a cohort of critically ill patients, including obese and morbidly obese patients. Critically ill patients who received piperacillin-tazobactam were classified according to their body mass index (BMI) as nonobese, obese, and morbidly obese. Plasma samples were collected, and piperacillin concentrations were determined by a validated chromatographic method. Population pharmacokinetic analysis and Monte Carlo dosing simulations were performed using Pmetrics software. Thirty-seven critically ill patients (including 12 obese patients and 12 morbidly obese patients) were enrolled. The patients' mean ± standard deviation age, weight, and BMI were 50 ± 15 years, 104 ± 35 kg, and 38.0 ± 15.0 kg/m(2), respectively. The concentration-time data were best described by a two-compartment linear model. The mean ± SD parameter estimates for the final covariate model were a clearance of 14.0 ± 7.1 liters/h, a volume of distribution of the central compartment of 49.0 ± 19.0 liters, an intercompartmental clearance from the central compartment to the peripheral compartment of 0.9 ± 0.6 liters · h(-1), and an intercompartmental clearance from the peripheral compartment to the central compartment of 2.3 ± 2.8 liters · h(-1) A higher measured creatinine clearance and shorter-duration infusions were associated with a lower likelihood of achieving therapeutic piperacillin exposures in patients in all BMI categories. Piperacillin pharmacokinetics are altered in the presence of obesity and critical illness. As with nonobese patients, prolonged infusions increase the likelihood of achieving therapeutic concentrations.</AbstractText><CopyrightInformation>Copyright © 2017 American Society for Microbiology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Alobaid</LastName><ForeName>Abdulaziz S</ForeName><Initials>AS</Initials><AffiliationInfo><Affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pharmacy, King Saud Medical City, Riyadh, Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wallis</LastName><ForeName>Steven C</ForeName><Initials>SC</Initials><AffiliationInfo><Affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jarrett</LastName><ForeName>Paul</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Starr</LastName><ForeName>Therese</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stuart</LastName><ForeName>Janine</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lassig-Smith</LastName><ForeName>Melissa</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mejia</LastName><ForeName>Jenny Lisette Ordóñez</ForeName><Initials>JL</Initials><AffiliationInfo><Affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roberts</LastName><ForeName>Michael S</ForeName><Initials>MS</Initials><AffiliationInfo><Affiliation>Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roger</LastName><ForeName>Claire</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Anesthesiology, Critical Care Pain, and Emergency Medicine, Nimes University Hospital, Nimes, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Udy</LastName><ForeName>Andrew A</ForeName><Initials>AA</Initials><AffiliationInfo><Affiliation>Department of Intensive Care and Hyperbaric Medicine, The Alfred, Prahran, Melbourne, Victoria, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Epidemiology and Preventive Medicine, The Alfred, Monash University, Prahran, Melbourne, Victoria, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lipman</LastName><ForeName>Jeffrey</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Faculty of Health, Queensland University of Technology, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roberts</LastName><ForeName>Jason A</ForeName><Initials>JA</Initials><AffiliationInfo><Affiliation>Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia j.roberts2@uq.edu.au.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre for Translational Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D064888">Observational Study</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>02</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Antimicrob Agents Chemother</MedlineTA><NlmUniqueID>0315061</NlmUniqueID><ISSNLinking>0066-4804</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000900">Anti-Bacterial Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>157044-21-8</RegistryNumber><NameOfSubstance UI="C085143">piperacillin, tazobactam drug combination</NameOfSubstance></Chemical><Chemical><RegistryNumber>87-53-6</RegistryNumber><NameOfSubstance UI="D010397">Penicillanic Acid</NameOfSubstance></Chemical><Chemical><RegistryNumber>AYI8EX34EU</RegistryNumber><NameOfSubstance UI="D003404">Creatinine</NameOfSubstance></Chemical><Chemical><RegistryNumber>X00B0D5O0E</RegistryNumber><NameOfSubstance 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Care Med. 1985 Oct;13(10):818-29</RefSource><PMID Version="1">3928249</PMID></CommentsCorrections></CommentsCorrectionsList><MeshHeadingList><MeshHeading><DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000900" MajorTopicYN="N">Anti-Bacterial Agents</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000493" MajorTopicYN="Y">pharmacokinetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D001424" MajorTopicYN="N">Bacterial Infections</DescriptorName><QualifierName UI="Q000097" MajorTopicYN="N">blood</QualifierName><QualifierName UI="Q000150" MajorTopicYN="N">complications</QualifierName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000382" 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MajorTopicYN="N">pharmacokinetics</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2016</Year><Month>06</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2016</Year><Month>12</Month><Day>24</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>1</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>9</Month><Day>21</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>1</Month><Day>6</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28052849</ArticleId><ArticleId IdType="pii">AAC.01276-16</ArticleId><ArticleId IdType="doi">10.1128/AAC.01276-16</ArticleId><ArticleId IdType="pmc">PMC5328553</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour 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