Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute pulmonary exacerbations
Given the high frequency of acute pulmonary exacerbations due to Pseudomonas aeruginosa in patients with cystic fibrosis (CF), piperacillin/tazobactam is commonly used in empirical regimens. While extended-infusion piperacillin/tazobactam has been employed as one strategy to optimize this agent'...
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| Veröffentlicht in: | Journal of antimicrobial chemotherapy 2014-01, Vol.69 (1), p.176-179 |
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| container_title | Journal of antimicrobial chemotherapy |
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| creator | Butterfield, Jill M Lodise, Thomas P Beegle, Scott Rosen, Jonathan Farkas, Joshua Pai, Manjunath P |
| description | Given the high frequency of acute pulmonary exacerbations due to Pseudomonas aeruginosa in patients with cystic fibrosis (CF), piperacillin/tazobactam is commonly used in empirical regimens. While extended-infusion piperacillin/tazobactam has been employed as one strategy to optimize this agent's pharmacodynamics, this approach has not been well characterized in patients with CF. The objectives of this study were to characterize the pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with CF and derive optimized piperacillin/tazobactam dosing recommendations.
Six serum samples were collected from nine adult patients with CF hospitalized for acute pulmonary exacerbations who received 3/0.375 g of piperacillin/tazobactam intravenously for 4 h every 8 h. Population pharmacokinetic models were fitted to the data utilizing first-order, Michaelis-Menten (MM) and parallel first-order/MM clearance. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) for regimens where free piperacillin concentrations were above the MIC for at least 50% of the dosing interval.
The model incorporating MM clearance best described the data. Results of our simulation revealed that piperacillin/tazobactam dosed at 3-4 g for 30 min every 6-8 h led to 4 mg/L. More intensive prolonged infusion regimens than are commonly used in practice, such as continuous infusions or 3 h infusions every 6 h, were needed to maximize the PTA for MICs ≥ 8 mg/L.
Intensive prolonged infusion regimens are the best option to ensure optimal exposures against most susceptible isolates in adult patients with CF. |
| doi_str_mv | 10.1093/jac/dkt300 |
| format | Article |
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Six serum samples were collected from nine adult patients with CF hospitalized for acute pulmonary exacerbations who received 3/0.375 g of piperacillin/tazobactam intravenously for 4 h every 8 h. Population pharmacokinetic models were fitted to the data utilizing first-order, Michaelis-Menten (MM) and parallel first-order/MM clearance. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) for regimens where free piperacillin concentrations were above the MIC for at least 50% of the dosing interval.
The model incorporating MM clearance best described the data. Results of our simulation revealed that piperacillin/tazobactam dosed at 3-4 g for 30 min every 6-8 h led to <90% PTA against MIC values >4 mg/L. More intensive prolonged infusion regimens than are commonly used in practice, such as continuous infusions or 3 h infusions every 6 h, were needed to maximize the PTA for MICs ≥ 8 mg/L.
Intensive prolonged infusion regimens are the best option to ensure optimal exposures against most susceptible isolates in adult patients with CF.</description><identifier>ISSN: 0305-7453</identifier><identifier>EISSN: 1460-2091</identifier><identifier>DOI: 10.1093/jac/dkt300</identifier><identifier>PMID: 23869050</identifier><language>eng</language><publisher>England: Oxford Publishing Limited (England)</publisher><subject>Adult ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - pharmacokinetics ; Anti-Bacterial Agents - pharmacology ; Antibiotics ; Cystic fibrosis ; Cystic Fibrosis - complications ; Female ; Humans ; Infusions, Intravenous - methods ; Kinetics ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Monte Carlo simulation ; Penicillanic Acid - administration & dosage ; Penicillanic Acid - analogs & derivatives ; Penicillanic Acid - pharmacokinetics ; Penicillanic Acid - pharmacology ; Pharmacology ; Piperacillin - administration & dosage ; Piperacillin - pharmacokinetics ; Piperacillin - pharmacology ; Pneumonia, Bacterial - drug therapy ; Pseudomonas aeruginosa ; Pseudomonas aeruginosa - drug effects ; Pseudomonas Infections - drug therapy ; Respiratory diseases ; Serum - chemistry ; Time Factors ; Treatment Outcome ; Young Adult</subject><ispartof>Journal of antimicrobial chemotherapy, 2014-01, Vol.69 (1), p.176-179</ispartof><rights>Copyright Oxford Publishing Limited(England) Jan 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-5952f20d470c5551dfc9cc407b916bfc4dc270b205a5ab389d7e20fca77fbb523</citedby><cites>FETCH-LOGICAL-c384t-5952f20d470c5551dfc9cc407b916bfc4dc270b205a5ab389d7e20fca77fbb523</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23869050$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Butterfield, Jill M</creatorcontrib><creatorcontrib>Lodise, Thomas P</creatorcontrib><creatorcontrib>Beegle, Scott</creatorcontrib><creatorcontrib>Rosen, Jonathan</creatorcontrib><creatorcontrib>Farkas, Joshua</creatorcontrib><creatorcontrib>Pai, Manjunath P</creatorcontrib><title>Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute pulmonary exacerbations</title><title>Journal of antimicrobial chemotherapy</title><addtitle>J Antimicrob Chemother</addtitle><description>Given the high frequency of acute pulmonary exacerbations due to Pseudomonas aeruginosa in patients with cystic fibrosis (CF), piperacillin/tazobactam is commonly used in empirical regimens. While extended-infusion piperacillin/tazobactam has been employed as one strategy to optimize this agent's pharmacodynamics, this approach has not been well characterized in patients with CF. The objectives of this study were to characterize the pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with CF and derive optimized piperacillin/tazobactam dosing recommendations.
Six serum samples were collected from nine adult patients with CF hospitalized for acute pulmonary exacerbations who received 3/0.375 g of piperacillin/tazobactam intravenously for 4 h every 8 h. Population pharmacokinetic models were fitted to the data utilizing first-order, Michaelis-Menten (MM) and parallel first-order/MM clearance. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) for regimens where free piperacillin concentrations were above the MIC for at least 50% of the dosing interval.
The model incorporating MM clearance best described the data. Results of our simulation revealed that piperacillin/tazobactam dosed at 3-4 g for 30 min every 6-8 h led to <90% PTA against MIC values >4 mg/L. More intensive prolonged infusion regimens than are commonly used in practice, such as continuous infusions or 3 h infusions every 6 h, were needed to maximize the PTA for MICs ≥ 8 mg/L.
Intensive prolonged infusion regimens are the best option to ensure optimal exposures against most susceptible isolates in adult patients with CF.</description><subject>Adult</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - pharmacokinetics</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibiotics</subject><subject>Cystic fibrosis</subject><subject>Cystic Fibrosis - complications</subject><subject>Female</subject><subject>Humans</subject><subject>Infusions, Intravenous - methods</subject><subject>Kinetics</subject><subject>Male</subject><subject>Microbial Sensitivity Tests</subject><subject>Middle Aged</subject><subject>Monte Carlo simulation</subject><subject>Penicillanic Acid - administration & dosage</subject><subject>Penicillanic Acid - analogs & derivatives</subject><subject>Penicillanic Acid - pharmacokinetics</subject><subject>Penicillanic Acid - pharmacology</subject><subject>Pharmacology</subject><subject>Piperacillin - administration & dosage</subject><subject>Piperacillin - pharmacokinetics</subject><subject>Piperacillin - pharmacology</subject><subject>Pneumonia, Bacterial - drug therapy</subject><subject>Pseudomonas aeruginosa</subject><subject>Pseudomonas aeruginosa - drug effects</subject><subject>Pseudomonas Infections - drug therapy</subject><subject>Respiratory diseases</subject><subject>Serum - chemistry</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0305-7453</issn><issn>1460-2091</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqN0c1q3DAQB3BRGppt2ksfoAh6KQFnx5Zl2ccS-gWB5tCezeiLaGNLriSTbF-mrxotu-2hp54Ew29m0PwJeVPDVQ0D2-5QbfV9ZgDPyKZuO6gaGOrnZAMMeCVazs7Jy5R2ANDxrn9BzhvWdwNw2JDft3cYZ1Th3nmTnUoUvabLqaj3HudDMVhqHrPx2ujKebsmFzxd3GIiKjdNzm8z_goSVcaZOk9Rr1OmC2ZnfE70weU7qvapLKDWyRiSS1U0E2ajKao1G7qs0xw8xn1ZhMpEWXqDT6_ImcUpmden94L8-PTx-_WX6ubb56_XH24qxfo2V3zgjW1AtwIU57zWVg1KtSDkUHfSqlarRoBsgCNHyfpBC9OAVSiElZI37IK8P85dYvi5mpTH2SVlpgm9CWsa63ZounYQ7f9QITjvgdeFvvuH7sIaffnIQUFfEONFXR6VKodJ0dhxiW4upxhrGA8JjyXh8ZhwwW9PI1c5G_2X_omUPQGbh6a1</recordid><startdate>201401</startdate><enddate>201401</enddate><creator>Butterfield, Jill M</creator><creator>Lodise, Thomas P</creator><creator>Beegle, Scott</creator><creator>Rosen, Jonathan</creator><creator>Farkas, Joshua</creator><creator>Pai, Manjunath P</creator><general>Oxford Publishing Limited (England)</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>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201401</creationdate><title>Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute pulmonary exacerbations</title><author>Butterfield, Jill M ; Lodise, Thomas P ; Beegle, Scott ; Rosen, Jonathan ; Farkas, Joshua ; Pai, Manjunath P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-5952f20d470c5551dfc9cc407b916bfc4dc270b205a5ab389d7e20fca77fbb523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adult</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Anti-Bacterial Agents - pharmacokinetics</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibiotics</topic><topic>Cystic fibrosis</topic><topic>Cystic Fibrosis - complications</topic><topic>Female</topic><topic>Humans</topic><topic>Infusions, Intravenous - methods</topic><topic>Kinetics</topic><topic>Male</topic><topic>Microbial Sensitivity Tests</topic><topic>Middle Aged</topic><topic>Monte Carlo simulation</topic><topic>Penicillanic Acid - administration & dosage</topic><topic>Penicillanic Acid - analogs & derivatives</topic><topic>Penicillanic Acid - pharmacokinetics</topic><topic>Penicillanic Acid - pharmacology</topic><topic>Pharmacology</topic><topic>Piperacillin - administration & dosage</topic><topic>Piperacillin - pharmacokinetics</topic><topic>Piperacillin - pharmacology</topic><topic>Pneumonia, Bacterial - drug therapy</topic><topic>Pseudomonas aeruginosa</topic><topic>Pseudomonas aeruginosa - drug effects</topic><topic>Pseudomonas Infections - drug therapy</topic><topic>Respiratory diseases</topic><topic>Serum - chemistry</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Butterfield, Jill M</creatorcontrib><creatorcontrib>Lodise, Thomas P</creatorcontrib><creatorcontrib>Beegle, Scott</creatorcontrib><creatorcontrib>Rosen, Jonathan</creatorcontrib><creatorcontrib>Farkas, Joshua</creatorcontrib><creatorcontrib>Pai, Manjunath P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of antimicrobial chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Butterfield, Jill M</au><au>Lodise, Thomas P</au><au>Beegle, Scott</au><au>Rosen, Jonathan</au><au>Farkas, Joshua</au><au>Pai, Manjunath P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute pulmonary exacerbations</atitle><jtitle>Journal of antimicrobial chemotherapy</jtitle><addtitle>J Antimicrob Chemother</addtitle><date>2014-01</date><risdate>2014</risdate><volume>69</volume><issue>1</issue><spage>176</spage><epage>179</epage><pages>176-179</pages><issn>0305-7453</issn><eissn>1460-2091</eissn><abstract>Given the high frequency of acute pulmonary exacerbations due to Pseudomonas aeruginosa in patients with cystic fibrosis (CF), piperacillin/tazobactam is commonly used in empirical regimens. While extended-infusion piperacillin/tazobactam has been employed as one strategy to optimize this agent's pharmacodynamics, this approach has not been well characterized in patients with CF. The objectives of this study were to characterize the pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with CF and derive optimized piperacillin/tazobactam dosing recommendations.
Six serum samples were collected from nine adult patients with CF hospitalized for acute pulmonary exacerbations who received 3/0.375 g of piperacillin/tazobactam intravenously for 4 h every 8 h. Population pharmacokinetic models were fitted to the data utilizing first-order, Michaelis-Menten (MM) and parallel first-order/MM clearance. Monte Carlo simulations were performed to determine the probability of target attainment (PTA) for regimens where free piperacillin concentrations were above the MIC for at least 50% of the dosing interval.
The model incorporating MM clearance best described the data. Results of our simulation revealed that piperacillin/tazobactam dosed at 3-4 g for 30 min every 6-8 h led to <90% PTA against MIC values >4 mg/L. More intensive prolonged infusion regimens than are commonly used in practice, such as continuous infusions or 3 h infusions every 6 h, were needed to maximize the PTA for MICs ≥ 8 mg/L.
Intensive prolonged infusion regimens are the best option to ensure optimal exposures against most susceptible isolates in adult patients with CF.</abstract><cop>England</cop><pub>Oxford Publishing Limited (England)</pub><pmid>23869050</pmid><doi>10.1093/jac/dkt300</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of antimicrobial chemotherapy, 2014-01, Vol.69 (1), p.176-179 |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adult Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - pharmacokinetics Anti-Bacterial Agents - pharmacology Antibiotics Cystic fibrosis Cystic Fibrosis - complications Female Humans Infusions, Intravenous - methods Kinetics Male Microbial Sensitivity Tests Middle Aged Monte Carlo simulation Penicillanic Acid - administration & dosage Penicillanic Acid - analogs & derivatives Penicillanic Acid - pharmacokinetics Penicillanic Acid - pharmacology Pharmacology Piperacillin - administration & dosage Piperacillin - pharmacokinetics Piperacillin - pharmacology Pneumonia, Bacterial - drug therapy Pseudomonas aeruginosa Pseudomonas aeruginosa - drug effects Pseudomonas Infections - drug therapy Respiratory diseases Serum - chemistry Time Factors Treatment Outcome Young Adult |
| title | Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute pulmonary exacerbations |
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