{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/22515"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/22515","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Antimicrobial pharmacodynamics: The gentamicin - Escherichia coli relationship","abstract":"The purpose of this thesis was to: (1) explore the in vitro dose-response relationship between gentamicin and Escherichia coli under conditions of constant and declining antibiotic concentrations and (2) to characterize the kinetics of the relationship in an attempt to better predict antimicrobial efficacy. A unique in vitro dynamic culture system was constructed to subject bacteria growing in broth culture to drug concentrations simulating in vivo gentamicin exposure. Changes in viability were monitored as a function of antibiotic concentration and duration of exposure following continuous and IV bolus dose simulations. Significant bacterial killing first occurred at gentamicin concentrations equal to 1/2 the MIC. Exposure to drug concentrations between 1/2 and 2 $\\times$ the MIC resulted in a 99.9% loss of viability, followed by resistant regrowth within 4 hours. Resistant bacteria were also identified after single IV bolus dose exposure. Drug resistance was increased up to 8 $\\times$ the original MIC and was unstable in antibiotic-free media.","abstract_html":"The purpose of this thesis was to: (1) explore the in vitro dose-response relationship between gentamicin and Escherichia coli under conditions of constant and declining antibiotic concentrations and (2) to characterize the kinetics of the relationship in an attempt to better predict antimicrobial efficacy. A unique in vitro dynamic culture system was constructed to subject bacteria growing in broth culture to drug concentrations simulating in vivo gentamicin exposure. Changes in viability were monitored as a function of antibiotic concentration and duration of exposure following continuous and IV bolus dose simulations. Significant bacterial killing first occurred at gentamicin concentrations equal to 1/2 the MIC. Exposure to drug concentrations between 1/2 and 2 $\\times$ the MIC resulted in a 99.9% loss of viability, followed by resistant regrowth within 4 hours. Resistant bacteria were also identified after single IV bolus dose exposure. Drug resistance was increased up to 8 $\\times$ the original MIC and was unstable in antibiotic-free media.","abstract_has_math":true,"creators":["Kilroy, Carolyn S."],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Comparative Biosciences","degree_department":null,"school":null,"contributors":["Bevill, R.F."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-05-07T13:42:18Z","date_published":"2011-05-07T13:42:18Z","updated_at":"2026-07-22T22:25:20Z","subjects":["Biology, Microbiology","Health Sciences, Pharmacology"],"languages":["eng"],"rights":["Copyright 1995 Kilroy, Carolyn S."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9624387","(UMI)AAI9624387"],"render_values":[{"text":"AAI9624387","href":null,"code":true},{"text":"(UMI)AAI9624387","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2142/22515","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Bevill, R.F."]},{"key":"dc:creator","label":"Author","values":["Kilroy, Carolyn S."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2011-05-07T13:42:18Z","10000-01-01","1995"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Comparative Biosciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology, Microbiology","Health Sciences, Pharmacology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 1995 Kilroy, Carolyn S."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["AAI9624387","(UMI)AAI9624387","http://hdl.handle.net/2142/22515"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The purpose of this thesis was to: (1) explore the in vitro dose-response relationship between gentamicin and Escherichia coli under conditions of constant and declining antibiotic concentrations and (2) to characterize the kinetics of the relationship in an attempt to better predict antimicrobial efficacy. A unique in vitro dynamic culture system was constructed to subject bacteria growing in broth culture to drug concentrations simulating in vivo gentamicin exposure. Changes in viability were monitored as a function of antibiotic concentration and duration of exposure following continuous and IV bolus dose simulations. Significant bacterial killing first occurred at gentamicin concentrations equal to 1/2 the MIC. Exposure to drug concentrations between 1/2 and 2 $\\times$ the MIC resulted in a 99.9% loss of viability, followed by resistant regrowth within 4 hours. Resistant bacteria were also identified after single IV bolus dose exposure. Drug resistance was increased up to 8 $\\times$ the original MIC and was unstable in antibiotic-free media.","Data from all experiments was analyzed using response surface methodologies and biological modeling techniques. The pharmacodynamics of the gentamicin-E. coli relationship were found to be similar under variable drug exposure conditions by response surface modeling. Duration of drug exposure was considered to be statistically significant, while drug concentration was considered significant only in relation to quadratic concentration-time interactions. Mechanistically, the biologically based pharmacodynamic model suggested that bacterial uptake of gentamicin could be explained by normal physiochemical processes, contrary to hypotheses proposing sophisticated uptake mechanisms. The role of adaptive down-regulation of drug uptake, as a mechanism of acquired resistance, was also explored.","Made available in DSpace on 2011-05-07T13:42:18Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9624387.pdf: 7349431 bytes, checksum: 99d840e8304986b2abfbb490583bfc84 (MD5) Previous issue date: 1995","Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:58:08Z Item is restricted indefinitely.","Restriction data tranferred 2014-07-01T11:27:19-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission","ETDs are only available to UIUC Users without author permission","U of I Only"]},{"key":"dc:title","label":"Title","values":["Antimicrobial pharmacodynamics: The gentamicin - Escherichia coli relationship"]}]}],"canonical_facts":{"dc:contributor":["Bevill, R.F."],"dc:creator":["Kilroy, Carolyn S."],"dc:date":["2011-05-07T13:42:18Z","10000-01-01","1995"],"dc:description":["The purpose of this thesis was to: (1) explore the in vitro dose-response relationship between gentamicin and Escherichia coli under conditions of constant and declining antibiotic concentrations and (2) to characterize the kinetics of the relationship in an attempt to better predict antimicrobial efficacy. A unique in vitro dynamic culture system was constructed to subject bacteria growing in broth culture to drug concentrations simulating in vivo gentamicin exposure. Changes in viability were monitored as a function of antibiotic concentration and duration of exposure following continuous and IV bolus dose simulations. Significant bacterial killing first occurred at gentamicin concentrations equal to 1/2 the MIC. Exposure to drug concentrations between 1/2 and 2 $\\times$ the MIC resulted in a 99.9% loss of viability, followed by resistant regrowth within 4 hours. Resistant bacteria were also identified after single IV bolus dose exposure. Drug resistance was increased up to 8 $\\times$ the original MIC and was unstable in antibiotic-free media.","Data from all experiments was analyzed using response surface methodologies and biological modeling techniques. The pharmacodynamics of the gentamicin-E. coli relationship were found to be similar under variable drug exposure conditions by response surface modeling. Duration of drug exposure was considered to be statistically significant, while drug concentration was considered significant only in relation to quadratic concentration-time interactions. Mechanistically, the biologically based pharmacodynamic model suggested that bacterial uptake of gentamicin could be explained by normal physiochemical processes, contrary to hypotheses proposing sophisticated uptake mechanisms. The role of adaptive down-regulation of drug uptake, as a mechanism of acquired resistance, was also explored.","Made available in DSpace on 2011-05-07T13:42:18Z (GMT). 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