{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:05:21Z","timestamp":1785207921181,"version":"3.55.0"},"reference-count":65,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Antimicrobial efficacy can be predicted based on infection site exposure to the antimicrobial agent relative to the in vitro susceptibility of the pathogen to that agent. When infections occur in soft tissues (e.g., muscle, blood, and ligaments), exposure at the infection site is generally assumed to reflect an equilibrium between the unbound concentrations in plasma and that in the interstitial fluids. In contrast, for sporadic urinary tract infections (UTIs) in dogs and uncomplicated UTIs in humans, the primary site of infection is the bladder wall. Infection develops when bacteria invade the host bladder urothelium (specifically, the umbrella cells that form the urine\u2010contacting layer of the stratified uroepithelium) within which these bacteria can avoid exposure to host defenses and antimicrobial agents. Traditionally, pathogen susceptibility has been estimated using standardized in vitro tests that measure the minimal concentration that will inhibit pathogen growth (MIC). When using exposure\u2013response relationships during drug development to explore dose optimization, these relationships can either be based upon an assessment of a correlation between clinical outcome, drug exposure at the infection site, and pathogen MIC, or upon benchmark exposure\u2010response relationships (i.e., pharmacokinetic\/pharmacodynamic indices) typically used for the various drug classes. When using the latter approach, it is essential that the unbound concentrations at the infection site be considered relative to the MIC within the biological matrix to which the pathogen will be exposed. For soft tissue infections, this typically is the unbound plasma concentrations versus MICs determined in standardized media such as cation\u2010adjusted Mueller Hinton broth, which is how many indices were originally established. However, for UTIs, it is the unbound drug concentrations within the urine versus the MICs in the actual urine biophase that needs to be considered. The importance of these relationships and how they are influenced by drug resistance, resilience, and inoculum are discussed in this review using fluoroquinolones and beta\u2010lactams as examples.<\/jats:p>","DOI":"10.1111\/jvp.13088","type":"journal-article","created":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T08:53:12Z","timestamp":1659171192000},"page":"415-425","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Application of pharmacokinetic\/pharmacodynamic concepts to the development of treatment regimens for sporadic canine urinary tract infections: Challenges and paths forward"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4512-853X","authenticated-orcid":false,"given":"Marilyn N.","family":"Martinez","sequence":"first","affiliation":[{"name":"Food and Drug Administration, Center for Veterinary Medicine Office of New Animal Drug Evaluation Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4063-9373","authenticated-orcid":false,"given":"Ron A.","family":"Miller","sequence":"additional","affiliation":[{"name":"Division of Human Food Safety, Food and Drug Administration, Center for Veterinary Medicine Office of New Animal Drug Evaluation Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1483-9950","authenticated-orcid":false,"given":"Tom\u00e1s","family":"Mart\u00edn\u2010Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Division of Scientific Support, Food and Drug Administration, Center for Veterinary Medicine Office of New Animal Drug Evaluation Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele J.","family":"Sharkey","sequence":"additional","affiliation":[{"name":"Division of Companion Animal Drugs, Food and Drug Administration, Center for Veterinary Medicine Office of New Animal Drug Evaluation Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,7,30]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2020.1813567"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3270"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.6.1665\u20101670.2002"},{"issue":"10","key":"e_1_2_14_5_1","first-page":"985","article-title":"Antimicrobial resistance and prevalence of canine uropathogens at the Western College of Veterinary Medicine Veterinary Teaching Hospital, 2002\u20102007","volume":"49","author":"Ball K. R.","year":"2008","journal-title":"Canadian Veterinary Journal"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4377-0657-4.00007-7"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.21.03.0123"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9112279"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.4.933\u2010951.2001"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/11.3.361"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cvsm.2018.11.005"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2019.2408"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2013.778827"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201065602\u2010z"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00913"},{"key":"e_1_2_14_16_1","volume-title":"Performance standards for antimicrobial disk and dilution susceptibility tests for bacteria isolated from animals","author":"Clinical and Laboratory Standards Institute VET01S","year":"2020"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/104063870301500406"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.2460\/javma.2002.220.190"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096\u2010016\u20102577\u20100"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02446\u201016"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg269"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/511642"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/595739"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2011.01.004"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.9.2047"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01371\u201007"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2505"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0924\u20108579(02)00105\u2010x"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.00042"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2004.02106.x"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsmc\/xtaa004"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.542755"},{"issue":"5","key":"e_1_2_14_34_1","first-page":"346","article-title":"The primary cause of infection\u2010induced urinary stones","volume":"13","author":"Griffith D. P.","year":"1976","journal-title":"Investigative Urology"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000507540"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2014.12.010"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2019.06.009"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz226"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.UTI\u20100026\u20102016"},{"key":"e_1_2_14_40_1","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1111\/j.1939-1676.2001.tb02327.x","article-title":"Interrelations of organism prevalence, specimen collection method, and host age, sex, and breed among 8,354 canine urinary tract infections (1969\u20131995)","volume":"15","author":"Ling G. V.","year":"2001","journal-title":"Journal of Veterinary Internal Medicine"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05360\u201011"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10156\u2010006\u20100499\u2010y"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki163"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.691210"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9071416"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/1120009X.2017.1380357"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cvsm.2015.02.005"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20100500\u20107\u2010499"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2016.124"},{"key":"e_1_2_14_50_1","volume-title":"Henry's clinical diagnosis and management by laboratory methods","author":"Riley R. S.","year":"2022"},{"key":"e_1_2_14_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12448"},{"key":"e_1_2_14_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e318180fe62"},{"key":"e_1_2_14_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsle\/fnaa012"},{"key":"e_1_2_14_54_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009734.2014.904457"},{"key":"e_1_2_14_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2015.04.002"},{"key":"e_1_2_14_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2013.03.006"},{"key":"e_1_2_14_57_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.000476"},{"key":"e_1_2_14_58_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197411282912204"},{"key":"e_1_2_14_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2010.11.013"},{"key":"e_1_2_14_60_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00477\u201006"},{"key":"e_1_2_14_61_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/263768"},{"key":"e_1_2_14_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2019.02.008"},{"key":"e_1_2_14_63_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvim.16246"},{"key":"e_1_2_14_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939\u20101676.2012.00914.x"},{"key":"e_1_2_14_65_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.4.1483\u20101494.2005"},{"key":"e_1_2_14_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.urology.2014.04.048"}],"container-title":["Journal of Veterinary Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvp.13088","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvp.13088","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvp.13088","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T04:31:18Z","timestamp":1700886678000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvp.13088"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,30]]},"references-count":65,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1111\/jvp.13088"],"URL":"https:\/\/doi.org\/10.1111\/jvp.13088","archive":["Portico"],"relation":{},"ISSN":["0140-7783","1365-2885"],"issn-type":[{"value":"0140-7783","type":"print"},{"value":"1365-2885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,30]]},"assertion":[{"value":"2022-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}