{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:13:01Z","timestamp":1792174381297,"version":"4.4.0"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Seventh EU Framework Programme"},{"name":"Project Information AIDA","award":["278348"],"award-info":[{"award-number":["278348"]}]},{"DOI":"10.13039\/100011272","name":"FP7 Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010897","name":"Newton Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010897","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Merck & Co"},{"name":"Paratek Pharmaceuticals"},{"name":"VenatorRx Pharmaceuticals"},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"name":"F2G"},{"DOI":"10.13039\/501100005612","name":"Shionogi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005612","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Tetracyclines are widely used as oral therapy of MRSA infection, however, the pharmacodynamic underpinning is absent.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>We employed an in vitro pharmacokinetic model to study the pharmacodynamics of minocycline alone and in combination with rifampicin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>An exposure-ranging design was used to establish fAUC\/MIC targets for static, \u22121\u2009log drop and \u22122\u2009log drop effects against Staphylococcus aureus for minocycline and in combination with rifampicin. We then simulated 7\u201310\u2009day human dosing of minocycline and the combination.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The minocycline fAUC\/MIC for 24\u2009h static effect and \u22121\u2009log drop in bacterial load were 12.5\u200a\u00b1\u200a7.1 and 23.3\u200a\u00b1\u200a12.4. fAUC\/MIC targets for static and \u22121\u2009log drop were greater at 48 and 72\u2009h. The addition of simulated free rifampicin associated with dosing 300\u2009mg q12h reduced the 24\u2009h minocycline fAUC\/MICs. Simulations performed over 7\u201310\u2009days exposure indicated that for minocycline standard human doses there was a 1\u20133\u2009log reduction in viable count and no changes in population profiles. Addition of rifampicin resulted in larger reductions in staphylococcal load but emergence of resistance to rifampicin. There was no resistance to minocycline.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>An fAUC\/MIC minocycline target of 12\u201336 is appropriate for S. aureus. Addition of rifampicin decreases bacterial load but results in emergence of resistance to rifampicin. Unusually, there was no emergence of resistance to minocycline.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkab112","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T19:28:06Z","timestamp":1620415686000},"page":"1840-1844","source":"Crossref","is-referenced-by-count":9,"title":["The pharmacodynamics of minocycline alone and in combination with rifampicin against <i>Staphylococcus aureus<\/i> studied in an <i>in vitro<\/i> pharmacokinetic model of infection"],"prefix":"10.1093","volume":"76","author":[{"given":"A R","family":"Noel","sequence":"first","affiliation":[{"name":"Bristol Centre for Antimicrobial Research & Evaluation (BCARE), North Bristol NHS Trust, Department of Infection Sciences, Pathology Sciences Building\u2014Phase 2, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Attwood","sequence":"additional","affiliation":[{"name":"Bristol Centre for Antimicrobial Research & Evaluation (BCARE), North Bristol NHS Trust, Department of Infection Sciences, Pathology Sciences Building\u2014Phase 2, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K E","family":"Bowker","sequence":"additional","affiliation":[{"name":"Bristol Centre for Antimicrobial Research & Evaluation (BCARE), North Bristol NHS Trust, Department of Infection Sciences, Pathology Sciences Building\u2014Phase 2, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A P","family":"MacGowan","sequence":"additional","affiliation":[{"name":"Bristol Centre for Antimicrobial Research & Evaluation (BCARE), North Bristol NHS Trust, Department of Infection Sciences, Pathology Sciences Building\u2014Phase 2, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, 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