{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:12:08Z","timestamp":1762542728468,"version":"3.41.2"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Ceftolozane-tazobactam displays potent activity against Gram-negative bacteria that can cause diabetic foot infections (DFI), making it an attractive treatment option when few alternatives exist. The pharmacokinetics and tissue penetration of ceftolozane-tazobactam at 1.5 g every 8 h (q8h) in patients (\n            <jats:italic>n<\/jats:italic>\n            = 10) with DFI were compared with those in healthy volunteers (\n            <jats:italic>n<\/jats:italic>\n            = 6) using\n            <jats:italic>in vivo<\/jats:italic>\n            microdialysis. In the patient participants, the median values of the pharmacokinetic parameters for ceftolozane in total plasma were as follows: maximum concentration (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ), 55.2 \u03bcg\/ml (range, 40.9 to 169.3 \u03bcg\/ml); half-life (\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>1\/2<\/jats:sub>\n            ), 3.5 h (range, 2.3 to 4.7 h); and area under the concentration-time curve (AUC) from time zero to 8 h (AUC\n            <jats:sub>0\u20138<\/jats:sub>\n            ), 191.6 \u03bcg \u00b7 h\/ml (range, 147.1 to 286.6 \u03bcg \u00b7 h\/ml). The median AUC for tissue (AUC\n            <jats:sub>tissue<\/jats:sub>\n            ; where AUC\n            <jats:sub>tissue<\/jats:sub>\n            was the AUC\n            <jats:sub>0\u20138<\/jats:sub>\n            for tissue for ceftolozane)\/AUC for plasma for each antibiotic corrected by the fraction of free drug (\n            <jats:italic>f<\/jats:italic>\n            AUC\n            <jats:sub>plasma<\/jats:sub>\n            ) was 0.75 (range, 0.35 to 1.00), resulting in a mean free time above 4 \u03bcg\/ml (the\n            <jats:named-content content-type=\"genus-species\">Pseudomonas aeruginosa<\/jats:named-content>\n            susceptibility breakpoint) in tissue of 99.8% (range, 87.5 to 100%). In the patient participants, the median values of the pharmacokinetic parameters for tazobactam in total plasma were as follows:\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            , 14.2 \u03bcg\/ml (range, 7.6 to 64.2 \u03bcg\/ml);\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>1\/2<\/jats:sub>\n            , 2.0 h (range, 0.7 to 2.4 h); and AUC\n            <jats:sub>0\u20138<\/jats:sub>\n            , 27.1 \u03bcg \u00b7 h\/ml (range, 15.0 to 70.0 \u03bcg \u00b7 h\/ml). The AUC\n            <jats:sub>tissue<\/jats:sub>\n            (where AUC\n            <jats:sub>tissue<\/jats:sub>\n            was the AUC from time zero to the time of the last measureable concentration in tissue for tazobactam)\/\n            <jats:italic>f<\/jats:italic>\n            AUC\n            <jats:sub>plasma<\/jats:sub>\n            for tazobactam was 1.18 (range, 0.54 to 1.44). In the healthy volunteers, the median values of the pharmacokinetic parameters for ceftolozane in total plasma were as follows:\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            , 91.5 \u03bcg\/ml (range, 65.7 to 110.7 \u03bcg\/ml);\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>1\/2<\/jats:sub>\n            , 1.9 h (range, 1.6 to 2.1 h); and AUC\n            <jats:sub>0\u20138<\/jats:sub>\n            , 191.3 \u03bcg \u00b7 h\/ml (range, 118.1 to 274.3 \u03bcg \u00b7 h\/ml). The median AUC\n            <jats:sub>tissue<\/jats:sub>\n            \/\n            <jats:italic>f<\/jats:italic>\n            AUC\n            <jats:sub>plasma<\/jats:sub>\n            was 0.87 (range, 0.54 to 2.20), resulting in a mean free time above 4 \u03bcg\/ml in tissue of 93.8% (range, 87.5 to 100%). In the healthy volunteers, the median values of the pharmacokinetic parameters for tazobactam in total plasma were as follows:\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            , 17.5 \u03bcg\/ml (range, 15.4 to 27.3 \u03bcg\/ml);\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>1\/2<\/jats:sub>\n            , 0.7 h (range, 0.6 to 0.8 h); and AUC\n            <jats:sub>0\u20138<\/jats:sub>\n            , 22.2 \u03bcg \u00b7 h\/ml (range, 19.2 to 36.4 \u03bcg \u00b7 h\/ml). The AUC\n            <jats:sub>tissue<\/jats:sub>\n            \/\n            <jats:italic>f<\/jats:italic>\n            AUC\n            <jats:sub>plasma<\/jats:sub>\n            for tazobactam was 0.85 (range, 0.63 to 2.10). Both ceftolozane and tazobactam penetrated into subcutaneous tissue with exposures similar to those of free drug in plasma in both patients with DFI and healthy volunteers. These data suggest that ceftolozane-tazobactam at 1.5 g q8h can achieve the optimal exposure with activity against susceptible Gram-negative pathogens in the tissue of patients with DFI. (This study has been registered at ClinicalTrials.gov under identifier NCT02620774.)\n          <\/jats:p>","DOI":"10.1128\/aac.01449-17","type":"journal-article","created":{"date-parts":[[2017,9,12]],"date-time":"2017-09-12T00:40:28Z","timestamp":1505176828000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Pharmacokinetics and Tissue Penetration of Ceftolozane-Tazobactam in Diabetic Patients with Lower Limb Infections and Healthy Adult Volunteers"],"prefix":"10.1128","volume":"61","author":[{"given":"Marguerite L.","family":"Monogue","sequence":"first","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean M.","family":"Stainton","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arlinda","family":"Baummer-Carr","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley K.","family":"Shepard","sequence":"additional","affiliation":[{"name":"Hartford Healthcare Medical Group, Podiatric Surgery, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James F.","family":"Nugent","sequence":"additional","affiliation":[{"name":"Hartford Healthcare Medical Group, Podiatric Surgery, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph L.","family":"Kuti","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David P.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA"},{"name":"Division of Infectious Diseases, Hartford Hospital, Hartford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v7.i7.153"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199409293311307"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2013.0518"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.828"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.22.3.382"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis346"},{"key":"e_1_3_2_8_2","volume-title":"Zerbaxa\u00ae (ceftolozane\/tazobactam) prescribing information","author":"Food and Drug Administration","year":"2014","unstructured":"Food and Drug Administration. 2014. 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