{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:05:08Z","timestamp":1790719508838,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T00:00:00Z","timestamp":1427846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Ceftazidime and the \u03b2-lactamase inhibitor avibactam constitute a new, potentially highly active combination in the battle against extended-spectrum-\u03b2-lactamase (ESBL)-producing bacteria. To determine possible clinical use, it is important to know the pharmacokinetic profiles of the compounds related to each other in plasma and the different compartments of infection in experimentally infected animals and in humans. We used a neutropenic murine thigh infection model and lung infection model to study pharmacokinetics in plasma and epithelial lining fluid (ELF). Mice were infected with ca. 10\n            <jats:sup>6<\/jats:sup>\n            CFU of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:named-content>\n            intramuscularly into the thigh or intranasally to cause pneumonia and were given 8 different (single) subcutaneous doses of ceftazidime and avibactam in various combined concentrations, ranging from 1 to 128 mg\/kg of body weight in 2-fold increases. Concomitant samples of serum and bronchoalveolar lavage fluid were taken at up to 12 time points until 6 h after administration. Pharmacokinetics of both compounds were linear and dose proportional in plasma and ELF and were independent of the infection type, with estimated half-lives (standard deviations [SD]) in plasma of ceftazidime of 0.28 (0.02) h and of avibactam of 0.24 (0.04) h and volumes of distribution of 0.80 (0.14) and 1.18 (0.34) liters\/kg. The ELF-plasma (area under the concentration-time curve [AUC]) ratios (standard errors [SE]) were 0.24 (0.03) for total ceftazidime and 0.27 (0.03) for unbound ceftazidime; for avibactam, the ratios were 0.20 (0.02) and 0.22 (0.02), respectively. No pharmacokinetic interaction between ceftazidime and avibactam was observed. Ceftazidime and avibactam showed linear plasma pharmacokinetics that were independent of the dose combinations used or the infection site in mice. Assuming pharmacokinetic similarity in humans, this indicates that similar dose ratios of ceftazidime and avibactam could be used for different types and sites of infection.\n          <\/jats:p>","DOI":"10.1128\/aac.04627-14","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T06:04:54Z","timestamp":1422943494000},"page":"2299-2304","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":58,"title":["Pharmacokinetics and Penetration of Ceftazidime and Avibactam into Epithelial Lining Fluid in Thigh- and Lung-Infected Mice"],"prefix":"10.1128","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4387-4464","authenticated-orcid":false,"given":"Johanna","family":"Berkhout","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Melchers","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita C.","family":"van Mil","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6194-7447","authenticated-orcid":false,"given":"Seyedmojtaba","family":"Seyedmousavi","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands"},{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M.","family":"Lagarde","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wright W.","family":"Nichols","sequence":"additional","affiliation":[{"name":"AstraZeneca Pharmaceuticals, Waltham, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6736-4149","authenticated-orcid":false,"given":"Johan W.","family":"Mouton","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands"},{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S0025-7125(16)30034-7","article-title":"Third-generation cephalosporins","volume":"79","author":"Klein NC","year":"1995","unstructured":"Klein NC, Cunha BA. 1995. 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