{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:56:12Z","timestamp":1785426972129,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002597","name":"Kyung Hee University","doi-asserted-by":"publisher","award":["KHU-20233275"],"award-info":[{"award-number":["KHU-20233275"]}],"id":[{"id":"10.13039\/501100002597","id-type":"DOI","asserted-by":"publisher"}]},{"award":["KHU-20233275"],"award-info":[{"award-number":["KHU-20233275"]}],"id":[{"id":"https:\/\/ror.org\/01zqcg218","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003569","name":"Ministry of Food and Drug Safety","doi-asserted-by":"publisher","award":["21153MFDS601-1"],"award-info":[{"award-number":["21153MFDS601-1"]}],"id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003569","name":"Ministry of Food and Drug Safety","doi-asserted-by":"publisher","award":["RS-2024-00331810"],"award-info":[{"award-number":["RS-2024-00331810"]}],"id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]},{"award":["21153MFDS601-1"],"award-info":[{"award-number":["21153MFDS601-1"]}],"id":[{"id":"https:\/\/ror.org\/01f7dp456","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2024-00331810"],"award-info":[{"award-number":["RS-2024-00331810"]}],"id":[{"id":"https:\/\/ror.org\/01f7dp456","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Ceftolozane\/tazobactam (C\/T) and ceftazidime\/avibactam (CZA) are critical therapeutic options for multidrug-resistant Gram-negative infections; however, their comparative pharmacodynamics against carbapenem-resistant Pseudomonas aeruginosa (CRPA) remain incompletely defined. This study aimed to compare the bactericidal activity of C\/T and CZA administered by intermittent infusion (II) or continuous infusion (CI) using a hollow fiber infection model (HFIM) against a clinical isolate of CRPA. Methods: Clinically relevant concentration\u2013time profiles for C\/T and CZA based on prescribing information were simulated in the HFIM. The standard P. aeruginosa strain ATCC 27853 and a GES-producing clinical CRPA isolate were utilized. The primary endpoint was bactericidal activity (\u22653 log10 CFU\/mL reduction from baseline), while secondary endpoints included regrowth prevention and resistance development based on population analysis profiles (PAPs). Results: Against the standard strain, both agents achieved rapid killing without regrowth. However, for the GES-producing clinical isolate, C\/T failed to achieve bactericidal activity. In contrast, CZA demonstrated sustained bacterial killing activity with the most pronounced early-phase bactericidal activity with CI of CZA (\u22124.25 log10 CFU\/mL at 24 h). The bactericidal activity was persistent over 7 days without bacterial regrowth after treatment discontinuation. Conversely, bacterial regrowth occurred with II of CZA after drug withdrawal. PAPs showed the lack of resistance development against CZA, whereas resistance to C\/T developed within 48 h after initiating therapy. Conclusions: In this HFIM study, CI of CZA demonstrated the most sustained suppression of bacterial growth and prevented resistance emergence against the tested clinical isolate of CRPA producing GES \u03b2-lactamases. Future clinical studies are warranted to assess the effectiveness of the CI regimen.<\/jats:p>","DOI":"10.3390\/pharmaceutics18040460","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T12:21:32Z","timestamp":1775737292000},"page":"460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacodynamic Comparison of Ceftolozane\/Tazobactam and Ceftazidime\/Avibactam, Administered by Intermittent or Continuous Infusion, Against a Clinical Isolate of Carbapenem-Resistant Pseudomonas aeruginosa Producing GES \u03b2-Lactamase in a Hollow Fiber Infection Model"],"prefix":"10.3390","volume":"18","author":[{"given":"Tae Kun","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Gun","family":"Kwack","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy and Critical Care Medicine, Kyung Hee University Hospital, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Young","family":"Im","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo Hyeon","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7087-4914","authenticated-orcid":false,"given":"Seok Jun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0000-9016","authenticated-orcid":false,"given":"Ki-Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Kyung Hee University School of Medicine, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9200-2799","authenticated-orcid":false,"given":"Eun Kyoung","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Regulatory Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Department of Pharmacy, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea"},{"name":"Institute of Regulatory Innovation Through Science (IRIS), Kyung Hee University, Seoul 02447, Republic of Korea"},{"name":"Institute of Integrated Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1086\/338782","article-title":"Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: Our worst nightmare?","volume":"34","author":"Livermore","year":"2002","journal-title":"Clin. 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