{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:14:24Z","timestamp":1791389664916,"version":"4.3.3"},"reference-count":33,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"EU funding within the NextGeneration EU-MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      To assess the impact of a multidisciplinary approach aimed at attaining aggressive joint pharmacokinetic\/pharmacodynamic (PK\/PD) target with ceftazidime\/avibactam on treatment outcome of KPC-\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      (Kp) infections and prevention of ceftazidime\/avibactam resistance development, a pre-post quasi-experimental study on adult patients with documented KPC-Kp who were treated with ceftazidime\/avibactam according to a multidisciplinary approach in the period 1 March 2021\u201331 October 2024 and patients receiving standard management with ceftazidime\/avibactam in the period 1 January 2018\u201328 February 2021 was performed. Multivariate analysis was performed to identify variables associated with microbiological failure and 90-day resistance development to ceftazidime\/avibactam in both pre- and post-intervention phases. A total of 116 and 102 patients in pre- and post-intervention phases were included. A significantly lower microbiological eradication rate (53.0% vs. 81.0%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001), a lower clinical cure rate (48.3% vs. 70.6%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001), and a higher rate of 90-day resistance development (15.5% vs. 5.9%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.02) were found in the pre-intervention phase. Continuous renal replacement therapy (odds ratio [OR] 5.20; 95% confidence interval [CI] 1.21\u201322.34) and a ceftazidime\/avibactam MIC value \u2265 4 mg\/L (OR 3.08; 95% CI 1.10\u20138.64) emerged as independent predictors of microbiological failure in the pre-intervention phase. Conversely, attaining aggressive joint PK\/PD target (OR 0.03; 95% CI 0.005\u20130.20) and bloodstream infections (OR 0.09; 95% CI 0.02\u20130.53) resulted in protection against microbiological failure in the post-intervention phase. Attaining aggressive joint PK\/PD targets resulted in protection against 90-day resistance development in the post-intervention phase (OR 0.07; 95% CI 0.01\u20130.69). Implementing a multidisciplinary approach for maximizing the attainment of aggressive joint PK\/PD targets of ceftazidime\/avibactam could represent an effective strategy for preventing resistance development to ceftazidime\/avibactam in KPC-Kp infections.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00488-25","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T09:42:11Z","timestamp":1749202931000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["A pre-post quasi-experimental study of antimicrobial stewardship exploring the impact of a multidisciplinary approach aimed at attaining an aggressive joint pharmacokinetic\/pharmacodynamic target with ceftazidime\/avibactam on treatment outcome of KPC-producing\n                    <i>Klebsiella pneumoniae<\/i>\n                    infections and on ceftazidime\/avibactam resistance development"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-3779","authenticated-orcid":true,"given":"Milo","family":"Gatti","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01111rn36","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna","place":["Bologna, Italy"]},{"name":"Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna","place":["Bologna, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Rinaldi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01111rn36","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna","place":["Bologna, Italy"]},{"name":"Infectious Diseases Unit, Department for Integrated Infectious Risk 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