{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:56:27Z","timestamp":1787028987835,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T00:00:00Z","timestamp":1705017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>(1) Objectives: To assess the impact of optimal joint pharmacokinetic\/pharmacodynamic (PK\/PD) target attainment of continuous infusion (CI) piperacillin\u2013tazobactam monotherapy on the microbiological outcome of documented ESBL-producing Enterobacterlaes secondary bloodstream infections (BSIs). (2) Methods: Patients hospitalized in the period January 2022\u2013October 2023, having a documented secondary BSI caused by ESBL-producing Enterobacterales, and being eligible for definitive targeted CI piperacillin\u2013tazobactam monotherapy according to specific pre-defined inclusion criteria (i.e., absence of septic shock at onset; favorable clinical evolution in the first 48 h after starting treatment; low\u2013intermediate risk primary infection source) were prospectively enrolled. A real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program was adopted for optimizing (PK\/PD) target attainment of CI piperacillin\u2013tazobactam monotherapy. Steady-state plasma concentrations (Css) of both piperacillin and tazobactam were measured, and the free fractions (f) were calculated based on theoretical protein binding. The joint PK\/PD target attainment was considered optimal whenever the piperacillin fCss\/MIC ratio was &gt;4 and the tazobactam fCss\/target concentration (CT) ratio was &gt;1 (quasi-optimal or suboptimal if only one or neither of the two thresholds were achieved, respectively). Univariate analysis was carried out for assessing variables potentially associated with failure in achieving the optimal joint PK\/PD target of piperacillin\u2013tazobactam and microbiological eradication. (3) Results: Overall, 35 patients (median age 79 years; male 51.4%) were prospectively included. Secondary BSIs resulted from urinary tract infections as a primary source in 77.2% of cases. The joint PK\/PD target attainment was optimal in as many as 97.1% of patients (34\/35). Microbiological eradication occurred in 91.4% of cases (32\/35). Attaining the quasi-optimal\/suboptimal joint PK\/PD target of CI piperacillin\u2013tazobactam showed a trend toward a higher risk of microbiological failure (33.3% vs. 0.0%; p = 0.08) (4) Conclusions: Real-time TDM-guided optimal joint PK\/PD target attainment of CI piperacillin\u2013tazobactam monotherapy may represent a valuable and effective carbapenem-sparing strategy when dealing with non-severe ESBL-producing Enterobacterales secondary BSIs.<\/jats:p>","DOI":"10.3390\/microorganisms12010151","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T03:54:34Z","timestamp":1705031674000},"page":"151","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Real-Time TDM-Guided Optimal Joint PK\/PD Target Attainment of Continuous Infusion Piperacillin\u2013Tazobactam Monotherapy Is an Effective Carbapenem-Sparing Strategy for Treating Non-Severe ESBL-Producing Enterobacterales Secondary Bloodstream Infections: Findings from a Prospective Pilot Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-3779","authenticated-orcid":false,"given":"Milo","family":"Gatti","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Bonazzetti","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Infectious Disease Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2687-4235","authenticated-orcid":false,"given":"Renato","family":"Pascale","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Infectious Disease Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Giannella","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Infectious Disease Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Viale","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Infectious Disease Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6966-7167","authenticated-orcid":false,"given":"Federico","family":"Pea","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 40138 Bologna, Italy"},{"name":"Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria of Bologna, 40138 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1056\/NEJMoa1914433","article-title":"Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients, 2012\u20132017","volume":"382","author":"Jernigan","year":"2020","journal-title":"N. 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