{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T16:44:24Z","timestamp":1778863464741,"version":"3.51.4"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bloodstream infections (BSIs) caused by KPC-producing Klebsiella pneumoniae (KPC-Kp) remain associated with high mortality, even outside intensive care units (ICUs). Optimizing early \u03b2-lactam exposure through a loading dose (LD) of ceftazidime\u2013avibactam or meropenem\u2013vaborbactam may improve outcomes, but evidence in non-ICU settings is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective single-centre study (January 2023\u2013June 2025) including adult non-ICU inpatients with genotypically confirmed KPC-Kp BSI. The control group received standard dosing (ceftazidime\u2013avibactam 2\u2005g\/0.5\u2005g q8h or meropenem\u2013vaborbactam 2\u2005g\/2\u2005g q8h, both over 3\u2005h). The LD group received either one standard dose infused over 30\u2005min (Scheme A) or one standard dose + 50% infused over 2\u20133\u2005h (Scheme B), followed by the standard regimen q8h. Primary outcomes were 7- and 30-day all-cause mortality; secondary outcomes included microbiological clearance \u226472\u2005h, ICU transfer and\/or vasopressor use, adverse events (AEs \u2265 grade 2), hospital stay, and recurrence \u226430\u2005days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 189 patients were included (140 controls, 49 LD). Groups were comparable in age (median 74\u2005years), comorbidities (Charlson 5), and renal function (eGFR \u224845\u2005mL\/min\/1.73\u2005m\u00b2). LD was associated with faster blood-culture clearance (78% versus 55%; RR 1.26, 95% CI 1.03\u20131.61, P\u200a=\u200a0.02) and lower ICU\/vasopressor requirement (7.5% versus 23%; RR 0.60, 95% CI 0.29\u20130.93, P\u200a=\u200a0.02). Median hospital stay was shorter (33 versus 37\u2005days, P\u200a=\u200a0.3). Thirty-day mortality was lower in LD (16.3% versus 21.0%; adjusted RR 0.62, 95% CI 0.39\u20131.29, P\u200a=\u200a0.23), indicating a non-significant but clinically relevant trend. No increase in adverse events or nephrotoxicity was observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In non-ICU KPC-Kp BSIs, a \u03b2-lactam loading dose regimen was associated with faster microbiological clearance, reduced ICU transfer and shorter hospital stay, without added toxicity. Mortality showed a non-significant trend towards improvement. Pragmatic LD strategies may enhance early \u03b2-lactam exposure where therapeutic drug monitoring (TDM) is unavailable. Prospective PK\/PD-guided studies are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag087","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:22:23Z","timestamp":1772454143000},"source":"Crossref","is-referenced-by-count":2,"title":["Impact of loading dose \u03b2-lactam therapy on outcomes of KPC-producing\n                    <i>Klebsiella pneumoniae<\/i>\n                    bloodstream infections in non-ICU patients: a real world study"],"prefix":"10.1093","volume":"81","author":[{"given":"Luisa","family":"Frallonardo","sequence":"first","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro , Bari 70124 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8783-7221","authenticated-orcid":false,"given":"Giacomo","family":"Guido","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro , Bari 70124 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicol\u00f2","family":"De Gennaro","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro , Bari 70124 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-8219","authenticated-orcid":false,"given":"Giuseppina","family":"De Iaco","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro , Bari 70124 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Signorile","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro , Bari 70124 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marinella","family":"Cibelli","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro , Bari 70124 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"De Luca","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro , Bari 70124 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annunziata Ilenia","family":"Ritacco","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro , Bari 70124 ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Stolfa","sequence":"additional","affiliation":[{"name":"Microbiology and Virology Unit, Department of Interdisciplinary Medicine, University of Bari \u2018A. 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