{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:02:31Z","timestamp":1792450951327,"version":"4.5.0"},"reference-count":28,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Multidrug-resistant (MDR) Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE) and difficult-to-treat Pseudomonas aeruginosa (DTR-Pa), present a growing global healthcare challenge, especially in critically ill populations. Imipenem\u2013relebactam (I\/R), a novel \u03b2-lactam\/\u03b2-lactamase inhibitor combination, has shown efficacy in clinical trials, but real-world data remain limited. Methods: We conducted a multicenter, retrospective\u2013prospective observational study across tertiary-care hospitals in Italy between January 2020 and May 2025. Adult patients (\u226518 years) treated with I\/R for \u226548 h for suspected or confirmed MDR Gram-negative infections were included. Primary endpoints were clinical success at the end of therapy and 30-day all-cause mortality. Secondary endpoints included microbiological eradication, recurrence, safety, and predictors of treatment failure. Statistical analysis involved descriptive methods and correlation analysis for mortality predictors. Results: Twenty-nine patients were included (median age 66 years; 58.6% ICU admission; 71.4% mechanical ventilation). Clinical success was achieved in 22\/29 patients (75.9%), while 30-day mortality was 24.1% (7\/29). The most common pathogen was Klebsiella pneumoniae (62.1%), with 41.4% of infections being polymicrobial. Microbiological eradication was confirmed in all the BSIs. Parenteral nutrition (p = 0.016), sepsis at presentation (p = 0.04), candidemia (p = 0.036), and arterial catheter use (p = 0.029) were significantly more frequent in non-survivors. Survivors showed significant reductions in CRP, PCT, and bilirubin at 48 h, while non-survivors did not. Parenteral nutrition (rho = 0.427, p = 0.023), sepsis (rho = 0.378, p = 0.043), and arterial catheter use (rho = 0.384, p = 0.04) were significantly correlated with mortality. Conclusions: In this Italian multicenter cohort of critically ill patients, imipenem\u2013relebactam demonstrated high clinical success and acceptable mortality rates in the treatment of severe MDR Gram-negative infections, particularly those caused by KPC-producing K. pneumoniae. Early biomarker dynamics may aid in monitoring treatment response. Larger prospective studies are needed to confirm these findings and define optimal treatment strategies.<\/jats:p>","DOI":"10.3390\/pathogens14070685","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T13:44:19Z","timestamp":1752241459000},"page":"685","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Restoring Control: Real-World Success with Imipenem\u2013Relebactam in Critical MDR Infections\u2014A Multicenter Observational Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5650-6911","authenticated-orcid":false,"given":"Andrea","family":"Marino","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, ARNAS Garibaldi Hospital, University of Catania, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3408-4877","authenticated-orcid":false,"given":"Giuseppe","family":"Pipitone","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, ARNAS Civico-Di Cristina, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8273-5382","authenticated-orcid":false,"given":"Emmanuele","family":"Venanzi Rullo","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, G. Martino University Hospital, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Cosentino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, ARNAS Garibaldi Hospital, University of Catania, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Ippolito","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, G. Martino University Hospital, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, ARNAS Garibaldi Hospital, University of Catania, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bagarello","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, ARNAS Civico-Di Cristina, 90127 Palermo, Italy"},{"name":"Infectious Diseases Unit, University Hospital P. Giaccone, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9514-133X","authenticated-orcid":false,"given":"Ylenia","family":"Russotto","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, G. Martino University Hospital, Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Iaria","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, ARNAS Civico-Di Cristina, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Cacopardo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, ARNAS Garibaldi Hospital, University of Catania, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8113-8452","authenticated-orcid":false,"given":"Giuseppe","family":"Nunnari","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Unit of Infectious Diseases, ARNAS Garibaldi Hospital, University of Catania, 95122 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Antimicrobial Resistance Collaborators (2024). 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