{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:24:47Z","timestamp":1786973087721,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Multidrug-resistant (MDR) Pseudomonas aeruginosa pneumonia and bloodstream infections (BSI) remain challenging because of their severity, limited therapeutic options, and high mortality, despite the availability of novel \u03b2-lactam-based agents. We aimed to describe real-world treatment patterns, characteristics associated with treatment and infusion-strategy selection, and the association of these strategies with clinical outcomes in the retrospective, multicentre Italian SUSANA cohort, an observational study evaluating the use, safety, and outcomes of novel antibiotics in hospitalized patients. Methods: Adults with MDR P. aeruginosa pneumonia and\/or BSI treated with novel antipseudomonal agents for \u226572 h were included. Treatment was classified as monotherapy or combination therapy, and infusion strategy as prolonged\/continuous or standard. The primary outcome was 28-day all-cause mortality. A multivariable Cox regression analysis was performed. Results: Among 173 patients, pneumonia was the most frequent clinical presentation (74.0%). Monotherapy was used in 111 patients (64.2%), combination therapy in 62 (35.8%), and prolonged\/continuous infusion in 120 (69.4%). Ceftolozane\u2013tazobactam (CT) (64.7%) and ceftazidime\u2013avibactam (CZA) (20.2%) were the most prescribed agents. Patients receiving prolonged\/continuous infusion, regardless of monotherapy or combination therapy, had greater baseline clinical severity than those receiving standard infusion. Overall, 28-day mortality was 23.7%. In the multivariable analysis, neither combination therapy nor prolonged\/continuous infusion was independently associated with reduced mortality, whereas septic shock (aHR 4.10, 95% CI 1.01\u201316.66) and ICU admission (aHR 2.53, 95% CI 1.06\u20136.08) increased mortality risk. Conclusions: In this multicentre real-world cohort, treatment strategies for MDR P. aeruginosa pneumonia and BSI appeared to be influenced by baseline severity and patient-related factors. Mortality was more strongly associated with markers of severe illness, including ICU admission and septic shock. No independent association with improved survival was observed for combination therapy compared with monotherapy or for prolonged\/continuous compared with standard infusion. These findings highlight the prognostic role of baseline clinical severity and support the need for prospective, randomized, pharmacokinetic\/pharmacodynamic (PK\/PD)-guided studies to identify patients who may benefit from these strategies.<\/jats:p>","DOI":"10.3390\/antibiotics15080796","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:01:26Z","timestamp":1786968086000},"page":"796","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Antibiotic Strategies for Multidrug-Resistant Pseudomonas aeruginosa: Evidence from the Italian SUSANA Multicentre Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Francesca","family":"Gavaruzzi","sequence":"first","affiliation":[{"name":"Systemic and Immune Depression-Associated Infections Unit, National Institute for Infectious Diseases Lazzaro Spallanzani, Istituto di Ricovero e Cura a Carattere Scientifico, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6099-2273","authenticated-orcid":false,"given":"Giordano","family":"Madeddu","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medicine, Surgery, and Pharmacy, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5279-0444","authenticated-orcid":false,"given":"Elena Delfina","family":"Ricci","sequence":"additional","affiliation":[{"name":"Fondazione ASIA Onlus, Buccinasco, 20900 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8794-984X","authenticated-orcid":false,"given":"Matteo","family":"Faltoni","sequence":"additional","affiliation":[{"name":"Fondazione San Gerardo dei Tintori, Istituto di Ricovero e Cura a Carattere Scientifico, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Bandera","sequence":"additional","affiliation":[{"name":"Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, Istituto di Ricovero e Cura a Carattere Scientifico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Colucci","sequence":"additional","affiliation":[{"name":"Azienda Ospedaliera di Rilievo Nazionale Sant\u2019Anna e San Sebastiano, 81100 Caserta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8265-5400","authenticated-orcid":false,"given":"Andrea","family":"De Vito","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medicine, Surgery, and Pharmacy, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0065-7251","authenticated-orcid":false,"given":"Angelo","family":"Maccaro","sequence":"additional","affiliation":[{"name":"Fondazione Ca\u2019 Granda Ospedale Maggiore Policlinico, Istituto di Ricovero e Cura a Carattere Scientifico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Maggi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7058-1048","authenticated-orcid":false,"given":"Stefania","family":"Piconi","sequence":"additional","affiliation":[{"name":"Alessandro Manzoni Hospital, 23900 Lecco, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Cenderello","sequence":"additional","affiliation":[{"name":"Sanremo Hospital, 18038 Sanremo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5081-8669","authenticated-orcid":false,"given":"Marco","family":"Merli","sequence":"additional","affiliation":[{"name":"Niguarda Hospital, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8014-4711","authenticated-orcid":false,"given":"Leonardo","family":"Luzi","sequence":"additional","affiliation":[{"name":"Niguarda Hospital, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8774-4843","authenticated-orcid":false,"given":"Giuseppe Vittorio De","family":"Socio","sequence":"additional","affiliation":[{"name":"Infectious Disease Unit, Department of Medicine and Surgery, Santa Maria Hospital, University of Perugia, 06156 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1696-1474","authenticated-orcid":false,"given":"Silvia","family":"Mascolo","sequence":"additional","affiliation":[{"name":"Cotugno Hospital, Azienda Ospedaliera dei Colli, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Bussini","sequence":"additional","affiliation":[{"name":"Humanitas Research Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, Rozzano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goffredo","family":"Angioni","sequence":"additional","affiliation":[{"name":"Santissima Trinit\u00e0 Hospital, 09121 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7289-8823","authenticated-orcid":false,"given":"Paolo","family":"Bonfanti","sequence":"additional","affiliation":[{"name":"Fondazione San Gerardo dei Tintori, Istituto di Ricovero e Cura a Carattere Scientifico, University of Milano-Bicocca, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0754-6917","authenticated-orcid":false,"given":"Stefania","family":"Cicalini","sequence":"additional","affiliation":[{"name":"Systemic and Immune Depression-Associated Infections Unit, National Institute for Infectious Diseases Lazzaro Spallanzani, Istituto di Ricovero e Cura a Carattere Scientifico, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0140-6736(24)02081-6","article-title":"Multidrug-resistant Gram-negative bacterial infections","volume":"405","author":"Macesic","year":"2025","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e00031-19","DOI":"10.1128\/CMR.00031-19","article-title":"Epidemiology and Treatment of Multidrug-Resistant and Extensively Drug-Resistant Pseudomonas aeruginosa Infections","volume":"32","author":"Horcajada","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Yuan, Q., Guo, L., Li, B., Zhang, S., Feng, H., Zhang, Y., Yu, M., Hu, H., Chen, H., and Yang, Q. (2023). Risk factors and outcomes of inpatients with carbapenem-resistant Pseudomonas aeruginosa bloodstream infections in China: A 9-year trend and multicenter cohort study. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1137811"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1093\/cid\/ciw243","article-title":"Ceftazidime\/Avibactam and Ceftolozane\/Tazobactam: Second-generation \u03b2-Lactam\/\u03b2-Lactamase Inhibitor Combinations","volume":"63","author":"Bonomo","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tamma, P.D., Aitken, S.L., Bonomo, R.A., Mathers, A.J., van Duin, D., and Clancy, C.J. (2023). Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. Clin. Infect. Dis., ciad428.","DOI":"10.1093\/cid\/ciad428"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1097\/QCO.0000000000000755","article-title":"Continuous versus intermittent infusion of antibiotics in Gram-negative multidrug-resistant infections","volume":"34","author":"Gatti","year":"2021","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s00134-020-06050-1","article-title":"Antimicrobial therapeutic drug monitoring in critically ill adult patients: A Position Paper#","volume":"46","author":"Alffenaar","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1007\/s40262-020-00919-6","article-title":"Prolonged Versus Intermittent Infusion of \u03b2-Lactam Antibiotics: A Systematic Review and Meta-Regression of Bacterial Killing in Preclinical Infection Models","volume":"59","author":"Dhaese","year":"2020","journal-title":"Clin. Pharmacokinet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1007\/s10096-019-03573-4","article-title":"Continuous infusion of ceftolozane\/tazobactam is associated with a higher probability of target attainment in patients infected with Pseudomonas aeruginosa","volume":"38","author":"Pilmis","year":"2019","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1128\/CMR.05041-11","article-title":"Combination Therapy for Treatment of Infections with Gram-Negative Bacteria","volume":"25","author":"Tamma","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1093\/jac\/dkab134","article-title":"Combination versus monotherapy as definitive treatment for Pseudomonas aeruginosa bacteraemia: A multicentre retrospective observational cohort study","volume":"76","author":"Babich","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e61","DOI":"10.1093\/cid\/ciw353","article-title":"Management of Adults with Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society","volume":"63","author":"Kalil","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1700582","DOI":"10.1183\/13993003.00582-2017","article-title":"International ERS\/ESICM\/ESCMID\/ALAT guidelines for the management of hospital-acquired pneumonia and ventilator-associated pneumonia: Guidelines for the Management of Hospital-Acquired Pneumonia (HAP)\/Ventilator-Associated Pneumonia (VAP) of the European Respiratory Society (ERS), European Society of Intensive Care Medicine (ESICM), European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and Asociaci\u00f3n Latinoamericana del T\u00f3rax (ALAT)","volume":"50","author":"Torres","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13054-023-04792-0","article-title":"Single-drug versus combination antimicrobial therapy in critically ill patients with hospital-acquired pneumonia and ventilator-associated pneumonia due to Gram-negative pathogens: A multicenter retrospective cohort study","volume":"28","author":"Barbier","year":"2024","journal-title":"Crit. Care"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e0073525","DOI":"10.1128\/aac.00735-25","article-title":"A systematic literature review and (network) meta-analysis of the effectiveness of ceftolozane\/tazobactam versus aminoglycosides\/polymyxins and ceftazidime\/avibactam for treating adult patients with multidrug-resistant Pseudomonas aeruginosa infections","volume":"70","author":"Collings","year":"2026","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1001\/jama.2024.9779","article-title":"Continuous vs Intermittent \u03b2-Lactam Antibiotic Infusions in Critically Ill Patients with Sepsis","volume":"332","author":"Dulhunty","year":"2024","journal-title":"JAMA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1001\/jama.2023.10598","article-title":"Continuous vs Intermittent Meropenem Administration in Critically Ill Patients with Sepsis","volume":"330","author":"Monti","year":"2023","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.jiac.2024.03.015","article-title":"Novel \u03b2-lactam-\u03b2-lactamase inhibitors as monotherapy versus combination for the treatment of drug-resistant Pseudomonas aeruginosa infections: A multicenter cohort study","volume":"30","author":"Almangour","year":"2024","journal-title":"J. Infect. Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/j.cmi.2025.08.018","article-title":"How do I manage difficult-to-treat Pseudomonas aeruginosa infections? Key questions for today\u2019s clinicians","volume":"31","author":"Horcajada","year":"2025","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.cmi.2021.11.025","article-title":"European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine)","volume":"28","author":"Paul","year":"2022","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Losito, A.R., Raffaelli, F., Del Giacomo, P., and Tumbarello, M. (2022). New Drugs for the Treatment of Pseudomonas aeruginosa Infections with Limited Treatment Options: A Narrative Review. Antibiotics, 11.","DOI":"10.3390\/antibiotics11050579"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"ofab371","DOI":"10.1093\/ofid\/ofab371","article-title":"Real-world, Multicenter Experience with Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa","volume":"8","author":"Alosaimy","year":"2021","journal-title":"Open Forum Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sophonsri, A., Kalu, M., and Wong-Beringer, A. (2024). Comparative In Vitro Activity of Ceftazidime-Avibactam, Imipenem-Relebactam, and Meropenem-Vaborbactam against Carbapenem-Resistant Clinical Isolates of Klebsiella pneumoniae and Pseudomonas aeruginosa. Antibiotics, 13.","DOI":"10.3390\/antibiotics13050416"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/S1473-3099(24)00648-0","article-title":"Effectiveness of ceftazidime\u2013avibactam versus ceftolozane\u2013tazobactam for multidrug-resistant Pseudomonas aeruginosa infections in the USA (CACTUS): A multicentre, retrospective, observational study","volume":"25","author":"Shields","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1001\/jama.2024.9803","article-title":"Prolonged vs Intermittent Infusions of \u03b2-Lactam Antibiotics in Adults with Sepsis or Septic Shock","volume":"332","author":"Hammond","year":"2024","journal-title":"JAMA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e2418234","DOI":"10.1001\/jamanetworkopen.2024.18234","article-title":"Extended-Infusion \u03b2-Lactam Therapy, Mortality, and Subsequent Antibiotic Resistance Among Hospitalized Adults with Gram-Negative Bloodstream Infections","volume":"7","author":"Karaba","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1093\/cid\/ciz032","article-title":"Extended Infusion of \u03b2-Lactams for Bloodstream Infection in Patients with Liver Cirrhosis: An Observational Multicenter Study","volume":"69","author":"Bartoletti","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1093\/cid\/ciab176","article-title":"Ceftazidime-Avibactam Use for Klebsiella pneumoniae Carbapenemase\u2013Producing K. pneumoniae Infections: A Retrospective Observational Multicenter Study","volume":"73","author":"Tumbarello","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Fois, M., De Vito, A., Cherchi, F., Ricci, E., Pontolillo, M., Falasca, K., Corti, N., Comelli, A., Bandera, A., and Molteni, C. (2024). Efficacy and Safety of Ceftazidime\u2013Avibactam Alone versus Ceftazidime\u2013Avibactam Plus Fosfomycin for the Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia: A Multicentric Retrospective Study from the SUSANA Cohort. Antibiotics, 13.","DOI":"10.3390\/antibiotics13070616"},{"key":"ref_30","unstructured":"World Health Organization (2014). Global Priority List of Antibiotic-Resistant Bacteria, WHO."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/s41579-024-01054-w","article-title":"ESKAPE pathogens: Antimicrobial resistance, epidemiology, clinical impact and therapeutics","volume":"22","author":"Miller","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e0132525","DOI":"10.1128\/aac.01325-25","article-title":"Effectiveness of imipenem-relebactam for multidrug-resistant Pseudomonas aeruginosa in pneumonia and bloodstream infections in the United States (MIRAGE)","volume":"69","author":"Wangchinda","year":"2025","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/8\/796\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:31:12Z","timestamp":1786969872000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/8\/796"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,17]]},"references-count":32,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["antibiotics15080796"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15080796","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,17]]}}}