{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:13:54Z","timestamp":1792782834797,"version":"4.5.0"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e0 degli Studi di Pavia","id":[{"id":"https:\/\/ror.org\/00s6t1f81","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Clin Microbiol Infect Dis"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      In vitro and in vivo studies suggest adding a second agent to ceftazidime\/avibactam (CZA) to enhance bactericidal activity against\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      (PA). Nevertheless, evidence supporting this practice is scarce.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study of patients admitted to 9 Italian hospitals with microbiologically confirmed PA infection and treated with CZA alone or in combination from 01\/01\/2015 to 31\/12\/2021. The primary endpoint was 14-day clinical cure. Secondary endpoints were 28-day all-cause mortality, 56-day microbiological failure, 56-day infection relapse, and emergence of CZA resistance. A generalized linear model extended to the binomial family, with identity link, weighted for IPTW (inverse probability of treatment weighting), was fitted to compare the two groups for 14-day clinical cure. Results were reported in terms of risk difference (RD) and 90% Confidence Interval (90%CI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eighty-seven patients with infection due to PA were included; 17 were treated with CZA monotherapy, and 70 with combination therapy with CZA plus another anti-pseudomonal agent. Sequential organ failure assessment was significantly higher (median 6 [3\u20139]) in the combination group compared to monotherapy (median 3 [1\u20135];\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.049). After weighting patients according to the IPTW, CZA monotherapy did not reach the clinical equipoise to combination therapy in terms of 14-day clinical cure (RD -0.28, 90% CI -0.41 to -0.14). No significant risk difference between groups was found for any of the secondary endpoints.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that combination therapy with CZA for treating PA infections may provide some clinical benefit over monotherapy despite the absence of a definitive survival advantage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10096-026-05599-x","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T13:16:59Z","timestamp":1784035019000},"page":"3217-3227","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Is less always more? Ceftazidime\/avibactam alone or in combination to treat infections caused by Pseudomonas aeruginosa: a retrospective observational multi-centre cohort study"],"prefix":"10.1007","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3425-9817","authenticated-orcid":false,"given":"Pietro","family":"Valsecchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Colaneri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lombardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Biscarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Azzar\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Bandera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2","family":"Corti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Bonfanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo Francesco","family":"Rezzonico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Travi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Pontiggia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Piconi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Lippi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Tumbarello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo Giovanni","family":"Lupi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Casalini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spinello","family":"Antinori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Calabresi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Chichino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia Valeria","family":"Ferretti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Gambini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Klersy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Bruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"5599_CR1","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1007\/s40265-021-01635-6","volume":"81","author":"D Reynolds","year":"2021","unstructured":"Reynolds D, Kollef M (2021) The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update. Drugs 81:2117\u20132131. https:\/\/doi.org\/10.1007\/s40265-021-01635-6","journal-title":"Drugs"},{"key":"5599_CR2","doi-asserted-by":"publisher","unstructured":"Suetens C, Latour K, K\u00e4rki T, Ricchizzi E, Kinross P, Moro ML et al (2018) Prevalence of healthcare-associated infections, estimated incidence and composite antimicrobial resistance index in acute care hospitals and long-term care facilities: results from two european point prevalence surveys, 2016 to 2017. Eurosurveillance 23. https:\/\/doi.org\/10.2807\/1560-7917.ES.2018.23.46.1800516","DOI":"10.2807\/1560-7917.ES.2018.23.46.1800516"},{"key":"5599_CR3","volume-title":"Antimicrobial resistance surveillance in Europe 2022\u20132020 data","author":"WHO Regional Office for Europe\/European Centre for Disease Prevention and Control","year":"2022","unstructured":"WHO Regional Office for Europe\/European Centre for Disease Prevention and Control (2022) Antimicrobial resistance surveillance in Europe 2022\u20132020 data. WHO Regional Office for Europe, Copenhagen"},{"key":"5599_CR4","doi-asserted-by":"publisher","unstructured":"Karruli A, Catalini C, D\u2019Amore C, Foglia F, Mari F, Harxhi A et al (2023) Evidence-based treatment of pseudomonas aeruginosa infections: a critical reappraisal. Antibiotics 12. https:\/\/doi.org\/10.3390\/antibiotics12020399","DOI":"10.3390\/antibiotics12020399"},{"key":"5599_CR5","unstructured":"WHO Bacterial Priority Pathogens List (2024) 2024: bacterial pathogens of public health importance to guide research, development and strategies to prevent and control antimicrobial resistance. Geneva: World Health Organization. Licence: CC BY-NC-SA 3.0 IGO"},{"key":"5599_CR6","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","volume":"18","author":"AP Magiorakos","year":"2012","unstructured":"Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG et al (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268\u2013281. https:\/\/doi.org\/10.1111\/j.1469-0691.2011.03570.x","journal-title":"Clin Microbiol Infect"},{"key":"5599_CR7","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1093\/cid\/ciy378","volume":"67","author":"SS Kadri","year":"2018","unstructured":"Kadri SS, Adjemian J, Lai YL, Spaulding AB, Ricotta E, Rebecca Prevots D et al (2018) Difficult-to-treat resistance in gram-negative bacteremia at 173 US hospitals: Retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents. Clin Infect Dis 67:1803\u20131814. https:\/\/doi.org\/10.1093\/cid\/ciy378","journal-title":"Clin Infect Dis"},{"key":"5599_CR8","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1007\/s40265-013-0013-7","volume":"73","author":"GG Zhanel","year":"2013","unstructured":"Zhanel GG, Lawson CD, Adam H, Schweizer F, Zelenitsky S, Lagac\u00e9-Wiens PRS et al (2013) Ceftazidime-Avibactam: a Novel Cephalosporin\/\u03b2-lactamase Inhibitor Combination. Drugs 73:159\u2013177. https:\/\/doi.org\/10.1007\/s40265-013-0013-7","journal-title":"Drugs"},{"key":"5599_CR9","doi-asserted-by":"publisher","unstructured":"Karlowsky JA, Lob SH, Bauer KA, Esterly J, Siddiqui F, Young K et al (2024) Activity of ceftolozane\/tazobactam, imipenem\/relebactam and ceftazidime\/avibactam against clinical Gram-negative isolates - SMART United States 2019-21. JAC Antimicrob Resist 6. https:\/\/doi.org\/10.1093\/jacamr\/dlad152","DOI":"10.1093\/jacamr\/dlad152"},{"key":"5599_CR10","doi-asserted-by":"publisher","unstructured":"Wise MG, Karlowsky JA, Lemos-Luengas EV, Valdez RR, Sahm DF (2023) Epidemiology and in vitro activity of ceftazidime-avibactam and comparator agents against multidrug-resistant isolates of Enterobacterales and Pseudomonas aeruginosa collected in Latin America as part of the ATLAS surveillance program in 2015\u20132020. Brazilian J Infect Dis 27. https:\/\/doi.org\/10.1016\/j.bjid.2023.102759","DOI":"10.1016\/j.bjid.2023.102759"},{"key":"5599_CR11","doi-asserted-by":"publisher","unstructured":"Gaibani P, Giani T, Bovo F, Lombardo D, Amadesi S, Lazzarotto T et al (2022) Resistance to ceftazidime\/avibactam, meropenem\/vaborbactam and imipenem\/relebactam in Gram-Negative MDR Bacilli: molecular mechanisms and susceptibility testing. Antibiotics 11. https:\/\/doi.org\/10.3390\/antibiotics11050628","DOI":"10.3390\/antibiotics11050628"},{"key":"5599_CR12","doi-asserted-by":"publisher","unstructured":"Mojica MF, De La Cadena E, Garc\u00eda-Betancur JC, Porras J, Novoa-Caicedo I, P\u00e1ez-Zamora L et al (2023) Molecular mechanisms of resistance to ceftazidime\/avibactam in clinical isolates of enterobacterales and pseudomonas aeruginosa in Latin American Hospitals. MSphere 8. https:\/\/doi.org\/10.1128\/msphere.00651-22","DOI":"10.1128\/msphere.00651-22"},{"issue":"9","key":"5599_CR13","doi-asserted-by":"publisher","first-page":"e01117","DOI":"10.1128\/AAC.01117-17","volume":"61","author":"PA Fraile-Ribot","year":"2017","unstructured":"Fraile-Ribot PA, Mulet X, Cabot G, Del Barrio-Tofi\u00f1o E, Juan C, P\u00e9rez JL, Oliver A (2017) Vivo Emergence of Resistance to Novel Cephalosporin-\u03b2-Lactamase Inhibitor Combinations through the Duplication of Amino Acid D149 from OXA-2 \u03b2-Lactamase (OXA-539) in Sequence Type 235 Pseudomonas aeruginosa. Antimicrob Agents Chemother 61(9):e01117\u2013e01117. https:\/\/doi.org\/10.1128\/AAC.01117-17 PMID: 28674059; PMCID: PMC5571340","journal-title":"Antimicrob Agents Chemother"},{"key":"5599_CR14","doi-asserted-by":"publisher","unstructured":"Compain F, Debray A, Adjadj P, Dorch\u00eane D, Arthur M (2020) Ceftazidime-avibactam resistance mediated by the N346Y substitution in various AmpC \u03b2-lactamases. Antimicrob Agents Chemother 64. https:\/\/doi.org\/10.1128\/AAC.02311-19","DOI":"10.1128\/AAC.02311-19"},{"key":"5599_CR15","doi-asserted-by":"publisher","unstructured":"Slater CL, Winogrodzki J, Fraile-Ribot PA, Oliver A, Khajehpour M, Mark BL (2020) Adding insult to injury: mechanistic basis for how AmpC mutations allow pseudomonas aeruginosa to accelerate cephalosporin hydrolysis and evade avibactam. Antimicrob Agents Chemother 64. https:\/\/doi.org\/10.1128\/AAC.00894-20","DOI":"10.1128\/AAC.00894-20"},{"key":"5599_CR16","doi-asserted-by":"publisher","unstructured":"Oliver A, Rojo-Molinero E, Arca-Suarez J, Be\u015fli Y, Bogaerts P et al (2024) Pseudomonas aeruginosa antimicrobial susceptibility profiles, resistance mechanisms and international clonal lineages: update from ESGARS-ESCMID\/ISARPAE Group. Clin Microbiol Infect 30(4):469\u2013480. https:\/\/doi.org\/10.1016\/j.cmi.2023.12.026","DOI":"10.1016\/j.cmi.2023.12.026"},{"key":"5599_CR17","doi-asserted-by":"publisher","unstructured":"Aslan AT, Ezure Y, Horcajada JP, Harris PNA, Paterson DL (2023) In vitro, in vivo and clinical studies comparing the efficacy of ceftazidime-avibactam monotherapy with ceftazidime-avibactam-containing combination regimens against carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas aeruginosa isolates or infections: a scoping review. Front Med (Lausanne) 10. https:\/\/doi.org\/10.3389\/fmed.2023.1249030","DOI":"10.3389\/fmed.2023.1249030"},{"key":"5599_CR18","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1093\/infdis\/jiz149","volume":"221","author":"KM Papp-Wallace","year":"2020","unstructured":"Papp-Wallace KM, Zeiser ET, Becka SA, Park S, Wilson BM, Winkler ML et al (2020) Ceftazidime-Avibactam in Combination with Fosfomycin: A Novel Therapeutic Strategy against Multidrug-Resistant Pseudomonas aeruginosa. J Infect Dis 221:666\u2013676. https:\/\/doi.org\/10.1093\/infdis\/jiz149","journal-title":"J Infect Dis"},{"key":"5599_CR19","doi-asserted-by":"publisher","unstructured":"Xu C, Zeng F, Huang Y, Xu Q, Yang Y, Gong W et al (2024) Clinical efficacy of ceftazidime\/avibactam combination therapy for severe hospital-acquired pulmonary infections caused by carbapenem-resistant and difficult-to-treat Pseudomonas aeruginosa. Int J Antimicrob Agents 63. https:\/\/doi.org\/10.1016\/j.ijantimicag.2023.107021","DOI":"10.1016\/j.ijantimicag.2023.107021"},{"key":"5599_CR20","doi-asserted-by":"publisher","unstructured":"Corbella L, Bo\u00e1n J, San-Juan R, Fern\u00e1ndez-Ruiz M, Carretero O, Lora D et al (2022) Effectiveness of ceftazidime-avibactam for the treatment of infections due to Pseudomonas aeruginosa. Int J Antimicrob Agents 59. https:\/\/doi.org\/10.1016\/j.ijantimicag.2021.106517","DOI":"10.1016\/j.ijantimicag.2021.106517"},{"key":"5599_CR21","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.cmi.2021.11.025","volume":"28","author":"M Paul","year":"2022","unstructured":"Paul M, Carrara E, Retamar P, T\u00e4ngd\u00e9n T, Bitterman R, Bonomo RA et al (2022) 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). Clin Microbiol Infect 28:521\u2013547. https:\/\/doi.org\/10.1016\/j.cmi.2021.11.025","journal-title":"Clin Microbiol Infect"},{"issue":"2","key":"5599_CR22","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1093\/cid\/ciac268","volume":"75","author":"PD Tamma","year":"2022","unstructured":"Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ (2022) Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum \u03b2-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis 75(2):187\u2013212. https:\/\/doi.org\/10.1093\/cid\/ciac268. PMID: 35439291; PMCID: PMC9890506","journal-title":"Clin Infect Dis"},{"key":"#cr-split#-5599_CR23.1","unstructured":"National Center for Emerging and Zoonotic Infectious Diseases (U.S.) (2023) Division of Healthcare Quality Promotion, National Healthcare Safety Network"},{"key":"#cr-split#-5599_CR23.2","unstructured":"CDC\/NHSN surveillance definitions for specific types of infections Published Date: January 2023 Pages in Document: 30 numbered pages Source : National Healthcare Safety Network (NHSN) patient safety component manual. Chapter 17. https:\/\/stacks.cdc.gov\/view\/cdc\/127235"},{"key":"5599_CR24","doi-asserted-by":"publisher","unstructured":"Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40(5):373\u2009\u2013\u200983. https:\/\/doi.org\/10.1016\/0021-9681(87)90171-8","DOI":"10.1016\/0021-9681(87)90171-8"},{"key":"5599_CR25","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1164\/rccm.200408-1044SO","volume":"171","author":"RT Sadikot","year":"2005","unstructured":"Sadikot RT, Blackwell TS, Christman JW, Prince AS (2005) Pathogen-host interactions in pseudomonas aeruginosa pneumonia. Am J Respir Crit Care Med 171:1209\u20131223. https:\/\/doi.org\/10.1164\/rccm.200408-1044SO","journal-title":"Am J Respir Crit Care Med"},{"key":"5599_CR26","doi-asserted-by":"publisher","unstructured":"Babich T, Naucler P, Valik JK, Giske CG, Benito N, Cardona R et al (2020) Risk factors for mortality among patients with Pseudomonas aeruginosa bacteraemia: a retrospective multicentre study. Int J Antimicrob Agents 55. https:\/\/doi.org\/10.1016\/j.ijantimicag.2019.11.004","DOI":"10.1016\/j.ijantimicag.2019.11.004"},{"key":"5599_CR27","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","volume":"315","author":"M Singer","year":"2016","unstructured":"Singer M, Deutschman CS, Seymour C, Shankar-Hari M, Annane D, Bauer M et al (2016) The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA - J Am Med Association 315:801\u2013810. https:\/\/doi.org\/10.1001\/jama.2016.0287","journal-title":"JAMA - J Am Med Association"},{"key":"5599_CR28","unstructured":"The European Committee on Antimicrobial Susceptibility Testing (2023) Breakpoint tables for interpretation of MICs and zone diameters. Version 13.0. http:\/\/www.eucast.org"},{"key":"5599_CR29","unstructured":"The European Committee on Antimicrobial Susceptibility Testing (2020) Implementation and use of the 2020 revised aminoglycoside breakpoints. http:\/\/www.eucast.org"},{"key":"5599_CR30","unstructured":"The European Committee on Antimicrobial Susceptibility Testing (2023) Fosfomycin intravenous: rationale for EUCAST clinical breakpoints. Version 1.0. http:\/\/www.eucast.org"},{"key":"5599_CR31","doi-asserted-by":"publisher","unstructured":"Lodise TP, Obi EN, Watanabe AH, Yucel E, Min J, Nathanson BH (2024) Comparative evaluation of early treatment with ceftolozane\/tazobactam versus ceftazidime\/avibactam for non-COVID-19 patients with pneumonia due to multidrug-resistant Pseudomonas aeruginosa. J Antimicrob Chemother 79(11):2954\u2013964. https:\/\/doi.org\/10.1093\/jac\/dkae313","DOI":"10.1093\/jac\/dkae313"},{"key":"5599_CR32","doi-asserted-by":"publisher","first-page":"e00405","DOI":"10.1128\/aac.00405-23","volume":"67","author":"TA Almangour","year":"2023","unstructured":"Almangour TA, Ghonem L, Alassiri D, Aljurbua A, Al Musawa M et al (2023) Ceftolozane-Tazobactam Versus Ceftazidime-Avibactam for the Treatment of Infections Caused by Multidrug-Resistant Pseudomonas aeruginosa: a Multicenter Cohort Study. Antimicrob Agents Chemother 67:e00405\u2013e00423. https:\/\/doi.org\/10.1128\/aac.00405-23","journal-title":"Antimicrob Agents Chemother"},{"key":"5599_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(24)00648-0","author":"RK Shields","year":"2024","unstructured":"Shields RK, Abbo LM, Ackley R, Aitken SL, Albrecht B, Babiker A et al (2024) Effectiveness of ceftazidime\u2013avibactam versus ceftolozane\u2013tazobactam for multidrug-resistant Pseudomonas aeruginosa infections in the USA (CACTUS): a multicentre, retrospective, observational study. Lancet Infect Dis. https:\/\/doi.org\/10.1016\/S1473-3099(24)00648-0","journal-title":"Lancet Infect Dis"},{"key":"5599_CR34","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/1471-2334-14-161","volume":"14","author":"YJ Kim","year":"2014","unstructured":"Kim YJ, Jun YH, Kim YR, Park KG, Park YJ, Kang JY, Kim SI (2014) Risk factors for mortality in patients with Pseudomonas aeruginosa bacteremia; retrospective study of impact of combination antimicrobial therapy. BMC Infect Dis 14:161. https:\/\/doi.org\/10.1186\/1471-2334-14-161. PMID: 24655422; PMCID: PMC3994322","journal-title":"BMC Infect Dis"},{"key":"5599_CR35","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1093\/cid\/cit223","volume":"57","author":"C Pe\u00f1a","year":"2013","unstructured":"Pe\u00f1a C, Suarez C, Ocampo-Sosa A, Murillas J, Almirante B, Pomar V et al (2013) Effect of adequate single-drug vs combination antimicrobial therapy on mortality in pseudomonas aeruginosa bloodstream infections: A post hoc analysis of a prospective cohort. Clin Infect Dis 57:208\u2013216. https:\/\/doi.org\/10.1093\/cid\/cit223","journal-title":"Clin Infect Dis"},{"key":"5599_CR36","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/s13054-023-04457-y","volume":"27","author":"A Foucrier","year":"2023","unstructured":"Foucrier A, Dessalle T, Tuffet S, Federici L, Dahyot-Fizelier C, Barbier F et al (2023) Association between combination antibiotic therapy as opposed as monotherapy and outcomes of ICU patients with Pseudomonas aeruginosa ventilator-associated pneumonia: an ancillary study of the iDIAPASON trial. Crit Care 27:211. https:\/\/doi.org\/10.1186\/s13054-023-04457-y","journal-title":"Crit Care"},{"key":"5599_CR37","doi-asserted-by":"publisher","unstructured":"Garnacho-Montero J, Sa-Borges M, Sole-Violan J, Barcenilla F, Escoresca-Ortega A et al (2007) Optimal management therapy for Pseudomonas aeruginosa ventilator-associated pneumonia: an observational, multicenter study comparing monotherapy with combination antibiotic therapy. Crit Care Med 35(8):1888\u201395. https:\/\/doi.org\/10.1097\/01.CCM.0000275389.31974.22","DOI":"10.1097\/01.CCM.0000275389.31974.22"},{"issue":"1","key":"5599_CR38","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/s40262-021-01061-7","volume":"61","author":"EN Drwiega","year":"2022","unstructured":"Drwiega EN, Rodvold KA (2022) Penetration of Antibacterial Agents into Pulmonary Epithelial Lining Fluid: An Update. Clin Pharmacokinet 61(1):17\u201346. https:\/\/doi.org\/10.1007\/s40262-021-01061-7. Epub 2021 Oct 15. PMID: 34651282; PMCID: PMC8516621","journal-title":"Clin Pharmacokinet"},{"key":"5599_CR39","doi-asserted-by":"publisher","unstructured":"Xu Y, Tang J, Yuan B, Luo X, Liang P, Liu N et al (2024) A descriptive pharmacokinetic\/pharmacodynamic analysis of ceftazidime-avibactam in a case series of critically ill patients with augmented renal clearance. Pharmacol Res Perspect 12. https:\/\/doi.org\/10.1002\/prp2.1163","DOI":"10.1002\/prp2.1163"},{"issue":"8","key":"5599_CR40","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1001\/jama.2024.9803","volume":"332","author":"MH Abdul-Aziz","year":"2024","unstructured":"Abdul-Aziz MH, Hammond NE, Brett SJ, Cotta MO, De Waele JJ et al (2024) Prolonged vs Intermittent Infusions of \u03b2-Lactam Antibiotics in Adults With Sepsis or Septic Shock: A Systematic Review and Meta-Analysis. JAMA 332(8):638\u2013648 PMID: 38864162; PMCID: PMC11170459","journal-title":"JAMA"},{"key":"5599_CR41","doi-asserted-by":"publisher","unstructured":"Sumi CD, Heffernan AJ, Lipman J, Roberts JA, Sime FB (2019) What antibiotic exposures are required to suppress the emergence of resistance for gram-negative bacteria? A systematic review. Clinical Pharmacokinetics 58(11):1407\u20131443. https:\/\/doi.org\/10.1007\/s40262-019-00791-z","DOI":"10.1007\/s40262-019-00791-z"},{"key":"5599_CR42","doi-asserted-by":"publisher","first-page":"e00969","DOI":"10.1128\/aac.00969-23","volume":"67","author":"M Gatti","year":"2023","unstructured":"Gatti M, Rinaldi M, Bonazzetti C, Gaibani P, Giannella M, Viale P, Pea F (2023) Could an optimized joint pharmacokinetic\/pharmacodynamic target attainment of continuous infusion ceftazidime-avibactam be a way to avoid the need for combo therapy in the targeted treatment of deep-seated DTR Gram-negative infections? Antimicrob Agents Chemother 67:e00969\u2013e00923. https:\/\/doi.org\/10.1128\/aac.00969-23","journal-title":"Antimicrob Agents Chemother"},{"key":"5599_CR43","doi-asserted-by":"publisher","first-page":"e00488","DOI":"10.1128\/aac.00488-25","volume":"69","author":"M Gatti","year":"2025","unstructured":"Gatti M, Rinaldi M, Cojutti PG, Bonazzetti C, Siniscalchi A et al (2025) 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 Klebsiella pneumoniae infections and on ceftazidime\/avibactam resistance development. Antimicrob Agents Chemother 69:e00488\u2013e00425. https:\/\/doi.org\/10.1128\/aac.00488-25","journal-title":"Antimicrob Agents Chemother"},{"key":"5599_CR44","doi-asserted-by":"publisher","unstructured":"Eljaaly K, Bidell MR, Gandhi RG, Alshehri S, Enani MA, Al-Jedai A et al (2021) Colistin nephrotoxicity: meta-analysis of randomized controlled trials. Open Forum Infect Dis 8. https:\/\/doi.org\/10.1093\/ofid\/ofab026","DOI":"10.1093\/ofid\/ofab026"},{"key":"5599_CR45","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1177\/0897190014546836","volume":"27","author":"KA Wargo","year":"2014","unstructured":"Wargo KA, Edwards JD (2014) Aminoglycoside-induced nephrotoxicity. J Pharm Pract 27:573\u2013577. https:\/\/doi.org\/10.1177\/0897190014546836","journal-title":"J Pharm Pract"},{"key":"5599_CR46","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00907-24","author":"DA Hareza","year":"2024","unstructured":"Hareza DA, Cosgrove SE, Bonomo RA, Dzintars K, Karaba SM, Hawes AM et al (2024) Clinical outcomes and emergence of resistance of Pseudomonas aeruginosa infections treated with ceftolozane-tazobactam versus ceftazidime-avibactam. Antimicrob Agents Chemother. https:\/\/doi.org\/10.1128\/aac.00907-24","journal-title":"Antimicrob Agents Chemother"},{"key":"5599_CR47","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciae332","author":"S Shah","year":"2024","unstructured":"Shah S, Kline EG, Haidar G, Squires KM, Pogue JM, McCreary EK et al (2024) Rates of Resistance to Ceftazidime-Avibactam and Ceftolozane-Tazobactam Among Patients Treated for Multidrug-Resistant Pseudomonas aeruginosa Bacteremia or Pneumonia. Clin Infect Dis. https:\/\/doi.org\/10.1093\/cid\/ciae332","journal-title":"Clin Infect Dis"},{"key":"5599_CR48","doi-asserted-by":"publisher","unstructured":"Lopez-Montesinos I, Montero MM, Domene-Ochoa S, L\u00f3pez-Causap\u00e9 C, Echeverria D, Sorl\u00ed L et al (2022) Suboptimal concentrations of ceftazidime\/avibactam (CAZ-AVI) may select for CAZ-AVI resistance in extensively drug-resistant pseudomonas aeruginosa: in vivo and in vitro evidence. Antibiotics 11. https:\/\/doi.org\/10.3390\/antibiotics11111456","DOI":"10.3390\/antibiotics11111456"},{"key":"5599_CR49","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.idc.2020.05.001","volume":"34","author":"KM Papp-Wallace","year":"2020","unstructured":"Papp-Wallace KM, Mack AR, Taracila MA, Bonomo RA (2020) Resistance to Novel \u03b2-Lactam\u2013\u03b2-Lactamase Inhibitor Combinations: The Price of Progress. Infect Dis Clin North Am 34:773\u2013819. https:\/\/doi.org\/10.1016\/j.idc.2020.05.001","journal-title":"Infect Dis Clin North Am"},{"key":"5599_CR50","doi-asserted-by":"publisher","unstructured":"Shields RK, Kline EG, Squires KM, Van Tyne D, Doi Y (2023) In vitro activity of cefiderocol against Pseudomonas aeruginosa demonstrating evolved resistance to novel \u03b2-lactam\/\u03b2-lactamase inhibitors. JAC Antimicrob Resist 5. https:\/\/doi.org\/10.1093\/jacamr\/dlad107","DOI":"10.1093\/jacamr\/dlad107"},{"key":"5599_CR51","doi-asserted-by":"publisher","unstructured":"Gomis-Font MA, Clari MA, L\u00f3pez-Causap\u00e9 C, Navarro D, Oliver A (2024) Emergence of cefiderocol resistance during ceftazidime\/ avibactam treatment caused by a large genomic deletion, including ampD and piuCD genes, in Pseudomonas aeruginosa. Antimicrob Agents Chemother 68. https:\/\/doi.org\/10.1128\/aac.01192-23","DOI":"10.1128\/aac.01192-23"},{"key":"5599_CR52","doi-asserted-by":"publisher","unstructured":"Appaneal HJ, Caffrey AR, Lopes V, Piehl EC, Puzniak LA, LaPlante KL (2022) Assessing rates of co-resistance and patient outcomes in multidrug-resistant pseudomonas aeruginosa. Microbiol Spectr 10. https:\/\/doi.org\/10.1128\/spectrum.02336-22","DOI":"10.1128\/spectrum.02336-22"}],"container-title":["European Journal of Clinical Microbiology &amp; Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10096-026-05599-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10096-026-05599-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10096-026-05599-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:02:45Z","timestamp":1792281765000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10096-026-05599-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,14]]},"references-count":53,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["5599"],"URL":"https:\/\/doi.org\/10.1007\/s10096-026-05599-x","relation":{},"ISSN":["0934-9723","1435-4373"],"issn-type":[{"value":"0934-9723","type":"print"},{"value":"1435-4373","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,14]]},"assertion":[{"value":"18 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the Internal Review Board of all the participating centres (N\u00b0 0025169\/22). Results were reported following the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Informed consent was waived due to the retrospective nature of the study.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflicts of interest.","order":3,"name":"Ethics","label":"Transparency","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":4,"name":"Ethics","label":"Sequence information","group":{"name":"EthicsHeading","label":"Declarations"}}]}}