{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T21:02:44Z","timestamp":1788901364376,"version":"build-2803163510"},"reference-count":83,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Doctor Kasem Pangsrivongse Foundation"},{"name":"Faculty of Medicine, Faculty of Pharmacy, and Faculty of Science at the Prince of Songkla University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is an important pathogen associated with high mortality and treatment failure rates. We aimed to assess the susceptibility of CRPA to antipseudomonal agents, identify its resistance mechanisms, and evaluate clinical outcomes in a sample of CRPA isolates. Methods: This was an in vitro study of a clinical isolate of CRPA from hospitalized patients with CRPA infection and a retrospective observational study of these patients, who were diagnosed between 14 February 2021 and 10 August 2023 at Songklanagarind Hospital in Songkhla, Thailand. In vitro experiments were conducted to determine the minimum inhibitory concentrations (MICs) of the antipseudomonal agents using the broth microdilution method. Resistance mechanisms were assessed using the modified carbapenem inactivation method, combined disk tests, and quantitative real-time reverse transcription polymerase chain reaction. Results: A total of 140 CRPA isolates were analyzed. Both traditional and novel \u03b2-lactams had high MICs. The most common resistance mechanism was the upregulation of the MexAB-OprM efflux pump (81.3%), followed by the downregulation of the OprD porin (48.9%) and metallo-\u03b2-lactamase (MBL) production (45.0%), and the overexpression of blaAmpC (41.0%). The 30-day all-cause mortality rate was 30.5%. The risk factors associated with 30-day mortality included a Charlson Comorbidity Index of \u22655 (OR: 3.43; 95% CI: 1.07\u201310.99; p = 0.03), sepsis (OR: 10.62; 95% CI: 1.26\u201389.44; p = 0.03), and septic shock (OR: 4.39; 95% CI: 1.67\u201311.55; p &lt; 0.01). In contrast, receiving active documented therapy was significantly associated with reduced mortality (OR: 0.17; 95% CI: 0.04\u20130.74; p = 0.01). Conclusions: This study revealed higher MIC values of all \u03b2-lactams for CRPA, while colistin and amikacin remained effective. The resistance mechanisms included MexAB-OprM overexpression, OprD downregulation, MBL production, and blaAmpC overexpression, with a higher prevalence of MBL than in other regions of Thailand. High 30-day mortality was associated with comorbidities, sepsis, and septic shock, but active therapy reduced mortality.<\/jats:p>","DOI":"10.3390\/antibiotics14030322","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T06:10:53Z","timestamp":1742364653000},"page":"322","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Antimicrobial Resistance and Mortality in Carbapenem-Resistant Pseudomonas aeruginosa Infections in Southern Thailand"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4912-2786","authenticated-orcid":false,"given":"Parichart","family":"Chotimakorn","sequence":"first","affiliation":[{"name":"College of Pharmacotherapy Thailand, Nonthaburi 11000, Thailand"},{"name":"Department of Pharmacy, Bhumibol Adulyadej Hospital, Bangkok 10220, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sutthiporn","family":"Pattharachayakul","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyut","family":"Lertsrisatit","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9974-957X","authenticated-orcid":false,"given":"Wichai","family":"Santimaleeworagun","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom 73000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9518-7888","authenticated-orcid":false,"given":"Pimpimon","family":"Tansakul","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6438-2202","authenticated-orcid":false,"given":"Mingkwan","family":"Yingkajorn","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sureerat","family":"Chelae","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9541-3224","authenticated-orcid":false,"given":"Rattanaruji","family":"Pomwised","sequence":"additional","affiliation":[{"name":"Division of Biological Science, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6999-5534","authenticated-orcid":false,"given":"Arnon","family":"Chukamnerd","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosesathorn","family":"Soontarach","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3116-2518","authenticated-orcid":false,"given":"Sarunyou","family":"Chusri","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1086\/432803","article-title":"Overview of nosocomial infections caused by gram-negative bacilli","volume":"41","author":"Weinstein","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1093\/jac\/dkg403","article-title":"Treatment and outcome of Pseudomonas aeruginosa bacteraemia: An antibiotic pharmacodynamic analysis","volume":"52","author":"Zelenitsky","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1469-0691.2005.01161.x","article-title":"Treatment and control of severe infections caused by multiresistant Pseudomonas aeruginosa","volume":"11","author":"Rossolini","year":"2005","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"ofx176","DOI":"10.1093\/ofid\/ofx176","article-title":"Prevalence of carbapenem-resistant gram-negative infections in the United States predominated by Acinetobacter baumannii and Pseudomonas aeruginosa","volume":"4","author":"Cai","year":"2017","journal-title":"Open Forum Infect. Dis."},{"key":"ref_5","first-page":"276","article-title":"Carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii in the nosocomial setting in latin america","volume":"42","author":"Labarca","year":"2016","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1590\/S1413-86702010000500002","article-title":"Prevalence of carbapenem resistant Pseudomonas aeruginosa and Acinetobacter baumannii in highcomplexity hospital","volume":"14","author":"Baumgart","year":"2010","journal-title":"Braz. J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4711","DOI":"10.1177\/0300060519864181","article-title":"Carbapenem-resistant Pseudomonas aeruginosa and carbapenem use in Japan: An ecological study","volume":"47","author":"Terahara","year":"2019","journal-title":"J. Int. Med. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e01243-16","DOI":"10.1128\/AAC.01243-16","article-title":"Carbapenem-resistant Pseudomonas aeruginosa bacteremia: Risk factors for mortality and microbiologic treatment failure","volume":"61","author":"Buehrle","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.2147\/IDR.S174876","article-title":"Carbapenem-resistant and cephalosporin-susceptible Pseudomonas aeruginosa: A notable phenotype in patients with bacteremia","volume":"11","author":"Li","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1099\/jmm.0.073262-0","article-title":"Pseudomonas aeruginosa bacteraemia: Independent risk factors for mortality and impact of resistance on outcome","volume":"63","author":"Dantas","year":"2014","journal-title":"J. Med. Microbiol."},{"key":"ref_11","unstructured":"WHO (2017). Who Publishes List of Bacteria for Which New Antibiotics Are Urgently Needed, WHO."},{"key":"ref_12","unstructured":"CDC (2018). Carbapenem-Resistant Pseudomonas aeruginosa."},{"key":"ref_13","unstructured":"National Antimicrobial Resistance Surveillance Team (NARST) (2021). Situation of Antimicrobial Resistance 2000\u20132021, NARST."},{"key":"ref_14","unstructured":"National Antimicrobial Resistance Surveillance Team (NARST) (2020). Antibiograms by Health Service Area, NARST."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1139\/cjm-2014-0239","article-title":"Simultaneous overexpression of multidrug efflux pumps in Pseudomonas aeruginosa non-cystic fibrosis clinical isolates","volume":"60","author":"Poonsuk","year":"2014","journal-title":"Can. J. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1086\/338782","article-title":"Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: Our worst nightmare?","volume":"34","author":"Livermore","year":"2002","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1093\/jac\/dkr232","article-title":"Pseudomonas aeruginosa carbapenem resistance mechanisms in spain: Impact on the activity of imipenem, meropenem and doripenem","volume":"66","author":"Riera","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1093\/jac\/dkz245","article-title":"Mortality dynamics of Pseudomonas aeruginosa bloodstream infections and the influence of defective oprd on mortality: Prospective observational study","volume":"74","author":"Yoon","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_19","first-page":"143","article-title":"Chapter 10\u2014Metallo-beta-lactamase producer Pseudomonas aeruginosa: An opportunistic pathogen in lungs","volume":"Volume 1","author":"Kon","year":"2016","journal-title":"The Microbiology of Respiratory System Infections"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1086\/375594","article-title":"Clinical and bacteriological characteristics of imp-type metallo-beta-lactamase-producing Pseudomonas aeruginosa","volume":"37","author":"Hirakata","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1128\/AAC.05991-11","article-title":"Prospective multicenter study of the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bloodstream infections","volume":"56","author":"Pena","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1089\/mdr.2010.0170","article-title":"Risk factors for mortality in patients with Pseudomonas aeruginosa bacteremia: Clinical impact of antimicrobial resistance on outcome","volume":"17","author":"Joo","year":"2011","journal-title":"Microb. Drug Resist."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.ajic.2018.10.025","article-title":"The impact of carbapenem-resistant Pseudomonas aeruginosa on clinical and economic outcomes in a Chinese tertiary care hospital: A propensity score-matched analysis","volume":"47","author":"Chen","year":"2019","journal-title":"Am. J. Infect. Control"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1016\/j.ijid.2009.11.019","article-title":"Influence of carbapenem resistance on mortality and the dynamics of mortality in Pseudomonas aeruginosa bloodstream infection","volume":"14","author":"Tubau","year":"2010","journal-title":"Int. J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jmii.2014.01.005","article-title":"Carbapenem-resistant Pseudomonas aeruginosa in Taiwan: Prevalence, risk factors, and impact on outcome of infections","volume":"49","author":"Lin","year":"2016","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.jmii.2015.06.003","article-title":"Risk factors and clinical significance of bacteremia caused by Pseudomonas aeruginosa resistant only to carbapenems","volume":"50","author":"Lee","year":"2017","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_27","unstructured":"CLSI (2023). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [33rd ed.]."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Worapong, N., Parnrada, N., Dhitiwat, C., Supanun, P., Patomroek, H., Tassanawan, C., and Wichai, S. (2022). Optimizing doses of ceftolozane\/tazobactam as monotherapy or in combination with amikacin to treat carbapenem-resistant Pseudomonas aeruginosa. Antibiotics, 11.","DOI":"10.3390\/antibiotics11040517"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.1128\/AAC.01172-08","article-title":"Surveillance of carbapenem-resistant Pseudomonas aeruginosa isolates from Puerto Rican Medical Center hospitals: Dissemination of kpc and IMP-18 beta-lactamases","volume":"53","author":"Wolter","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.3201\/eid2507.181200","article-title":"Carbapenem-resistant Pseudomonas aeruginosa at US emerging infections program sites, 2015","volume":"25","author":"Walters","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"ofy241","DOI":"10.1093\/ofid\/ofy241","article-title":"Carbapenem-nonsusceptible gram-negative pathogens in icu and non-icu settings in us hospitals in 2017: A multicenter study","volume":"5","author":"McCann","year":"2018","journal-title":"Open Forum Infect. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.3201\/eid2510.181699","article-title":"Risk factors for carbapenem-resistant Pseudomonas aeruginosa, zhejiang province, china","volume":"25","author":"Hu","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e00875-17","DOI":"10.1128\/AAC.00875-17","article-title":"Multicenter evaluation of ceftazidime-avibactam and ceftolozane-tazobactam inhibitory activity against meropenem-nonsusceptible Pseudomonas aeruginosa from blood, respiratory tract, and wounds","volume":"61","author":"Grupper","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1093\/jac\/dku048","article-title":"Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009-11 in 14 European and mediterranean countries","volume":"69","author":"Castanheira","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1093\/cid\/ciw243","article-title":"Ceftazidime\/avibactam and ceftolozane\/tazobactam: Second-generation beta-lactam\/beta-lactamase inhibitor combinations","volume":"63","author":"Bonomo","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.jinf.2014.04.004","article-title":"Ceftolozane\/tazobactam activity tested against aerobic gram-negative organisms isolated from intra-abdominal and urinary tract infections in European and United States hospitals (2012)","volume":"69","author":"Sader","year":"2014","journal-title":"J. Infect."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ijid.2021.09.064","article-title":"Ceftolozane-tazobactam activity against clinical isolates of Pseudomonas aeruginosa from icu patients with pneumonia: United states, 2015\u20132018","volume":"112","author":"Pfaller","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.diagmicrobio.2018.11.021","article-title":"Antimicrobial activity of ceftolozane\u2013tazobactam tested against gram-negative contemporary (2015\u20132017) isolates from hospitalized patients with pneumonia in us medical centers","volume":"94","author":"Carvalhaes","year":"2019","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.ijantimicag.2014.01.032","article-title":"Ceftolozane\/tazobactam activity tested against gram-negative bacterial isolates from hospitalised patients with pneumonia in us and European medical centres (2012)","volume":"43","author":"Farrell","year":"2014","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1128\/AAC.02429-13","article-title":"Antimicrobial activity of ceftazidime-avibactam against gram-negative organisms collected from U.S. Medical centers in 2012","volume":"58","author":"Sader","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/1348-0421.12021","article-title":"Molecular investigation of carbapenem resistance among multidrug-resistant Pseudomonas aeruginosa isolated clinically in Thailand","volume":"57","author":"Khuntayaporn","year":"2013","journal-title":"Microbiol. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"991","DOI":"10.15537\/smj.2022.43.9.20220219","article-title":"Prevalence of carbapenemase genes among multidrug-resistant Pseudomonas aeruginosa isolates from tertiary care centers in southern Thailand","volume":"43","author":"Saengsuwan","year":"2022","journal-title":"Saudi Med. J."},{"key":"ref_43","unstructured":"CLSI (2024). Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [34th ed.]."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ijantimicag.2012.04.004","article-title":"Oprd mutations and inactivation, expression of efflux pumps and ampc, and metallo-beta-lactamases in carbapenem-resistant Pseudomonas aeruginosa isolates from south korea","volume":"40","author":"Lee","year":"2012","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s10096-008-0475-9","article-title":"Nosocomial acquisition of Pseudomonas aeruginosa resistant to both ciprofloxacin and imipenem: A risk factor and laboratory analysis","volume":"27","author":"Mueller","year":"2008","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3795","DOI":"10.1128\/AAC.00464-08","article-title":"Fluoroquinolone enhances the mutation frequency for meropenem-selected carbapenem resistance in Pseudomonas aeruginosa, but use of the high-potency drug doripenem inhibits mutant formation","volume":"52","author":"Tanimoto","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1128\/AAC.44.3.710-712.2000","article-title":"Molecular mechanisms of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients","volume":"44","author":"Jalal","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/S0255-0857(21)02891-7","article-title":"The resistance of Pseudomonas aeruginosa strains to fluoroquinolone group of antibiotics","volume":"22","author":"Algun","year":"2004","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Palavutitotai, N., Jitmuang, A., Tongsai, S., Kiratisin, P., and Angkasekwinai, N. (2018). Epidemiology and risk factors of extensively drug-resistant Pseudomonas aeruginosa infections. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193431"},{"key":"ref_50","first-page":"S35","article-title":"Epidemiology of infections caused by multidrug-resistant gram-negative bacteria in adult hospitalized patients at siriraj hospital","volume":"97","author":"Chaisathaphol","year":"2014","journal-title":"J. Med. Assoc. Thai"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"dlab187","DOI":"10.1093\/jacamr\/dlab187","article-title":"Mortality in patients with carbapenem-resistant Pseudomonas aeruginosa with and without susceptibility to traditional antipseudomonal beta-lactams","volume":"3","author":"Bower","year":"2021","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/S1473-3099(19)30403-7","article-title":"Ceftolozane-tazobactam versus meropenem for treatment of nosocomial pneumonia (ASPECT-NP): A randomised, controlled, double-blind, phase 3, non-inferiority trial","volume":"19","author":"Kollef","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1093\/cid\/civ097","article-title":"Ceftolozane\/tazobactam plus metronidazole for complicated intra-abdominal infections in an era of multidrug resistance: Results from a randomized, double-blind, phase 3 trial (ASPECT-CIAI)","volume":"60","author":"Solomkin","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1016\/S0140-6736(14)62220-0","article-title":"Ceftolozane-tazobactam compared with levofloxacin in the treatment of complicated urinary-tract infections, including pyelonephritis: A randomised, double-blind, phase 3 trial (ASPECT-CUTI)","volume":"385","author":"Wagenlehner","year":"2015","journal-title":"Lancet"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1093\/cid\/ciw378","article-title":"Ceftazidime-avibactam versus doripenem for the treatment of complicated urinary tract infections, including acute pyelonephritis: Recapture, a phase 3 randomized trial program","volume":"63","author":"Wagenlehner","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S1473-3099(17)30747-8","article-title":"Ceftazidime-avibactam versus meropenem in nosocomial pneumonia, including ventilator-associated pneumonia (REPROVE): A randomised, double-blind, phase 3 non-inferiority trial","volume":"18","author":"Torres","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1093\/cid\/ciw133","article-title":"Efficacy and safety of ceftazidime-avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infection: Results from a randomized, controlled, double-blind, phase 3 program","volume":"62","author":"Mazuski","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/S1473-3099(16)30004-4","article-title":"Ceftazidime-avibactam or best available therapy in patients with ceftazidime-resistant Enterobacteriaceae and Pseudomonas aeruginosa complicated urinary tract infections or complicated intra-abdominal infections (REPRISE): A randomised, pathogen-directed, phase 3 study","volume":"16","author":"Carmeli","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1093\/cid\/ciz530","article-title":"Restore-imi 1: A multicenter, randomized, double-blind trial comparing efficacy and safety of imipenem\/relebactam vs colistin plus imipenem in patients with imipenem-nonsusceptible bacterial infections","volume":"70","author":"Motsch","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/S1473-3099(24)00499-7","article-title":"Aztreonam-avibactam versus meropenem for the treatment of serious infections caused by gram-negative bacteria (REVISIT): A descriptive, multinational, open-label, phase 3, randomised trial","volume":"25","author":"Carmeli","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Mauri, C., Maraolo, A.E., Di Bella, S., Luzzaro, F., and Principe, L. (2021). The revival of aztreonam in combination with avibactam against metallo-\u03b2-lactamase-producing gram-negatives: A systematic review of in vitro studies and clinical cases. Antibiotics, 10.","DOI":"10.3390\/antibiotics10081012"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/cid\/ciac268","article-title":"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)","volume":"75","author":"Tamma","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_63","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_64","doi-asserted-by":"crossref","unstructured":"Tamma, P., Aitken, S., Bonomo, R., Mathers, A., van Duin, D., and Clancy, C. (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_65","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/S1473-3099(20)30796-9","article-title":"Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant gram-negative bacteria (CREDIBLE-CR): A randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial","volume":"21","author":"Bassetti","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"dlad107","DOI":"10.1093\/jacamr\/dlad107","article-title":"In vitro activity of cefiderocol against Pseudomonas aeruginosa demonstrating evolved resistance to novel beta-lactam\/beta-lactamase inhibitors","volume":"5","author":"Shields","year":"2023","journal-title":"JAC Antimicrob. Resist."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1093\/cid\/ciz668","article-title":"Ceftazidime, carbapenems, or piperacillin-tazobactam as single definitive therapy for Pseudomonas aeruginosa bloodstream infection: A multisite retrospective study","volume":"70","author":"Babich","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2907","DOI":"10.1128\/AAC.02365-12","article-title":"Extended-infusion cefepime reduces mortality in patients with Pseudomonas aeruginosa infections","volume":"57","author":"Bauer","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"4087","DOI":"10.1128\/AAC.00521-12","article-title":"Population pharmacokinetics of extended-infusion piperacillin-tazobactam in hospitalized patients with nosocomial infections","volume":"56","author":"Felton","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kim, Y.K., Kang, G., Zang, D.Y., and Lee, D.H. (2024). Precision dosing of meropenem in adults with normal renal function: Insights from a population pharmacokinetic and monte carlo simulation study. Antibiotics, 13.","DOI":"10.3390\/antibiotics13090849"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ijid.2016.06.017","article-title":"Optimizing intravenous fosfomycin dosing in combination with carbapenems for treatment of Pseudomonas aeruginosa infections in critically ill patients based on pharmacokinetic\/pharmacodynamic (pk\/pd) simulation","volume":"50","author":"Asuphon","year":"2016","journal-title":"Int. J. Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Tamma, P.D., Heil, E.L., Justo, J.A., Mathers, A.J., Satlin, M.J., and Bonomo, R.A. (2024). Infectious diseases society of america 2024 guidance on the treatment of antimicrobial-resistant gram-negative infections. Clin. Infect. Dis., ciae403.","DOI":"10.1093\/cid\/ciae403"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/cid\/ciz816","article-title":"Ceftolozane\/tazobactam vs polymyxin or aminoglycoside-based regimens for the treatment of drug-resistant Pseudomonas aeruginosa","volume":"71","author":"Pogue","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1002\/phar.2209","article-title":"International consensus guidelines for the optimal use of the polymyxins: Endorsed by the american college of clinical pharmacy (ACCP), european society of clinical microbiology and infectious diseases (ESCMID), infectious diseases society of america (IDSA), international society for anti-infective pharmacology (ISAP), society of critical care medicine (SCCM), and society of infectious diseases pharmacists (SIDP)","volume":"39","author":"Tsuji","year":"2019","journal-title":"Pharmacotherapy"},{"key":"ref_75","unstructured":"CDC (2023). CDC\/NHSN Surveillance Definitions for Specific Types of Infections, National Healthcare Safety Network (NHSN)."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Seo, Y.B., Lee, J., Kim, Y.K., Lee, S.S., Lee, J.-a., Kim, H.Y., Uh, Y., Kim, H.-S., and Song, W. (2017). Randomized controlled trial of piperacillin-tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum beta-lactamase-producing escherichia coli. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2502-x"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1093\/clind\/15.Supplement_1.S5","article-title":"General guidelines for the clinical evaluation of anti-infective drug products. Infectious diseases society of america and the food and drug administration","volume":"15","author":"Beam","year":"1992","journal-title":"Clin. Infect. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1093\/clind\/15.Supplement_1.S62","article-title":"Evaluation of new anti-infective drugs for the treatment of respiratory tract infections. Infectious diseases society of america and the food and drug administration","volume":"15","author":"Chow","year":"1992","journal-title":"Clin. Infect. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1093\/cid\/ciw741","article-title":"Comparing the outcomes of patients with carbapenemase-producing and non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae bacteremia","volume":"64","author":"Tamma","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1128\/JCM.00818-07","article-title":"Metallo-beta-lactamase detection: Comparative evaluation of double-disk synergy versus combined disk tests for imp-, gim-, sim-, spm-, or vim-producing isolates","volume":"46","author":"Picao","year":"2008","journal-title":"J. Clin. Microbiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1128\/AAC.01645-10","article-title":"Overexpression of ampc and efflux pumps in Pseudomonas aeruginosa isolates from bloodstream infections: Prevalence and impact on resistance in a spanish multicenter study","volume":"55","author":"Cabot","year":"2011","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/3\/322\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:56:26Z","timestamp":1760028986000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/3\/322"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":83,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["antibiotics14030322"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14030322","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,19]]}}}