{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:10:03Z","timestamp":1793059803710,"version":"4.5.0"},"reference-count":241,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T00:00:00Z","timestamp":1747699200000},"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>Pseudomonas aeruginosa is a significant threat to public health as an aggressive, opportunistic pathogen. The use of \u03b2-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems remains a front-line treatment against P. aeruginosa. However, the widespread use of \u03b2-lactams has led to the emergence of \u03b2-lactam-resistant isolates that significantly increase the economic burden and risk of mortality in patients. With the declining productivity of the antibiotic discovery pipeline, research has investigated synergistic agents to revive the use of \u03b2-lactam antibiotics against \u03b2-lactam-resistant P. aeruginosa. In this review, we summarize the mechanism of \u03b2-lactam antibiotics and provide an overview of major mechanisms associated with \u03b2-lactam resistance in P. aeruginosa. We then describe the background and use of three promising classes of agents that have shown extensive beneficial effects with \u03b2-lactam antibiotics against P. aeruginosa, namely \u03b2-lactamase inhibitors, bacteriophages, and antimicrobial peptides. The current understanding of the mechanisms of these synergistic agents is discussed. Lastly, we provide an overview of the current barriers impeding antibiotic development, and offer a glimpse into recent advances of artificial intelligence-based discovery that may serve as a new foundation for antimicrobial discovery and treatment.<\/jats:p>","DOI":"10.3390\/antibiotics14050526","type":"journal-article","created":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T11:50:31Z","timestamp":1747741831000},"page":"526","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Combatting Pseudomonas aeruginosa with \u03b2-Lactam Antibiotics: A Revived Weapon?"],"prefix":"10.3390","volume":"14","author":[{"given":"Dylan W.","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1094-0349","authenticated-orcid":false,"given":"Christopher T.","family":"Lohans","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1056\/NEJMoa1306801","article-title":"Multistate point-prevalence survey of health care\u2013associated infections","volume":"370","author":"Magill","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1007\/s40265-021-01635-6","article-title":"The Epidemiology and Pathogenesis and Treatment of Pseudomonas aeruginosa Infections: An Update","volume":"81","author":"Reynolds","year":"2021","journal-title":"Drugs"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1017\/ice.2016.174","article-title":"Antimicrobial-resistant pathogens associated with healthcare-associated infections: Summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011\u20132014","volume":"37","author":"Weiner","year":"2016","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1016\/S0140-6736(22)02185-7","article-title":"Global mortality associated with 33 bacterial pathogens in 2019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"400","author":"Ikuta","year":"2022","journal-title":"Lancet"},{"key":"ref_5","first-page":"68","article-title":"Antimicrobial activity of ceftolozane-tazobactam against multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa clinical isolates from a Spanish hospital","volume":"32","author":"Morales","year":"2019","journal-title":"Rev. Esp. Quimioter."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"20316","DOI":"10.2807\/ese.17.46.20316-en","article-title":"The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial use","volume":"17","author":"Zarb","year":"2012","journal-title":"Eurosurveillance"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Cooke, A.C., Nello, A.V., Ernst, R.K., and Schertzer, J.W. (2019). Analysis of Pseudomonas aeruginosa biofilm membrane vesicles supports multiple mechanisms of biogenesis. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0212275"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Metruccio, M.M., Evans, D.J., Gabriel, M.M., Kadurugamuwa, J.L., and Fleiszig, S.M. (2016). Pseudomonas aeruginosa outer membrane vesicles triggered by human mucosal fluid and lysozyme can prime host tissue surfaces for bacterial adhesion. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.00871"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1128\/jb.178.10.2767-2774.1996","article-title":"Bacteriolytic effect of membrane vesicles from Pseudomonas aeruginosa on other bacteria including pathogens: Conceptually new antibiotics","volume":"178","author":"Kadurugamuwa","year":"1996","journal-title":"J. Bacteriol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Koeppen, K., Barnaby, R., Jackson, A.A., Gerber, S.A., Hogan, D.A., and Stanton, B.A. (2019). Tobramycin reduces key virulence determinants in the proteome of Pseudomonas aeruginosa outer membrane vesicles. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0211290"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"He, C., Zhou, Y., Liu, F., Liu, H., Tan, H., Jin, S., Wu, W., and Ge, B. (2017). Bacterial nucleotidyl cyclase inhibits the host innate immune response by suppressing TAK1 activation. Infect. Immun., 85.","DOI":"10.1128\/IAI.00239-17"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12088-016-0625-1","article-title":"Bacterial virulence factors: Secreted for survival","volume":"57","author":"Sharma","year":"2017","journal-title":"Indian J. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/nrd3013","article-title":"Anti-virulence strategies to combat bacteria-mediated disease","volume":"9","author":"Rasko","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/nrmicro2199","article-title":"The type III secretion system of Pseudomonas aeruginosa: Infection by injection","volume":"7","author":"Hauser","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bagayoko, S., Leon-Icaza, S.A., Pinilla, M., Hessel, A., Santoni, K., P\u00e9ricat, D., Bordignon, P.-J., Moreau, F., Eren, E., and Boyanc\u00e9, A. (2021). Host phospholipid peroxidation fuels ExoU-dependent cell necrosis and supports Pseudomonas aeruginosa-driven pathology. PLoS Path., 17.","DOI":"10.1101\/2021.02.17.431580"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1046\/j.1365-2958.1997.4891851.x","article-title":"ExoU expression by Pseudomonas aeruginosa correlates with acute cytotoxicity and epithelial injury","volume":"25","author":"Goranson","year":"1997","journal-title":"Mol. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12934-021-01593-4","article-title":"Anaerobic biosynthesis of rhamnolipids by Pseudomonas aeruginosa: Performance, mechanism and its application potential for enhanced oil recovery","volume":"20","author":"Zhao","year":"2021","journal-title":"Microb. Cell Factories"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.bbrc.2009.08.082","article-title":"The role of lipopolysaccharide moieties in macrophage response to Escherichia coli","volume":"389","author":"Eder","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/2049-632X.12033","article-title":"Pseudomonas aeruginosa: New insights into pathogenesis and host defenses","volume":"67","author":"Gellatly","year":"2013","journal-title":"Pathog. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.2165\/00003495-200060050-00006","article-title":"The treatment of respiratory pseudomonas infection in cystic fibrosis: What drug and which way?","volume":"60","author":"Banerjee","year":"2000","journal-title":"Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bush, K., and Bradford, P.A. (2016). \u03b2-Lactams and \u03b2-lactamase inhibitors: An overview. Cold Spring Harb. Perspect. Med., 6.","DOI":"10.1101\/cshperspect.a025247"},{"key":"ref_22","first-page":"1207","article-title":"The Beta Lactam Antibiotics as an Empirical Therapy in a Developing Country: An Update on Their Current Status and Recommendations to Counter the Resistance against Them","volume":"7","author":"Thakuria","year":"2013","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E3463","DOI":"10.1073\/pnas.1717295115","article-title":"Global increase and geographic convergence in antibiotic consumption between 2000 and 2015","volume":"115","author":"Klein","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bankar, N.J., Ugemuge, S., Ambad, R.S., Hawale, D.V., and Timilsina, D.R. (2022). Implementation of Antimicrobial Stewardship in the Healthcare Setting. Cureus, 14.","DOI":"10.7759\/cureus.26664"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Poole, K. (2011). Pseudomonas aeruginosa: Resistance to the max. Front. Microbiol., 2.","DOI":"10.3389\/fmicb.2011.00065"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.tim.2011.04.005","article-title":"Pseudomonas aeruginosa: All roads lead to resistance","volume":"19","author":"Breidenstein","year":"2011","journal-title":"Trends Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1128\/JCM.00102-11","article-title":"Most multidrug-resistant Pseudomonas aeruginosa isolates from hospitals in eastern France belong to a few clonal types","volume":"49","author":"Cholley","year":"2011","journal-title":"J. Clin. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.cmi.2017.06.018","article-title":"Global emergence of the widespread Pseudomonas aeruginosa ST235 clone","volume":"24","author":"Treepong","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Feretzakis, G., Loupelis, E., Sakagianni, A., Skarmoutsou, N., Michelidou, S., Velentza, A., Martsoukou, M., Valakis, K., Petropoulou, S., and Koutalas, E. (2019). A 2-year single-centre audit on antibiotic resistance of Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae strains from an intensive care unit and other wards in a general public hospital in Greece. Antibiotics, 8.","DOI":"10.3390\/antibiotics8020062"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1590\/0037-8682-0506-2017","article-title":"Mortality in patients with multidrug-resistant Pseudomonas aeruginosa infections: A meta-analysis","volume":"51","author":"Matos","year":"2018","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/2047-2994-3-32","article-title":"Clinical and economic consequences of hospital-acquired resistant and multidrug-resistant Pseudomonas aeruginosa infections: A systematic review and meta-analysis","volume":"3","author":"Nathwani","year":"2014","journal-title":"Antimicrob. Resist. Infect. Control."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3109\/03009734.2014.899279","article-title":"Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria","volume":"119","year":"2014","journal-title":"Ups. J. Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.tibtech.2012.12.006","article-title":"Combination approaches to combat multidrug-resistant bacteria","volume":"31","author":"Worthington","year":"2013","journal-title":"Trends Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"310","DOI":"10.4103\/0972-5229.132495","article-title":"Current concepts in combination antibiotic therapy for critically ill patients","volume":"18","author":"Ahmed","year":"2014","journal-title":"Indian J. Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/S1473-3099(17)30233-5","article-title":"Who benefits from antimicrobial combination therapy?","volume":"17","author":"Pletz","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, N., Luo, J., Deng, F., Huang, Y., and Zhou, H. (2022). Antibiotic combination therapy: A strategy to overcome bacterial resistance to aminoglycoside antibiotics. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.839808"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"141","DOI":"10.4062\/biomolther.2023.008","article-title":"Structural Insights for \u03b2-Lactam Antibiotics","volume":"31","author":"Kim","year":"2023","journal-title":"Biomol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/j.bcp.2005.12.003","article-title":"Redefining penems","volume":"71","author":"Dalhoff","year":"2006","journal-title":"Biochem. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.1128\/AAC.00296-11","article-title":"Carbapenems: Past, present, and future","volume":"55","author":"Endimiani","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Flores-Kim, J., Dobihal, G.S., Fenton, A., Rudner, D.Z., and Bernhardt, T.G. (2019). A switch in surface polymer biogenesis triggers growth-phase-dependent and antibiotic-induced bacteriolysis. Elife, 8.","DOI":"10.7554\/eLife.44912"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1039\/D1MD00200G","article-title":"\u03b2-Lactam antibiotic targets and resistance mechanisms: From covalent inhibitors to substrates","volume":"12","author":"Lohans","year":"2021","journal-title":"RSC Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1098\/rstb.1980.0049","article-title":"The structure of \u03b2-lactamases","volume":"289","author":"Ambler","year":"1980","journal-title":"Philos. Trans. R. Soc. London. B Biol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"245","DOI":"10.3109\/1040841X.2010.481763","article-title":"\u03b2-lactamases identified in clinical isolates of Pseudomonas aeruginosa","volume":"36","author":"Zhao","year":"2010","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3472","DOI":"10.1016\/j.jmb.2019.04.002","article-title":"\u03b2-Lactamases and \u03b2-Lactamase Inhibitors in the 21st Century","volume":"431","author":"Tooke","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/cc8892","article-title":"Bench-to-bedside review: The role of \u03b2-lactamases in antibiotic-resistant Gram-negative infections","volume":"14","author":"Bush","year":"2010","journal-title":"Crit. Care"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1128\/CMR.00036-08","article-title":"AmpC \u03b2-Lactamases","volume":"22","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1128\/CMR.00117-13","article-title":"OXA \u03b2-Lactamases","volume":"27","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1080\/14756366.2017.1344235","article-title":"Beta-lactamase database (BLDB)\u2013structure and function","volume":"32","author":"Naas","year":"2017","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bonomo, R.A. (2017). \u03b2-Lactamases: A Focus on Current Challenges. Cold Spring Harb. Perspect. Med., 7.","DOI":"10.1101\/cshperspect.a025239"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bush, K., and Bradford, P.A. (2020). Epidemiology of \u03b2-lactamase-producing pathogens. Clin. Microbiol. Rev., 33.","DOI":"10.1128\/CMR.00047-19"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41579-019-0159-8","article-title":"Interplay between \u03b2-lactamases and new \u03b2-lactamase inhibitors","volume":"17","author":"Bush","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"dlab092","DOI":"10.1093\/jacamr\/dlab092","article-title":"Extended-spectrum \u03b2-lactamases: An update on their characteristics, epidemiology and detection","volume":"3","author":"Castanheira","year":"2021","journal-title":"JAC-Antimicrob. Resist."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/jac\/dki482","article-title":"OXA-type carbapenemases","volume":"57","year":"2006","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1093\/clinids\/24.Supplement_1.S19","article-title":"Evolution and dissemination of \u03b2-lactamases accelerated by generations of \u03b2-lactam antibiotics","volume":"24","author":"Medeiros","year":"1997","journal-title":"Clin. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1093\/jac\/dkm226","article-title":"Class A carbapenemases","volume":"60","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1093\/jac\/dks121","article-title":"OXA-48-like carbapenemases: The phantom menace","volume":"67","author":"Poirel","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e00216","DOI":"10.1128\/aac.00216-22","article-title":"OXA-48-like \u03b2-lactamases: Global epidemiology, treatment options, and development pipeline","volume":"66","author":"Boyd","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_58","unstructured":"Halat, D.H., and Moubareck, C.A. (2022). The Intriguing Carbapenemases of Pseudomonas aeruginosa: Current Status, Genetic Profile, and Global Epidemiology. Yale J. Biol. Med., 95."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.ijantimicag.2015.03.001","article-title":"Emerging broad-spectrum resistance in Pseudomonas aeruginosa and Acinetobacter baumannii: Mechanisms and epidemiology","volume":"45","author":"Potron","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1128\/CMR.18.2.306-325.2005","article-title":"Metallo-\u03b2-lactamases: The quiet before the storm?","volume":"18","author":"Walsh","year":"2005","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.tips.2018.03.007","article-title":"The Continuing Challenge of Metallo-\u03b2-Lactamase Inhibition: Mechanism Matters","volume":"39","author":"Ju","year":"2018","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.3201\/eid2910.230509","article-title":"Pseudomonas aeruginosa High-Risk Sequence Type 463 Co-Producing KPC-2 and AFM-1 Carbapenemases, China, 2020\u20132022","volume":"29","author":"Zhang","year":"2023","journal-title":"Emerging Infect. Dis."},{"key":"ref_63","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":"Suarez","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e159","DOI":"10.1016\/S2666-5247(22)00329-9","article-title":"Global epidemiology and clinical outcomes of carbapenem-resistant Pseudomonas aeruginosa and associated carbapenemases (POP): A prospective cohort study","volume":"4","author":"Reyes","year":"2023","journal-title":"Lancet Microbe"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Thaden, J.T., Park, L.P., Maskarinec, S.A., Ruffin, F., Fowler, V.G., and Van Duin, D. (2017). Results from a 13-year prospective cohort study show increased mortality associated with bloodstream infections caused by Pseudomonas aeruginosa compared to other bacteria. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.02671-16"},{"key":"ref_66","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_67","doi-asserted-by":"crossref","unstructured":"Liu, Q., Li, X., Li, W., Du, X., He, J.-Q., Tao, C., and Feng, Y. (2015). Influence of carbapenem resistance on mortality of patients with Pseudomonas aeruginosa infection: A meta-analysis. Sci. Rep., 5.","DOI":"10.1038\/srep11715"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1086\/377200","article-title":"Pseudomonas aeruginosa bacteremia: Risk factors for mortality and influence of delayed receipt of effective antimicrobial therapy on clinical outcome","volume":"37","author":"Kang","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1128\/AAC.49.2.760-766.2005","article-title":"Bloodstream infections caused by antibiotic-resistant gram-negative bacilli: Risk factors for mortality and impact of inappropriate initial antimicrobial therapy on outcome","volume":"49","author":"Kang","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"S82","DOI":"10.1086\/499406","article-title":"The relationship between antimicrobial resistance and patient outcomes: Mortality, length of hospital stay, and health care costs","volume":"42","author":"Cosgrove","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S1473-3099(20)30477-1","article-title":"Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: A retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals","volume":"21","author":"Kadri","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Chumbita, M., Puerta-Alcalde, P., Y\u00e1\u00f1ez, L., Angeles Cuesta, M., Chinea, A., Espa\u00f1ol-Morales, I., Fernandez-Abell\u00e1n, P., Gudiol, C., Gonz\u00e1lez-Sierra, P., and Rojas, R. (2023). High rate of inappropriate antibiotics in patients with hematologic malignancies and Pseudomonas aeruginosa bacteremia following international guideline recommendations. Microbiol. Spectr., 11.","DOI":"10.1128\/spectrum.00674-23"},{"key":"ref_73","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":"Suarez","year":"2010","journal-title":"Int. J. Infect. Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/s13756-020-00838-y","article-title":"\u03b2-lactamase-mediated resistance in MDR-Pseudomonas aeruginosa from Qatar","volume":"9","author":"Khan","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1007\/s42770-021-00576-2","article-title":"Emergence of rmtD1 gene in clinical isolates of Pseudomonas aeruginosa carrying bla KPC and\/or bla VIM-2 genes in Brazil","volume":"52","author":"Cavalcanti","year":"2021","journal-title":"Braz. J. Microbiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis","volume":"399","author":"Murray","year":"2022","journal-title":"Lancet"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Chen, W., Zhang, Y.-M., and Davies, C. (2017). Penicillin-binding protein 3 is essential for growth of Pseudomonas aeruginosa. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.01651-16"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1080\/14787210.2016.1204911","article-title":"The antibiotic pipeline for multi-drug resistant gram negative bacteria: What can we expect?","volume":"14","author":"Falagas","year":"2016","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e40","DOI":"10.1016\/S1473-3099(18)30513-9","article-title":"Analysis of the clinical antibacterial and antituberculosis pipeline","volume":"19","author":"Theuretzbacher","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Diaz Caballero, J., Clark, S.T., Coburn, B., Zhang, Y., Wang, P.W., Donaldson, S.L., Tullis, D.E., Yau, Y.C., Waters, V.J., and Hwang, D.M. (2015). Selective sweeps and parallel pathoadaptation drive Pseudomonas aeruginosa evolution in the cystic fibrosis lung. mBio, 6.","DOI":"10.1128\/mBio.00981-15"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/j.ijantimicag.2019.01.009","article-title":"Penicillin-binding protein 3 is a common adaptive target among Pseudomonas aeruginosa isolates from adult cystic fibrosis patients treated with \u03b2-lactams","volume":"53","author":"Clark","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1128\/MMBR.67.4.593-656.2003","article-title":"Molecular basis of bacterial outer membrane permeability revisited","volume":"67","author":"Nikaido","year":"2003","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/nrmicro1994","article-title":"The porin and the permeating antibiotic: A selective diffusion barrier in Gram-negative bacteria","volume":"6","author":"James","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1093\/femsre\/fux020","article-title":"Structure, function and regulation of Pseudomonas aeruginosa porins","volume":"41","author":"Chevalier","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1093\/jac\/dkt115","article-title":"Diversity of \u03b2-lactam resistance mechanisms in cystic fibrosis isolates of Pseudomonas aeruginosa: A French multicentre study","volume":"68","author":"Llanes","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1089\/mdr.2008.0778","article-title":"Alterations of porin, pumps, and penicillin-binding proteins in carbapenem resistant clinical isolates of Pseudomonas aeruginosa","volume":"14","author":"Giske","year":"2008","journal-title":"Microb. Drug Resist."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ijmm.2011.10.001","article-title":"Structure and function of OprD protein in Pseudomonas aeruginosa: From antibiotic resistance to novel therapies","volume":"302","author":"Li","year":"2012","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1128\/AAC.43.5.1085","article-title":"Negative regulation of the Pseudomonas aeruginosa outer membrane porin OprD selective for imipenem and basic amino acids","volume":"43","author":"Ochs","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1021\/acsinfecdis.6b00197","article-title":"Whole-cell-based assay to evaluate structure permeation relationships for carbapenem passage through the Pseudomonas aeruginosa porin OprD","volume":"3","author":"Iyer","year":"2017","journal-title":"ACS Infect. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Ude, J., Tripathi, V., Buyck, J.M., S\u00f6derholm, S., Cunrath, O., Fanous, J., Claudi, B., Egli, A., Schleberger, C., and Hiller, S. (2021). Outer membrane permeability: Antimicrobials and diverse nutrients bypass porins in Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA, 118.","DOI":"10.1073\/pnas.2107644118"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.chembiol.2015.03.018","article-title":"Toward the rational design of carbapenem uptake in Pseudomonas aeruginosa","volume":"22","author":"Isabella","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1128\/JB.01296-06","article-title":"Characterization of OpdH, a Pseudomonas aeruginosa porin involved in the uptake of tricarboxylates","volume":"189","author":"Tamber","year":"2007","journal-title":"J. Bacteriol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.pbiomolbio.2018.07.008","article-title":"Efflux pumps and antimicrobial resistance: Paradoxical components in systems genomics","volume":"141","author":"Kabra","year":"2019","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.bbapap.2008.10.004","article-title":"Mechanisms of RND multidrug efflux pumps","volume":"1794","author":"Nikaido","year":"2009","journal-title":"Biochim. Biophys. Acta (BBA)-Proteins Proteom."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"163","DOI":"10.3390\/antibiotics2010163","article-title":"Resistance-nodulation-division multidrug efflux pumps in gram-negative bacteria: Role in virulence","volume":"2","author":"Fernando","year":"2013","journal-title":"Antibiotics"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"5479","DOI":"10.1021\/acs.chemrev.1c00055","article-title":"Structure, assembly, and function of tripartite efflux and type 1 secretion systems in gram-negative bacteria","volume":"121","author":"Alav","year":"2021","journal-title":"Chem. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"del Barrio-Tofi\u00f1o, E., L\u00f3pez-Causap\u00e9, C., Cabot, G., Rivera, A., Benito, N., Segura, C., Montero, M.M., Sorl\u00ed, L., Tubau, F., and G\u00f3mez-Zorrilla, S. (2017). Genomics and susceptibility profiles of extensively drug-resistant Pseudomonas aeruginosa isolates from Spain. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.01589-17"},{"key":"ref_98","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-\u03b2-lactamases in carbapenem-resistant Pseudomonas aeruginosa isolates from South Korea","volume":"40","author":"Lee","year":"2012","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ijid.2019.04.027","article-title":"Role of outer membrane permeability, efflux mechanism, and carbapenemases in carbapenem-nonsusceptible Pseudomonas aeruginosa from Dubai hospitals: Results of the first cross-sectional survey","volume":"84","author":"Moubareck","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1046\/j.1365-2958.1997.2281594.x","article-title":"Characterization of MexE\u2013MexF\u2013OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa","volume":"23","author":"Henze","year":"1997","journal-title":"Mol. Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4771","DOI":"10.1128\/AAC.00680-12","article-title":"Pan-\u03b2-lactam resistance development in Pseudomonas aeruginosa clinical strains: Molecular mechanisms, penicillin-binding protein profiles, and binding affinities","volume":"56","author":"Beceiro","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s00203-016-1215-7","article-title":"Overexpression of MexAB-OprM efflux pump in carbapenem-resistant Pseudomonas aeruginosa","volume":"198","author":"Pan","year":"2016","journal-title":"Arch. Microbiol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Chalhoub, H., Pletzer, D., Weingart, H., Braun, Y., Tunney, M.M., Elborn, J.S., Rodriguez-Villalobos, H., Pl\u00e9siat, P., Kahl, B.C., and Denis, O. (2017). Mechanisms of intrinsic resistance and acquired susceptibility of Pseudomonas aeruginosa isolated from cystic fibrosis patients to temocillin, a revived antibiotic. Sci. Rep., 7.","DOI":"10.1038\/srep40208"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3322","DOI":"10.1128\/AAC.44.12.3322-3327.2000","article-title":"Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXY-oprM efflux pumps in Pseudomonas aeruginosa","volume":"44","author":"Masuda","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Frimodt-M\u00f8ller, J., Rossi, E., Haagensen, J.A.J., Falcone, M., Molin, S., and Johansen, H.K. (2018). Mutations causing low level antibiotic resistance ensure bacterial survival in antibiotic-treated hosts. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-30972-y"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1128\/AAC.44.9.2242-2246.2000","article-title":"Contribution of the MexX-MexY-OprM efflux system to intrinsic resistance in Pseudomonas aeruginosa","volume":"44","author":"Masuda","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Gomis-Font, M.A., Pitart, C., del Barrio-Tofi\u00f1o, E., Zboromyrska, Y., Cortes-Lara, S., Mulet, X., Marco, F., Vila, J., L\u00f3pez-Causap\u00e9, C., and Oliver, A. (2021). Emergence of Resistance to Novel Cephalosporin\u2013\u03b2-lactamase Inhibitor Combinations through the Modification of the Pseudomonas aeruginosa MexCD-OprJ Efflux Pump. Antimicrob. Agents Chemother., 65.","DOI":"10.1128\/AAC.00089-21"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1128\/JB.183.3.807-812.2001","article-title":"MexR repressor of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa: Identification of MexR binding sites in the mexA-mexR intergenic region","volume":"183","author":"Evans","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_109","first-page":"23","article-title":"Molecular mechanism of MexR-mediated regulation of MexAB\u2013OprM efflux pump expression in Pseudomonas aeruginosa","volume":"195","author":"Saito","year":"2001","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1128\/AAC.40.9.2021","article-title":"Expression of the multidrug resistance operon mexA-mexB-oprM in Pseudomonas aeruginosa: mexR encodes a regulator of operon expression","volume":"40","author":"Poole","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1128\/AAC.49.5.1782-1786.2005","article-title":"Mutations in PA3574 (nalD) lead to increased MexAB-OprM expression and multidrug resistance in laboratory and clinical isolates of Pseudomonas aeruginosa","volume":"49","author":"Sobel","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/j.1574-6968.1999.tb08709.x","article-title":"nalB-type mutations causing the overexpression of the MexAB-OprM efflux pump are located in the mexR gene of the Pseudomonas aeruginosa chromosome","volume":"179","author":"Saito","year":"1999","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"8649","DOI":"10.1128\/JB.01342-06","article-title":"nalD encodes a second repressor of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa","volume":"188","author":"Morita","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1128\/AAC.43.2.424","article-title":"Carbapenem activities against Pseudomonas aeruginosa: Respective contributions of OprD and efflux systems","volume":"43","author":"Epp","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1128\/JB.187.4.1246-1253.2005","article-title":"Mutations in PA2491 (mexS) promote MexT-dependent mexEF-oprN expression and multidrug resistance in a clinical strain of Pseudomonas aeruginosa","volume":"187","author":"Sobel","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"6300","DOI":"10.1128\/JB.181.20.6300-6305.1999","article-title":"Characterization of MexT, the regulator of the MexE-MexF-OprN multidrug efflux system of Pseudomonas aeruginosa","volume":"181","author":"Epp","year":"1999","journal-title":"J. Bacteriol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1128\/AAC.11.5.852","article-title":"Clavulanic acid: A beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus","volume":"11","author":"Reading","year":"1977","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2185","DOI":"10.1021\/bi00604a025","article-title":"Chemical studies on the inactivation of Escherichia coli RTEM \u03b2-lactamase by clavulanic acid","volume":"17","author":"Charnas","year":"1978","journal-title":"Biochemistry"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.1021\/bi00514a035","article-title":"Inactivation of radiolabeled RTEM. beta.-lactamase from Escherichia coli by clavulanic acid and 9-deoxyclavulanic acid","volume":"20","author":"Charnas","year":"1981","journal-title":"Biochemistry"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.ijantimicag.2015.08.011","article-title":"A resurgence of \u03b2-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens","volume":"46","author":"Bush","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"3881","DOI":"10.1128\/AAC.47.12.3881-3889.2003","article-title":"Carbapenem-resistant strain of Klebsiella oxytoca harboring carbapenem-hydrolyzing\u03b2-lactamase KPC-2","volume":"47","author":"Yigit","year":"2003","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4793","DOI":"10.1128\/AAC.48.12.4793-4799.2004","article-title":"Outbreak of Klebsiella pneumoniae producing a new carbapenem-hydrolyzing class A \u03b2-lactamase, KPC-3, in a New York medical center","volume":"48","author":"Woodford","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1128\/AAC.01143-06","article-title":"Klebsiella pneumoniae isolate producing at least eight different \u03b2-lactamases, including AmpC and KPC \u03b2-lactamases","volume":"51","author":"Moland","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Yahav, D., Giske, C.G., Gr\u0101matniece, A., Abodakpi, H., Tam, V.H., and Leibovici, L. (2020). New \u03b2-lactam\u2013\u03b2-lactamase inhibitor combinations. Clin. Microbiol. Rev., 34.","DOI":"10.1128\/CMR.00115-20"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.mib.2011.07.026","article-title":"Diazabicyclooctanes (DBOs): A potent new class of non-\u03b2-lactam \u03b2-lactamase inhibitors","volume":"14","author":"Coleman","year":"2011","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Rubino, C.M., Bhavnani, S.M., Loutit, J.S., Morgan, E.E., White, D., Dudley, M.N., and Griffith, D.C. (2018). Phase 1 study of the safety, tolerability, and pharmacokinetics of vaborbactam and meropenem alone and in combination following single and multiple doses in healthy adult subjects. Antimicrob. Agents Chemother., 62.","DOI":"10.1128\/AAC.02228-17"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1021\/acs.jmedchem.5b00127","article-title":"Discovery of a cyclic boronic acid \u03b2-lactamase inhibitor (RPX7009) with utility vs. class A serine carbapenemases","volume":"58","author":"Hecker","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1093\/jac\/dkad225","article-title":"Activity of novel \u03b2-lactam\/\u03b2-lactamase inhibitor combinations against serine carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa","volume":"78","author":"Lee","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1093\/jac\/dkad412","article-title":"Assessing the in vivo impact of novel \u03b2-lactamase inhibitors on the efficacy of their partner \u03b2-lactams against serine carbapenemase-producing Pseudomonas aeruginosa using human-simulated exposures","volume":"79","author":"Ruiz","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1093\/jac\/dkae263","article-title":"Impact of chromosomally encoded resistance mechanisms and transferable \u03b2-lactamases on the activity of cefiderocol and innovative \u03b2-lactam\/\u03b2-lactamase inhibitor combinations against Pseudomonas aeruginosa","volume":"79","author":"Maceiras","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Carvalhaes, C.G., Shortridge, D., Sader, H.S., and Castanheira, M. (2020). Activity of Meropenem-Vaborbactam against Bacterial Isolates Causing Pneumonia in Patients in U.S. Hospitals during 2014 to 2018. Antimicrob. Agents Chemother., 64.","DOI":"10.1128\/AAC.02177-19"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1093\/jac\/dkaa456","article-title":"Activity of imipenem\/relebactam against Pseudomonas aeruginosa producing ESBLs and carbapenemases","volume":"76","author":"Mushtaq","year":"2021","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.1093\/jac\/dkv239","article-title":"Activity of OP0595\/\u03b2-lactam combinations against Gram-negative bacteria with extended-spectrum, AmpC and carbapenem-hydrolysing \u03b2-lactamases","volume":"70","author":"Livermore","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_134","first-page":"2286","article-title":"Activity of MK-7655 combined with imipenem against Enterobacteriaceae and Pseudomonas aeruginosa","volume":"68","author":"Livermore","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/jac\/dkac360","article-title":"In vitro activity of aztreonam in combination with newly developed \u03b2-lactamase inhibitors against MDR Enterobacterales and Pseudomonas aeruginosa producing metallo-\u03b2-lactamases","volume":"78","author":"Nordmann","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Thomson, K.S., AbdelGhani, S., Snyder, J.W., and Thomson, G.K. (2019). Activity of cefepime-zidebactam against multidrug-resistant (MDR) Gram-negative pathogens. Antibiotics, 8.","DOI":"10.3390\/antibiotics8010032"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Lomovskaya, O., Rubio-Aparicio, D., Nelson, K., Sun, D., Tsivkovski, R., Castanheira, M., Lindley, J., Loutit, J., and Dudley, M. (2021). In Vitro Activity of the Ultrabroad-Spectrum Beta-Lactamase Inhibitor QPX7728 in Combination with Multiple Beta-Lactam Antibiotics against Pseudomonas aeruginosa. Antimicrob. Agents Chemother., 65.","DOI":"10.1128\/AAC.00210-21"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Slater, C.L., Winogrodzki, J., Fraile-Ribot, P.A., Oliver, A., Khajehpour, M., and Mark, B.L. (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.","DOI":"10.1128\/AAC.00894-20"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1093\/jac\/dkad062","article-title":"Simultaneous and divergent evolution of resistance to cephalosporin\/\u03b2-lactamase inhibitor combinations and imipenem\/relebactam following ceftazidime\/avibactam treatment of MDR Pseudomonas aeruginosa infections","volume":"78","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Ruedas-L\u00f3pez, A., Alonso-Garc\u00eda, I., Lasarte-Monterrubio, C., Guijarro-S\u00e1nchez, P., Gato, E., V\u00e1zquez-Ucha, J.C., Vallejo, J.A., Fraile-Ribot, P.A., Fern\u00e1ndez-P\u00e9rez, B., and Velasco, D. (2022). Selection of AmpC \u03b2-Lactamase Variants and Metallo-\u03b2-Lactamases Leading to Ceftolozane\/Tazobactam and Ceftazidime\/Avibactam Resistance during Treatment of MDR\/XDR Pseudomonas aeruginosa Infections. Antimicrob. Agents Chemother., 66.","DOI":"10.1128\/aac.02067-21"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Hujer, A.M., Bethel, C.R., Taracila, M.A., Marshall, S.H., Rojas, L.J., Winkler, M.L., Painter, R.E., Domitrovic, T.N., Watkins, R.R., and Abdelhamed, A.M. (2022). Imipenem\/Relebactam Resistance in Clinical Isolates of Extensively Drug Resistant Pseudomonas aeruginosa: Inhibitor-Resistant \u03b2-Lactamases and Their Increasing Importance. Antimicrob. Agents Chemother., 66.","DOI":"10.1128\/aac.01790-21"},{"key":"ref_142","first-page":"1120","article-title":"Essais de th\u00e9rapeutique au moyen du bacteriophage","volume":"85","author":"Bruynoghe","year":"1921","journal-title":"CR Soc. Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1126\/science.298.5594.728","article-title":"Stalin\u2019s forgotten cure","volume":"298","author":"Stone","year":"2002","journal-title":"Science"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.medmal.2008.06.023","article-title":"Phage therapy experience at the Eliava Institute","volume":"38","author":"Kutateladze","year":"2008","journal-title":"Med. Mal. Infect."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"66","DOI":"10.4161\/bact.1.2.15845","article-title":"Phage treatment of human infections","volume":"1","author":"Abedon","year":"2011","journal-title":"Bacteriophage"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Schooley, R.T., Biswas, B., Gill, J.J., Hernandez-Morales, A., Lancaster, J., Lessor, L., Barr, J.J., Reed, S.L., Rohwer, F., and Benler, S. (2017). Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob. Agents Chemother., 61.","DOI":"10.1128\/AAC.00954-17"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/cid\/ciy947","article-title":"A systematic and critical review of bacteriophage therapy against multidrug-resistant ESKAPE organisms in humans","volume":"69","author":"Harb","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/s41591-019-0437-z","article-title":"Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus","volume":"25","author":"Dedrick","year":"2019","journal-title":"Nat. Med."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Thi, M.T.T., Wibowo, D., and Rehm, B.H.A. (2020). Pseudomonas aeruginosa Biofilms. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228671"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1093\/jac\/38.5.757","article-title":"Mathematical model of \u03b2-lactam penetration into a biofilm of Pseudomonas aeruginosa while undergoing simultaneous inactivation by released \u03b2-lactamases","volume":"38","author":"Dibdin","year":"1996","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1128\/AAC.01393-12","article-title":"High \u03b2-lactamase levels change the pharmacodynamics of \u03b2-lactam antibiotics in Pseudomonas aeruginosa biofilms","volume":"57","author":"Wang","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Knecht, L.E., Veljkovic, M., and Fieseler, L. (2020). Diversity and function of phage encoded depolymerases. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02949"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Danis-Wlodarczyk, K., Olszak, T., Arabski, M., Wasik, S., Majkowska-Skrobek, G., Augustyniak, D., Gula, G., Briers, Y., Jang, H.B., and Vandenheuvel, D. (2015). Characterization of the newly isolated lytic bacteriophages KTN6 and KT28 and their efficacy against Pseudomonas aeruginosa biofilm. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0137015"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1128\/AEM.67.6.2746-2753.2001","article-title":"Reduction in exopolysaccharide viscosity as an aid to bacteriophage penetration through Pseudomonas aeruginosa biofilms","volume":"67","author":"Hanlon","year":"2001","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Henriksen, K., R\u00f8rbo, N., Rybtke, M.L., Martinet, M.G., Tolker-Nielsen, T., H\u00f8iby, N., Middelboe, M., and Ciofu, O.P. (2019). aeruginosa flow-cell biofilms are enhanced by repeated phage treatments but can be eradicated by phage\u2013ciprofloxacin combination: \u2014Monitoring the phage\u2013P. aeruginosa biofilms interactions. Pathog. Dis., 77.","DOI":"10.1093\/femspd\/ftz011"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Franklin, M.J., Nivens, D.E., Weadge, J.T., and Howell, P.L. (2011). Biosynthesis of the Pseudomonas aeruginosa extracellular polysaccharides, alginate, Pel, and Psl. Front. Microbiol., 2.","DOI":"10.3389\/fmicb.2011.00167"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1365-2672.2009.04469.x","article-title":"Bacteriophage-derived enzyme that depolymerizes the alginic acid capsule associated with cystic fibrosis isolates of Pseudomonas aeruginosa","volume":"108","author":"Glonti","year":"2010","journal-title":"J. Appl. Microbiol."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Ertesv\u00e5g, H. (2015). Alginate-modifying enzymes: Biological roles and biotechnological uses. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.00523"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s40259-013-0081-y","article-title":"Bacteriophage polysaccharide depolymerases and biomedical applications","volume":"28","author":"Yan","year":"2014","journal-title":"Biodrugs"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.micro.54.1.289","article-title":"Alginate lyase: Review of major sources and enzyme characteristics, structure-function analysis, biological roles, and applications","volume":"54","author":"Wong","year":"2000","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.jmb.2004.10.081","article-title":"Crystal structure of the alginate (poly \u03b1-L-guluronate) lyase from Corynebacterium sp. at 1.2 \u00c5 resolution","volume":"345","author":"Osawa","year":"2005","journal-title":"J. Mol. Biol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.biologicals.2019.10.003","article-title":"Isolation and characterization of bacteriophage to control multidrug-resistant Pseudomonas aeruginosa planktonic cells and biofilm","volume":"63","author":"Adnan","year":"2020","journal-title":"Biologicals"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"5340","DOI":"10.1128\/AEM.01434-14","article-title":"Inhibition of biofilm formation by T7 bacteriophages producing quorum-quenching enzymes","volume":"80","author":"Pei","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Latz, S., Kr\u00fcttgen, A., H\u00e4fner, H., Buhl, E.M., Ritter, K., and Horz, H.-P. (2017). Differential effect of newly isolated phages belonging to PB1-like, phiKZ-like and LUZ24-like viruses against multi-drug resistant Pseudomonas aeruginosa under varying growth conditions. Viruses, 9.","DOI":"10.3390\/v9110315"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/1751-7915.12316","article-title":"A novel bacteriophage cocktail reduces and disperses P seudomonas aeruginosa biofilms under static and flow conditions","volume":"9","author":"Alves","year":"2016","journal-title":"Microb. Biotechnol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/apm.12691","article-title":"Assessment of biofilm removal capacity of a broad host range bacteriophage JHP against Pseudomonas aeruginosa","volume":"125","author":"Shafique","year":"2017","journal-title":"APMIS"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1128\/AAC.03786-14","article-title":"Bacteriophage-mediated control of a two-species biofilm formed by microorganisms causing catheter-associated urinary tract infections in an in vitro urinary catheter model","volume":"59","author":"Lehman","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.resmic.2011.06.010","article-title":"Use of newly isolated phages for control of Pseudomonas aeruginosa PAO1 and ATCC 10145 biofilms","volume":"162","author":"Pires","year":"2011","journal-title":"Res. Microbiol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1365-2672.2011.05043.x","article-title":"Phages of Pseudomonas aeruginosa: Response to environmental factors and in vitro ability to inhibit bacterial growth and biofilm formation","volume":"111","author":"Knezevic","year":"2011","journal-title":"J. Appl. Microbiol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1128\/AAC.00669-09","article-title":"Bacteriophage cocktail for the prevention of biofilm formation by Pseudomonas aeruginosa on catheters in an in vitro model system","volume":"54","author":"Fu","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.lfs.2017.09.034","article-title":"Isolation and characterization of a bacteriophage and its utilization against multi-drug resistant Pseudomonas aeruginosa-2995","volume":"190","author":"Jamal","year":"2017","journal-title":"Life Sci."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.resmic.2016.10.009","article-title":"Isolation of bacteriophages and their application to control Pseudomonas aeruginosa in planktonic and biofilm models","volume":"168","author":"Kwiatek","year":"2017","journal-title":"Res. Microbiol."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Fong, S.A., Drilling, A., Morales, S., Cornet, M.E., Woodworth, B.A., Fokkens, W.J., Psaltis, A.J., Vreugde, S., and Wormald, P.-J. (2017). Activity of bacteriophages in removing biofilms of Pseudomonas aeruginosa isolates from chronic rhinosinusitis patients. Front. Cell. Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00418"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"e02900","DOI":"10.1128\/AEM.02900-18","article-title":"Two novel bacteriophages improve survival in Galleria mellonella infection and mouse acute pneumonia models infected with extensively drug-resistant Pseudomonas aeruginosa","volume":"85","author":"Jeon","year":"2019","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"4602","DOI":"10.3390\/v7082835","article-title":"Phage \u03a6Pan70, a putative temperate phage, controls Pseudomonas aeruginosa in planktonic, biofilm and burn mouse model assays","volume":"7","author":"Rangel","year":"2015","journal-title":"Viruses"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Alemayehu, D., Casey, P., McAuliffe, O., Guinane, C., Martin, J., Shanahan, F., Coffey, A., Ross, R., and Hill, C. (2012). Bacteriophages MR299-2 and NH-4 can eliminate Pseudomonas aeruginosa in the murine lung and on cystic fibrosis lung airway cells. mBio, 3.","DOI":"10.1128\/mBio.00029-12"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Forti, F., Roach, D.R., Cafora, M., Pasini, M.E., Horner, D.S., Fiscarelli, E.V., Rossitto, M., Cariani, L., Briani, F., and Debarbieux, L. (2018). Design of a broad-range bacteriophage cocktail that reduces Pseudomonas aeruginosa biofilms and treats acute infections in two animal models. Antimicrob. Agents Chemother., 62.","DOI":"10.1128\/AAC.02573-17"},{"key":"ref_178","first-page":"16","article-title":"An In vivo Wound Model Utilizing Bacteriophage Therapy of Pseudomonas aeruginosa Biofilms","volume":"61","author":"Basu","year":"2015","journal-title":"Ostomy Wound Manag."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.bcp.2016.09.018","article-title":"Antimicrobial peptides (AMPs): Ancient compounds that represent novel weapons in the fight against bacteria","volume":"133","author":"Ageitos","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Savini, F., Loffredo, M., Troiano, C., Bobone, S., Malanovic, N., Eichmann, T., Caprio, L., Canale, V., Park, Y., and Mangoni, M. (2020). Binding of an antimicrobial peptide to bacterial cells: Interaction with different species, strains and cellular components. Biochim. Biophys. Acta (BBA)-Biomembr., 1862.","DOI":"10.1016\/j.bbamem.2020.183291"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.3390\/ph6121543","article-title":"Antimicrobial peptides","volume":"6","author":"Bahar","year":"2013","journal-title":"Pharmaceuticals"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.fsi.2019.07.015","article-title":"Characterization and antimicrobial mechanism of CF-14, a new antimicrobial peptide from the epidermal mucus of catfish","volume":"92","author":"Li","year":"2019","journal-title":"Fish Shellfish Immunol."},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Luo, Y., and Song, Y. (2021). Mechanism of Antimicrobial Peptides: Antimicrobial, Anti-Inflammatory and Antibiofilm Activities. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111401"},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-981-13-3588-4_11","article-title":"Selectivity of Antimicrobial Peptides: A Complex Interplay of Multiple Equilibria","volume":"1117","author":"Bobone","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Harder, J., and Schr\u00f6der, J.-M. (2015). Antimicrobial Peptides: Role in Human Health and Disease, Springer.","DOI":"10.1007\/978-3-319-24199-9"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"675391","DOI":"10.1155\/2013\/675391","article-title":"Antimicrobial peptides: Versatile biological properties","volume":"2013","author":"Pushpanathan","year":"2013","journal-title":"Int. J. Pept."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1124\/pr.55.1.2","article-title":"Mechanisms of antimicrobial peptide action and resistance","volume":"55","author":"Yeaman","year":"2003","journal-title":"Pharmacol. Rev."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"6521","DOI":"10.1021\/bi00019a033","article-title":"Translocation of a channel-forming antimicrobial peptide, magainin 2, across lipid bilayers by forming a pore","volume":"34","author":"Matsuzaki","year":"1995","journal-title":"Biochemistry"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"11361","DOI":"10.1021\/bi960016v","article-title":"An antimicrobial peptide, magainin 2, induced rapid flip-flop of phospholipids coupled with pore formation and peptide translocation","volume":"35","author":"Matsuzaki","year":"1996","journal-title":"Biochemistry"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2174\/1568026615666150703121700","article-title":"Antimicrobial peptide structure and mechanism of action: A focus on the role of membrane structure","volume":"16","author":"Lee","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_191","doi-asserted-by":"crossref","unstructured":"Kumar, P., Kizhakkedathu, J.N., and Straus, S.K. (2018). Antimicrobial peptides: Diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo. Biomolecules, 8.","DOI":"10.3390\/biom8010004"},{"key":"ref_192","first-page":"236","article-title":"Mode of action of membrane active antimicrobial peptides","volume":"66","author":"Shai","year":"2002","journal-title":"Pept. Sci. Orig. Res. Biomol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nrmicro1098","article-title":"Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria?","volume":"3","author":"Brogden","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"508","DOI":"10.2174\/1568026616666160713122404","article-title":"Membrane-active antimicrobial peptides as template structures for novel antibiotic agents","volume":"17","author":"Lohner","year":"2017","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1021\/bi00509a019","article-title":"Pyranine (8-hydroxy-1, 3, 6-pyrenetrisulfonate) as a probe of internal aqueous hydrogen ion concentration in phospholipid vesicles","volume":"20","author":"Clement","year":"1981","journal-title":"Biochemistry"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"104700","DOI":"10.1016\/j.micpath.2020.104700","article-title":"Synergistic effect of two antimicrobial peptides, Nisin and P10 with conventional antibiotics against extensively drug-resistant Acinetobacter baumannii and colistin-resistant Pseudomonas aeruginosa isolates","volume":"150","author":"Jahangiri","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_197","doi-asserted-by":"crossref","unstructured":"Field, D., Seisling, N., Cotter, P.D., Ross, R.P., and Hill, C. (2016). Synergistic nisin-polymyxin combinations for the control of Pseudomonas biofilm formation. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01713"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.ijantimicag.2019.03.009","article-title":"Synergistic effect between nisin and polymyxin B against pandrug-resistant and extensively drug-resistant Acinetobacter baumannii","volume":"53","author":"Thomas","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1128\/AAC.02328-12","article-title":"Synergistic effect between colistin and bacteriocins in controlling Gram-negative pathogens and their potential to reduce antibiotic toxicity in mammalian epithelial cells","volume":"57","author":"Naghmouchi","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1111\/j.1742-4658.2010.07581.x","article-title":"Functional interaction of human neutrophil peptide-1 with the cell wall precursor lipid II","volume":"584","author":"Li","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"3062","DOI":"10.1016\/j.bbamem.2015.04.014","article-title":"Structural variations of the cell wall precursor lipid II in Gram-positive bacteria\u2014Impact on binding and efficacy of antimicrobial peptides","volume":"1848","author":"Sahl","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.bbamem.2015.11.003","article-title":"The human cathelicidin LL-37\u2014A pore-forming antibacterial peptide and host-cell modulator","volume":"1858","author":"Xhindoli","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Ridyard, K.E., and Overhage, J. (2021). The potential of human peptide LL-37 as an antimicrobial and anti-biofilm agent. Antibiotics, 10.","DOI":"10.3390\/antibiotics10060650"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1128\/AAC.02554-14","article-title":"LL-37-derived peptides eradicate multidrug-resistant Staphylococcus aureus from thermally wounded human skin equivalents","volume":"58","author":"Haisma","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.bbamem.2019.05.008","article-title":"Synergistic and antibiofilm activity of the antimicrobial peptide P5 against carbapenem-resistant Pseudomonas aeruginosa","volume":"1861","author":"Martinez","year":"2019","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1016\/j.colsurfb.2016.02.003","article-title":"Role of amphipathicity and hydrophobicity in the balance between hemolysis and peptide\u2013membrane interactions of three related antimicrobial peptides","volume":"141","author":"Hollmann","year":"2016","journal-title":"Colloids Surf. B. Biointerfaces"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ejmech.2013.10.065","article-title":"Antimicrobial activity of de novo designed cationic peptides against multi-resistant clinical isolates","volume":"71","author":"Faccone","year":"2014","journal-title":"Eur. J. Med. Chem."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Rudilla, H., Fust\u00e9, E., Cajal, Y., Rabanal, F., Vinuesa, T., and Vi\u00f1as, M. (2016). Synergistic antipseudomonal effects of synthetic peptide AMP38 and carbapenems. Molecules, 21.","DOI":"10.3390\/molecules21091223"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"7235","DOI":"10.1021\/bi9826299","article-title":"Mechanism of interaction of different classes of cationic antimicrobial peptides with planar bilayers and with the cytoplasmic membrane of Escherichia coli","volume":"38","author":"Wu","year":"1999","journal-title":"Biochemistry"},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Shang, D., Han, X., Du, W., Kou, Z., and Jiang, F. (2021). Trp-containing antibacterial peptides impair quorum sensing and biofilm development in multidrug-resistant Pseudomonas aeruginosa and exhibit synergistic effects with antibiotics. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.611009"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40409-017-0094-y","article-title":"Ocellatin peptides from the skin secretion of the South American frog Leptodactylus labyrinthicus (Leptodactylidae): Characterization, antimicrobial activities and membrane interactions","volume":"23","author":"Santos","year":"2017","journal-title":"J. Venom. Anim. Tox. incl. Trop. Dis."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2217\/fmb-2017-0175","article-title":"Synergistic and antibiofilm properties of ocellatin peptides against multidrug-resistant Pseudomonas aeruginosa","volume":"13","author":"Bessa","year":"2018","journal-title":"Future Microbiol."},{"key":"ref_213","doi-asserted-by":"crossref","unstructured":"Pandidan, S., and Mechler, A. (2019). Nano-viscosimetry analysis of the membrane disrupting action of the bee venom peptide melittin. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-47325-y"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1089\/mdr.2018.0016","article-title":"Highly synergistic effects of melittin with conventional antibiotics against multidrug-resistant isolates of Acinetobacter baumannii and Pseudomonas aeruginosa","volume":"25","author":"Akbari","year":"2019","journal-title":"Microb. Drug Resist."},{"key":"ref_215","unstructured":"Stoner, I. (Endpoints News, 2019). Biopharma has abandoned antibiotic development. Here\u2019s why we did too, Endpoints News."},{"key":"ref_216","unstructured":"(2003). Geneva Pharmaceuticals v. GlaxoSmithKline."},{"key":"ref_217","first-page":"411","article-title":"Achaogen bankruptcy highlights antibacterial development woes","volume":"18","author":"Mullard","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/s41587-022-01327-w","article-title":"Antibiotic discovery with machine learning","volume":"40","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"ref_219","doi-asserted-by":"crossref","unstructured":"Stokes, J.M., Yang, K., Swanson, K., Jin, W., Cubillos-Ruiz, A., Donghia, N.M., MacNair, C.R., French, S., Carfrae, L.A., and Bloom-Ackermann, Z. (2020). A deep learning approach to antibiotic discovery. Cell, 180.","DOI":"10.1016\/j.cell.2020.01.021"},{"key":"ref_220","doi-asserted-by":"crossref","unstructured":"Juki\u010d, M., and Bren, U. (2022). Machine learning in antibacterial drug design. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.864412"},{"key":"ref_221","doi-asserted-by":"crossref","unstructured":"Liu, G., and Stokes, J.M. (2022). A brief guide to machine learning for antibiotic discovery. Curr. Opin. Microbiol., 69.","DOI":"10.1016\/j.mib.2022.102190"},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"David, L., Brata, A.M., Mogosan, C., Pop, C., Czako, Z., Muresan, L., Ismaiel, A., Dumitrascu, D.I., Leucuta, D.C., and Stanculete, M.F. (2021). Artificial Intelligence and Antibiotic Discovery. Antibiotics, 10.","DOI":"10.3390\/antibiotics10111376"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1038\/s41589-023-01349-8","article-title":"Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii","volume":"19","author":"Liu","year":"2023","journal-title":"Nat. Chem. Biol."},{"key":"ref_224","doi-asserted-by":"crossref","unstructured":"Parvaiz, N., Ahmad, F., Yu, W., MacKerell, A.D., and Azam, S.S. (2021). Discovery of beta-lactamase CMY-10 inhibitors for combination therapy against multi-drug resistant Enterobacteriaceae. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0244967"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-1-4939-7343-9_17","article-title":"Phage genome annotation using the RAST pipeline","volume":"3","author":"McNair","year":"2018","journal-title":"Bacteriophages Methods Protoc."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"4537","DOI":"10.1093\/bioinformatics\/btz265","article-title":"PHANOTATE: A novel approach to gene identification in phage genomes","volume":"35","author":"McNair","year":"2019","journal-title":"Bioinformatics"},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Thung, T.Y., White, M.E., Dai, W., Wilksch, J.J., Bamert, R.S., Rocker, A., Stubenrauch, C.J., Williams, D., Huang, C., and Schittelhelm, R. (2021). Component parts of bacteriophage virions accurately defined by a machine-learning approach built on evolutionary features. Msystems, 6.","DOI":"10.1128\/mSystems.00242-21"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"W348","DOI":"10.1093\/nar\/gkaa432","article-title":"PaCRISPR: A server for predicting and visualizing anti-CRISPR proteins","volume":"48","author":"Wang","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_229","doi-asserted-by":"crossref","unstructured":"Bhadra, P., Yan, J., Li, J., Fong, S., and Siu, S.W. (2018). AmPEP: Sequence-based prediction of antimicrobial peptides using distribution patterns of amino acid properties and random forest. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-19752-w"},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Karp, N.A. (2018). Reproducible preclinical research-Is embracing variability the answer?. PLoS Biol., 16.","DOI":"10.1371\/journal.pbio.2005413"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"114118","DOI":"10.1016\/j.addr.2022.114118","article-title":"Reproducibility, relevance and reliability as barriers to efficient and credible biomedical technology translation","volume":"182","author":"Dirnagl","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_232","doi-asserted-by":"crossref","unstructured":"Samuel, S., and K\u00f6nig-Ries, B. (2021). Understanding experiments and research practices for reproducibility: An exploratory study. PeerJ, 9.","DOI":"10.7717\/peerj.11140"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ijpsycho.2019.05.006","article-title":"What the replication crisis means for intervention science","volume":"154","author":"Hillary","year":"2020","journal-title":"Int. J. Psychophysiol."},{"key":"ref_234","doi-asserted-by":"crossref","unstructured":"Papp-Wallace, K.M., Bethel, C.R., Caillon, J., Barnes, M.D., Potel, G., Bajaksouzian, S., Rutter, J.D., Reghal, A., Shapiro, S., and Taracila, M.A. (2019). Beyond piperacillin-tazobactam: Cefepime and AAI101 as a potent \u03b2-lactam\u2212 \u03b2-lactamase inhibitor combination. Antimicrob. Agents Chemother., 63.","DOI":"10.1128\/AAC.00105-19"},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s15010-020-01547-9","article-title":"Are antibacterial effects of non-antibiotic drugs random or purposeful because of a common evolutionary origin of bacterial and mammalian targets?","volume":"49","author":"Dalhoff","year":"2021","journal-title":"Infection"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1113\/jphysiol.1983.sp014769","article-title":"Reserpine has a direct action as a calcium antagonist on mammalian smooth muscle cells","volume":"340","author":"Casteels","year":"1983","journal-title":"J. Physiol."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2165\/00003495-198733060-00003","article-title":"Sulbactam\/ampicillin: A review of its antibacterial activity, pharmacokinetic properties, and therapeutic use","volume":"33","author":"Brogden","year":"1987","journal-title":"Drugs"},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"5728","DOI":"10.1128\/JB.01184-12","article-title":"The CRISPR\/Cas Adaptive Immune System of Pseudomonas aeruginosa Mediates Resistance to Naturally Occurring and Engineered Phages","volume":"194","year":"2012","journal-title":"J. Bacteriol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1099\/mic.0.024554-0","article-title":"The sensor kinase PhoQ mediates virulence in Pseudomonas aeruginosa","volume":"155","author":"Gooderham","year":"2009","journal-title":"Microbiology"},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1046\/j.1365-2958.2003.03673.x","article-title":"Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in Pseudomonas aeruginosa","volume":"50","author":"McPhee","year":"2003","journal-title":"Mol. Microbiol."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"3877","DOI":"10.1099\/mic.0.2008\/022301-0","article-title":"Capsule polysaccharide is a bacterial decoy for antimicrobial peptides","volume":"154","author":"Llobet","year":"2008","journal-title":"Microbiology"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/5\/526\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:36:05Z","timestamp":1760031365000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/5\/526"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,20]]},"references-count":241,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["antibiotics14050526"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14050526","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,20]]}}}