{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T18:13:47Z","timestamp":1792692827146,"version":"4.5.0"},"reference-count":331,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","award":["17\/372 and 20\/812"],"award-info":[{"award-number":["17\/372 and 20\/812"]}],"id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Pseudomonas aeruginosa is a major opportunistic pathogen, causing a wide range of acute and chronic infections. \u03b2-lactam antibiotics including penicillins, carbapenems, monobactams, and cephalosporins play a key role in the treatment of P. aeruginosa infections. However, a significant number of isolates of these bacteria are resistant to \u03b2-lactams, complicating treatment of infections and leading to worse outcomes for patients. In this review, we summarize studies demonstrating the health and economic impacts associated with \u03b2-lactam-resistant P. aeruginosa. We then describe how \u03b2-lactams bind to and inhibit P. aeruginosa penicillin-binding proteins that are required for synthesis and remodelling of peptidoglycan. Resistance to \u03b2-lactams is multifactorial and can involve changes to a key target protein, penicillin-binding protein 3, that is essential for cell division; reduced uptake or increased efflux of \u03b2-lactams; degradation of \u03b2-lactam antibiotics by increased expression or altered substrate specificity of an AmpC \u03b2-lactamase, or by the acquisition of \u03b2-lactamases through horizontal gene transfer; and changes to biofilm formation and metabolism. The current understanding of these mechanisms is discussed. Lastly, important knowledge gaps are identified, and possible strategies for enhancing the effectiveness of \u03b2-lactam antibiotics in treating P. aeruginosa infections are considered.<\/jats:p>","DOI":"10.3390\/pathogens10121638","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T02:50:18Z","timestamp":1639968618000},"page":"1638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":167,"title":["\u03b2-lactam Resistance in Pseudomonas aeruginosa: Current Status, Future Prospects"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9370-3893","authenticated-orcid":false,"given":"Karl A.","family":"Glen","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7601-6354","authenticated-orcid":false,"given":"Iain L.","family":"Lamont","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1111\/apm.13010","article-title":"The environmental occurrence of Pseudomonas aeruginosa","volume":"128","author":"Crone","year":"2020","journal-title":"APMIS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"212527","DOI":"10.7573\/dic.212527","article-title":"How to manage Pseudomonas aeruginosa infections","volume":"7","author":"Bassetti","year":"2018","journal-title":"Drugs Context"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1097\/QCO.0000000000000505","article-title":"Rational approach in the management of Pseudomonas aeruginosa infections","volume":"31","author":"Bassetti","year":"2018","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/668770","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, 2009\u20132010","volume":"34","author":"Sievert","year":"2013","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1097\/MCC.0000000000000526","article-title":"Microbial cause of ICU-acquired pneumonia: Hospital-acquired pneumonia versus ventilator-associated pneumonia","volume":"24","author":"Luyt","year":"2018","journal-title":"Curr. Opin. Crit. Care"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1080\/17476348.2019.1632195","article-title":"Management of ventilator-associated pneumonia (VAP) caused by resistant gram-negative bacteria: Which is the best strategy to treat?","volume":"13","author":"Sarda","year":"2019","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_8","first-page":"1","article-title":"Ventilator-Associated Pneumonia Caused by Pseudomonas aeruginosa in Intensive Care Unit: Epidemiology and Risk Factors","volume":"3","author":"Raineri","year":"2014","journal-title":"J. Med. Microbiol. Diagn."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1099\/jmm.0.001110","article-title":"Pseudomonas aeruginosa and microbial keratitis","volume":"69","author":"Hilliam","year":"2020","journal-title":"J. Med. Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1097\/QCO.0000000000000217","article-title":"Managing Pseudomonas aeruginosa respiratory infections in cystic fibrosis","volume":"28","author":"Langan","year":"2015","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Garcia-Clemente, M., de la Rosa, D., M\u00e1iz, L., Gir\u00f3n, R., Blanco, M., Olveira, C., Canton, R., and Martinez-Garc\u00eda, M.A. (2020). Impact of Pseudomonas aeruginosa Infection on Patients with Chronic Inflammatory Airway Diseases. J. Clin. Med., 9.","DOI":"10.3390\/jcm9123800"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1469-0691.1995.tb00455.x","article-title":"Risk factors and a clinical index for diagnosis of Pseudomonas aeruginosa bacteremia","volume":"1","author":"Gransden","year":"1995","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.burns.2003.08.007","article-title":"Pseudomonas infections in the thermally injured patient","volume":"30","author":"Tredget","year":"2004","journal-title":"Burns"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S1526-0550(02)00005-7","article-title":"Airway mucus in cystic fibrosis","volume":"3","author":"Puchelle","year":"2002","journal-title":"Paediatr. Respir. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1093\/cid\/civ377","article-title":"Impact of sustained eradication of new Pseudomonas aeruginosa infection on long-term outcomes in cystic fibrosis","volume":"61","author":"Kloster","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1183\/09031936.05.00009605","article-title":"Early eradication therapy against Pseudomonas aeruginosa in cystic fibrosis patients","volume":"26","author":"Taccetti","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zolin, A., Bossi, A., Cirilli, N., Kashirskaya, N., and Padoan, R. (2018). Cystic Fibrosis Mortality in Childhood. Data from European Cystic Fibrosis Society Patient Registry. Int. J. Environ. Res. Public Health, 15.","DOI":"10.3390\/ijerph15092020"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"R183","DOI":"10.1186\/cc8170","article-title":"The leading causes of death after burn injury in a single pediatric burn center","volume":"13","author":"Williams","year":"2009","journal-title":"Crit. Care"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1089\/sur.2013.134","article-title":"Infection in Burns","volume":"17","author":"Norbury","year":"2016","journal-title":"Surg. Infect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1128\/CMR.19.2.403-434.2006","article-title":"Burn wound infections","volume":"19","author":"Church","year":"2006","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1399-3062.2009.00380.x","article-title":"Pseudomonas aeruginosa bacteremia over a 10-year period: Multidrug resistance and outcomes in transplant recipients","volume":"11","author":"Johnson","year":"2009","journal-title":"Transpl. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7581036","DOI":"10.1155\/2018\/7581036","article-title":"Clinical predictors of Pseudomonas aeruginosa bacteremia in emergency department","volume":"2018","author":"Choi","year":"2018","journal-title":"Emerg. Med. Int."},{"key":"ref_23","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_24","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_25","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1093\/cid\/cix682","article-title":"Bacterial infections after burn injuries: Impact of multidrug resistance","volume":"65","author":"Lachiewicz","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/mbo3.391","article-title":"Pseudomonas aeruginosa in premise plumbing of large buildings","volume":"5","year":"2016","journal-title":"MicrobiologyOpen"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1016\/j.ajic.2005.03.006","article-title":"Ecology of Pseudomonas aeruginosa in the intensive care unit and the evolving role of water outlets as a reservoir of the organism","volume":"33","author":"Trautmann","year":"2005","journal-title":"Am. J. Infect. Control"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.jhin.2017.12.005","article-title":"Pseudomonas aeruginosa intensive care unit outbreak: Winnowing of transmissions with molecular and genomic typing","volume":"98","author":"Parcell","year":"2018","journal-title":"J. Hosp. Infect."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e006278","DOI":"10.1136\/bmjopen-2014-006278","article-title":"Seeking the source of Pseudomonas aeruginosa infections in a recently opened hospital: An observational study using whole-genome sequencing","volume":"4","author":"Quick","year":"2014","journal-title":"BMJ Open"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lanini, S., D\u2019Arezzo, S., Puro, V., Martini, L., Imperi, F., Piselli, P., Montanaro, M., Paoletti, S., Visca, P., and Ippolito, G. (2011). Molecular epidemiology of a Pseudomonas aeruginosa hospital outbreak driven by a contaminated disinfectant-soap dispenser. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0017064"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1111\/j.1469-0691.2008.01949.x","article-title":"An outbreak of hospital-acquired Pseudomonas aeruginosa infection caused by contaminated bottled water in intensive care units","volume":"14","author":"Eckmanns","year":"2008","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1183\/09031936.00088907","article-title":"Pseudomonas aeruginosa in the home environment of newly infected cystic fibrosis patients","volume":"31","author":"Schelstraete","year":"2008","journal-title":"Eur. Respir. J."},{"key":"ref_33","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_34","unstructured":"CDC (2019). Antibiotic Resistance Threats in the United States, 2019, Centers for Disease Control and Prevention."},{"key":"ref_35","first-page":"441","article-title":"Impact of multidrug-resistant Pseudomonas aeruginosa infection on patient outcomes","volume":"10","author":"Hirsch","year":"2010","journal-title":"Expert Rev. Pharm. Outcomes Res."},{"key":"ref_36","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_37","doi-asserted-by":"crossref","first-page":"10063","DOI":"10.1038\/ncomms10063","article-title":"Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis","volume":"6","author":"Bradley","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1586\/eri.13.12","article-title":"Clinical relevance of the ESKAPE pathogens","volume":"11","author":"Pendleton","year":"2013","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e00181-19","DOI":"10.1128\/CMR.00181-19","article-title":"Antimicrobial resistance in ESKAPE pathogens","volume":"33","author":"Forde","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_40","unstructured":"Taconelli, E., and Magrini, N. (2017). Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics, World Health Organization."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.clinthera.2016.08.014","article-title":"Comparison of inhaled antibiotics for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis: Systematic literature review and network meta-analysis","volume":"38","author":"Elborn","year":"2016","journal-title":"Clin. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e00031-19","DOI":"10.1128\/CMR.00031-19","article-title":"Epidemiology and treatment of multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa infections","volume":"32","author":"Horcajada","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ccm.2015.10.004","article-title":"The approach to Pseudomonas aeruginosa in cystic fibrosis","volume":"37","author":"Talwalkar","year":"2016","journal-title":"Clin. Chest Med."},{"key":"ref_44","unstructured":"Enna, S.J., and Bylund, D.B. (2007). Ticarcillin. xPharm: The Comprehensive Pharmacology Reference, Elsevier."},{"key":"ref_45","unstructured":"Enna, S.J., and Bylund, D.B. (2007). Piperacillin. xPharm: The Comprehensive Pharmacology Reference, Elsevier."},{"key":"ref_46","unstructured":"Enna, S.J., and Bylund, D.B. (2007). Aztreonam. xPharm: The Comprehensive Pharmacology Reference, Elsevier."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1177\/1753465814561624","article-title":"Evidence for the efficacy of aztreonam for inhalation solution in the management of Pseudomonas aeruginosa in patients with cystic fibrosis","volume":"9","author":"Hansen","year":"2015","journal-title":"Ther. Adv. Respir. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Taccetti, G., Francalanci, M., Pizzamiglio, G., Messore, B., Carnovale, V., Cimino, G., and Cipolli, M. (2021). Cystic Fibrosis: Recent Insights into Inhaled Antibiotic Treatment and Future Perspectives. Antibiotics, 10.","DOI":"10.3390\/antibiotics10030338"},{"key":"ref_49","first-page":"1","article-title":"Eradication of Pseudomonas aeruginosa with inhaled colistin in adults with non-cystic fibrosis bronchiectasis","volume":"16","year":"2019","journal-title":"Chronic Respir. Dis."},{"key":"ref_50","first-page":"2741","article-title":"New classification and update on the quinolone antibiotics","volume":"61","author":"King","year":"2000","journal-title":"Am. Fam. Physician"},{"key":"ref_51","first-page":"CD008319","article-title":"Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis","volume":"10","author":"Smith","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_52","unstructured":"Pandey, N., and Cascella, M. (2021). Beta Lactam Antibiotics. StatPearls, StatPearls."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4297","DOI":"10.2147\/IDR.S224228","article-title":"A clinical review and critical evaluation of Imipenem-Relebactam: Evidence to date","volume":"13","author":"Campanella","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-0463.2009.02563.x","article-title":"\u03b2-lactam antibiotics: From antibiosis to resistance and bacteriology","volume":"118","author":"Kong","year":"2010","journal-title":"APMIS"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4159","DOI":"10.1128\/AAC.00257-10","article-title":"Genetic determinants involved in the susceptibility of Pseudomonas aeruginosa to \u03b2-lactam antibiotics","volume":"54","author":"Wiegand","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_56","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_57","doi-asserted-by":"crossref","first-page":"913","DOI":"10.3389\/fmicb.2019.00913","article-title":"Tolerance and Resistance of Pseudomonas aeruginosa Biofilms to Antimicrobial Agents-How P. aeruginosa Can Escape Antibiotics","volume":"10","author":"Ciofu","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.tig.2020.10.007","article-title":"Metabolic Microenvironments Drive Microbial Differentiation and Antibiotic Resistance","volume":"37","author":"Povolotsky","year":"2021","journal-title":"Trends Genet."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.3389\/fmicb.2020.02057","article-title":"Tolerance and Persistence of Pseudomonas aeruginosa in Biofilms Exposed to Antibiotics: Molecular Mechanisms, Antibiotic Strategies and Therapeutic Perspectives","volume":"11","author":"Soares","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_60","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":"Hengzhuang","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1099\/jmm.0.001085","article-title":"Genomic and phenotypic comparison of environmental and patient-derived isolates of Pseudomonas aeruginosa suggest that antimicrobial resistance is rare within the environment","volume":"68","author":"Ramsay","year":"2019","journal-title":"J. Med. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"S521","DOI":"10.1093\/cid\/ciz824","article-title":"Epidemiology and Diagnostics of Carbapenem Resistance in Gram-negative Bacteria","volume":"69","author":"Nordmann","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"S63","DOI":"10.1093\/ofid\/ofy343","article-title":"Geographic and Temporal Patterns of Antimicrobial Resistance in Pseudomonas aeruginosa Over 20 Years From the SENTRY Antimicrobial Surveillance Program, 1997\u20132016","volume":"6","author":"Shortridge","year":"2019","journal-title":"Open Forum Infect. Dis."},{"key":"ref_64","first-page":"112","article-title":"Antibiotic resistance and frequency of class 1 integrons among Pseudomonas aeruginosa isolates obtained from wastewaters of a burn center in Northern Iran","volume":"30","author":"Ebrahimpour","year":"2018","journal-title":"Ann. Ig."},{"key":"ref_65","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_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/ice.2017.236","article-title":"Pathogen distribution and antimicrobial resistance among pediatric healthcare-associated infections reported to the National Healthcare Safety Network, 2011\u20132014","volume":"39","author":"Lake","year":"2018","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_67","first-page":"1","article-title":"Mortality attributable to carbapenem-resistant Pseudomonas aeruginosa bacteremia: A meta-analysis of cohort studies","volume":"5","author":"Zhang","year":"2016","journal-title":"Emerg. Microbes Infect."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"11715","DOI":"10.1038\/srep11715","article-title":"Influence of carbapenem resistance on mortality of patients with Pseudomonas aeruginosa infection: A meta-analysis","volume":"5","author":"Liu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ijid.2019.05.004","article-title":"Prevalence and 30-day all-cause mortality of carbapenem-and colistin-resistant bacteraemia caused by Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae: Description of a decade-long trend","volume":"85","author":"Balkhair","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_70","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_71","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S1473-3099(18)30605-4","article-title":"Attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the EU and the European Economic Area in 2015: A population-level modelling analysis","volume":"19","author":"Cassini","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Kaier, K., Heister, T., Gotting, T., Wolkewitz, M., and Mutters, N.T. (2019). Measuring the in-hospital costs of Pseudomonas aeruginosa pneumonia: Methodology and results from a German teaching hospital. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4660-5"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1128\/CMR.00040-09","article-title":"Antibacterial-Resistant Pseudomonas aeruginosa: Clinical Impact and Complex Regulation of Chromosomally Encoded Resistance Mechanisms","volume":"22","year":"2009","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"685","DOI":"10.3389\/fmicb.2018.00685","article-title":"The Versatile Mutational Resistome of Pseudomonas aeruginosa","volume":"9","author":"Cabot","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1586\/17476348.2015.995640","article-title":"The problems of antibiotic resistance in cystic fibrosis and solutions","volume":"9","author":"Oliver","year":"2015","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_76","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_77","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1053\/jhin.2000.0880","article-title":"Transmission of a multiresistant Pseudomonas aeruginosa strain at a German University Hospital","volume":"47","author":"Pitten","year":"2001","journal-title":"J. Hosp. Infect."},{"key":"ref_78","first-page":"47","article-title":"Extensively drug-resistant Pseudomonas aeruginosa outbreak in a burn unit: Management and solutions","volume":"32","author":"Campins","year":"2019","journal-title":"Ann. Burn. Fire Disasters"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0305-4179(00)00084-X","article-title":"Multi-drug resistant Pseudomonas aeruginosa outbreak in a burns unit\u2014An infection control study","volume":"27","author":"Douglas","year":"2001","journal-title":"Burns"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5978","DOI":"10.1128\/JB.186.18.5978-5987.2004","article-title":"The architecture of the murein (peptidoglycan) in gram-negative bacteria: Vertical scaffold or horizontal layer(s)?","volume":"186","author":"Vollmer","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.3389\/fmicb.2019.01868","article-title":"Comparative analysis of peptidoglycans from Pseudomonas aeruginosa isolates recovered from chronic and acute infections","volume":"10","author":"Torrens","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1574-6976.2007.00094.x","article-title":"Peptidoglycan structure and architecture","volume":"32","author":"Vollmer","year":"2008","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_83","first-page":"1505","article-title":"Teruhiko Beppu and Kei Arima. Peptidoglycan of Pseudomonas aeruginosa","volume":"40","year":"1975","journal-title":"Agric. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1574-6976.2008.00105.x","article-title":"The penicillin-binding proteins: Structure and role in peptidoglycan biosynthesis","volume":"32","author":"Sauvage","year":"2008","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1093\/femsre\/fuaa036","article-title":"Cell envelope proteases and peptidases of Pseudomonas aeruginosa: Multiple roles, multiple mechanisms","volume":"44","author":"Heywood","year":"2020","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e01651-16","DOI":"10.1128\/AAC.01651-16","article-title":"Penicillin-binding protein 3 is essential for growth of Pseudomonas aeruginosa","volume":"61","author":"Chen","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1128\/MMBR.66.4.702-738.2002","article-title":"Biochemistry and comparative genomics of SxxK superfamily acyltransferases offer a clue to the mycobacterial paradox: Presence of penicillin-susceptible target proteins versus lack of efficiency of penicillin as therapeutic agent","volume":"66","author":"Goffin","year":"2002","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5028","DOI":"10.1073\/pnas.97.10.5028","article-title":"Correlation between the structure of the bacterial peptidoglycan monomer unit, the specificity of transpeptidation, and susceptibility to \u03b2-lactams","volume":"97","author":"Gutmann","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1128\/MMBR.62.4.1079-1093.1998","article-title":"Multimodular penicillin-binding proteins: An enigmatic family of orthologs and paralogs","volume":"62","author":"Goffin","year":"1998","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1021\/bi2017987","article-title":"A highly conserved interaction involving the middle residue of the SXN active-site motif is crucial for function of class B penicillin-binding proteins: Mutational and computational analysis of PBP 2 from N. gonorrhoeae","volume":"51","author":"Tomberg","year":"2012","journal-title":"Biochemistry"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1111\/j.1574-6976.2006.00024.x","article-title":"Penicillin Binding Proteins: Key players in bacterial cell cycle and drug resistance processes","volume":"30","author":"Macheboeuf","year":"2006","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Sauvage, E., and Terrak, M. (2016). Glycosyltransferases and transpeptidases\/penicillin-binding proteins: Valuable targets for new antibacterials. Antibiotics, 5.","DOI":"10.3390\/antibiotics5010012"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.1128\/AAC.05150-14","article-title":"Role of Pseudomonas aeruginosa low-molecular-mass penicillin-binding proteins in AmpC expression, \u03b2-lactam resistance, and peptidoglycan structure","volume":"59","author":"Ropy","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.tim.2008.04.006","article-title":"Physiological functions of D-alanine carboxypeptidases in Escherichia coli","volume":"16","author":"Ghosh","year":"2008","journal-title":"Trends Microbiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e00524-19","DOI":"10.1128\/mSystems.00524-19","article-title":"Regulation of AmpC-driven \u03b2-lactam resistance in Pseudomonas aeruginosa: Different pathways, different signaling","volume":"4","author":"Torrens","year":"2019","journal-title":"mSystems"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.1574-6976.2007.00099.x","article-title":"Bacterial peptidoglycan (murein) hydrolases","volume":"32","author":"Vollmer","year":"2008","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1186\/s12866-016-0853-x","article-title":"In vivo functional and molecular characterization of the Penicillin-Binding Protein 4 (DacB) of Pseudomonas aeruginosa","volume":"16","year":"2016","journal-title":"BMC Microbiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1021\/ja5111706","article-title":"Catalytic spectrum of the penicillin-binding protein 4 of Pseudomonas aeruginosa, a nexus for the induction of \u03b2-lactam antibiotic resistance","volume":"137","author":"Lee","year":"2015","journal-title":"J. Am. Chem. Soc."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1093\/jac\/dku379","article-title":"Bacteriostatic versus bactericidal antibiotics for patients with serious bacterial infections: Systematic review and meta-analysis","volume":"70","author":"Nemeth","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_100","unstructured":"Wexler, P. (2014). Penicillins. Encyclopedia of Toxicology, Academic Press. [3rd ed.]."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"128","DOI":"10.3389\/fmicb.2013.00128","article-title":"\u03b2-lactamase induction and cell wall metabolism in gram-negative bacteria","volume":"4","author":"Zeng","year":"2013","journal-title":"Front. Microbiol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"22002","DOI":"10.1073\/pnas.1013092107","article-title":"Structural basis for effectiveness of siderophore-conjugated monocarbams against clinically relevant strains of Pseudomonas aeruginosa","volume":"107","author":"Han","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1110\/ps.52001","article-title":"Interaction energies between \u03b2-lactam antibiotics and E. coli penicillin-binding protein 5 by reversible thermal denaturation","volume":"10","author":"Beadle","year":"2001","journal-title":"Protein Sci."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.cell.2014.11.017","article-title":"\u03b2-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery","volume":"159","author":"Cho","year":"2014","journal-title":"Cell"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.molcel.2012.09.016","article-title":"Distinct single-cell morphological dynamics under \u03b2-lactam antibiotics","volume":"48","author":"Yao","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1099\/00222615-48-3-309","article-title":"Relationship between morphological changes and endotoxin release induced by carbapenems in Pseudomonas aeruginosa","volume":"48","author":"Horii","year":"1999","journal-title":"J. Med. Microbiol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Lee, D., Das, S., Dawson, N.L., Dobrijevic, D., Ward, J., and Orengo, C. (2016). Novel computational protocols for functionally classifying and characterising serine \u03b2-lactamases. PLoS Comput. Biol., 12.","DOI":"10.1371\/journal.pcbi.1004926"},{"key":"ref_108","unstructured":"Schaechter, M. (2009). \u03b2-lactam Antibiotics. Encyclopedia of Microbiology, Academic Press. [3rd ed.]."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1128\/AAC.45.7.1964-1971.2001","article-title":"Pseudomonas aeruginosa reveals high intrinsic resistance to penem antibiotics: Penem resistance mechanisms and their interplay","volume":"45","author":"Okamoto","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1128\/AAC.01529-07","article-title":"Affinity of doripenem and comparators to penicillin-binding proteins in Escherichia coli and Pseudomonas aeruginosa","volume":"52","author":"Davies","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2621","DOI":"10.1128\/AAC.00029-07","article-title":"Binding of ceftobiprole and comparators to the penicillin-binding proteins of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae","volume":"51","author":"Davies","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1469-0691.2000.tb02038.x","article-title":"The final goal: Penicillin-binding proteins and the target of cephalosporins","volume":"6","author":"Fontana","year":"2000","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1021\/acschembio.8b01025","article-title":"Slt, MltD, and MltG of Pseudomonas aeruginosa as targets of Bulgecin A in potentiation of \u03b2-lactam antibiotics","volume":"14","author":"Dik","year":"2019","journal-title":"ACS Chem. Biol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1002\/mbo3.286","article-title":"Loss of membrane-bound lytic transglycosylases increases outer membrane permeability and \u03b2-lactam sensitivity in Pseudomonas aeruginosa","volume":"4","author":"Lamers","year":"2015","journal-title":"MicrobiologyOpen"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1073\/pnas.1801298115","article-title":"Exolytic and endolytic turnover of peptidoglycan by lytic transglycosylase Slt of Pseudomonas aeruginosa","volume":"115","author":"Lee","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1097\/00007890-200103270-00009","article-title":"Continuous \u03b2-lactam antibiotic therapy in a double-lung transplanted patient with a multidrug-resistant Pseudomonas aeruginosa infection","volume":"71","author":"Domenig","year":"2001","journal-title":"Transplantation"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1345\/aph.1M717","article-title":"High-dose continuous infusion \u03b2-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections in immunocompromised patients","volume":"44","author":"Moriyama","year":"2010","journal-title":"Ann. Pharmacother."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Yu, Z., Pang, X., Wu, X., Shan, C., and Jiang, S. (2018). Clinical outcomes of prolonged infusion (extended infusion or continuous infusion) versus intermittent bolus of meropenem in severe infection: A meta-analysis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0201667"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"9098","DOI":"10.1038\/s41598-019-45550-z","article-title":"Dual \u03b2-lactam combination therapy for multi-drug resistant Pseudomonas aeruginosa infection: Enhanced efficacy in vivo and comparison with monotherapies of penicillin-binding protein inhibition","volume":"9","author":"Siriyong","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e00779-19","DOI":"10.1128\/AAC.00779-19","article-title":"Evaluation of the synergy of ceftazidime-avibactam in combination with meropenem, amikacin, aztreonam, colistin, or fosfomycin against well-characterized multidrug-resistant Klebsiella pneumoniae and Pseudomonas aeruginosa","volume":"63","author":"Mikhail","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"482","DOI":"10.3934\/microbiol.2018.3.482","article-title":"An overview of the antimicrobial resistance mechanisms of bacteria","volume":"4","author":"Reygaert","year":"2018","journal-title":"AIMS Microbiol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4.2.15","DOI":"10.1128\/microbiolspec.VMBF-0016-2015","article-title":"Mechanisms of antibiotic resistance","volume":"4","author":"Munita","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1089\/mdr.2019.0274","article-title":"Meta-analysis of biofilm formation, antibiotic resistance pattern, and biofilm-related genes in Pseudomonas aeruginosa isolated from clinical samples","volume":"26","author":"Morshedi","year":"2020","journal-title":"Microb. Drug Resist."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"e01619-19","DOI":"10.1128\/AAC.01619-19","article-title":"A large-scale whole-genome comparison shows that experimental evolution in response to antibiotics predicts changes in naturally evolved clinical Pseudomonas aeruginosa","volume":"63","author":"Wardell","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Yen, P., and Papin, J.A. (2017). History of antibiotic adaptation influences microbial evolutionary dynamics during subsequent treatment. PLoS Biol., 15.","DOI":"10.1371\/journal.pbio.2001586"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e00517-17","DOI":"10.1128\/mBio.00517-17","article-title":"Evolved aztreonam resistance is multifactorial and can produce hypervirulence in Pseudomonas aeruginosa","volume":"8","author":"Jorth","year":"2017","journal-title":"mBio"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"e01379-18","DOI":"10.1128\/AAC.01379-18","article-title":"Mutation-Driven Evolution of Pseudomonas aeruginosa in the Presence of either Ceftazidime or Ceftazidime-Avibactam","volume":"62","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/ng.3148","article-title":"Convergent evolution and adaptation of Pseudomonas aeruginosa within patients with cystic fibrosis","volume":"47","author":"Marvig","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/jac\/36.1.53","article-title":"Potent activity of meropenem against Escherichia coli arising from its simultaneous binding to penicillin-binding proteins 2 and 3","volume":"36","author":"Sumita","year":"1995","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1128\/AAC.04552-14","article-title":"Profiling of \u03b2-Lactam selectivity for penicillin-binding proteins in Escherichia coli strain DC2","volume":"59","author":"Kocaoglu","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1186\/s13104-018-3719-5","article-title":"Analysis of amino acid motif of penicillin-binding proteins 1a, 2b, and 2x in invasive Streptococcus pneumoniae nonsusceptible to penicillin isolated from pediatric patients in Casablanca, Morocco","volume":"11","author":"Diawara","year":"2018","journal-title":"BMC Res. Notes"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1128\/AAC.02676-15","article-title":"Evolution of Pseudomonas aeruginosa antimicrobial resistance and fitness under low and high mutation rates","volume":"60","author":"Cabot","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1093\/jac\/dkz243","article-title":"Combination of MexAB-OprM overexpression and mutations in efflux regulators, PBPs and chaperone proteins is responsible for ceftazidime\/avibactam resistance in Pseudomonas aeruginosa clinical isolates from US hospitals","volume":"74","author":"Castanheira","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_134","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_135","doi-asserted-by":"crossref","first-page":"5555","DOI":"10.1038\/s41598-017-05621-5","article-title":"Evolution of the Pseudomonas aeruginosa mutational resistome in an international cystic fibrosis clone","volume":"7","author":"Sommer","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/1873-3468.12054","article-title":"Crystal structures of penicillin-binding protein 3 in complexes with azlocillin and cefoperazone in both acylated and deacylated forms","volume":"590","author":"Ren","year":"2016","journal-title":"FEBS Lett."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jmb.2010.10.024","article-title":"Crystal structures of penicillin-binding protein 3 from Pseudomonas aeruginosa: Comparison of native and antibiotic-bound forms","volume":"405","author":"Sainsbury","year":"2011","journal-title":"J. Mol. Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"e01589-17","DOI":"10.1128\/AAC.01589-17","article-title":"Genomics and susceptibility profiles of extensively drug-resistant Pseudomonas aeruginosa isolates from Spain","volume":"61","author":"Cabot","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1128\/AAC.01720-16","article-title":"Deciphering the resistome of the widespread Pseudomonas aeruginosa sequence type 175 international high-risk clone through whole-genome sequencing","volume":"60","author":"Cabot","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"e00981-15","DOI":"10.1128\/mBio.00981-15","article-title":"Selective sweeps and parallel pathoadaptation drive Pseudomonas aeruginosa evolution in the cystic fibrosis lung","volume":"6","author":"Clark","year":"2015","journal-title":"mBio"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.chom.2015.07.006","article-title":"Regional isolation drives bacterial diversification within cystic fibrosis lungs","volume":"18","author":"Jorth","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e01592-14","DOI":"10.1128\/mBio.01592-14","article-title":"Environmental heterogeneity drives within-host diversification and evolution of Pseudomonas aeruginosa","volume":"5","author":"Markussen","year":"2014","journal-title":"mBio"},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Marvig, R.L., Johansen, H.K., Molin, S., and Jelsbak, L. (2013). Genome analysis of a transmissible lineage of Pseudomonas aeruginosa reveals pathoadaptive mutations and distinct evolutionary paths of hypermutators. PLoS Genet., 9.","DOI":"10.1371\/journal.pgen.1003741"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"7481","DOI":"10.1073\/pnas.1018249108","article-title":"Evolutionary dynamics of bacteria in a human host environment","volume":"108","author":"Yang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Chotirmall, S.H., Sherrard, L.J., Tai, A.S., Wee, B.A., Ramsay, K.A., Kidd, T.J., Ben Zakour, N.L., Whiley, D.M., Beatson, S.A., and Bell, S.C. (2017). Within-host whole genome analysis of an antibiotic resistant Pseudomonas aeruginosa strain sub-type in cystic fibrosis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172179"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e02142-19","DOI":"10.1128\/AAC.02142-19","article-title":"Hypermutator Pseudomonas aeruginosa exploits multiple genetic pathways to develop multidrug resistance during long-term infections in the airways of cystic fibrosis patients","volume":"64","author":"Colque","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"e00866-19","DOI":"10.1128\/AAC.00866-19","article-title":"Genomic analysis identifies novel Pseudomonas aeruginosa resistance genes under selection during inhaled aztreonam therapy in vivo","volume":"63","author":"McLean","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"4229","DOI":"10.1128\/AAC.00434-16","article-title":"Dynamics of Mutations during Development of Resistance by Pseudomonas aeruginosa against Five Antibiotics","volume":"60","author":"Feng","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_149","first-page":"1","article-title":"A novel PBP3 substitution in Haemophilus influenzae confers reduced aminopenicillin susceptibility","volume":"18","author":"Matuschek","year":"2018","journal-title":"BMC Microbiol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.jmgm.2018.12.002","article-title":"Influence of the T to S mutation at the STMK motif on antibiotic resistance of penicillin binding protein 1A: A comprehensive computational study","volume":"87","author":"Behmard","year":"2019","journal-title":"J. Mol. Graph. Model."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1128\/AAC.46.5.1273-1280.2002","article-title":"Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci","volume":"46","author":"Nagai","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_152","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_153","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_154","doi-asserted-by":"crossref","first-page":"137","DOI":"10.4103\/ijmm.IJMM_15_220","article-title":"Carbapenem nonsusceptibility with modified OprD in clinical isolates of Pseudomonas aeruginosa from India","volume":"35","author":"Choudhury","year":"2017","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1093\/jac\/dkx158","article-title":"Development of carbapenem resistance in Pseudomonas aeruginosa is associated with OprD polymorphisms, particularly the amino acid substitution at codon 170","volume":"72","author":"Shu","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_156","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_157","doi-asserted-by":"crossref","first-page":"ftw031","DOI":"10.1093\/femspd\/ftw031","article-title":"Identification of unique in-frame deletions in OprD among clinical isolates of Pseudomonas aeruginosa","volume":"74","author":"Kos","year":"2016","journal-title":"Pathog. Dis."},{"key":"ref_158","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_159","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_160","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1078\/1438-4221-00256","article-title":"Effect of basic amino acids on susceptibility to carbapenems in clinical Pseudomonas aeruginosa isolates","volume":"293","author":"Muramatsu","year":"2003","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"20747","DOI":"10.1073\/pnas.1221552110","article-title":"Enhanced in vivo fitness of carbapenem-resistant oprD mutants of Pseudomonas aeruginosa revealed through high-throughput sequencing","volume":"110","author":"Skurnik","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"e2107644118","DOI":"10.1073\/pnas.2107644118","article-title":"Outer membrane permeability: Antimicrobials and diverse nutrients bypass porins in Pseudomonas aeruginosa","volume":"118","author":"Ude","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_163","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_164","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_165","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1021\/acsinfecdis.8b00149","article-title":"Getting drugs through small pores: Exploiting the porins pathway in Pseudomonas aeruginosa","volume":"4","author":"Samanta","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"40208","DOI":"10.1038\/srep40208","article-title":"Mechanisms of intrinsic resistance and acquired susceptibility of Pseudomonas aeruginosa isolated from cystic fibrosis patients to temocillin, a revived antibiotic","volume":"7","author":"Chalhoub","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/jac\/dkr543","article-title":"Role of MexAB-OprM in intrinsic resistance of Pseudomonas aeruginosa to temocillin and impact on the susceptibility of strains isolated from patients suffering from cystic fibrosis","volume":"67","author":"Buyck","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1038\/s41598-019-39659-4","article-title":"A permeability-increasing drug synergizes with bacterial efflux pump inhibitors and restores susceptibility to antibiotics in multi-drug resistant Pseudomonas aeruginosa strains","volume":"9","author":"Shahrour","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_169","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_170","doi-asserted-by":"crossref","first-page":"2540","DOI":"10.1128\/AAC.41.11.2540","article-title":"Differential selection of multidrug efflux systems by quinolones in Pseudomonas aeruginosa","volume":"41","author":"Plesiat","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1128\/AAC.01252-13","article-title":"Multiple mutations lead to MexXY-OprM-dependent aminoglycoside resistance in clinical strains of Pseudomonas aeruginosa","volume":"58","author":"Muller","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"5676","DOI":"10.1128\/AAC.00101-11","article-title":"Role of the MexEF-OprN efflux system in low-level resistance of Pseudomonas aeruginosa to ciprofloxacin","volume":"55","author":"Llanes","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1093\/jac\/45.4.433","article-title":"Interplay between the MexA-MexB-OprM multidrug efflux system and the outer membrane barrier in the multiple antibiotic resistance of Pseudomonas aeruginosa","volume":"45","author":"Li","year":"2000","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_174","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_175","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":"Akkawi","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Choudhury, D., Das Talukdar, A., Dutta Choudhury, M., Maurya, A.P., Paul, D., Dhar Chanda, D., Chakravorty, A., and Bhattacharjee, A. (2015). Transcriptional analysis of MexAB-OprM efflux pumps system of Pseudomonas aeruginosa and its role in carbapenem resistance in a tertiary referral hospital in India. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133842"},{"key":"ref_177","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_178","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_179","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_180","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1128\/AAC.43.11.2624","article-title":"Involvement of an active efflux system in the natural resistance of Pseudomonas aeruginosa to aminoglycosides","volume":"43","author":"Aires","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"408","DOI":"10.3389\/fmicb.2012.00408","article-title":"MexXY multidrug efflux system of Pseudomonas aeruginosa","volume":"3","author":"Morita","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref_182","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_183","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":"Neshat","year":"2005","journal-title":"J. Bacteriol."},{"key":"ref_184","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_185","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_186","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_187","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_188","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/embor.2010.96","article-title":"Structural insight into the oxidation-sensing mechanism of the antibiotic resistance of regulator MexR","volume":"11","author":"Chen","year":"2010","journal-title":"EMBO Rep."},{"key":"ref_189","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_190","doi-asserted-by":"crossref","first-page":"6195","DOI":"10.1128\/JB.185.20.6195-6198.2003","article-title":"Mutations affecting DNA-binding activity of the MexR repressor of mexR-mexA-mexB-oprM operon expression","volume":"185","author":"Saito","year":"2003","journal-title":"J. Bacteriol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1111\/j.1365-2958.2004.04210.x","article-title":"MexAB-OprM hyperexpression in NalC-type multidrug-resistant Pseudomonas aeruginosa: Identification and characterization of the nalC gene encoding a repressor of PA3720-PA3719","volume":"53","author":"Cao","year":"2004","journal-title":"Mol. Microbiol."},{"key":"ref_192","first-page":"23","article-title":"MexZ-mediated regulation of mexXY multidrug efflux pump expression in Pseudomonas aeruginosa by binding on the mexZ-mexX intergenic DNA","volume":"238","author":"Matsuo","year":"2004","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_193","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_194","doi-asserted-by":"crossref","first-page":"12512","DOI":"10.1038\/s41598-018-30972-y","article-title":"Mutations causing low level antibiotic resistance ensure bacterial survival in antibiotic-treated hosts","volume":"8","author":"Rossi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"e01166-20","DOI":"10.1128\/AAC.01166-20","article-title":"Expression of the MexXY aminoglycoside efflux pump and presence of an aminoglycoside-modifying enzyme in clinical Pseudomonas aeruginosa isolates are highly correlated","volume":"65","author":"Seupt","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1128\/AAC.42.8.1938","article-title":"Characterization of the MexC-MexD-OprJ multidrug efflux system in \u0394mexA-mexB-oprM mutants of Pseudomonas aeruginosa","volume":"42","author":"Gotoh","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"4478","DOI":"10.1128\/AAC.01072-08","article-title":"MexCD-OprJ multidrug efflux system of Pseudomonas aeruginosa: Involvement in chlorhexidine resistance and induction by membrane-damaging agents dependent upon the AlgU stress response sigma factor","volume":"52","author":"Fraud","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"2058","DOI":"10.1099\/mic.0.069286-0","article-title":"Functional characterization of the NfxB repressor of the mexCD\u2013oprJ multidrug efflux operon of Pseudomonas aeruginosa","volume":"159","author":"Purssell","year":"2013","journal-title":"Microbiology"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0924-8579(03)00009-8","article-title":"Mutations in GyrA, ParC, MexR and NfxB in clinical isolates of Pseudomonas aeruginosa","volume":"21","author":"Higgins","year":"2003","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"e0008921","DOI":"10.1128\/AAC.00089-21","article-title":"Emergence of resistance to novel cephalosporin-\u03b2-lactamase inhibitor combinations through the modification of the Pseudomonas aeruginosa MexCD-OprJ efflux pump","volume":"65","author":"Pitart","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"5213","DOI":"10.1128\/JB.183.18.5213-5222.2001","article-title":"Overexpression of the MexEF-OprN multidrug efflux system affects cell-to-cell signaling in Pseudomonas aeruginosa","volume":"183","author":"Curty","year":"2001","journal-title":"J. Bacteriol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1128\/AAC.44.3.658-664.2000","article-title":"Assignment of the substrate-selective subunits of the MexEF-OprN multidrug efflux pump of Pseudomonas aeruginosa","volume":"44","author":"Maseda","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1574-6968.2010.02063.x","article-title":"Transcriptional regulation of the mexEF-oprN multidrug efflux pump operon by MexT and an unidentified repressor in nfxC-type mutant of Pseudomonas aeruginosa","volume":"311","author":"Maseda","year":"2010","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1128\/AAC.01107-07","article-title":"Resistance and virulence of Pseudomonas aeruginosa clinical strains overproducing the MexCD-OprJ efflux pump","volume":"52","author":"Jeannot","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_205","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_206","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1128\/AAC.01009-09","article-title":"Updated functional classification of \u03b2-lactamases","volume":"54","author":"Bush","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"e00397-20","DOI":"10.1128\/AAC.00397-20","article-title":"Metallo-\u03b2-lactamases: Structure, function, epidemiology, treatment options, and the development pipeline","volume":"64","author":"Boyd","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/j.1749-6632.2012.06796.x","article-title":"Metallo-\u03b2-lactamase structure and function","volume":"1277","author":"Palzkill","year":"2013","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1128\/CMR.00001-07","article-title":"Carbapenemases: The versatile \u03b2-lactamases","volume":"20","author":"Queenan","year":"2007","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Adam, M.A., and Elhag, W.I. (2018). Prevalence of metallo-\u03b2-lactamase acquired genes among carbapenems susceptible and resistant Gram-negative clinical isolates using multiplex PCR, Khartoum hospitals, Khartoum Sudan. BMC Infect. Dis., 18.","DOI":"10.1186\/s12879-018-3581-z"},{"key":"ref_211","first-page":"15","article-title":"Carbapenem resistance: Overview of the problem and future perspectives","volume":"3","author":"Meletis","year":"2016","journal-title":"Ther. Adv. Infect. Dis."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"122","DOI":"10.37201\/req\/086.2019","article-title":"Epidemiology and clinical of infections and colonizations caused by Enterobacterales producing carbapenemases in a tertiary hospital","volume":"33","year":"2020","journal-title":"Rev. Espa\u00f1ola Quimioter."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/14787210.2020.1813023","article-title":"Update on the epidemiology of carbapenemases in Latin America and the Caribbean","volume":"19","author":"Appel","year":"2021","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"100660","DOI":"10.1016\/j.nmni.2020.100660","article-title":"Detection of two simultaneous outbreaks of Klebsiella pneumoniae coproducing OXA-48 and NDM-1 carbapenemases in a tertiary-care hospital in Valencia, Spain","volume":"34","author":"Fuster","year":"2020","journal-title":"New Microbes New Infect."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1556\/1886.2018.00033","article-title":"Screening for Carbapenemases in Ertapenem-Resistant Enterobacteriaceae Collected at a Tunisian Hospital Between 2014 and 2018","volume":"9","author":"Kollenda","year":"2019","journal-title":"Eur. J. Microbiol. Immunol."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s40168-019-0710-x","article-title":"Sewage effluent from an Indian hospital harbors novel carbapenemases and integron-borne antibiotic resistance genes","volume":"7","author":"Marathe","year":"2019","journal-title":"Microbiome"},{"key":"ref_217","doi-asserted-by":"crossref","unstructured":"Hammoudi Halat, D., and Ayoub Moubareck, C. (2020). The current burden of carbapenemases: Review of significant properties and dissemination among gram-negative bacteria. Antibiotics, 9.","DOI":"10.3390\/antibiotics9040186"},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"5704","DOI":"10.1128\/AAC.03057-14","article-title":"Avibactam and class C \u03b2-lactamases: Mechanism of inhibition, conservation of the binding pocket, and implications for resistance","volume":"58","author":"Lahiri","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_219","doi-asserted-by":"crossref","unstructured":"Silva, M.P., Saraiva, L., Pinto, M., and Sousa, M.E. (2020). Boronic acids and their derivatives in medicinal chemistry: Synthesis and biological applications. Molecules, 25.","DOI":"10.3390\/molecules25184323"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"3737","DOI":"10.1021\/acs.jmedchem.0c00127","article-title":"6-arylmethylidene penicillin-based sulfone inhibitors for repurposing antibiotic efficiency in priority pathogens","volume":"63","author":"Maneiro","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1128\/AAC.00743-09","article-title":"Penicillin sulfone inhibitors of class D \u03b2-lactamases","volume":"54","author":"Drawz","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_222","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_223","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3389\/fmicb.2011.00065","article-title":"Pseudomonas aeruginosa: Resistance to the max","volume":"2","author":"Poole","year":"2011","journal-title":"Front. Microbiol."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"e01783-16","DOI":"10.1128\/mBio.01783-16","article-title":"Impact of AmpC derepression on fitness and virulence: The mechanism or the pathway?","volume":"7","author":"Torrens","year":"2016","journal-title":"mBio"},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"e16436","DOI":"10.5812\/jjm.16436","article-title":"Prevalence of extended-spectrum and metallo \u03b2-lactamase production in AmpC \u03b2-lactamase producing Pseudomonas aeruginosa isolates from burns","volume":"7","author":"Rafiee","year":"2014","journal-title":"Jundishapur J. Microbiol."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/pro.3737","article-title":"Constructing and deconstructing the bacterial cell wall","volume":"29","author":"Fisher","year":"2020","journal-title":"Protein Sci."},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"2630","DOI":"10.1074\/jbc.M114.618199","article-title":"The \u03b2-lactamase gene regulator AmpR is a tetramer that recognizes and binds the d-Ala-d-Ala motif of its repressor UDP-N-acetylmuramic ccid (MurNAc)-pentapeptide","volume":"290","author":"Vadlamani","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1021\/jacs.6b12819","article-title":"Muropeptide Binding and the X-ray Structure of the Effector Domain of the Transcriptional Regulator AmpR of Pseudomonas aeruginosa","volume":"139","author":"Dik","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"4733","DOI":"10.1128\/AAC.49.11.4733-4738.2005","article-title":"Molecular mechanisms of \u03b2-lactam resistance mediated by AmpC hyperproduction in Pseudomonas aeruginosa clinical strains","volume":"49","author":"Juan","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"3922","DOI":"10.1128\/AAC.00341-08","article-title":"Role of ampD homologs in overproduction of AmpC in clinical isolates of Pseudomonas aeruginosa","volume":"52","author":"Schmidtke","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"4567","DOI":"10.1128\/AAC.49.11.4567-4575.2005","article-title":"Pseudomonas aeruginosa AmpR is a global transcriptional factor that regulates expression of AmpC and PoxB \u03b2-lactamases, proteases, quorum sensing, and other virulence factors","volume":"49","author":"Kong","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.1128\/JB.01997-14","article-title":"Structural and functional characterization of Pseudomonas aeruginosa global regulator AmpR","volume":"196","author":"Caille","year":"2014","journal-title":"J. Bacteriol."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"ofw188","DOI":"10.1093\/ofid\/ofw188","article-title":"Multidrug resistant Pseudomonas aeruginosa causing prosthetic valve endocarditis: A genetic-based chronicle of evolving antibiotic resistance","volume":"3","author":"Domitrovic","year":"2016","journal-title":"Open Forum Infect Dis."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1128\/AAC.46.11.3406-3411.2002","article-title":"Constitutive high expression of chromosomal \u03b2-lactamase in Pseudomonas aeruginosa caused by a new insertion sequence (IS1669) located in ampD","volume":"46","author":"Bagge","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_235","doi-asserted-by":"crossref","unstructured":"Moya, B., D\u00f6tsch, A., Juan, C., Bl\u00e1zquez, J., Zamorano, L., Haussler, S., and Oliver, A. (2009). \u03b2-lactam resistance response triggered by inactivation of a nonessential penicillin-binding protein. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000353"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"5084","DOI":"10.1128\/AAC.02556-14","article-title":"The Pseudomonas aeruginosa CreBC two-component system plays a major role in the response to \u03b2-lactams, fitness, biofilm growth, and global regulation","volume":"58","author":"Zamorano","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"ofab311","DOI":"10.1093\/ofid\/ofab311","article-title":"Cefiderocol activity against clinical Pseudomonas aeruginosa isolates exhibiting ceftolozane-tazobactam resistance","volume":"8","author":"Simner","year":"2021","journal-title":"Open Forum Infect Disease."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/j.1469-0691.2006.01674.x","article-title":"Prevalence of AmpC over-expression in bloodstream isolates of Pseudomonas aeruginosa","volume":"13","author":"Tam","year":"2007","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"e00894-20","DOI":"10.1128\/AAC.00894-20","article-title":"Adding insult to injury: Mechanistic basis for how AmpC mutations allow Pseudomonas aeruginosa to accelerate cephalosporin hydrolysis and evade avibactam","volume":"64","author":"Slater","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"6248","DOI":"10.1128\/AAC.00825-15","article-title":"Mutations in \u03b2-lactamase AmpC increase resistance of Pseudomonas aeruginosa isolates to antipseudomonal cephalosporins","volume":"59","author":"Berrazeg","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"e02311-19","DOI":"10.1128\/AAC.02311-19","article-title":"Ceftazidime-avibactam resistance mediated by the N346Y substitution in various AmpC \u03b2-lactamases","volume":"64","author":"Compain","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.eimc.2020.01.017","article-title":"Characterization of AmpC \u03b2-lactamase mutations of extensively drug-resistant Pseudomonas aeruginosa isolates that develop resistance to ceftolozane\/tazobactam during therapy","volume":"38","author":"Mulet","year":"2020","journal-title":"Enferm. Infecc. Microbiol. Cl\u00ednica"},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"2972","DOI":"10.1093\/jac\/dku267","article-title":"Characterization of a novel Zn(2)(+)-dependent intrinsic imipenemase from Pseudomonas aeruginosa","volume":"69","author":"Fajardo","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1128\/AAC.48.6.2043-2048.2004","article-title":"Biochemical characterization of the naturally occurring oxacillinase OXA-50 of Pseudomonas aeruginosa","volume":"48","author":"Girlich","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1128\/AAC.01807-15","article-title":"Characterization of a Carbapenem-Hydrolyzing Enzyme, PoxB, in Pseudomonas aeruginosa PAO1","volume":"60","author":"Zincke","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1128\/AAC.02247-12","article-title":"Structural Insight into Potent Broad-Spectrum Inhibition with Reversible Recyclization Mechanism: Avibactam in Complex with CTX-M-15 and Pseudomonas aeruginosa AmpC \u03b2-Lactamases","volume":"57","author":"Lahiri","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1128\/AAC.35.1.147","article-title":"Transferable imipenem resistance in Pseudomonas aeruginosa","volume":"35","author":"Watanabe","year":"1991","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"7100","DOI":"10.1128\/AAC.01512-15","article-title":"Dissemination of carbapenemase-producing Enterobacteriaceae and Pseudomonas aeruginosa in Romania","volume":"59","author":"Dortet","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1128\/CMR.00117-13","article-title":"OXA \u03b2-lactamases","volume":"27","author":"Evans","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.2147\/IDR.S255292","article-title":"Distribution of Class B and Class A \u03b2-Lactamases in Clinical Strains of Pseudomonas aeruginosa: Comparison of Phenotypic Methods and High-Resolution Melting Analysis (HRMA) Assay","volume":"13","author":"Dehbashi","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1093\/jac\/dkh395","article-title":"Frequency and diversity of Class A extended-spectrum \u03b2-lactamases in hospitals of the Auvergne, France: A 2 year prospective study","volume":"54","author":"Chanal","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1093\/jac\/dkz536","article-title":"GPC-1, a novel class A carbapenemase detected in a clinical Pseudomonas aeruginosa isolate","volume":"75","author":"Schauer","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_253","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_254","doi-asserted-by":"crossref","first-page":"e00047-19","DOI":"10.1128\/CMR.00047-19","article-title":"Epidemiology of \u03b2-Lactamase-Producing Pathogens","volume":"33","author":"Bush","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1515\/labmed-2019-0162","article-title":"Prevalence of metallo-\u03b2-lactamase genes among Pseudomonas aeruginosa isolated from various clinical samples in China","volume":"44","author":"Wang","year":"2020","journal-title":"J. Lab. Med."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/AAC.46.1.1-11.2002","article-title":"Plasmid-determined AmpC-type \u03b2-lactamases","volume":"46","author":"Philippon","year":"2002","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.ijid.2006.07.008","article-title":"Detection of plasmid-mediated class C \u03b2-lactamases","volume":"11","author":"Doi","year":"2007","journal-title":"Int. J. Infect. Dis."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"e02112-19","DOI":"10.1128\/AAC.02112-19","article-title":"Emergence of resistance to novel \u03b2-lactam-\u03b2-lactamase inhibitor combinations due to horizontally acquired AmpC (FOX-4) in Pseudomonas aeruginosa sequence type 308","volume":"64","author":"Oliver","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"257","DOI":"10.4103\/0255-0857.115629","article-title":"Co-existence of Pseudomonas-derived cephalosporinase among plasmid encoded CMY-2 harbouring isolates of Pseudomonas aeruginosa in north India","volume":"31","author":"Upadhyay","year":"2013","journal-title":"Indian J. Med Microbiol."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"398","DOI":"10.3390\/antibiotics3030398","article-title":"Acquired Class D \u03b2-lactamases","volume":"3","author":"Antunes","year":"2014","journal-title":"Antibiotics"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jgar.2020.01.011","article-title":"Prevalence of \u03b2-lactamase and antibiotic-resistant Pseudomonas aeruginosa in the Arab region","volume":"22","author":"Nasser","year":"2020","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1590\/0037-8682-0478-2016","article-title":"Distribution of the bla OXA, bla VEB-1, and bla GES-1 genes and resistance patterns of ESBL-producing Pseudomonas aeruginosa isolated from hospitals in Tehran and Qazvin, Iran","volume":"50","author":"Amirkamali","year":"2017","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"26","DOI":"10.5578\/mb.8563","article-title":"The presence of OXA type carbapenemases in Pseudomonas strains: First report from Turkey","volume":"49","year":"2015","journal-title":"Mikrobiyoloji Bul."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fmicb.2021.614058","article-title":"Mobile carbapenemase genes in Pseudomonas aeruginosa","volume":"12","author":"Yoon","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"106026","DOI":"10.1016\/j.ijantimicag.2020.106026","article-title":"Carbapenemase-producing Pseudomonas aeruginosa in Spain: Interregional dissemination of the high-risk clones ST175 and ST244 carrying blaVIM-2, blaVIM-1, blaIMP-8, blaVIM-20 and blaKPC-2","volume":"56","author":"Zurita","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"e02496-17","DOI":"10.1128\/AAC.02496-17","article-title":"Molecular characterization of OXA-198 carbapenemase-producing Pseudomonas aeruginosa clinical isolates","volume":"62","author":"Bonnin","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/jac\/dkx337","article-title":"Unravelling the genome of a Pseudomonas aeruginosa isolate belonging to the high-risk clone ST235 reveals an integrative conjugative element housing a blaGES-6 carbapenemase","volume":"73","author":"Botelho","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.tim.2020.05.011","article-title":"The role of integrative and conjugative elements in antibiotic resistance evolution","volume":"29","author":"Botelho","year":"2021","journal-title":"Trends Microbiol."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/j.1469-0691.2012.03815.x","article-title":"Identification and screening of carbapenemase-producing Enterobacteriaceae","volume":"18","author":"Nordmann","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"139","DOI":"10.3389\/fcimb.2021.638087","article-title":"Novel chromosome-borne accessory genetic elements carrying multiple antibiotic resistance genes in Pseudomonas aeruginosa","volume":"11","author":"Yu","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13100-018-0141-4","article-title":"Carbapenemases on the move: It\u2019s good to be on ICEs","volume":"9","author":"Botelho","year":"2018","journal-title":"Mob. DNA"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"211","DOI":"10.4161\/mge.22967","article-title":"Integrons: Vehicles and pathways for horizontal dissemination in bacteria","volume":"2","author":"Domingues","year":"2012","journal-title":"Mob. Genet. Elem."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1089\/mdr.2019.0406","article-title":"Antimicrobial resistance and molecular characterization of gene cassettes from class 1 integrons in Pseudomonas aeruginosa strains","volume":"26","author":"Liu","year":"2020","journal-title":"Microb. Drug Resist."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.2147\/IDR.S263759","article-title":"Distribution and molecular characterization of resistance gene cassettes containing class 1 integrons in multi-drug resistant (MDR) clinical isolates of Pseudomonas aeruginosa","volume":"13","author":"Ahmadian","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.jhin.2020.09.007","article-title":"Carbapenemase-producing Enterobacterales in hospital drains in Southern Ontario, Canada","volume":"106","author":"Jamal","year":"2020","journal-title":"J. Hosp. Infect."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"e01715-20","DOI":"10.1128\/AEM.01715-20","article-title":"Risk factors associated with carbapenemase-producing enterobacterales (CPE) positivity in the hospital wastewater environment","volume":"86","author":"Park","year":"2020","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"e187660","DOI":"10.1001\/jamanetworkopen.2018.7660","article-title":"Contamination of Hospital Plumbing: A Source or a Sink for Antibiotic-Resistant Organisms?","volume":"2","author":"Snitkin","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.scitotenv.2019.03.428","article-title":"Hospital effluent: A reservoir for carbapenemase-producing Enterobacterales?","volume":"672","author":"Cahill","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.jgar.2021.03.024","article-title":"Carbapenemase-producing Gram-negative bacteria in aquatic environments: A review","volume":"25","author":"Cherak","year":"2021","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"115081","DOI":"10.1016\/j.envpol.2020.115081","article-title":"Environmental dissemination of carbapenemase-producing Enterobacteriaceae in rivers in Switzerland","volume":"265","author":"Bleichenbacher","year":"2020","journal-title":"Environ. Pollut."},{"key":"ref_281","doi-asserted-by":"crossref","unstructured":"Colosi, I.A., Baciu, A.M., Opris, R.V., Peca, L., Gudat, T., Simon, L.M., Colosi, H.A., and Costache, C. (2020). Prevalence of ESBL, AmpC and carbapenemase-producing enterobacterales isolated from raw vegetables retailed in Romania. Foods, 9.","DOI":"10.3390\/foods9121726"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/j.1365-2958.2009.06991.x","article-title":"Pseudomonas aeruginosa uses a cyclic-di-GMP-regulated adhesin to reinforce the biofilm extracellular matrix","volume":"75","author":"Borlee","year":"2010","journal-title":"Mol. Microbiol."},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"e01698-19","DOI":"10.1128\/mBio.01698-19","article-title":"Pseudomonas aeruginosa Interstrain Dynamics and Selection of Hyperbiofilm Mutants during a Chronic Infection","volume":"10","author":"Gloag","year":"2019","journal-title":"mBio"},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41522-016-0007-9","article-title":"Evolutionary adaptations of biofilms infecting cystic fibrosis lungs promote mechanical toughness by adjusting polysaccharide production","volume":"3","author":"Kovach","year":"2017","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.1128\/JB.00119-09","article-title":"Pseudomonas aeruginosa rugose small-colony variants have adaptations that likely promote persistence in the cystic fibrosis lung","volume":"191","author":"Starkey","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"14422","DOI":"10.1073\/pnas.0507170102","article-title":"A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels","volume":"102","author":"Hickman","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s13578-021-00655-9","article-title":"rpoS-mutation variants are selected in Pseudomonas aeruginosa biofilms under imipenem pressure","volume":"11","author":"Duan","year":"2021","journal-title":"Cell Biosci."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1046\/j.1365-2672.2000.00995.x","article-title":"Role of RpoS and AlgT in Pseudomonas aeruginosa biofilm resistance to hydrogen peroxide and monochloramine","volume":"88","author":"Cochran","year":"2000","journal-title":"J. Appl. Microbiol."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1128\/AAC.01583-12","article-title":"Characterization of the polymyxin B resistome of Pseudomonas aeruginosa","volume":"57","author":"Wiegand","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1574-6968.2009.01657.x","article-title":"Novel persistence genes in Pseudomonas aeruginosa identified by high-throughput screening","volume":"297","author":"Verstraeten","year":"2009","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"e01652-19","DOI":"10.1128\/mBio.01652-19","article-title":"Resistance evolution against phage combinations depends on the timing and order of exposure","volume":"10","author":"Wright","year":"2019","journal-title":"mBio"},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.1038\/s41467-021-23451-y","article-title":"Compensatory evolution of Pseudomonas aeruginosa\u2019s slow growth phenotype suggests mechanisms of adaptation in cystic fibrosis","volume":"12","author":"Rossi","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"eaba0862","DOI":"10.1126\/science.aba0862","article-title":"Clinically relevant mutations in core metabolic genes confer antibiotic resistance","volume":"371","year":"2021","journal-title":"Science"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2147\/IDR.S68214","article-title":"Role of small colony variants in persistence of Pseudomonas aeruginosa infections in cystic fibrosis lungs","volume":"8","author":"Malone","year":"2015","journal-title":"Infect. Drug Resist."},{"key":"ref_295","first-page":"e00575-18","article-title":"Pyrimidine biosynthesis regulates the small-colony variant and mucoidy in Pseudomonas aeruginosa through sigma factor competition","volume":"201","author":"Kirby","year":"2019","journal-title":"J. Bacteriol."},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/nyas.13358","article-title":"Genomics of antibiotic-resistance prediction in Pseudomonas aeruginosa","volume":"1435","author":"Jeukens","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"e10264","DOI":"10.15252\/emmm.201910264","article-title":"Predicting antimicrobial resistance in Pseudomonas aeruginosa with machine learning-enabled molecular diagnostics","volume":"12","author":"Khaledi","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.1128\/jcm.32.7.1768-1772.1994","article-title":"Multiplex PCR for identification of methicillin-resistant staphylococci in the clinical laboratory","volume":"32","author":"Geha","year":"1994","journal-title":"J. Clin. Microbiol."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"S293","DOI":"10.12980\/APJTB.4.2014C423","article-title":"PCR-based identification of methicillin-resistant Staphylococcus aureus strains and their antibiotic resistance profiles","volume":"4","author":"Pournajaf","year":"2014","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"794","DOI":"10.3389\/fmicb.2019.00794","article-title":"Molecular Diagnosis of Drug-Resistant Tuberculosis; A Literature Review","volume":"10","author":"Nguyen","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s11908-019-0689-2","article-title":"Antimicrobial stewardship interventions to combat antibiotic resistance: An update on targeted strategies","volume":"21","author":"Cole","year":"2019","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"86","DOI":"10.17305\/bjbms.2018.3826","article-title":"Analysis of multidrug-resistant bacteria in 3223 patients with hospital-acquired infections (HAI) from a tertiary general hospital in China","volume":"19","author":"Wang","year":"2019","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.ajic.2019.05.001","article-title":"Antimicrobial stewardship impact on Pseudomonas aeruginosa susceptibility to meropenem at a tertiary pediatric institution","volume":"47","author":"Stultz","year":"2019","journal-title":"Am. J. Infect. Control"},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1111\/eva.12808","article-title":"Five rules for resistance management in the antibiotic apocalypse, a road map for integrated microbial management","volume":"12","author":"Raymond","year":"2019","journal-title":"Evol. Appl."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"327","DOI":"10.3389\/fmicb.2020.00327","article-title":"Development of a Bacteriophage Cocktail to Constrain the Emergence of Phage-Resistant Pseudomonas aeruginosa","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_306","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_307","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.7150\/ijbs.60551","article-title":"A combination therapy of phages and antibiotics: Two is better than one","volume":"17","author":"Li","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_308","first-page":"703","article-title":"Synergistic interaction between phage therapy and antibiotics clears Pseudomonas aeruginosa infection in endocarditis and reduces virulence","volume":"215","author":"Oechslin","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"e01462-20","DOI":"10.1128\/mBio.01462-20","article-title":"Phage-antibiotic synergy is driven by a unique combination of antibacterial mechanism of action and stoichiometry","volume":"11","author":"Green","year":"2020","journal-title":"mBio"},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"120200","DOI":"10.1016\/j.ijpharm.2021.120200","article-title":"Phage cocktail powder for Pseudomonas aeruginosa respiratory infections","volume":"596","author":"Li","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.mib.2016.05.016","article-title":"Anti-biofilm peptides as a new weapon in antimicrobial warfare","volume":"33","author":"Pletzer","year":"2016","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41429-020-0291-8","article-title":"Antibiotics in the clinical pipeline in October 2019","volume":"73","author":"Butler","year":"2020","journal-title":"J. Antibiot."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"e02188-18","DOI":"10.1128\/AAC.02188-18","article-title":"A first-in-human safety, tolerability, and pharmacokinetics study of benapenem in healthy Chinese volunteers","volume":"63","author":"Zhao","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.bmcl.2018.01.006","article-title":"Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae\u2013identification of LYS228","volume":"28","author":"Reck","year":"2018","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.12688\/f1000research.19509.1","article-title":"Emerging therapies against infections with Pseudomonas aeruginosa","volume":"8","year":"2019","journal-title":"F1000Research"},{"key":"ref_316","doi-asserted-by":"crossref","unstructured":"V\u00e1zquez-Ucha, J.C., Arca-Su\u00e1rez, J., Bou, G., and Beceiro, A. (2020). New Carbapenemase Inhibitors: Clearing the Way for the \u03b2-lactams. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21239308"},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"e00074-18","DOI":"10.1128\/AAC.00074-18","article-title":"Discovery of a novel metallo-\u03b2-lactamase inhibitor that potentiates meropenem activity against carbapenem-resistant enterobacteriaceae","volume":"62","author":"Everett","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1021\/acsinfecdis.0c00207","article-title":"ANT2681: SAR studies leading to the identification of a metallo-\u03b2-lactamase inhibitor with potential for clinical use in combination with meropenem for the treatment of infections caused by NDM-producing enterobacteriaceae","volume":"6","author":"Davies","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s10928-017-9506-4","article-title":"What we may expect from novel antibacterial agents in the pipeline with respect to resistance and pharmacodynamic principles","volume":"44","author":"Bush","year":"2017","journal-title":"J. Pharmacokinet. Pharmacodyn."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/s41586-021-03899-0","article-title":"Rational design of a new antibiotic class for drug-resistant infections","volume":"597","author":"Miller","year":"2021","journal-title":"Nature"},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1007\/s10534-009-9219-2","article-title":"Siderophores as drug delivery agents: Application of the \u201cTrojan Horse\u201d strategy","volume":"22","author":"Heinisch","year":"2009","journal-title":"BioMetals"},{"key":"ref_322","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s10534-008-9185-0","article-title":"Utilization of microbial iron assimilation processes for the development of new antibiotics and inspiration for the design of new anticancer agents","volume":"22","author":"Miller","year":"2009","journal-title":"BioMetals"},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s40265-019-1055-2","article-title":"Cefiderocol: A siderophore cephalosporin with activity against carbapenem-resistant and multidrug-resistant Gram-negative bacilli","volume":"79","author":"Zhanel","year":"2019","journal-title":"Drugs"},{"key":"ref_324","doi-asserted-by":"crossref","unstructured":"Hori, T., Owusu, Y.B., and Sun, D. (2021). US FDA-Approved Antibiotics During the 21st Century. Reference Module in Biomedical Sciences, Elsevier.","DOI":"10.1016\/B978-0-12-818731-9.00144-0"},{"key":"ref_325","doi-asserted-by":"crossref","first-page":"106128","DOI":"10.1016\/j.ijantimicag.2020.106128","article-title":"In vitro activity of cefiderocol against aerobic Gram-negative bacterial pathogens from Germany","volume":"56","author":"Kresken","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"e00097-18","DOI":"10.1128\/AAC.00097-18","article-title":"TonB-dependent receptor repertoire of Pseudomonas aeruginosa for uptake of siderophore-drug conjugates","volume":"62","author":"Luscher","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"e4472","DOI":"10.1093\/cid\/ciaa1909","article-title":"Evolution of Cefiderocol Non-Susceptibility in Pseudomonas aeruginosa in a Patient Without Previous Exposure to the Antibiotic","volume":"73","author":"Streling","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_328","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1021\/acsinfecdis.9b00357","article-title":"Liposomes for antibiotic encapsulation and delivery","volume":"6","author":"Hosseinidoust","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_329","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/s12951-019-0537-4","article-title":"Targeted delivery of antibiotics to the infected pulmonary tissues using ROS-responsive nanoparticles","volume":"17","author":"Wang","year":"2019","journal-title":"J. Nanobiotechnology"},{"key":"ref_330","doi-asserted-by":"crossref","unstructured":"Lamers, R.P., Cavallari, J.F., and Burrows, L.L. (2013). The efflux inhibitor phenylalanine-arginine \u03b2-naphthylamide (PA\u03b2N) permeabilizes the outer membrane of gram-negative bacteria. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060666"},{"key":"ref_331","doi-asserted-by":"crossref","first-page":"11392","DOI":"10.1038\/s41598-017-11892-9","article-title":"Effect of efflux pump inhibition on Pseudomonas aeruginosa transcriptome and virulence","volume":"7","author":"Rampioni","year":"2017","journal-title":"Sci. Rep."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/12\/1638\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:27Z","timestamp":1760169087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/12\/1638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,18]]},"references-count":331,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["pathogens10121638"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10121638","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,18]]}}}