{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T20:35:37Z","timestamp":1781123737449,"version":"3.54.1"},"reference-count":117,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,8,17]],"date-time":"2020-08-17T00:00:00Z","timestamp":1597622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:p>Multidrug resistance(MDR) among <jats:italic>Pseudomonas aeruginosa<\/jats:italic> (PSA) isolates presents a significant clinical challenge and can substantially complicate the approach to selection of optimal antibiotic therapy. This review addresses major considerations in antibiotic selection for patients with suspected or documented serious MDR\u2010PSA infections. Common mechanisms contributing to MDR among clinical PSA isolates are summarized. Empiric and definitive therapy considerations are addressed including the potential role of combination therapy. Newer agents with in vitro activity against MDR\u2010PSA (e.g., ceftolozane\u2010tazobactam, ceftazidime\u2010avibactam, imipenem\u2010relebactam, and cefiderocol) and their potential roles in clinical settings are discussed. Although these newer agents are promising options for the treatment of MDR\u2010PSA, clinical data remain generally limited. Future studies are needed to determine optimal agents for the empiric and definitive treatment of MDR\u2010PSA.<\/jats:p>","DOI":"10.1002\/phar.2449","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T00:23:08Z","timestamp":1595377388000},"page":"952-969","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Approach to the Treatment of Patients with Serious Multidrug\u2010Resistant <i>Pseudomonas aeruginosa<\/i> Infections"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5184-1385","authenticated-orcid":false,"given":"J. Nicholas","family":"O'Donnell,","sequence":"first","affiliation":[{"name":"Department of Pharmacy Practice Albany College of Pharmacy and Health Sciences Albany New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique R.","family":"Bidell,","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4730-0655","authenticated-orcid":false,"given":"Thomas P.","family":"Lodise","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice Albany College of Pharmacy and Health Sciences Albany New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00355-19"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1017\/ice.2016.174"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1086\/338782"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00039"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2011.03570.x"},{"key":"e_1_2_8_7_1","volume-title":"Antibiotic Resistance Threats in the United States, 2019","author":"CDC","year":"2019"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy343"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00043-12"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00040-09"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.12.4920-4927.2005"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.2016.1159131"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5MD00344J"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03681-14"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1592\/phco.23.7.916.32722"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx001"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041359"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1086\/504477"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00825-15"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00680-12"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.9.2046"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00117-13"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02379-15"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.18.2.306-325.2005"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01008-17"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00472-17"},{"key":"e_1_2_8_27_1","first-page":"109","article-title":"Comparison of epidemiological and antibiotic susceptibility pattern of metallo\u2010Beta\u2010lactamase\u2010positive and metallo\u2010Beta\u2010lactamase\u2010negative strains of Pseudomonas aeruginosa","volume":"2","author":"Ranjan S","year":"2014","journal-title":"J Lab Physicians"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2010.08.003"},{"key":"e_1_2_8_29_1","first-page":"3346","article-title":"Activity of plazomicin compared with other aminoglycosides against isolates from European and adjacent countries, including Enterobacteriaceae molecularly characterized for aminoglycoside\u2010modifying enzymes and other resistance mechanisms","volume":"12","author":"Castanheira M","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2010.07.021"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1086\/428052"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02676-15"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00517-17"},{"key":"e_1_2_8_34_1","first-page":"3322","article-title":"Deciphering beta\u2010lactamase\u2010independent beta\u2010lactam resistance evolution trajectories in Pseudomonas aeruginosa","volume":"12","author":"Cabot G","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05150-14"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13756-018-0388-z"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-015-0926-5"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-019-4363-y"},{"issue":"1","key":"e_1_2_8_39_1","first-page":"79","article-title":"Risk factors for hospitalized patients with resistant or multidrug\u2010resistant Pseudomonas aeruginosa infections: a systematic review and meta\u2010analysis. Antimicrob Resist","volume":"7","author":"Raman G","year":"2018","journal-title":"Infect Control"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2017.06.009"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03419-14"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw353"},{"key":"e_1_2_8_43_1","first-page":"78","article-title":"Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa: guidelines by the Spanish Society of Chemotherapy","volume":"1","author":"Mensa J","year":"2018","journal-title":"Rev Esp Quimioter"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.05041-11"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.115.2.462"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2007.08.007"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00338-07"},{"issue":"322","key":"e_1_2_8_48_1","first-page":"e7","article-title":"The adequacy of timely empiric antibiotic therapy for ventilator\u2010associated pneumonia: an important determinant of outcome","volume":"3","author":"Muscedere JG","year":"2012","journal-title":"J Crit Care"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-012-1758-8"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00093010"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhin.2006.12.019"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.CCM.0000217961.75225.E9"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-017-4683-6"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.7573\/dic.212527"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky267"},{"key":"e_1_2_8_56_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.diagmicrobio.2018.04.012","article-title":"Antimicrobial Susceptibility of Enterobacteriaceae and Pseudomonas aeruginosa Isolates from United States Medical Centers Stratified by Infection Type: results from the International Network for Optimal Resistance Monitoring (INFORM) Surveillance Program, 2015\u20132016","volume":"1","author":"Sader HS","year":"2018","journal-title":"Diagn Microbiol Infect Dis"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01587-18"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhm.869"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2009.11.026"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000002836"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30615-1"},{"key":"e_1_2_8_62_1","article-title":"In vitro activity of imipenem\/relebactam and ceftolozane\/tazobactam against clinical isolates of gram\u2010negative bacilli with difficult\u2010to\u2010treat resistance and multidrug\u2010resistant phenotypes\u2013SMART United States 2015\u20132017 [published online ahead of print April 3, 2020]","author":"Karlowsky JA","journal-title":"Clin Infect Dis"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix014"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix182"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2018.01.016"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2016.11.005"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02136-16"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz816"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-018-3535-y"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2018.07.010"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy280"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2018.11.001"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1622"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-013-0013-7"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.11.074"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw243"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01752-10"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00834-09"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2009.03.021"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01282-16"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00220-16"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01858-17"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00875-17"},{"key":"e_1_2_8_84_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz522"},{"key":"e_1_2_8_85_1","first-page":"ofz149","article-title":"Randomized trial of Ceftazidime\u2010Avibactam vs Meropenem for Treatment of Hospital\u2010Acquired and Ventilator\u2010Associated Bacterial Pneumonia (REPROVE): analyses per US FDA\u2010Specified End Points","volume":"4","author":"Torres A","year":"2019","journal-title":"Open Forum Infect Dis"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2018.04.011"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz668"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30403-7"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0851-9"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz191"},{"key":"e_1_2_8_91_1","volume-title":"Recarbrio (imipenem, cilastatin, and relebactam) package insert","author":"Merck and Co, Inc","year":"2019"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2019.05.001"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz133"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12866-019-1522-7"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz530"},{"key":"e_1_2_8_96_1","volume-title":"Fetroja (cefiderocol) package insert","author":"Shionogi, Inc.","year":"2019"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2018.11.007"},{"key":"e_1_2_8_98_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.ijantimicag.2018.10.007","article-title":"In vitro activity of cefiderocol, a siderophore cephalosporin, against a recent collection of clinically relevant carbapenem\u2010non\u2010susceptible Gram\u2010negative bacilli, including serine carbapenemase\u2010 and metallo\u2010beta\u2010lactamase\u2010producing isolates (SIDERO\u2010WT\u20102014 Study)","volume":"2","author":"Kazmierczak KM","year":"2019","journal-title":"Int J Antimicrob Agents"},{"key":"e_1_2_8_99_1","doi-asserted-by":"crossref","unstructured":"LongshawC TsujiM HackelM SahmDF YamanoY.In vitro activity of cefiderocol (CFDC) a novel siderophore cephalosporin against difficult\u2010to\u2010treat resistant (DTR) gram\u2010negative bacterial pathogens from the multi\u2010national sentinel surveillance study SIDERO\u2010WT (2014\u20132017) [poster]. Presented at Infectious Diseases Week 2019.Washington DC October 2\u20136 2019.","DOI":"10.1093\/ofid\/ofz360.747"},{"key":"e_1_2_8_100_1","unstructured":"Shionogi Inc.Antimicrobial Drugs Advisory Committee Cefiderocol Briefing Document. Available fromhttps:\/\/www.fda.gov\/media\/131705\/download. Accessed March 11 2020."},{"key":"e_1_2_8_101_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004090740"},{"key":"e_1_2_8_102_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2209"},{"key":"e_1_2_8_103_1","doi-asserted-by":"publisher","DOI":"10.4187\/respcare.04208"},{"key":"e_1_2_8_104_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy1054"},{"key":"e_1_2_8_105_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-019-03467-5"},{"key":"e_1_2_8_106_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix767"},{"key":"e_1_2_8_107_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz223"},{"key":"e_1_2_8_108_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw378"},{"key":"e_1_2_8_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)62220-0"},{"key":"e_1_2_8_110_1","volume-title":"Performance standards for antimicrobial susceptibility testing: twenty\u2010ninth informal supplement","author":"Clinical Laboratory and Standards Institute","year":"2019"},{"key":"e_1_2_8_111_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01426-19"},{"key":"e_1_2_8_112_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01989-12"},{"key":"e_1_2_8_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2014.07.007"},{"key":"e_1_2_8_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2007.07.024"},{"key":"e_1_2_8_115_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02134-16"},{"key":"e_1_2_8_116_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.2193"},{"key":"e_1_2_8_117_1","volume-title":"Avycaz (ceftazidime and avibactam) package insert","author":"Allergan","year":"2019"},{"key":"e_1_2_8_118_1","unstructured":"Merck and Co Inc.Zerbaxa (ceftolozane\/tazobactam) package insert.Whitehouse Station NJ;2019."}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.2449","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/phar.2449","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.2449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:39:33Z","timestamp":1761053973000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.2449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,17]]},"references-count":117,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1002\/phar.2449"],"URL":"https:\/\/doi.org\/10.1002\/phar.2449","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,17]]},"assertion":[{"value":"2020-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}