{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T22:59:41Z","timestamp":1788303581879,"version":"build-2803163510"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,22]],"date-time":"2022-10-22T00:00:00Z","timestamp":1666396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"the Ministerio de Econom\u00eda y Competitividad of Spain, Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/00251"],"award-info":[{"award-number":["PI17\/00251"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"the Ministerio de Econom\u00eda y Competitividad of Spain, Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["138\/U\/2018"],"award-info":[{"award-number":["138\/U\/2018"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Marato TV3","award":["PI17\/00251"],"award-info":[{"award-number":["PI17\/00251"]}]},{"name":"the Marato TV3","award":["138\/U\/2018"],"award-info":[{"award-number":["138\/U\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>This study correlates in vivo findings in a patient with an extensively drug-resistant (XDR) P. aeruginosa infection who developed resistance to ceftazidime-avibactam (CAZ-AVI) with in vitro results of a 7-day hollow-fiber infection model (HFIM) testing the same bacterial strain. The patient was critically ill with ventilator-associated pneumonia caused by XDR P. aeruginosa ST175 with CAZ-AVI MIC of 6 mg\/L and was treated with CAZ-AVI in continuous infusion at doses adjusted for renal function. Plasma concentrations of CAZ-AVI were analyzed on days 3, 7, and 10. In the HIFM, the efficacy of different steady-state concentrations (Css) of CAZ-AVI (12, 18, 30 and 48 mg\/L) was evaluated. In both models, a correlation was observed between the decreasing plasma levels of CAZ-AVI and the emergence of resistance. In the HIFM, a Css of 30 and 48 mg\/L (corresponding to 5\u00d7 and 8\u00d7 MIC) had a bactericidal effect without selecting resistant mutants, whereas a Css of 12 and 18 mg\/L (corresponding to 2\u00d7 and 3\u00d7 MIC) failed to prevent the emergence of resistance. CAZ\/AVI resistance development was caused by the selection of a single ampC mutation in both patient and HFIM. Until further data are available, strategies to achieve plasma CAZ-AVI levels at least 4\u00d7 MIC could be of interest, particularly in severe and high-inoculum infections caused by XDR P. aeruginosa with high CAZ-AVI MICs.<\/jats:p>","DOI":"10.3390\/antibiotics11111456","type":"journal-article","created":{"date-parts":[[2022,10,23]],"date-time":"2022-10-23T20:43:50Z","timestamp":1666557830000},"page":"1456","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Suboptimal Concentrations of Ceftazidime\/Avibactam (CAZ-AVI) May Select for CAZ-AVI Resistance in Extensively Drug-Resistant Pseudomonas aeruginosa: In Vivo and In Vitro Evidence"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2675-4412","authenticated-orcid":false,"given":"Inmaculada","family":"Lopez-Montesinos","sequence":"first","affiliation":[{"name":"Infectious Diseases Service, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"},{"name":"Department of Medicine, Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Spain"},{"name":"Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra Barcelona, 08002 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Milagro","family":"Montero","sequence":"additional","affiliation":[{"name":"Infectious Diseases Service, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"},{"name":"Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra Barcelona, 08002 Barcelona, Spain"},{"name":"CIBER of Infectious Diseases (CIBERINFEC CB21\/13\/00002 and CB21\/13\/00099), Institute of Health Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Domene-Ochoa","sequence":"additional","affiliation":[{"name":"Infectious Diseases Service, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"},{"name":"Department of Medicine, Universitat Aut\u00f2noma de Barcelona (UAB), 08193 Bellaterra, Spain"},{"name":"Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra Barcelona, 08002 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"L\u00f3pez-Causap\u00e9","sequence":"additional","affiliation":[{"name":"CIBER of Infectious Diseases (CIBERINFEC CB21\/13\/00002 and CB21\/13\/00099), Institute of Health Carlos III, 28029 Madrid, Spain"},{"name":"Servicio de Microbiolog\u00eda y Unidad de Investigaci\u00f3n, Hospital Son Espases, IdISBa, 07120 Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4975-8798","authenticated-orcid":false,"given":"Daniel","family":"Echeverria","sequence":"additional","affiliation":[{"name":"Pharmacy Service, Hospital del Mar, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Sorl\u00ed","sequence":"additional","affiliation":[{"name":"Infectious Diseases Service, Hospital del Mar, 08003 Barcelona, Spain"},{"name":"Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"},{"name":"Department of Medicine and Life Sciences (MELIS), Universitat Pompeu Fabra Barcelona, 08002 Barcelona, Spain"},{"name":"CIBER of Infectious Diseases (CIBERINFEC CB21\/13\/00002 and CB21\/13\/00099), Institute of Health Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Campillo","sequence":"additional","affiliation":[{"name":"Pharmacy Service, Hospital del Mar, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Luque","sequence":"additional","affiliation":[{"name":"Infectious Pathology and Antimicrobials Research Group (IPAR), Institut Hospital del Mar d\u2019Investigacions M\u00e8diques (IMIM), 08003 Barcelona, Spain"},{"name":"CIBER of Infectious Diseases (CIBERINFEC CB21\/13\/00002 and CB21\/13\/00099), Institute of Health Carlos III, 28029 Madrid, Spain"},{"name":"Pharmacy Service, Hospital del Mar, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Padilla","sequence":"additional","affiliation":[{"name":"Microbiology Service, Laboratori de Refer\u00e8ncia de Catalunya, 08820 Barcelona, 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