{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:28:42Z","timestamp":1789954122221,"version":"4.0.1"},"reference-count":11,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2016,11,25]],"date-time":"2016-11-25T00:00:00Z","timestamp":1480032000000},"content-version":"vor","delay-in-days":329,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI100560"],"award-info":[{"award-number":["R01AI100560"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI063517"],"award-info":[{"award-number":["R01AI063517"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI072219"],"award-info":[{"award-number":["R01AI072219"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cleveland Department of Veterans Affairs","award":["1I01BX001974"],"award-info":[{"award-number":["1I01BX001974"]}]},{"name":"Biomedical Laboratory Research & Development Service of the VA Office of Research and Development"},{"name":"and the Geriatric Research Education and Clinical Center"},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["UL1 RR024989"],"award-info":[{"award-number":["UL1 RR024989"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institutes of Health or the Department of Veterans Affairs"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Background. \u2003Successful treatment of infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa is thwarted by the emergence of antibiotic resistance and biofilm formation on prosthetic devices. Our aims were to decipher the molecular basis of resistance in a unique case of prosthetic valve endocarditis (PVE) caused by MDR P. aeruginosa.<\/jats:p>\n               <jats:p>Methods. \u2003Five sequential MDR P. aeruginosa blood isolates collected during a 7-month period were recovered from a patient suffering from PVE previously exposed to \u03b2-lactam antibiotics. Minimum inhibitory concentrations (MICs) of several classes of antibiotics were used to indicate clinical resistance characteristics; relatedness of the isolates was determined using multilocus sequence typing and repetitive sequence-based polymerase chain reaction. Amplification and sequencing of regulatory and resistance genes was performed.<\/jats:p>\n               <jats:p>Results. \u2003All isolates belonged to ST 298, possessed blaPDC-16, and were resistant to fluoroquinolones and carbapenems. In the course of therapy, we observed a &amp;gt;2-fold increase in cephalosporin resistance (4 \u00b5g\/mL to &amp;gt;16 \u00b5g\/mL). Sequencing of the AmpC regulator, ampR, revealed a D135N point mutation in cephalosporin-resistant isolates. Common carbapenemase genes were not identified. All isolates demonstrated a premature stop codon at amino acid 79 of the outer membrane protein OprD and mutations in the quinolone resistance-determining regions of gyrA and parC. Point mutations in nalC, an efflux pump regulator, were also observed.<\/jats:p>\n               <jats:p>Conclusions. \u2003In this analysis, we chart the molecular evolution of \u03b2-lactam resistance in a case of PVE. We show that mutations in regulatory genes controlling efflux and cephalosporinase production contributed to the MDR phenotype.<\/jats:p>","DOI":"10.1093\/ofid\/ofw188","type":"journal-article","created":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T02:50:07Z","timestamp":1477536607000},"source":"Crossref","is-referenced-by-count":27,"title":["Multidrug Resistant Pseudomonas aeruginosa Causing Prosthetic Valve Endocarditis: A Genetic-Based Chronicle of Evolving Antibiotic Resistance"],"prefix":"10.1093","volume":"3","author":[{"given":"T. Nicholas","family":"Domitrovic","sequence":"first","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center"},{"name":"Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Hujer","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center"},{"name":"Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Perez","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center"},{"name":"Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven H.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine M.","family":"Hujer","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department of Veterans Affairs Medical Center"},{"name":"Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila E.","family":"Woc-Colburn","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Parta","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Bonomo","sequence":"additional","affiliation":[{"name":"Louis Stokes Cleveland Department 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