{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:12:45Z","timestamp":1791421965474,"version":"4.3.3"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"41","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,10,11]]},"abstract":"<jats:p>\n                    Known mechanisms of resistance to \u03b2-lactam antibiotics include \u03b2-lactamase expression, altered drug target, decreased bacterial permeability, and increased drug efflux. Here, we describe a unique mechanism of \u03b2-lactam resistance in the biothreat organism\n                    <jats:italic>Burkholderia pseudomallei<\/jats:italic>\n                    (the cause of melioidosis), associated with treatment failure during prolonged ceftazidime therapy of natural infection. Detailed comparisons of the initial ceftazidime-susceptible infecting isolate and subsequent ceftazidime-resistant variants from six patients led us to identify a common, large-scale genomic loss involving a minimum of 49 genes in all six resistant strains. Mutational analysis of wild-type\n                    <jats:italic>B. pseudomallei<\/jats:italic>\n                    demonstrated that ceftazidime resistance was due to deletion of a gene encoding a penicillin-binding protein 3 (BPSS1219) present within the region of genomic loss. The clinical ceftazidime-resistant variants failed to grow using commonly used laboratory culture media, including commercial blood cultures, rendering the variants almost undetectable in the diagnostic laboratory. Melioidosis is notoriously difficult to cure and clinical treatment failure is common in patients treated with ceftazidime, the drug of first choice across most of Southeast Asia where the majority of cases are reported. The mechanism described here represents an explanation for ceftazidime treatment failure, and may be a frequent but undetected resistance event.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1111020108","type":"journal-article","created":{"date-parts":[[2011,10,4]],"date-time":"2011-10-04T00:09:41Z","timestamp":1317686981000},"page":"17165-17170","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":113,"title":["Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in\n                    <i>Burkholderia pseudomallei<\/i>"],"prefix":"10.1073","volume":"108","author":[{"given":"Narisara","family":"Chantratita","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;"},{"name":"Mahidol\u2013Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Drew A.","family":"Rholl","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, Rocky Mountain Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, Colorado State University, Fort Collins, CO 80523-0922;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernice","family":"Sim","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore, Singapore 138672, Republic of Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanaporn","family":"Wuthiekanun","sequence":"additional","affiliation":[{"name":"Mahidol\u2013Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Direk","family":"Limmathurotsakul","sequence":"additional","affiliation":[{"name":"Mahidol\u2013Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;"},{"name":"Department of Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Premjit","family":"Amornchai","sequence":"additional","affiliation":[{"name":"Mahidol\u2013Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aunchalee","family":"Thanwisai","sequence":"additional","affiliation":[{"name":"Mahidol\u2013Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Hoon","family":"Chua","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore, Singapore 138672, Republic of Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen Fong","family":"Ooi","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore, Singapore 138672, Republic of Singapore;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew T. G.","family":"Holden","sequence":"additional","affiliation":[{"name":"The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas P.","family":"Day","sequence":"additional","affiliation":[{"name":"Mahidol\u2013Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;"},{"name":"Center for Clinical Vaccinology and Tropical Medicine, Nuffield Department of Clinical Medicine, University of Oxford, Headington, Oxford OX3 7LJ, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Tan","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore, Singapore 138672, Republic of Singapore;"},{"name":"Duke\u2013National University of Singapore Graduate Medical School, Singapore 169547, Republic of Singapore; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herbert P.","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Pathology, Rocky Mountain Regional Center of Excellence for Biodefense and Emerging Infectious Diseases Research, Colorado State University, Fort Collins, CO 80523-0922;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon J.","family":"Peacock","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;"},{"name":"Mahidol\u2013Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand;"},{"name":"The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom;"},{"name":"Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2011,10,3]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/S0163-4453(09)60003-7","article-title":"Infections caused by Gram-positive bacteria: A review of the global challenge","volume":"59","author":"Woodford N","year":"2009","unstructured":"N Woodford, DM Livermore, Infections caused by Gram-positive bacteria: A review of the global challenge. 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