{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T01:19:09Z","timestamp":1768526349139,"version":"3.49.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,3,29]],"date-time":"2019-03-29T00:00:00Z","timestamp":1553817600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["K12-HD000850"],"award-info":[{"award-number":["K12-HD000850"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["U54-HD090259"],"award-info":[{"award-number":["U54-HD090259"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["U01-AI124316"],"award-info":[{"award-number":["U01-AI124316"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Infections caused by New Delhi metallo-\u03b2-lactamase (NDM)\u2013producing strains of multidrug-resistant Klebsiella pneumoniae are a global public health threat lacking reliable therapies. NDM is impervious to all existing \u03b2-lactamase inhibitor (BLI) drugs, including the non\u2013\u03b2-lactam BLI avibactam (AVI). Though lacking direct activity against NDMs, AVI can interact with penicillin-binding protein 2 in a manner that may influence cell wall dynamics. We found that exposure of NDM-1\u2013producing K. pneumoniae to AVI led to striking bactericidal interactions with human cathelicidin antimicrobial peptide LL-37, a frontline component of host innate immunity. Moreover, AVI markedly sensitized NDM-1\u2013producing K. pneumoniae to killing by freshly isolated human neutrophils, platelets, and serum when complement was active. Finally, AVI monotherapy reduced lung counts of NDM-1\u2013producing K. pneumoniae in a murine pulmonary challenge model. AVI sensitizes NDM-1\u2013producing K. pneumoniae to innate immune clearance in ways that are not appreciated by standard antibiotic testing and that merit further study.<\/jats:p>","DOI":"10.1093\/infdis\/jiz128","type":"journal-article","created":{"date-parts":[[2019,3,25]],"date-time":"2019-03-25T20:17:34Z","timestamp":1553545054000},"page":"484-493","source":"Crossref","is-referenced-by-count":26,"title":["Avibactam Sensitizes Carbapenem-Resistant NDM-1\u2013Producing Klebsiella pneumoniae to Innate Immune Clearance"],"prefix":"10.1093","volume":"220","author":[{"given":"Erlinda R","family":"Ulloa","sequence":"first","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, La Jolla"},{"name":"Division of Infectious Disease, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Pennsylvania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Dillon","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, La Jolla"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Tsunemoto","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of California\u2013San Diego, La Jolla"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joe","family":"Pogliano","sequence":"additional","affiliation":[{"name":"Division of Biological Sciences, University of California\u2013San Diego, La Jolla"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George","family":"Sakoulas","sequence":"additional","affiliation":[{"name":"Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, La Jolla"},{"name":"Sharp Healthcare System, San Diego, 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