{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:28:34Z","timestamp":1787016514501,"version":"build-2736575974"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","award":["R01AI173064"],"award-info":[{"award-number":["R01AI173064"]}]},{"name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","award":["R21AI182709"],"award-info":[{"award-number":["R21AI182709"]}]},{"name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","award":["U19AI135964"],"award-info":[{"award-number":["U19AI135964"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Meropenem\/vaborbactam is a preferred treatment option for KPC-producing\n                      <jats:italic toggle=\"yes\">Klebsiella pneumoniae<\/jats:italic>\n                      (KPC-Kp) infections, but clinical cure rates remain suboptimal when it is used alone. This study aimed to assess the pharmacodynamic activity of meropenem\/vaborbactam alone and in combination with an aminoglycoside in the hollow fiber infection model (HFIM). The HFIM was used to simulate meropenem\/vaborbactam and aminoglycoside pharmacokinetic profiles that approximated antibiotic exposures in the plasma and lung epithelial lining fluid (ELF) following human doses against four meropenem\/vaborbactam-susceptible KPC-Kp isolates. Two isolates had lower meropenem\/vaborbactam MICs (0.125\/8 to 0.25\/8 mg\/L; NU-CRE105 and NU-CRE244), and two had higher MICs (2\/8 mg\/L; AR-1049 and AR-1054). Against NU-CRE105 and NU-CRE244, meropenem\/vaborbactam was bactericidal and caused &gt;5.7 log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/mL reductions by 48 h. Antibiotic exposures mimicking those in plasma and ELF yielded similar bacterial killing. Despite the robust activity of meropenem\/vaborbactam alone, combinations with an aminoglycoside were synergistic, providing \u22652 log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/mL better killing of NU-CRE105 and NU-CRE244 than either monotherapy for ~40% of the experiment. Against AR-1049 and AR-1054, meropenem\/vaborbactam monotherapy mimicking ELF exposures generated 2.9\u20135.2 log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/mL reductions at 48 h. However, meropenem\/vaborbactam resistance emerged by 168 h. Combinations with an aminoglycoside displayed 4.7\u20137.5 log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/mL greater killing than either monotherapy at 168 h and repressed meropenem\/vaborbactam resistance. Meropenem\/vaborbactam remains an important agent against KPC-Kp. However, pneumonia caused by KPC-Kp isolates with MICs near the susceptibility breakpoint (\u22644\/8 mg\/L) may reduce the pharmacodynamic activity of meropenem\/vaborbactam and permit resistance to emerge. Aminoglycosides represent a promising adjunct to meropenem\/vaborbactam for select KPC-Kp isolates, owing to their capacity to enhance bacterial killing and suppress resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.01365-25","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T15:07:51Z","timestamp":1771513671000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Aminoglycosides enhance meropenem\/vaborbactam activity against KPC-producing\n                    <i>Klebsiella pneumoniae<\/i>\n                    in the hollow fiber infection model"],"prefix":"10.1128","volume":"70","author":[{"given":"Nidhi","family":"Singh","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02mpq6x41","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Practice, Retzky College of Pharmacy, University of Illinois Chicago","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christin M. 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