{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:19:37Z","timestamp":1785410377089,"version":"3.56.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Carbapenem resistance in non-carbapenemase producing Enterobacterales can display susceptibility discordance (e.g., ertapenem-non-susceptible, meropenem-susceptible), often in patients with prior antimicrobial use. We aim to characterize risk factors for carbapenem susceptibility discordant Enterobacterales (CSD-E) bloodstream infections in immunocompromised patients. We performed a retrospective, single-center study comparing adults with Enterobacterales BSI who developed subsequent carbapenem susceptibility concordant (CSC; meropenem and ertapenem susceptible) or CSD-E BSI with the same organism within 1 year. Patients who developed subsequent CSD-E BSI were matched to those with repeat CSC-E BSI based on organism. Logistic regression models evaluated CSD-E risk factors. Time-varying covariate Cox proportional hazards models evaluated time-dependent changes in antibiotic exposure when estimating the association between antibiotic use and CSD-E. Comparative genomics of available paired whole-genome sequencing (WGS) data was performed to assess genetic relatedness and antimicrobial resistance (AMR) gene content. Beta-lactam survival mechanisms (BLSM) were assessed via Tolerance Disk Test (TDTest) and Population Analysis Profiling (PAP). We evaluated 829 patients with Enterobacterales BSI. Repeat BSI was CSC-E in 81 patients (9.8%) and CSD-E in 14 patients (1.7%). Matching provided 43 CSC-E controls and 14 CSD-E cases. Univariate analysis revealed any ceftazidime-avibactam (CZA) exposure was associated with developing CSD-E BSI (odds ratio [OR], 7.41;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.01). Time-varying covariate Cox regression identified each additional day of cefepime is associated with CSD-E BSI development (hazard ratio [HR], 1.055;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.016). Genomic data suggest beta-lactamase amplification and outer membrane porin mutations may be potential CSD-E development mechanisms. CSD-E BSI risk factors in immunocompromised patients may include any CZA exposure and cumulative cefepime exposure. Further studies are warranted to validate CSD-E risk factors.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>Non-carbapenemase-producing (non-CP) carbapenem-resistant Enterobacterales (CRE) are an important classification of CRE. Increasing rates of non-CP CRE that display carbapenem susceptibility discordance (CSD-E; ertapenem-resistant, meropenem susceptible) have been observed globally and at our institution. Our article aims to characterize risk factors, including cumulative antibiotic exposure, leading to carbapenem susceptibility discordant Enterobacterales (CSD-E) bloodstream infection (BSI) in immunocompromised patients with a history of Enterobacterales BSI. In addition, we analyzed paired whole-genome sequencing data to assess antimicrobial gene content for mechanistic rationales supporting our clinical findings. The risk factors for CSD-E development identified in this study require further validation in multicenter cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.02781-25","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T13:02:10Z","timestamp":1773320530000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Cumulative cefepime exposure in cancer patients is associated with an increased risk of ertapenem non-susceptible, meropenem susceptible Enterobacterales bacteremia"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4762-7824","authenticated-orcid":true,"given":"Alex V.","family":"Stabler","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pharmacy, The University of Texas MD Anderson Cancer Center","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8556-3248","authenticated-orcid":true,"given":"William C.","family":"Shropshire","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyson","family":"Young","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Feng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pharmacy Quality-Regulatory, The University of Texas MD Anderson Cancer Center","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0308-5145","authenticated-orcid":true,"given":"Hyunsoo","family":"Hwang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biostatistics, The University of Texas MD Anderson Cancer Center","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9721-263X","authenticated-orcid":true,"given":"Samuel A.","family":"Shelburne","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy N.","family":"Vuong","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pharmacy, The University of Texas MD Anderson Cancer Center","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6323-6211","authenticated-orcid":true,"given":"Jovan","family":"Borjan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Pharmacy, The University of Texas MD Anderson Cancer Center","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/657138"},{"key":"e_1_3_4_3_2","unstructured":"Centers for Disease Control and Prevention. 2019. Antibiotic resistance threats in the United States 2019. Available from: https:\/\/www.cdc.gov\/hai\/organisms\/cre\/cre-clinicians.html. Retrieved 29 Sep 2023."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab643"},{"key":"e_1_3_4_5_2","unstructured":"Centers for Disease Control and Prevention. 2019. Clinicians: information about CRE. Available from: https:\/\/www.cdc.gov\/hai\/organisms\/cre\/cre-clinicians.html. Retrieved 29 Sep 2023."},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.623574"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S219635"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11111670"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics13020185"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2018.08.001"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw741"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkae186"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30755-8"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa447"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.00476-22"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz360.1944"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz360.1924"},{"key":"e_1_3_4_18_2","volume-title":"Performance standards for antimicrobial susceptibility testing: approved thirty-fourth edition: document M100-ED34","author":"CLSI","year":"2024","unstructured":"CLSI. 2024. Performance standards for antimicrobial susceptibility testing: approved thirty-fourth edition: document M100-ED34. 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