{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:07:39Z","timestamp":1791266859910,"version":"4.1.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T00:00:00Z","timestamp":1533081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["F32 AI124590"],"award-info":[{"award-number":["F32 AI124590"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["UL1 TR001102"],"award-info":[{"award-number":["UL1 TR001102"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The observed MIC may depend on the number of bacteria initially inoculated into the assay. This phenomenon is termed the inoculum effect (IE) and is often most pronounced for \u03b2-lactams in strains expressing \u03b2-lactamase enzymes. The Clinical and Laboratory Standards Institute (CLSI)-recommended inoculum is 5 \u00d7 10\n            <jats:sup>5<\/jats:sup>\n            CFU ml\n            <jats:sup>\u22121<\/jats:sup>\n            with an acceptable range of 2 \u00d7 10\n            <jats:sup>5<\/jats:sup>\n            to 8 \u00d7 10\n            <jats:sup>5<\/jats:sup>\n            CFU ml\n            <jats:sup>\u22121<\/jats:sup>\n            . IE testing is typically performed using an inoculum 100-fold greater than the CLSI-recommended inoculum. Therefore, it remains unknown whether the IE influences MICs during testing performed according to CLSI guidelines. Here, we utilized inkjet printing technology to test the IE on cefepime, meropenem, and ceftazidime-avibactam. First, we determined that the inkjet dispense volume correlated well with the number of bacteria delivered to microwells in 2-fold (\n            <jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\n            = 0.99) or 1.1-fold (\n            <jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\n            = 0.98) serial dilutions. We then quantified the IE by dispensing orthogonal titrations of bacterial cells and antibiotics. For cefepime-resistant and susceptible dose-dependent strains, a 2-fold increase in inoculum resulted in a 1.6 log\n            <jats:sub>2<\/jats:sub>\n            -fold increase in MIC. For carbapenemase-producing strains, each 2-fold reduction in inoculum resulted in a 1.26 log\n            <jats:sub>2<\/jats:sub>\n            -fold reduction in meropenem MIC. At the lower end of the CLSI-allowable inoculum range, minor error rates of 34.8% were observed for meropenem when testing a resistant-strain set. Ceftazidime-avibactam was not subject to an appreciable IE. Our results suggest that IE is sufficiently pronounced for meropenem and cefepime in multidrug-resistant Gram-negative pathogens to affect categorical interpretations during standard laboratory testing.\n          <\/jats:p>","DOI":"10.1128\/aac.00433-18","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T09:34:03Z","timestamp":1526895243000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":115,"title":["The Inoculum Effect in the Era of Multidrug Resistance: Minor Differences in Inoculum Have Dramatic Effect on MIC Determination"],"prefix":"10.1128","volume":"62","author":[{"given":"Kenneth P.","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Kirby","sequence":"additional","affiliation":[{"name":"Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA"},{"name":"Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/11.3.361"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12677"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1198-743x.2001.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/20.2.191"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/514619"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.9.3.440"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.24.4.568"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.13.2.249"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.1.403-409.2003"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.4.808"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.33.5.1302-1307.1995"},{"key":"e_1_3_2_13_2","volume-title":"CLSI document M07-A10","author":"Clinical and Laboratory Standards Institute","year":"2015","unstructured":"Clinical and Laboratory Standards Institute. 2015. 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