{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:23:19Z","timestamp":1780503799054,"version":"3.54.1"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019089","name":"Alberta Precision Laboratories","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019089","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2023,12,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            is the most prevalent cystic fibrosis (CF) pathogen. Several phenotypes are associated with worsened CF clinical outcomes including methicillin-resistance and small-colony-variants. The inoculum effect (IE) is characterized by reduced \u03b2-lactam susceptibility when assessed at high inoculum. The IE associates with worse outcomes in bacteremia and other high-density infections, and may therefore be relevant to CF. The prevalence of IE amongst a CF cohort (age \u226518 years), followed from 2013 to 2016, was investigated. Yearly methicillin-sensitive\n            <jats:italic>S. aureus<\/jats:italic>\n            (MSSA) isolates were screened at standard (5 \u00d7 10\n            <jats:sup>5<\/jats:sup>\n            CFU\/mL) and high (5 \u00d7 10\n            <jats:sup>7<\/jats:sup>\n            CFU\/mL) inoculum against narrow-spectrum anti-Staphylococcal \u03b2-lactams and those with anti-pseudomonal activity common to CF. A \u2265 4-fold increase in minimum inhibitory concentration between standard and high inoculum defined IE. Isolates underwent\n            <jats:italic>blaZ<\/jats:italic>\n            sequencing and genotyping and were compared against published genomes. Fifty-six percent (99\/177) of individuals had MSSA infection. MSSA was observed at \u226510\n            <jats:sup>5<\/jats:sup>\n            CFU\/mL in 44.8% of entry sputum samples. The prevalence of the IE was 25.0%-cefazolin; 13.5%-cloxacillin; 0%-meropenem; 1.0%-cefepime; 5.2%-ceftazidime; and 34.4%-piperacillin-tazobactam amongst baseline MSSA isolates assessed.\n            <jats:italic>blaZ<\/jats:italic>\n            A associated with cefazolin IE (\n            <jats:italic>P<\/jats:italic>\n            = 0.0011), whereas\n            <jats:italic>blaZ<\/jats:italic>\n            C associated with piperacillin-tazobactam IE (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001). Baseline demographics did not reveal specific risk factors for IE-associated infections, nor were long-term outcomes different. Herein, we observed the IE in CF-derived MSSA disproportionally for cefazolin and piperacillin-tazobactam and this phenotype strongly associated with underlying\n            <jats:italic>blaZ<\/jats:italic>\n            genotype. The confirmation of CF being a high density infection, and the identification of high prevalence of MSSA with IE in CF supports the need for prospective pulmonary exacerbation treatment studies to understand the impact of this phenotype.\n          <\/jats:p>","DOI":"10.1128\/aac.00136-23","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T14:01:18Z","timestamp":1700056878000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Epidemiology and impact of methicillin-sensitive\n            <i>Staphylococcus aureus<\/i>\n            with \u03b2-lactam antibiotic inoculum effects in adults with cystic fibrosis"],"prefix":"10.1128","volume":"67","author":[{"given":"J.","family":"Svishchuk","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Ebbert","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Waddell","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Izydorczyk","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Acosta","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Somayaji","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Medicine, University of Calgary and Alberta Health Services, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. R.","family":"Rabin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. L.","family":"Bjornson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Lisboa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Calgary and Alberta Health Services, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. B.","family":"Gregson","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary and Alberta Health Services, Calgary, Alberta, Canada"},{"name":"Department of Pathology and Laboratory Medicine, University of Calgary and Alberta Health Services, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"Conly","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada"},{"name":"Department of Medicine, University of Calgary and Alberta Health Services, Calgary, Alberta, Canada"},{"name":"Department of Pathology and Laboratory Medicine, University of Calgary and Alberta Health Services, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0086-4995","authenticated-orcid":false,"given":"M. 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