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The Cefazolin Inoculum Effect Is Associated With Increased Mortality in Methicillin-Susceptible Staphylococcus aureus Bacteremia

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dc.contributor.author Miller, William R.
dc.contributor.author Seas, Carlos
dc.contributor.author Carvajal, Lina P.
dc.contributor.author Diaz, Lorena
dc.contributor.author Echeverri, Aura M.
dc.contributor.author Ferro, Carolina
dc.contributor.author Rios, Rafael
dc.contributor.author Porras, Paola
dc.contributor.author Luna, Carlos
dc.contributor.author Gotuzzo, Eduardo
dc.contributor.author Munita, Jose M.
dc.contributor.author Nannini, Esteban
dc.contributor.author Carcamo, Cesar
dc.contributor.author Reyes, Jinnethe
dc.contributor.author Arias, Cesar A.
dc.date.accessioned 2018-08-10T20:11:15Z
dc.date.available 2018-08-10T20:11:15Z
dc.date.issued 2018
dc.identifier.uri https://hdl.handle.net/20.500.12866/3769
dc.description.abstract Background: Recent studies have favored the use of cefazolin over nafcillin for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. The clinical influence of the cefazolin inoculum effect (CzIE) in the effectiveness of cephalosporins for severe MSSA infections has not been evaluated. Methods: We prospectively included patients from 3 Argentinian hospitals with S. aureus bacteremia. Cefazolin minimum inhibitory concentrations (MICs) were determined at standard (105 colony-forming units [CFU]/mL) and high (107 CFU/mL) inoculum. The CzIE was defined as an increase of MIC to ≥16 µg/mL when tested at high inoculum. Whole-genome sequencing was performed in all isolates. Results: A total of 77 patients, contributing 89 MSSA isolates, were included in the study; 42 patients (54.5%) had isolates with the CzIE. In univariate analysis, patients with MSSA exhibiting the CzIE had increased 30-day mortality (P = .034) and were more likely to have catheter-associated or unknown source of bacteremia (P = .033) compared with patients infected with MSSA isolates without the CzIE. No statistically significant difference between the groups was observed in age, clinical illness severity, place of acquisition (community vs hospital), or presence of endocarditis. The CzIE remained associated with increased 30-day mortality in multivariate analysis (risk ratio, 2.65; 95% confidence interval, 1.10–6.42; P = .03). MSSA genomes displayed a high degree of heterogeneity, and the CzIE was not associated with a specific lineage. Conclusions: In patients with MSSA bacteremia where cephalosporins are used as firstline therapy, the CzIE was associated with increased 30-day mortality. Clinicians should be cautious when using cefazolin as firstline therapy for these infections. en_US
dc.language.iso eng
dc.publisher Oxford University Press
dc.relation.ispartof urn:issn:2328-8957
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Cephalosporins en_US
dc.subject Endocarditis en_US
dc.subject Inoculum effect en_US
dc.subject Methicillin-susceptible Staphylococcus aureus en_US
dc.title The Cefazolin Inoculum Effect Is Associated With Increased Mortality in Methicillin-Susceptible Staphylococcus aureus Bacteremia en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1093/ofid/ofy123
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08


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