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Adoption would decrease empiric selection of anti-MRSA (ward 27% to 1%; ICU 61% to 8%) and antipseudomonal (ward 25% to 1%; ICU 54% to 9%) therapies. This would correspond to greatly decreased MRSA overcoverage (ward 27% to 1%; ICU 56% to 8%), slightly increased MRSA undercoverage (ward 0.6% to 1.3%; ICU 0.5% to 3.3%), with similar findings for P. aeruginosa. For all comparisons, P  .001. Adoption of the 2019 CAP guidelines in this population would substantially change culturing and empiric antibiotic selection practices, with a dec