|Step 1 The clinical question||Define A) the clinical syndrome for which empiric treatment is re-evaluated, B) the patient population and C) the current empiric treatment guideline.||The clinical syndrome is sepsis. The target patient population is adult patients in an academic medical center. The current empiric treatment for sepsis is C-2GC-AG.|
|Step 2 Susceptibility data||Determine the local prevalence of resistance to the current empiric treatment (syndrome and population specific).||Of all patients with suspected sepsis, 6.7% are diagnosed with Gram-negative bacteremia.* Gram-negative resistance for C-2GC-AG in blood culture isolates is 8.8%. In the study center. Methicillin resistant Staphylococcus aureus (MRSA) and penicillin resistant pneumococcal species are very rare in the Netherlands.|
|Step 3 Definition of risk factors||Identify available predictors for resistance to the current empiric treatment.||Independent risk factors of resistance to empiric sepsis therapy in the study population are prior antimicrobial use and prior isolates with a DRP.|
|Step 4 Targeted strategies||Identify potential targeted treatment strategies.||
Option A: A carbapenem in patients with a DRP cultured the previous 6 months and C-2GC-AG in other patients.|
Option B: a carbapenem in all patients with sepsis.
|Step 5 Estimating benefit||Estimate the proportion of patients that would be adequately treated if empiric sepsis therapy was changed.||
Option A: 95.2% of Gram-negative bloodstream infections would be treated adequately.|
Option B: 99.8% of Gram-negative bloodstream infections would be treated adequately.
|Step 6 Estimating costs||Identify the number needed to treat (NNTC).||
Option A: NNTC is 42 patients.|
Option B: NNTC is 173 patients.
|Step 7 Selection of empiric treatment strategy||Balance the cost and benefits of phase 5 and 6 to select the most appropriate strategy.||A moral deliberation with stakeholders was performed to decide on the most appropriate antibiotic therapy for sepsis in the institution. Option A was selected.|
|Implementation and evaluation||Evaluate the costs and benefits of the selected approach.||After implementation of strategy A, adequacy rates, outcome, side-effects of antimicrobials and antimicrobial consumption were evaluated.|