• One important revision is the distinction between low, increased and high risk of infection with Enterobacterales resistant to third generation cephalosporins (3GRC-E) to guide the choice of empirical therapy. 3GCR-E is often used as a proxy for ESBL-production. The committee recommends covering 3GCR-E in patients if prior (1-year) culture revealed 3GCR-E. In patients without prior (1-year) cultures showing 3GCR-E the decision to empirically cover 3GCR-E should be made on an individual patient basis, taking into account multiple risk factors

• The choice of empirical antibacterial treatment of sepsis is dictated by the likelihood of involvement of a resistant causative pathogen, by the desire to prevent overuse of reserve antibiotics from a stewardship perspective and by risks of toxicity and other potential adverse events for the patient. Strong recommendations on the best empirical treatment in sepsis based on the currently available literature cannot be given since only subtle differences between strategies on clinical outcomes are found in studies that were also frequently not generalizable to the Dutch clinical setting. Every strategy has advantages and disadvantages depending on the mentioned perspectives (resistance epidemiology, pharmacokinetic/pharmacodynamic (PK/PD) properties, antibiotic stewardship, adverse events). Consequently, the committee provided pragmatic suggestions for empirical treatment choices in patients with sepsis based on current evidence, reported resistance rates nationally, the antibiotic stewardship perspective and risk of adverse events

• In patients with sepsis, we generally recommend using a beta-lactam antibiotic covering the most likely involved pathogens. Also, we recommend covering pathogens in prior (1-year) relevant cultures in general. We added suggestions on empirical therapy in case Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus spp are considered

• We provided new suggestions for empirical therapy in patients with sepsis and a reported penicillin allergy

• Regarding the duration of therapy, we generally recommended shorter treatment durations of patients with sepsis than the previous guidelines. The committee also underscores the responsibility of clinicians to de-escalate antibacterial therapy in patients with sepsis. Due to toxicity concerns, we strongly recommend stopping empirical aminoglycoside treatment after 2 days

• Among recommendations on PK/PD considerations in patients with sepsis, the committee strongly recommends continuous or prolonged infusion of piperacillin-tazobactam and meropenem based on high quality evidence. Therapeutic drug monitoring is recommended for all patients on aminoglycoside and vancomycin treatment