AbstractIntroductionTreatment of infections in patients with burn injuries is challenging due to altered antimicrobial pharmacokinetics. Continuous infusion β‐lactam therapy may be a useful antimicrobial stewardship strategy to improve pharmacodynamic target attainment in this population.Case SummariesThis report highlights the use of continuous infusion ceftolozane/tazobactam (C/T) in two patients with extensive total body surface area (TBSA) burns, suspected augmented renal clearance (ARC), and bloodstream infections caused by Pseudomonas aeruginosa with difficult‐to‐treat resistance (DTR P. aeruginosa). Both patients received C/T 9 g/day via continuous infusion. Minimum inhibitory concentrations (MIC) of C/T were 8/4 and 4/4 μg/mL in Cases 1 and 2, respectively.DiscussionDespite similar patient characteristics, average free plasma ceftolozane concentrations were 41.6 mg/L in Case 1 and 22.8 mg/L in Case 2. Measured free concentrations exceeded 4 times the MIC for 100% of each 24‐h infusion (fT > 4xMIC), and bacteremia was successfully cleared in each case.ConclusionThese cases highlight the variability of drug exposure in patients with extensive TBSA burn injuries and support continuous infusion β‐lactam therapy as a proactive strategy to optimize pharmacodynamic target attainment when pharmacokinetics are unpredictable.