Pharmacokinetics of Ceftolozane/Tazobactam in Patients With Partial- and Full-Thickness Skin Burns

Patients with burns are at an increased risk of multidrug-resistant pathogens including Pseudomonas aeruginosa and may need specialized dosing regimens due to alterations in physiology due to their injuries.

Therefore, we conducted a single-dose, open-label, pharmacokinetic study of ceftolozane (2 g)/tazobactam (1 g) infused over 60 min in six patients with partial- or full-thickness burns and central line access. Serial blood samples were obtained at the following time points: 0 (predose) and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 h following the start of infusion for determination of plasma drug concentrations.

Similar estimates of clearance (CL) were observed between the groups, and as a consequence the half-life (T1/2) was longer in the six patients with burns in the current study compared to previous studies of healthy volunteers on average. Although these mean comparisons suggest similarity in exposure based on area under the curve (AUC) and maximum concentration (Cmax), it is important to recognize that the interindividual variability is approximately 2- to 5-fold higher in patients with burns compared to healthy volunteers.

We did not find sufficient deviations in the concentrations of ceftolozane/tazobactam to recommend an empiric dose adjustment for patients with burns. However, this finding is limited by our small sample size and lack of clinical outcome data. Therefore, we also provide a conditional recommendation to conduct therapeutic drug monitoring to adjust ceftolozane/tazobactam dosing or to switch to a continuous infusion approach in cases of a suboptimal clinical response.