Ceftobiprole in Critically Ill Patients: Proposal for New Dosage Regimens

Ceftobiprole is a broad-spectrum cephalosporin. It is currently approved for the treatment of community- and hospital-acquired pneumonia. However, the recommended dosage regimen of ceftobiprole may not be sufficient to achieve the optimal pharmacokinetic/pharmacodynamic criterion in critically ill patients. The study aimed to evaluate whether the dosage regimens proposed by the manufacturers ensure that the optimal pharmacokinetic/pharmacodynamic criterion is achieved in over 90% of critically ill patients.

Ceftobiprole concentrations were measured in 27 patients admitted to intensive care unit. An external evaluation of published population pharmacokinetic models was performed using simulations. The model that best described the data was used to evaluate the dosage regimens proposed for intensive care unit patients by evaluating the probability of attaining the optimal pharmacokinetic/pharmacodynamic criterion (100% fT > 4 * minimum inhibitory concentration). In addition, the same model was used to suggest dosage regimen adjustments for these patients.

Of the 4 models evaluated, Muller's population pharmacokinetic model was selected as the best for describing the concentrations observed in 27 patients. Simulations performed with this model have shown that the manufacturer's dosing regimens do not achieve the optimal pharmacokinetic/pharmacodynamic criterion in critically ill patients. Consequently, adaptation of dosing regimens to ensure ceftobiprole effectiveness in at least 90% of the patients was proposed.

The proposed dosing regimens can be used to guide ceftobiprole administration in critically ill patients. However, measurement of ceftobiprole plasma concentration remains essential, at least once, to confirm patient exposure.