Impact of obesity on clinical outcomes in patients treated with ceftobiprole: Results from Phase 3 clinical trials

Abstract

Background Ceftobiprole was non-inferior to comparators for the treatment of Staphylococcus aureus bloodstream infection (bacteraemia) (SAB), acute bacterial skin and skin structure infection (ABSSSI), and community-acquired bacterial pneumonia (CABP), leading to regulatory approval for these indications. Whether dosing should be modified for patients with obesity is unknown. Objectives This post hoc analysis evaluated the relationship of obesity and clinical outcomes in patients treated with ceftobiprole for SAB, ABSSSI or CABP. Methods Efficacy and safety outcomes were assessed based on BMI from three registrational clinical trials that evaluated ceftobiprole against comparators. Results Overall, 1641 patients were included from the three Phase 3 clinical trials (802 ceftobiprole; 839 comparators). When stratifying by BMI, ceftobiprole had similar outcomes to the overall ceftobiprole population (80.4%) including patients with obesity (BMI = 30-40 kg/m2) (81.7%). Severe obesity (BMI ≥ 40 kg/m2) was associated with decreased clinical cure rates overall (68.2%) compared with the overall ceftobiprole population, and this was especially noted in the clinically evaluable patient population with CABP receiving ceftobiprole (66.7% in severe obesity versus 86.6% overall). This was also seen in the comparator group (33.3% in severe obesity versus 87.4% overall). However, the number of patients with severe obesity was low in the CABP trial. The safety profile was similar between treatment groups in all studies and not influenced by BMI. Conclusions This analysis further supports the efficacy and safety of ceftobiprole at current recommended doses in obese patients with SAB, ABSSSI or CABP.