In the Journals

Ceftobiprole noninferior to combination treatment for HAP

The novel cephalosporin ceftobiprole was noninferior to combined therapy with ceftazidime and linezolid for the treatment of hospital-acquired pneumonia, excluding ventilator-associated pneumonia, according to recent data.

“Whether the early improvement observed in a higher proportion of [hospital-acquired pneumonia] patients in the ceftobiprole group translates into additional benefits from the use of ceftobiprole requires further investigation,” the researchers wrote in Clinical Infectious Diseases.

The double blind, randomized study included 781 patients with hospital-acquired pneumonia (HAP), including 210 with ventilator-associated pneumonia (VAP). The patients were randomly assigned to 500 mg ceftobiprole (Basilea Pharmaceutica) every 8 hours or combination treatment with 2 g ceftazidime every 8 hours and 600 mg linezolid every 12 hours. The primary outcome was clinical cure.

The cure rates in the intention-to-treat analysis were 49.9% in the ceftobiprole arm and 52.8% in the combination arm, a difference of –2.9 (95% CI, –10 to 4.1). The clinically evaluable analysis included 251 patients in the ceftobiprole arm and 244 patients in the combination arm. In this analysis, the cure rates were 69.3% for the ceftobiprole arm and 71.3% in the combination arm, a percentage point difference of –2 (95% CI, –10 to 6.1).

In a subgroup analysis excluding patients with VAP, the cure rates in the intention-to-treat analysis were 59.6% for ceftobiprole and 58.8% for the combination treatment, a percentage point difference of 0.8 (95% CI, –7.3 to 8.8). In the clinically evaluable analysis, the rates were 77.8% for ceftobiprole and 76.2% for the combination treatment, a percentage point difference of 1.6 (95% CI, –6.9 to 10).

Ceftobiprole did not demonstrate noninferiority for the subgroup of patients with VAP. The cure rates for VAP patients in the intention-to-treat analysis were 23.1% for ceftobiprole vs. 36.8% for the combination treatment, a percentage point difference of –13.7 (95% CI, –26 to –1.5).

The researchers also measured microbiological eradication rates at the test of cure for patients with HAP (excluding VAP). In the microbiologically evaluable analysis, the eradication rates were 62.9% for ceftobiprole and 67.5% for the combination, a percentage point difference of –4.6 (95% CI, –16.7 to 7.6). For VAP, the eradication rates were 30.4% for ceftobiprole and 50% for the combination, a percentage point difference of –19.6 (95% CI, –38.8 to –0.4).

Disclosure: One researcher is a full-time employee of Basilea. Other researchers report financial relationships with Aptiv Solutions, Astellas, Gilead Sciences, MSD, Novartis, Pfizer and Thermo Fisher.

The novel cephalosporin ceftobiprole was noninferior to combined therapy with ceftazidime and linezolid for the treatment of hospital-acquired pneumonia, excluding ventilator-associated pneumonia, according to recent data.

“Whether the early improvement observed in a higher proportion of [hospital-acquired pneumonia] patients in the ceftobiprole group translates into additional benefits from the use of ceftobiprole requires further investigation,” the researchers wrote in Clinical Infectious Diseases.

The double blind, randomized study included 781 patients with hospital-acquired pneumonia (HAP), including 210 with ventilator-associated pneumonia (VAP). The patients were randomly assigned to 500 mg ceftobiprole (Basilea Pharmaceutica) every 8 hours or combination treatment with 2 g ceftazidime every 8 hours and 600 mg linezolid every 12 hours. The primary outcome was clinical cure.

The cure rates in the intention-to-treat analysis were 49.9% in the ceftobiprole arm and 52.8% in the combination arm, a difference of –2.9 (95% CI, –10 to 4.1). The clinically evaluable analysis included 251 patients in the ceftobiprole arm and 244 patients in the combination arm. In this analysis, the cure rates were 69.3% for the ceftobiprole arm and 71.3% in the combination arm, a percentage point difference of –2 (95% CI, –10 to 6.1).

In a subgroup analysis excluding patients with VAP, the cure rates in the intention-to-treat analysis were 59.6% for ceftobiprole and 58.8% for the combination treatment, a percentage point difference of 0.8 (95% CI, –7.3 to 8.8). In the clinically evaluable analysis, the rates were 77.8% for ceftobiprole and 76.2% for the combination treatment, a percentage point difference of 1.6 (95% CI, –6.9 to 10).

Ceftobiprole did not demonstrate noninferiority for the subgroup of patients with VAP. The cure rates for VAP patients in the intention-to-treat analysis were 23.1% for ceftobiprole vs. 36.8% for the combination treatment, a percentage point difference of –13.7 (95% CI, –26 to –1.5).

The researchers also measured microbiological eradication rates at the test of cure for patients with HAP (excluding VAP). In the microbiologically evaluable analysis, the eradication rates were 62.9% for ceftobiprole and 67.5% for the combination, a percentage point difference of –4.6 (95% CI, –16.7 to 7.6). For VAP, the eradication rates were 30.4% for ceftobiprole and 50% for the combination, a percentage point difference of –19.6 (95% CI, –38.8 to –0.4).

Disclosure: One researcher is a full-time employee of Basilea. Other researchers report financial relationships with Aptiv Solutions, Astellas, Gilead Sciences, MSD, Novartis, Pfizer and Thermo Fisher.