Early improvement in severely ill patients with pneumonia treated with ceftobiprole: a retrospective analysis of two major trials

Abstract

Background: Patients with pneumonia who are elderly or severely ill are at a particularly high risk of mortality. This post hoc retrospective analysis of data from two Phase III studies evaluated early improvement outcomes in subgroups of high-risk patients with community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP, excluding ventilator-associated pneumonia [VAP]).

Methods: One study included hospitalised CAP patients randomised to ceftobiprole or ceftriaxone ± linezolid treatment. The other study included HAP patients, who were randomised to ceftobiprole or ceftazidime plus linezolid treatment. The primary outcome was rate of early clinical response (Day 3 in CAP and Day 4 in HAP patients). Additional outcome measures included clinical cure at a test-of-cure visit, 30-day all-cause mortality and safety.

Results: The overall high-risk group comprised 398 CAP patients and 307 HAP patients with risk factors present at baseline. The rate of early response was numerically higher in ceftobiprole-treated patients vs comparator-treated patients in the following high-risk groups: CAP patients aged ≥75 years (16.3% difference, 95% confidence interval [CI]: 1.8, 30.8); CAP patients with COPD (20.1% difference, 95% CI: 8.8, 31.1); all high-risk HAP patients (12.5% difference, 95% CI: 3.5, 21.4); HAP patients with >10 baseline comorbidities (15.3% difference, 95% CI: 0.3, 30.4).

Conclusions: Previous studies show that ceftobiprole is an efficacious therapy for patients with pneumonia who are at high risk of poor outcomes. This post hoc analysis provides preliminary evidence that ceftobiprole treatment may have advantages over other antibiotics in terms of achieving early improvement in high-risk patients with HAP (excluding VAP) and in some subgroups of high-risk CAP patients.

Trial registration: NCT00210964 : registered September 21, 2005; NCT00229008 : registered September 29, 2005; NCT00326287 : registered May 16, 2006.

Keywords: Ceftobiprole; Cephalosporin; Community-acquired pneumonia; Hospital-acquired pneumonia.

Conflict of interest statement

Ethics approval and consent to participate

Both studies were conducted in accordance with International Conference on Harmonization Guidelines for Good Clinical Practice, the Declaration of Helsinki, and applicable local regulations. Each study protocol was approved by an Independent Ethics Committee, and all patients provided written informed consent before any study procedures were carried out.

Consent for publication

Not applicable.

Competing interests

KH is an employee of Basilea Pharmaceutica Ltd. ME is an employee of Basilea Pharmaceutica Ltd. AS-H was previously an employee of Basilea Pharmaceutica Ltd. MS is an employee of Icon plc, who were paid by Basilea Pharmaceutica Ltd. to perform the statistical analyses for this study. TW received fees from AstraZeneca, Basilea Pharmaceutica Ltd. and Pfizer for lectures in relation to this study, and fees from AstraZeneca, Bayer AG, Basilea Pharmaceutica Ltd., Merck Sharp & Dohme, Novartis AG and Pfizer for lectures and advisory boards unrelated to this study during the 36 months prior to publication of this article. TWLS has no conflicts of interest to declare.

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Figures

Fig. 1

Early improvement in CAP or HAP patients, by risk factors and causative pathogen. Top panel. Early improvement at Day 3 in patients with CAP, by risk factor (CE population). Middle panel. Early improvement at Day 4 in patients with HAP (excluding VAP) by risk factor (CE population). Lower panel. Early improvement in high-risk group patients by pathogen type (CE population). aThe comparator treatment was ceftriaxone ± linezolid in CAP patients and ceftazidime plus linezolid in HAP (excluding VAP) patients. bBetween treatment difference calculated as ceftobiprole minus comparator cTwo-sided 95% confidence interval is based on a normal approximation to the difference of the two proportions. Analyses were not conducted in bacteraemia high-risk groups as the number of CAP and HAP patients in both treatment arms was <20. Early clinical improvement is defined as improved or cured at Day 3 in patients with CAP, and improved or cured at Day 4 in patients with HAP (excluding VAP). Early clinical improvements were evaluated by the investigator, based on an assessment of symptoms using standardised criteria

Fig. 2

30-day all-cause mortality in CAP or HAP patients, by risk factors and causative pathogen. Top panel. 30-day all-cause mortality in patients with CAP, by risk factor (CE population). Middle panel. 30-day all-cause mortality in patients with HAP (excluding VAP) by risk factor (CE population). Lower panel. 30-day all-cause mortality in high-risk group patients by pathogen type (CE population). aThe comparator treatment was ceftriaxone ± linezolid in CAP patients and ceftazidime plus linezolid in HAP (excluding VAP) patients. bBetween treatment difference calculated as ceftobiprole minus comparator. cTwo-sided 95% confidence interval is based on a normal approximation to the difference of the two proportions