Advanz Pharma Switzerland SARL

Ceftobiprole, an advanced-generation cephalosporin with broad bactericidal activity, is approved for community-acquired and hospital-acquired pneumonia (excluding ventilator-associated pneumonia). We aimed to evaluate, in a real-world setting, the safety profile of ceftobiprole in patients with risk conditions (severe renal impairment, hepatic impairment, and immunocompromised status), groups excluded from clinical trials. In this retrospective study (NCT04170309), 396 consecutive charts of patients treated with ceftobiprole during 2016-2022 in 15 centers in France, Italy, and Spain were analyzed: 62 had severe renal impairment, 51 had hepatic impairment, 120 were immunocompromised, and 203 had no predefined risk condition (controls). Ceftobiprole was used for off-label indications in 110/396 (27.8%) patients; 46/396 (11.6%) patients received a higher-than-recommended dose. Treatment-emergent adverse events (TEAEs) considered as ceftobiprole-related occurred in 44 patients, more frequently in the risk groups compared to controls (severe renal impairment: 8/62 [12.9%]; hepatic impairment: 7/51 [13.7%]; immunocompromised: 19/120 [15.8%]; controls: 15/203, [7.4%]); in 7/44 patients, these events were serious. Compared to controls, liver-related AEs occurred more frequently in the impaired hepatic function (17/51 [33.3%] vs 22/203 [10.8%], odds ratio [OR:]: 4.11; 95% confidence interval [CI]: 1.98-8.55) and immunocompromised (30/120 [25.0%] vs 22/203 [10.8%], OR: 2.74; 95%CI: 1.50-5.02) groups. Hyponatremia was also more frequent in immunocompromised patients than controls (14/120 [11.7%] vs 9/203 [4.4%], OR: 2.85; 95%CI: 1.19-6.80). Underlying disease, concomitant medications and the poor health status of the patients likely affected these imbalances. Overall, no new safety concerns related to ceftobiprole use in real-world patients with severe renal impairment, hepatic impairment or immunocompromised status were identified.

Dalbavancin is a lipoglycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections. However, several studies have suggested that it is used mostly for off-label indications. We aimed to describe the use of dalbavancin in patients who received at least one dose of the antibiotic in France.

Prospective, observational, multicentre study conducted in France from September 2018 to April 2020. The primary outcome was the clinical response at 30 days after the last dalbavancin dose.

A total of 151 patients in 16 centres were included in this study. The main infection sites were bone and joint infections (55.0%), multisite infections (15.9%), and vascular infections (14.6%), and the primary pathogens were coagulase-negative staphylococci (N = 82), Staphylococcus aureus (N = 51), and enterococci (N = 27). Most patients (71.5%) received three previous antibiotic treatments. The number of dalbavancin injections per patient was 1 in 26 patients (17.2%), 2 in 95 patients (62.9%), 3 in 17 patients (11.3%), and more than 3 in 13 patients (8.6%), with a mean cumulative dose of 3089 ± 1461 mg per patient. Among the 129 patients with a complete follow-up, clinical success was achieved in 119 patients (92.2%). At least 1 adverse event was reported in 67 patients (44.4%), including 12 (7.9%) patients with dalbavancin-related adverse events.

The results of the study showed that dalbavancin is used mostly for off-label indications and in heavily pretreated patients in France. The clinical response at 30 days after the last dose was favourable in most patients, with a good safety profile.

Ceftobiprole is approved for use in treatment of hospital-associated and community-acquired pneumonia in 16 different European countries and is currently undergoing clinical trials in the United States.

Isolates were collected from hospital laboratories from 16 European countries during 2019 as part of an ongoing post-marketing surveillance study. MICs were determined using EUCAST broth microdilution methodology and interpreted using 2020 EUCAST breakpoints.

Ceftobiprole was active (MIC, ≤2 mg/L) against 100% and 99.3% of methicillin-susceptible Staphylococcus aureus and MRSA isolates collected in 2019. Against Streptococcus pneumoniae, ceftobiprole was active (MIC, ≤0.5 mg/L) against 98.4% of isolates. Overall, 77.4% of Enterobacterales were susceptible though isolate numbers in certain countries were notably low. In addition, based on non-species-related PK/PD breakpoints, 69.7% of Pseudomonas aeruginosa isolates were susceptible to ceftobiprole. Analysis of data by geographical regions showed that susceptibility to ceftobiprole by region or country was not significantly varied though MRSA, S. pneumoniae, Enterobacterales and P. aeruginosa. Isolates from Italy had lower susceptibilities to ceftobiprole: 98% of MRSA, 94% of S. pneumoniae and 61% of Enterobacterales isolates were susceptible to ceftobiprole.

The data for ceftobiprole for isolates from 2019 are encouragingly very similar to studies performed on isolates from earlier years showing that susceptibility to ceftobiprole has not changed and, importantly, that resistance emergence remains low throughout Europe.