Safety of ceftobiprole in patients with impaired renal, hepatic or immune function: A multinational retrospective hospital chart review (RETRACE study)

Abstract

Comorbidity; Liver toxicity; Safety

Comorbilitat; Toxicitat hepàtica; Seguretat

Comorbilidad; Toxicidad hepática; Seguridad

Background and Aim 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. Methods In this retrospective study (NCT04170309), 396 consecutive charts of patients treated with ceftobiprole during 2016–2022 in 15 centres in France, Italy, and Spain were analysed: 62 had severe renal impairment, 51 had a hepatic impairment, 120 were immunocompromised, and 203 had no predefined risk condition (controls). Results 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. Conclusion Overall, no new safety concerns related to ceftobiprole use in real-world patients with severe renal impairment, hepatic impairment or immunocompromised status were identified.

This study was sponsored by ADVANZ PHARMA Switzerland SARL, a company of the ADVANZ PHARMA group, previously known as Correvio International. The content of this article is solely the responsibility of the authors. No honoraria or payments were made for authorship.