头孢比普在肾功能、肝功能或免疫功能受损患者中的安全性：一项多国回顾性医院病历审查（RETRACE研究）。

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

作者信息

Membrillo de Novales Francisco Javier, Falcone Marco, Soriano Alex, Fernández-Hidalgo Nuria, Francisci Daniela, Gentile Ivan, Cedar Eve, Jemmely Noëlle, Quevedo Juan, Estébanez Miriam, Durante-Mangoni Emanuele

机构信息

Hospital Central de La Defensa "Gómez Ulla", Latina, Madrid, Spain; Hospital Universitario La Moraleja, Hortaleza, Madrid, Spain.

Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Pisa, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.

出版信息

Int J Antimicrob Agents. 2025 Apr;65(4):107450. doi: 10.1016/j.ijantimicag.2025.107450. Epub 2025 Jan 24.

DOI:10.1016/j.ijantimicag.2025.107450

PMID:39864599

Abstract

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.

摘要

背景与目的

头孢比普是一种具有广泛杀菌活性的新一代头孢菌素，已被批准用于社区获得性和医院获得性肺炎（不包括呼吸机相关性肺炎）。我们旨在在真实世界环境中评估头孢比普在有风险状况（严重肾功能损害、肝功能损害和免疫功能低下状态）患者中的安全性，这些患者群体被排除在临床试验之外。

方法

在这项回顾性研究（NCT04170309）中，分析了2016年至2022年期间法国、意大利和西班牙15个中心连续396例接受头孢比普治疗的患者病历：62例有严重肾功能损害，51例有肝功能损害，120例免疫功能低下，203例无预先定义的风险状况（对照组）。

结果

110/396（27.8%）例患者使用头孢比普用于非标签适应证；46/396（11.6%）例患者接受了高于推荐剂量的治疗。被认为与头孢比普相关的治疗中出现的不良事件（TEAE）发生在44例患者中，与对照组相比，在风险组中更常见（严重肾功能损害：8/62 [12.9%]；肝功能损害：7/51 [13.7%]；免疫功能低下：19/120 [15.8%]；对照组：15/203 [7.4%]）；在7/44例患者中，这些事件很严重。与对照组相比，肝功能受损组（17/51 [33.3%] 对 22/203 [10.8%]，优势比 [OR]：4.11；95% 置信区间 [CI]：1.98 - 8.55）和免疫功能低下组（30/120 [25.0%] 对 22/203 [10.8%]，OR：2.74；95% CI：1.50 - 5.02）中与肝脏相关的不良事件更频繁发生。免疫功能低下患者的低钠血症也比对照组更常见（14/120 [11.7%] 对 9/203 [4.4%]，OR：2.85；95% CI：1.19 - 6.80）。基础疾病、合并用药和患者的健康状况不佳可能影响了这些失衡。