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.