Real-world use of novel β-lactams in immunologically vulnerable patients: insights from an Italian retrospective cohort.

BACKGROUND AND OBJECTIVES: Multidrug-resistant gram-negative bacteria pose a significant global health threat, particularly among vulnerable populations, such as the elderly and immunocompromised patients. Novel β-lactam (NBL) antibiotics offer promising treatment options, but real-world evidence on their efficacy in these populations remains limited. To describe the use of NBLs in clinical practice, focusing on immunologically vulnerable patients, including those with immunosuppression due to underlying disease or immunosuppressive therapy, as well as elderly individuals. Clinical characteristics, outcomes and microbiological data were descriptively analysed. METHODS: This retrospective cohort study was conducted at two university hospitals in Milan, Italy, from 2019 to 2024. Adult patients receiving NBLs (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, imipenem/relebactam or meropenem/vaborbactam) were included. Immunologically vulnerable patients were identified by at least one of the following conditions: active oncological disease, solid organ transplantation, autoimmune or rheumatological disorder requiring immunosuppressive therapy, HIV infection or age >85 years. A descriptive analysis of clinical and microbiological data was performed, and the clinical course was described using clinical and biochemical parameters. RESULTS: Overall, 233 patients were included, 80 (34.3%) of whom were immunologically vulnerable; 308 NBL prescriptions were recorded. Ceftazidime/avibactam was the most prescribed agent (61.4%). Carbapenem-resistant Klebsiella pneumoniae (50.0%) and Pseudomonas aeruginosa (41.4%) were predominant pathogens. Despite greater baseline clinical severity among non-vulnerable patients, all-cause mortality and clinical improvement at T1 were similar between the two groups. CONCLUSIONS: In a real-world Italian cohort spanning 5 years, NBLs were widely used in immunologically vulnerable patients, a population often underrepresented in pivotal antibiotic trials, with K. pneumoniae carbapenemase-producing K. pneumoniae and P. aeruginosa as predominant pathogens. Unadjusted comparisons showed similar clinical outcomes despite greater baseline severity among non-vulnerable patients, a hypothesis-generating finding warranting confirmation in adjusted, prospective studies.