How to use novel antimicrobials beyond official indications: an expert consensus

To establish a regional expert consensus on off-label indications for recently approved antimicrobials, based on a structured Delphi methodology, to support antimicrobial stewardship programs (ASPs) in Andalusia, Spain.

As part of the NEW_SAFE project, a modified Delphi process was employed involving 32 experts in Infectious Diseases and Intensive Care from 14 Andalusian hospitals. The process comprised three survey rounds evaluating off-label uses of eight drugs: ceftazidime-avibactam, ceftolozane-tazobactam, cefiderocol, ceftaroline, ceftobiprole, dalbavancin, tedizolid, and isavuconazole. Clinical scenarios were assessed under predefined conditions (efficacy/safety, ecological impact, and cost) and circumstances (empirical versus targeted use, resistance prevalence, PK/PD advantage).

The expert panel reached positive consensus (≥80% agreement) on specific off-label targeted uses for all drugs except ceftobiprole. Empirical use was generally discouraged except under clear PK/PD advantages or resistance profiles without alternatives. Notably, dalbavancin, ceftaroline, and ceftazidime-avibactam received multiple targeted-use endorsements, particularly for endocarditis, osteoarticular infections, and bacteraemia. Isavuconazole was recommended for rare fungal infections and in cases where it offers pharmacological advantages.

This consensus supports the judicious off-label use of new antimicrobials in specific clinical scenarios where therapeutic gaps exist. The guidance prioritizes targeted treatment over empirical use, aligning with international ASP principles and WHO recommendations. These results provide a regional reference to optimize ASP initiatives focus on new antibiotic use while minimizing ecological impact and resistance development.