How to tailor recommendations on the treatment of multi-drug resistant Gram-negative infections at country level integrating antibiotic stewardship principles within the GRADE-ADOLOPMENT framework

: Promoting the optimal use of antibiotics through evidence-based recommendations should be regarded as a crucial step in the global fight against antimicrobial resistance. Within this scope, several guidelines and guidance documents for antibiotic therapy have been published in recent years. All documents underline the limitations of existing evidence and remark on the need for tailoring recommendations at the national level, based on local epidemiology, availability of diagnostics and drugs, and antimicrobial stewardship principles. The GRADE-ADOLOPMENT methodology is an evidence-based methodology that allows the adoption, adaptation, and update of existing recommendations to specific settings without performing de novo systematic reviews and grading of the evidence. However, procedures to integrate this evidence with stewardship principles, countries' surveillance data, and capacity in terms of diagnostics and antibiotics' availability have never been defined. This Personal View provides the first example of a country's calibration of international evidence-based guidance documents on treating infections caused by multidrug-resistant bacteria. A panel of experts convened by the Italian Medicine Agency (AIFA) used the GRADE methodology for systematically extracting and evaluating 100 recommendations on the treatment of infections due to multidrug-resistant Gram-negative bacteria from 11 guidance documents and 24 systematic reviews. The ADOLOPMENT procedure was used to calibrate the existing recommendations to the national context, leading to the adoption of 64, the adaptation of 27, and the rejection of nine recommendations. We discuss the technical details of the GRADE-ADOLOPMENT application, the calibration process, and the human resources required to support such an effort. This Personal View also covers the challenges of integrating antibiotic stewardship principles in evidence-based recommendations for treating infections with very limited therapeutic and diagnostic options. The details presented here could support the easy transferability of the methodology to other countries and settings, particularly where the incidence of antibiotic-resistant infections is high.