Innovations in the Treatment of Antibiotic-Resistant Infections in Internal Medicine

Antimicrobial resistance (AMR) is one of the major contemporary challenges in internal medicine, impairing the effectiveness of empirical antibiotic regimens and increasing mortality, hospital length of stay, and healthcare costs. The rising prevalence of multidrug-resistant Gram-negative organisms calls for a clinical response grounded in therapeutic innovation, antimicrobial rationalisation, and institutional reorganisation. We conducted a narrative review of the literature from 2020 to 2025, integrating recommendations from international guidelines, including the Infectious Diseases Society of America (IDSA) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), epidemiological data from the European Centre for Disease Prevention and Control (ECDC) and the Portuguese PPCIRA (Programa de Prevenção e Controlo de Infeções e de Resistência aos Antimicrobianos) programme, and institutional implementation examples from Portuguese hospitals. Several newly approved antibiotics were identified with documented efficacy against resistant pathogens (e.g., ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol), along with promising therapeutic approaches such as bacteriophage therapy and immunomodulation. Clinical decision support tools (algorithms, dashboards, checklists) and institutional models demonstrated positive impact on key indicators such as time to active therapy, de-escalation rates, and reduced use of reserve antibiotics. Managing resistant infections in internal medicine requires an integrated, patient-centred approach supported by updated evidence. Internists must take a strategic role in therapeutic decision-making, clinical governance, and the implementation of tailored protocols, actively contributing to AMR containment and improved clinical outcomes.