Gram-Negative Infections in Orthopedic Surgery: Current Challenges for Anesthesiologists and Intensive Care Physicians—A SANRA Narrative Review

Background: Gram-negative bacterial infections represent an increasingly relevant challenge in orthopedic surgery, particularly in complex patients exposed to major trauma, revision procedures, prolonged hospitalization, previous antimicrobial therapy, and intensive care. Although Gram-positive organisms remain predominant in prosthetic joint infections (PJIs) and fracture-related infections (FRIs), the emergence of multidrug-resistant (MDR) Gram-negative pathogens has important implications for perioperative management, antimicrobial prophylaxis, and treatment. Objective: This narrative review examines the epidemiology, pathogenesis, antimicrobial resistance, and management of Gram-negative orthopedic infections, with particular emphasis on issues relevant to anesthesiologists and intensive care physicians. Methods: A structured narrative literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science from database inception to July 2026, according to the principles of the Scale for the Assessment of Narrative Review Articles (SANRA). Original studies, systematic reviews, meta-analyses, guidelines, consensus statements, and relevant narrative reviews addressing Gram-negative infections in orthopedic surgery were considered. Results: Gram-negative pathogens account for a minority of orthopedic infections but become increasingly relevant in complex PJIs, FRIs, open fractures, revision surgery, and patients with substantial healthcare exposure. Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii are among the principal pathogens involved. Their clinical relevance is amplified by biofilm formation and increasingly complex antimicrobial resistance mechanisms. Perioperative antibiotic prophylaxis should remain individualized in patients colonized or previously infected with MDR Gram-negative organisms, avoiding indiscriminate broad-spectrum prophylaxis. Once infection is established, management requires adequate microbiological sampling, surgical source control, and susceptibility-guided antimicrobial therapy. New β-lactam/β-lactamase inhibitor combinations and cefiderocol have expanded therapeutic options against resistant Gram-negative pathogens; however, evidence specifically supporting cefiderocol for bone and joint infections remains limited. Conclusions: Gram-negative orthopedic infections represent an emerging challenge at the intersection of orthopedic surgery, infectious diseases, anesthesiology, and critical care. Early recognition of high-risk patients, individualized perioperative strategies, effective source control, resistance-guided antimicrobial therapy, and multidisciplinary management are essential.