Antimicrobial Treatment Options for Multidrug Resistant Gram-Negative Pathogens in Bone and Joint Infections

Multidrug (MDR) and extensive drug (XDR) resistance in Gram-negative bacteria (GNB) emerges worldwide. Although bone and joint infections are mostly caused by Gram-positive bacteria, mainly Staphylococci, MDR GNB substantially increase also as a complication of hospitalization and previous antibiotic administration. This narrative review analyzes the epidemiological trend, current experimental data, and clinical experience with available therapeutic options for the difficult to treat (DTR) GNB implicated in bone and joint infections with or without orthopedic implants. The radical debridement and removal of the implant is adequate therapy for most cases, along with prompt and prolonged combined antimicrobial treatment by older and novel antibiotics. Current research and clinical data suggest that fluoroquinolones well penetrate bone tissue and are associated with improved outcomes in DTR GNB; if not available, carbapenems can be used in cases of MDR GNB. For XDR GNB, colistin, fosfomycin, tigecycline, and novel beta-lactam/beta-lactamase inhibitors can be initiated as combination schemas in intravenous administration, along with local elution from impregnated spacers. However, current data are scarce and large multicenter studies are mandatory in the field.