Challenges and strategies in the treatment of periprosthetic joint infection caused by multidrug-resistant Gram-negative bacteria: a narrative review.

Background: Multidrug-resistant Gram-negative bacteria (MDR-GNB) are an increasing cause of periprosthetic joint infection (PJI), limit the available antibiotic options and affect patient outcomes.

Objectives: We reviewed the therapeutic strategies for managing PJI caused by MDR-GNB, including surgical and antibiotic options.

Sources: We performed a search regarding PJI caused by MDR-GNB without date restrictions, including experimental and clinical studies.

Content: Surgery plays a central role in the therapeutic approach to PJI caused by MDR-GNB. Although prosthesis removal provides higher cure rates than debridement, antibiotics, and implant retention (DAIR), also allowing the addition of local active antibiotics, the surgical risks should be considered when using it as an elective procedure in acute PJI. DAIR may be a valid option for selected patients, but this is the most challenging scenario. The selection of antibiotic treatment is limited by antimicrobial susceptibility, with fluoroquinolone resistance being a particular problem, and mostly requires long-term intravenous therapy. β-Lactams represent the first-line therapy, ideally in combination in cases managed with DAIR, and should be used at high doses and in extended/continuous infusion to optimize their anti-biofilm efficacy. Colistin in combination with β-lactams is the therapy with the most substantial clinical experience, although clinicians may also consider the use of trimethoprim-sulfamethoxazole, fosfomycin, or tigecycline depending on their susceptibility. Outpatient parenteral antibiotic therapy is a valid strategy to minimize lengthy hospitalizations while ensuring good outcomes.

Implications: The management of PJI caused by MDR-GNB is complex. Because of limited available evidence, an individualized approach is needed regarding the type of surgery and antimicrobial therapy, balancing the clinical effectiveness and toxicity risks. Currently, intravenous β-lactams are commonly the first-line therapy, which should be administered for long periods, mainly in combination. The optimization of the anti-biofilm effects of therapy and drug monitoring during the treatment is advisable.