Antimicrobial Resistance in Periprosthetic Joint Infection: Use Correct Definitions for Better Clinical Decisions

The global threat of antimicrobial resistance (AMR) has escalated over the past 3 decades, prompting coordinated responses from international health agencies1. Since 2015, the World Health Organization (WHO) has implemented a global action plan focused on surveillance and antimicrobial stewardship. According to the Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report 20252, approximately 1 in 6 bacterial infections in 2023 was resistant to standard antibiotics, with resistance increasing in >40% of pathogen-drug pairs since 2018. The report also highlights pronounced regional disparities, with the highest AMR rates observed in Southeast Asia, the Eastern Mediterranean, Africa, and Latin America and the lowest AMR rates observed in the Western Pacific region. In the field of periprosthetic joint infection (PJI), the analysis of antimicrobial resistance patterns and related risk factors for multidrug-resistant organisms remains challenging, as few large studies have addressed this issue comprehensively. Moreover, culture-negative PJIs remain common due to prior antibiotic exposure, suboptimal diagnostic methods such as superficial wound swabbing, or the presence of slow-growing organisms3. For these reasons, epidemiological studies defining local AMR patterns in the PJI setting are particularly valuable. Guo et al. recently investigated a large cohort of first-episode knee PJIs following total knee arthroplasty across 3 New Zealand tertiary hospitals over a 24-year period, aiming to identify temporal shifts in microbial epidemiology and AMR profiles and to update their local empirical antibiotic policy. They also assessed independent risk factors for polymicrobial and resistant infections. Notably, 19% to 24% of PJIs were caused by antimicrobial-resistant organisms and the rate was persistently high over 24 years. This finding contrasts with WHO data suggesting low AMR rates for countries in the Western Pacific region2. However, local studies often report higher resistance rates than national surveillance data sets, probably reflecting referral bias from tertiary hospitals managing more complex cases3. For instance, a multicenter Spanish study of 156 PJIs (51% associated with knee prostheses) demonstrated increasing rates of both gram-positive and gram-negative multidrug-resistant organisms3. Given the sustained higher rates of AMR since the early 2020s, targeted infection-control interventions and strengthened antimicrobial stewardship should have been implemented in the orthopaedic units concerned. Evidence-based, modifiable risk factors to mitigate AMR in PJI include avoiding preoperative systemic or topical antibiotics, performing Staphylococcus aureus screening, and ensuring appropriate perioperative prophylaxis4. Nevertheless, a major methodological concern in the study by Guo et al. is their definition of “resistant” organisms. The authors classified isolates with “intermediate” susceptibility as “resistant,” which diverges from the internationally accepted 2019 European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines5. According to EUCAST, “intermediate” isolates should not be deemed resistant; instead, higher antibiotic doses may achieve therapeutic concentrations sufficient for bacterial eradication. This arbitrary definition undermines the external validity of the findings. Indeed, among the 103 (21%) of 487 cases (with 608 cultures) attributed to resistant pathogens, only 12 (2%) involved methicillin-resistant S. aureus (MRSA). The apparent overrepresentation of AMR may therefore relate mainly to coagulase-negative staphylococci or gram-negative bacilli, or to definitional bias. If MRSA accounted for merely 2% of isolates, the rationale for empirical vancomycin therapy warrants reevaluation. Vancomycin levels in patients with PJI frequently fall outside the therapeutic range, necessitating repeated dose adjustments to maintain adequate trough concentrations6. Such fluctuations increase the risk of nephrotoxicity, particularly when combined with aminoglycosides in elderly patients or patients with sepsis. Finally, to achieve better outcomes and reduce the impact of AMR in musculoskeletal infections, health institutions should implement a multidisciplinary management team comprising orthopaedic surgeons, infectious disease specialists, clinical microbiologists, and pharmacists. Such a collaboration enables early and accurate diagnosis, optimized antimicrobial use, and improved surgical and pharmacological decision-making, ultimately enhancing patient safety and treatment efficacy.