Management of Gram-positive multiresistant bacteria prosthetic joint infection: a narrative review on current and innovative strategies.

Background: Prosthetic joint infection (PJI) is a devastating complication of arthroplasty surgery, mostly caused by Gram-positive pathogens, including Staphylococcus aureus and coagulase-negative staphylococci. Multidrug resistance is of major concern in this setting: (a) it can negatively impact outcome, restricting the use of the most effective antimicrobials; (b) it may influence the choice of surgical strategies; and (c) it restrains the therapeutic options to newly labelled antimicrobials with limited experience in PJI.

Objectives: To provide a comprehensive overview of the clinical impact of antimicrobial resistance in Gram-positive PJI and on current and innovative therapeutic strategies.

Sources: The review is based on PubMed searches for relevant topics, including multiresistant staphylococci PJI and the discussed specific therapeutic approaches. Given the very few randomized trials in this setting, discussion is mostly based on observational studies and the experience and opinion of the authors.

Content: Methicillin resistance is an important concern in staphylococcal PJI, especially in coagulase-negative staphylococci. However, its impact on the outcome is controversial. Conversely, rifampicin and/or fluoroquinolone resistance are associated with worse prognosis and might be considered when defining difficult-to-treat pathogens in the PJI setting. There is very little experience with recently developed anti-Gram-positive antimicrobial in PJI, but evaluations of their antibiofilm activities are promising, and some of them might represent significant advances regarding antimicrobial tolerance (such as tedizolid) or pharmacokinetic profiles (such as dalbavancin) during long-term treatment required for PJI. Evaluation of innovative strategies in this setting is crucial, including repositioning of current surgical options using local antimicrobial delivery, pharmacokinetic monitoring and modelling to optimize antimicrobial therapy, suppressive antimicrobial treatment and/or phage-based approaches.

Implications: PJIs caused by resistant Gram-positive bacteria-including rifampicin- and/or fluoroquinolone-resistant staphylococci-may be associated with a poorer prognosis. It is therefore essential to optimize medical and surgical management, and to find new therapeutic alternatives.