Orthopaedic Implant-Associated Staphylococcal Infections: A Critical Reappraisal of Unmet Clinical Needs Associated with the Implementation of the Best Antibiotic Choice

Abstract

Infections associated with orthopaedic implants represent a major health concern characterized by a remarkable incidence of morbidity and mortality. The wide variety of clinical scenarios encountered in the heterogeneous world of infections associated with orthopaedic implants makes the implementation of an optimal and standardized antimicrobial treatment challenging. Antibiotic bone penetration, anti-biofilm activity, long-term safety, and drug choice/dosage regimens favouring outpatient management (i.e., long-acting or oral agents) play a major role in regards to the chronic evolution of these infections. The aim of this multidisciplinary opinion article is to summarize evidence supporting the use of the different anti-staphylococcal agents in terms of microbiological and pharmacological optimization according to bone penetration, anti-biofilm activity, long-term safety, and feasibility for outpatient regimens, and to provide a useful guide for clinicians in the management of patients affected by staphylococcal infections associated with orthopaedic implants Novel long-acting lipoglycopeptides, and particularly dalbavancin, alone or in combination with rifampicin, could represent the best antibiotic choice according to real-world evidence and pharmacokinetic/pharmacodynamic properties. The implementation of a multidisciplinary taskforce and close cooperation between microbiologists and clinicians is crucial for providing the best care in this scenario.

Keywords: anti-staphylococcal agents; antibiotic bone penetration; biofilm; long-term safety; orthopaedic implant-associated infections; outpatient management.

Figure 1

The major determinants involved in the choice of the best antibiotic strategy for the management of orthopaedic implant-associated infections.

Figure 2

The role of biofilm formation and the major determinants involved in the choice of antibiofilm agents. CoNS: coagulase-negative Staphylococci; MBBC: minimal biofilm bactericidal concentration; MBEC: minimal biofilm eradication concentration; MBIC: minimal biofilm inhibitory concentration; PK/PD: pharmacokinetic/pharmacodynamic SCV: small colony variants.

Figure 3

The features of selected anti-staphylococcal agents in relationship with major determinants required for the management of orthopaedic implant-associated infections. Green box: optimal activity/efficacy; yellow box: some concerns in activity/efficacy; red box: limited or absent activity/efficacy.