Bromelain and N-acetylcysteine (BromAc) as novel adjunctive therapy for prosthetic joint infection: a narrative review.

Abstract

Background: Prosthetic joint infection (PJI) complicates 0.5 %-2.0 % of total joint arthroplasties and remains the leading cause of implant failure. Bacterial biofilm confers marked antimicrobial resistance, and current strategies, including debridement, antibiotics, and implant retention (DAIR), carry a pooled failure rate of $\sim$ 36 %. Novel biofilm-disrupting adjuncts are urgently needed. Purpose: The aim is to examine preclinical evidence of bromelain and N-acetylcysteine (BromAc) as a combination antibiofilm therapy in PJI management and to critically appraise its translational readiness. Methods: A narrative literature search was conducted for studies examining N-acetylcysteine, bromelain, and BromAc in the context of biofilm disruption on orthopaedic prosthetic materials. Eligible studies were appraised qualitatively for pathogen, substrate, exposure conditions, outcome measures, and methodological limitations to allow comparative interpretation rather than narrative summary alone. Results: N-acetylcysteine demonstrates concentration-dependent antibiofilm activity, achieving approximately 50 % biofilm reduction on polyethylene and 20 % on titanium at minimum inhibitory concentrations, rising to 81.5 % eradication of staphylococcal biofilms at higher concentrations in non-orthopaedic substrates. Bromelain achieves significant biofilm reduction from orthopaedic hardware via proteolytic degradation of extracellular polymeric substance protein scaffolds. In the principal proof-of-concept study on hernia mesh, BromAc achieved $>$ 80 % biofilm removal (quantified by crystal violet biomass reduction) across three Pseudomonas aeruginosa strains, exceeding either agent alone; activity against staphylococci has been reported in unpublished sponsor data but is not yet independently replicated in peer-reviewed orthopaedic models. Conclusions: BromAc represents a mechanistically rational adjunctive therapy for PJI, targeting distinct biofilm matrix components. However, current evidence is largely preclinical, much of it derived from non-orthopaedic substrates and pathogens, and several supporting datasets are unpublished sponsor data. Important translational gaps remain in peer-reviewed staphylococcal validation on prosthetic materials, formulation stability (particularly the susceptibility of N-acetylcysteine to oxidation in aqueous solution), intra-articular safety with respect to cartilage and osseointegration, and the absence of an in vivo orthopaedic implant model. These limitations must be resolved before clinical translation can be responsibly considered.