Complementary Time-Kill Activity Displayed by Povidone-Iodine and Hydrogen Peroxide Against Shoulder Arthroplasty–Associated Pathogens, Envisaging Intraoperative Irrigation

Background: Prosthetic joint infection (PJI) following total shoulder arthroplasty (TSA) is a rare but clinically relevant complication, largely attributable to the distinctive shoulder skin microbiome, predominantly composed of Cutibacterium acnes and coagulase-negative staphylococci (CoNS), which are considered low-virulence pathogens. Standard skin disinfection protocols do not completely prevent bacterial infiltration into the surgical field; therefore, the World Health Organization (WHO) recommends the use of intraoperative irrigation to reduce the risk of shoulder PJIs. Recently, the use of povidone–iodine (PVI) irrigation has been shown to significantly reduce both bacterial load and diversity after TSA; however, its activity against C. acnes remains suboptimal. Therefore, the aim of this study was to evaluate improved in vitro disinfection protocols by combining PVI and hydrogen peroxide for use as intraoperative irrigation in shoulder arthroplasty, which is characterized by a distinctive microbiome. Methods: In vitro broth dilution assays and time-kill experiments were performed to test PVI and H2O2, alone or in combination, against CoNS, Staphylococcus aureus, and Escherichia coli as representative aerobic bacteria, and against C. acnes as an anaerobic pathogen. Results: The results revealed that, when used alone, PVI exerted a more pronounced bactericidal effect against staphylococci, whereas H2O2 was more effective against C. acnes, even at a high bacterial inoculum, although at cytotoxic concentrations, particularly for PVI. Notably, when the disinfectants were used in combination, bacterial killing was achieved against all the tested pathogens, starting from short exposure times, mainly 3 min, and at low concentrations. Moreover, the antiseptics significantly reduced mature biofilm, although complete eradication was not achieved. Conclusions: A targeted irrigation protocol to prevent shoulder PJI can be achieved by combining PVI and H2O2 at non-toxic concentrations and for short exposure times that do not interfere with operating room costs or increase the risk of infection.