Objectives. Vancomycin and fosfomycin are antibiotics commonly used to treat methicillin-resistant Staphylococcus aureus (MRSA) infection. This study compares the in vitro inhibitory effects against MRSA of articulating cement spacers impregnated with either vancomycin or fosfomycin. Methods. Vancomycin-impregnated articulating cement spacers and fosfomycin-impregnated articulating cement spacers were immersed in sterile phosphate-buffered saline (PBS) solutions and then incubated. Samples were collected for bioactivity evaluation. The aliquots were tested for MRSA inhibition with the disc diffusion method, and the inhibition zone diameters were measured. The inhibition zone differences were evaluated using the Wilcoxon Rank Sum Test. Results. The vancomycin group had significantly larger inhibition zones than the fosfomycin group from day three through to completion of the fourth week of incubation (p < 0.001). The vancomycin group exhibited a MRSA inhibition zone up to four weeks but the fosfomycin group showed an inhibition zone for only three days and after that did not show the the potential to inhibit MRSA. Conclusion. This in vitro study found that the inhibitory effect of vancomycin-impregnated articulating cement spacers against MRSA outperformed fosfomycin-impregnated articulating cement spacers. Further comparing our results to other published reports suggests there might be a limitation of the disc diffusion bioassay to show a large inhibitory zone in a high concentration of a highly soluble antibiotic. Cite this article: V. Yuenyongviwat, N. Ingviya, P. Pathaburee, B. Tangtrakulwanich. Inhibitory effects of vancomycin and fosfomycin on methicillin-resistant Staphylococcus aureus from antibiotic-impregnated articulating cement spacers. Bone Joint Res 2017;6:132–136. DOI: 10.1302/2046-3758.63.2000639

Summary Statement. Combination of antibiotics with N-acetylcisteine and sub-MIC concentration of erythromycin was evaluated in two collection and 16 clinical strains of staphylococci isolated from PJI. The results were strain-dependent, so it evidences the necessity of perform individual studies of biofilm susceptibility. Objectives. Staphylococci are the most common cause of prosthetic joint infections (PJI) (1), making the treatment of this disease difficult due to the increased resistance to antibiotics of biofilms. Combination between antibiotics and other compounds could be a good alternative. The aim of this study was to evaluate the effect of the combination of two compounds with nine antibiotics in biofilms formed by staphylococcal strains isolated from PJI. Methods. 16 clinical strains (8 S. aureus and 8 S. epidermidis) isolated from patients with PJI as well as 2 collection strains (S. aureus 15981 and S. epidermidis ATCC 35984) were tested against 9 antibiotics (rifampin, vancomycin, tigecycline, clindamycin, cotrimoxazole, ciprofloxacin, cloxacillin, daptomycin and fosfomycin) in combination with NAC 1024 μg/mL and erythromycin at subinhibitory concentration (0.12 μg/mL), which was established after the determination of MIC according to EUCAST recommendations. The Calgary Biofilm Device (CBD) was used to determine the susceptibility of the biofilms to these combinations. The Minimal Biofilm Eradication Concentration (MBEC) for the all the antibiotics alone was determined in a previous study. All the experiments were performed by triplicate. Results. All the S. aureus strains showed homogeneous results, and the addition of NAC or erythromycin at the tested concentrations has not a clear effect in the antibiotic susceptibility of the biofilm, although combination of tigecycline with NAC seems even to increase the MBEC in most cases. Almost all clinical strains were MRSA. Regarding S. epidermidis strains, the results were strain-dependant. The combination with NAC seems to increase the MBEC for rifampin and tigecycline in some strains. However, there was a slight MBEC decrease with cotrimoxazole, ciprofloxacin, cloxacillin, daptomycin and fosfomycin. Erythromycin combinations resulted to be successful only in a few cases, and there is no an apparent relationship between erythromycin resistance and combination results. It is especially remarkable that one strain (P-23.2) showed a slight decrease of the MBEC combining both substances with most of the antibiotics tested. Conclusion. None of the combinations tested was clearly effective against biofilms for all strains of both species. This heterogeneity showed the necessity of making an individual study of each strain. The search of new strategies to fight against PJI is mandatory and further investigation is needed