Objectives

Thermal stability is a key property in determining the suitability of an antibiotic agent for local application in the treatment of orthopaedic infections. Despite the fact that long-term therapy is a stated goal of novel local delivery carriers, data describing thermal stability over a long period are scarce, and studies that avoid interference from specific carrier materials are absent from the orthopaedic literature.

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

Objectives

The objective of this study was to determine if combining variations in mixing technique of antibiotic-impregnated polymethylmethacrylate (PMMA) cement with low frequency ultrasound (LFUS) improves antibiotic elution during the initial high phase (Phase I) and subsequent low phase (Phase II) while not diminishing mechanical strength.

Objectives. The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. Methods. Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. Results. Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. Conclusions. Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs. Cite this article: Bone Joint Res 2014;3:246–51

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed.

In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups.

After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate.

Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes.

Cite this article: Bone Joint J 2014; 96-B:845–50.

Objectives . The objective of this study is to determine an optimal antibiotic-loaded bone cement (ALBC) for infection prophylaxis in total joint arthroplasty (TJA). Methods. We evaluated the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with vancomycin, teicoplanin, ceftazidime, imipenem, piperacillin, gentamicin, and tobramycin against methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staph. aureus (MRSA), coagulase-negative staphylococci (CoNS), Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. Standardised cement specimens made from 40 g PMMA loaded with 1 g antibiotics were tested for elution characteristics, antibacterial activities, and compressive strength in vitro. . Results. The ALBC containing gentamicin provided a much longer duration of antibiotic release than those containing other antibiotic. Imipenem-loading on the cement had a significant adverse effect on the compressive strength of the ALBC, which made it insufficient for use in prosthesis fixation. All of the tested antibiotics maintained their antibacterial properties after being mixed with PMMA. The gentamicin-loaded ALBC provided a broad antibacterial spectrum against all the test organisms and had the greatest duration of antibacterial activity against MSSA, CoNS, P. aeruginosa and E. coli. . Conclusion. When considering the use of ALBC as infection prophylaxis in TJA, gentamicin-loaded ALBC may be a very effective choice. Cite this article: Bone Joint Res 2013;2:220–6

We studied the effects of coating titanium implants with teicoplanin and clindamycin in 30 New Zealand White rabbits which were randomly assigned to three groups. The intramedullary canal of the left tibia of each rabbit was inoculated with 500 colony forming units of Staphylococcus aureus. Teicoplanin-coated implants were implanted into rabbits in group 1, clindamycin-coated implants into rabbits in group 2, and uncoated implants into those in group 3. All the rabbits were killed one week later. The implants were removed and cultured together with pieces of tibial bone and wound swabs. The rate of colonisation of the organisms in the three groups was compared.

Organisms were cultured from no rabbits in group 1, one in group 2 but from all in group 3. There was no significant difference between groups 1 and 2 (p = 1.000). There were significant differences between groups 1 and 3 and groups 2 and 3 (p < 0.001). Significant protection against bacterial colonisation and infection was found with teicoplanin- and clindamycin-coated implants in this experimental model.

Clinical experience indicates the beneficial effects of antibiotic-loaded bone cement. Although in vitro studies have shown the formation of a biofilm on its surface they have not considered the gap between the cement and the bone. We have investigated bacterial survival in that gap. Samples with gaps 200 μm wide were made of different bone cements. These were stored dry (‘pre-elution’) or submersed in phosphate-buffered saline to simulate the initial release of gentamicin (‘post-elution’). The gaps were subsequently inoculated with bacteria, which had been isolated from infected orthopaedic prostheses and assessed for their sensitivity to gentamicin. Bacterial survival was measured 24 hours after inoculation. All the strains survived in plain cements. In the pre-elution gentamicin-loaded cements only the most gentamicin-resistant strain, CN5115, survived, but in post-elution samples more strains did so, depending on the cement tested. Although high concentrations of gentamicin were demonstrated in the gaps only the gentamicin-sensitive strains were killed. This could explain the increased prevalence of gentamicin-resistant infections which are seen clinically.

Infection of orthopaedic implants is a significant problem, with increased antibiotic resistance of adherent ‘biofilm’ bacteria causing difficulties in treatment. We have investigated the in vitro effect of a pulsed electromagnetic field (PEMF) on the efficacy of antibiotics in the treatment of infection of implants. Five-day biofilms of Staphylococcus epidermidis were grown on the tips of stainless-steel pegs. They were exposed for 12 hours to varying concentrations of gentamicin or vancomycin in microtitre trays at 37°C and 5% CO. 2. The test group were exposed to a PEMF. The control tray was not exposed to a PEMF. After exposure to antibiotic the pegs were incubated overnight, before standard plating onto blood agar for colony counting. Exposure to a PEMF increased the effectiveness of gentamicin against the five-day biofilms of Staphylococcus epidermidis. In three of five experiments there was reduction of at least 50% in the minimum biofilm inhibitory concentration. In a fourth experiment there was a two-log difference in colony count at 160 mg/l of gentamicin. Analysis of variance (ANOVA) confirmed an effect by a PEMF on the efficacy of gentamicin which was significant at p < 0.05. There was no significant effect with vancomycin