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Published on 1 July 2007

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Prophylactic use of antibiotic-loaded bone cements

teaser

Lehel Bálint
MD PhD

Consultant Orthopaedic Surgeon

Kidderminster Hospital
Kidderminster
UK

E: lelu@blueyonder.co.uk

In 1958 Sir John Charnley devised the ­revolutionary method of joint replacement, which has been a key treatment ever since and mainly relies on the use of polymethyl methacrylate (PMMA) bone cement.(1) In 1970 Buchholz and Engelbrecht ­demonstrated that pulverised antibiotic mixed with the bone cement had the potential to dissolve and thus provide prophylaxis after solidification of the cement.(2) Since then, results from a great number of patients have suggested that combined local and systemic antibiotic prophylaxis is the most effective method of infection control.(3) The antibiotics added should be water-soluble, heat-resistant and ­powder formulation-available, but should not adversely affect the cement’s mechanical properties. More than 40 antibiotics currently satisfy these criteria and can be used for this purpose, including the aminoglucosides gentamicin, oxacillin, tobramycin, ­vancomycin, ­clindamycin and erythromycin, as well as the cephalosporins cefasoline, cefuroxime and cefamandol.(4) Nevertheless, it is mandatory to know whether the concentration of antibiotic is above the minimal inhibitory concentration (MIC), and is therefore effective, or below it, which could lead to antibiotic resistance, or even serve as a substrate for bacteria and play a role in biofilm formation.(6,7) The MIC value of gentamicin sulphate is 1 µg/ml, against the sensitive ­staphylococci strains.(8) Although the exact details of the elution of antibiotics are not fully understood, polymethyl ­metacrylate bone cement is currently used in more than one million joint replacements a year worldwide.

Discussion
Several reports discuss the pharmacodynamic ­properties of cephalosporins and other antibiotics added to bone cement.(9–15) Aminoglycosides are the most frequently used antibiotics in orthopaedic surgery but because of their toxicity it is essential to be aware of their circulating concentration.(16–18)

In primary prosthesis implantation, the antibiotics most frequently used for adding into bone cement as a local prophylaxis are tobramycin in the USA and gentamicin sulphate in Europe (typically at 1 g ­gentamicin sulphate to 40 g bone cement).(3,18–26)

In the past three decades, several publications have discussed the emission of antibiotics from bone cement. They focused on the ­characteristics of tobramycin, the bone-penetrating capacity of ­ciprofloxacin, cefuroxime, cephaloridin, other ­cephalosporins, neomycin-bacitracin combination and cephalothin.(9,10,12,15,19–21,25,27–29)

Electron microscopy pictures reveal that after fixation, bone cement has a porous surface.(30) There is no consensus in the literature regarding ­antibiotic discharge from the cement. Emission can take place from the surface of the cement or through the pores and clefts within the matrix of the cement. Experiments suggest that gentamicin, after being mixed with the cement, is generally emitted from microfractures and cavities in the cement via simple diffusion.(5) Each of the different modes of antibiotic emission is dominant at different times.(14) Picknell et al observed that, regardless of which antibiotic was examined, emission correlated mainly with the extent of surface area of the cement.18 Repro­ducing the periprosthetic space in vitro, Hendriks et al found that the antibiotic concentration remained as high as 1,000 times above MIC,(31) and so would have a prophylactic effect against the sensitive ­Staphylococcus aureus strains.

Kendall et al found that in two-step hip revision surgery performed due to pyogenic infection, the antibiotic spacer had no bacteria attached to its ­surface.6 However, numerous publications discuss the dangers of drug resistance.(7,28,32–37)

Conclusion
The conclusion could be drawn from that of a study by Heck et al, who randomly questioned 2,139 orthopaedic surgeons in the USA on the use of antibiotic-loaded bone cement for prophylactic purposes: despite the lack of FDA approval, the vast majority responded that the use of antibiotic-loaded bone cement for infection prophylaxis was a routine feature of their practice.(38,39)

References
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3. Espehaug B, Engesæter LB, Vollset SE, et al. Antibiotic prophylaxis in total hip arthroplasty. J Bone Joint Surg Br 1997;79(4):590-5.
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