in Joint Replacement Surgery
A. Lundberg, H. Hedlund
Department of Orthopaedics, Karolinska University Hospital, Stockholm, Sweden
Introduction
The use of some form of cement as an alternative to direct mechanical fixation (press- fit, screws etc) dates back to the earliest period of joint replacement surgery. The first void-filling agent to be tried by Gluck in 1890 was a combination of plaster, pumice and resin. At this time there were no antibiotics, and the experiments failed for this and other obvious reasons [13]. When methyl methacrylate as a bone cement was made popular in the field of implant fixation in the 1960’s, antibiotics were available and the first documented use of antibiotic loaded bone cement occurred within this decade [4].
From the start of the joint replacement era, gentamicin and other agents belonging to the aminoglycoside group, which has heat resistance as a major characteristic, dominated the market. However, many other agents have been used, and in recent years there has been an upsurge in the attention given to several of the many heat resistant antibiotics avaiable, mainly as a result of increased presence of gentamycin resistant bacteria [17].
Over the years, many combinations of cement and antibiotic have also been used in the treatment of manifest infection. however, this review only covers prophylactic use of bone cement/antibiotic.
In this field, the main points of controversy have been:
) The efficacy of antibiotic loaded cement in preventing implant infection ) The risk of allergic reaction to the antibiotic agent
) The risk of alterations in the mechanical properties of bone cement caused by the antibiotic additive
) The risk of toxic reaction to the antibiotic agent
) The risk of altered resistance patterns of different bacteria caused by extensive use of antibiotic additives in routine joint replacement surgery, and
) The risk of the presence of antibiotics influencing assessment of infection in the patient.
Available Documentation
Experimental
There are large volumes of documentation available, relating to the antibiotic release properties, the influence (or lack of influence) of antibiotic agents on the mechanical properties of different bone cements as well as the in vitro antimicrobial effects of dif- ferent combinations of bone cement and antibiotic agent.
Antibiotic Release Properties
These properties vary between different combinations of cement and antibiotic agent. The period of described elution of significant amounts of antibiotics has usu- ally been in the range from 7 to 14 days, but considerably higher values have also been suggested [2, 4, 9, 16, 18, 21]
Mechanical Properties
The results generally support the view that the mechanical properties of bone cement are not significantly altered by up to 4 – 5 % by volume of an antibiotic additive. This corresponds to the range where antibiotic additives for prophylactic use are normally kept, and there seems to be relative consensus that influence on mechanical proper- ties is not a problem with these amounts of antibiotic [7, 14].
Antimicrobial Efficacy
In vitro studies have shown inhibition of bacterial growth by antibiotic loaded cement [3, 17], but also increased presence of strains resistant to the used antibiotic [20].
Clinical Efficacy
1. RCT evidence
Few RCT studies have been performed where different cements and/or antibiotic prophylaxis regimens have been compared. Chiu et al have shown in two studies, one on otherwise healthy patients, the other on diabetic patients, that there was a significant reduction in the incidence of infection when an antibiotic was added to the cement [5, 6]. In another study antibiotic loaded cement was also found to be efficient in reducing the risk of infection in the early postoperative period [12].
2. Epidemiological evidence
Most of the national registers of implant surgery have addressed the issues of pro- phylactic antibiotics. The most commonly quoted publication today comes from the Norwegian national register [8] and shows that antibiotics administered sys- temically and locally as an additive to the cement have cumulative effect on the risk of revision for septic loosening. Data from the Swedish national hip register have also shown a decreased incidence of septic loosening of hip implants with the use of antibiotic loaded cement [15].
Excluding the few studies that have shown no difference in joint infection inci- dence, the difference in the rate of deep infection between cement containing antibi- otic and not containing antibiotic has varied between 1:2 and 1:4 [5, 6, 8, 12, 15]. A very rough estimate of the corresponding cost difference at the time of primary sur- gery (assuming a cost of USD 30,000 for a two-stage procedure and not including other costs) would yield USD 200 – 400. The cost for the antibiotic additive is approxi- mately USD 40.
Safety
1. Influence on mechanical properties of the bone cement
There are few clinical studies of the influence of antibiotics on the mechanical properties of cement. Studies using radiostereometric analysis have supported the experimental finding that the addition of antibiotics in prophylactic amounts does not significantly alter the mechanical properties of bone cement [1]
2. Toxic effects
The most commonly used agent, gentamicin, was known at the time that it was first used as an adjunct in bone cement to show a large variation in uptake when administered systemically. The amounts used in bone cement are large, but clini- cal studies have not shown risks of toxic reactions even in the presence of renal impairment [10].
3. Hypersensitivity
Hypersensitivity is much less common for aminoglycosides than for q -lactam antibiotics, which are less commonly used in cement. As with the metals contained in joint implants, final proof that there is no risk of hypersensitivity at all is lack- ing.
4. Influence on bacterial resistance patterns and clinical decision making
Influence of antibiotic additives on bacterial resistance patterns can mainly be expected in situations where the release rate of the antibiotic gives lower concen- trations than the MIC value. This has been seen as related to the increased inci- dence of gentamicin resistance in particularly coagulase-negative staphylococci (CNS) [11].
5. Clinical decision making
A further possible problem relates to clinical decision making. It has been shown that the antibiotic contained in old cement mantles may influence the reliability of cultures taken from the joint by aspiration [9] as well as during revision surgery [19].
Discussion
There is wide consensus that the addition of antibiotics to bone cement reduces the risk of septic loosening, although there is a possibility that this correlation is much stronger in patients with an increased risk of infection due to risk factors such as dia- betes. Toxicity is according to most investigators not a problem. There are now sev-
eral studies conclusively showing that the quality of the cement mantle is not signifi- cantly impaired by the addition of antibiotic in the amounts used for prophylactic purposes.
The main concerns voiced against the routine use of prophylactic antibiotic addi- tives in bone cement relate to the risk of hypersensitivity and the risk of adverse influ- ence on bacterial patterns of resistance to antibiotics. While the latter is a real and important concern, it seems unlikely that the use of antibiotics as additives to bone cement should constitute a more serious risk for future multi-resistance patterns in bacteria. Hypersensitivity to antibiotics may be a more serious concern, particularly as the spectrum of agents used widens. A single case of serious allergic reaction to an antibiotic agent may overthrow the gains from a decade of persistent use of all means available to reduce the infection rate after total joint reaction. It is also important to consider the presence of antibiotics in the cement mantle of patients with joint implants when evaluating aspirate and tissue cultures.
References
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