JBJS | Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Treatment of Infection at the Site of Total Hip Replacement*†

The Journal of Bone & Joint Surgery, Volume 79, Issue 11

Instructional Course Lecture | November 01, 1997

Instructional Course Lectures, The American Academy of Orthopaedic Surgeons - Treatment of Infection at the Site of Total Hip Replacement*†

ERIC L. MASTERSON, B.SC., M.CH., F.R.C.S.(ORTH)‡; BASSAM A. MASRI, M.D., F.R.C.S.(C)‡; CLIVE P. DUNCAN, M.B., M.SC., F.R.C.S.(C)‡, VANCOUVER, BRITISH COLUMBIA, CANADA

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An Instructional Course Lecture, The American Academy of Orthopaedic Surgeons

The Journal of Bone & Joint Surgery. 1997; 79:1740-9

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Introduction

The modern era of total hip arthroplasty is little more than thirty years old, and during that time the procedure has proved to be highly effective in improving the physical function, social interaction, and over-all health of millions of patients⁴⁷. Initially, the procedure was associated with notable rates of infection¹⁶, but these have since been reduced considerably with measures such as prophylactic antibiotics, ultraclean-air operating rooms, and careful selection of patients³⁶. However, this reduction in the prevalence of postoperative deep infection has been accompanied by a steady increase in the frequency with which the operation is performed.

It has been estimated that the prevalence of infection after all total hip replacements performed on Medicare patients in the United States, between 1986 and 1989, was approximately 2.3 per cent (5370 of 236,140)⁶⁶. Extrapolation of these figures to the estimated 200,000 such procedures that are performed annually in the United States suggests that more than 4000 new cases of periprosthetic hip infection need treatment annually. These figures do not distinguish between infections that originated in the operating room and those of hematogenous origin. The total represents a sizable number of dissatisfied patients for whom the success or failure of treatment to eradicate the infection will have major implications for their quality of life.

In addition to the obvious human cost of an infection at the site of a total hip prosthesis are the considerable financial implications for the individual or the institution that must pay for the treatment. Revision hip operations necessitate a longer stay in the hospital than do primary procedures²⁵. In addition, the operating time is longer, the blood loss is greater, and the rate of complications as well as the cost of implants are higher⁷. A number of factors increase the cost of revision of infected joints. These include the necessity for more than one operative procedure for most patients, prolonged courses of parenteral antimicrobial chemotherapy, and the frequent need for periods of hospitalization between staged operative procedures and after the completion of treatment. It has been estimated⁶⁶ that the cost of treatment of an infection at the site of a total hip prosthesis was at least $50,000 in 1990, and current figures may well be higher. It is important that the additional costs of care be recognized by funding bodies such as Medicare and by other third-party payers.

Progress in the development of the optimum treatment of infection at the site of a total hip replacement has been slow. Such infections are sufficiently uncommon that only large tertiary referral centers can accumulate sufficient numbers of patients for study. In addition, the large number of variables in these complex cases makes it difficult to plan well controlled prospective trials of different treatment modalities.

One of the difficulties in comparing the results of different treatment modalities is the variability in the durations of follow-up among reported series. There is evidence that the risk of recurrent infection remains increased for several years after a revision for an infection at the site of a total hip prosthesis and that the rate of recurrence increases as the duration of follow-up increases^61,74. Whether these delayed infections are due to recurrence of the original infection or represent a new infection remains uncertain, but both mechanisms are probably important. Treatment should therefore be aimed at reducing the rate of recurrence of infection regardless of the mechanism.

Possible options for the operative treatment of an infection at the site of a total hip prosthesis include débridement with retention of the prosthesis; immediate one-stage exchange arthroplasty; and excision arthroplasty, either as a definitive, permanent procedure or as the first of a two or even three-stage reconstructive procedure. The use of a temporary prosthesis between the first and second stages of a two-stage exchange also has been advocated.

Antibiotics may be used as an adjunct to operative treatment and may be administered either systemically or locally (with use of bone cement as a vehicle), or both. Antibiotics may be used either to eradicate the infection or as a means of chronically suppressing a periprosthetic infection without concomitant operative intervention. Occasionally, an infection at the site of a hip replacement is treated with débridement, retention of the prosthesis, and long-term administration of suppressive antibiotics. This method is particularly useful for elderly or medically unwell patients who cannot tolerate a two-stage exchange arthroplasty.

The choice of a particular treatment is influenced by a number of factors, including the acuteness or chronicity of the infection; the infecting organism, its sensitivity profile to antibiotics, and its ability to manufacture glycocalyx; the health of the patient; the fixation of the prosthesis; the available bone stock; and the particular philosophy and training of the surgeon.

*Printed with permission of The American Academy of Orthopaedic Surgeons. This article will appear in Instructional Course Lectures, Volume 47, The American Academy of Orthopaedic Surgeons, Rosemont, Illinois, March 1998.

†Although none of the authors has received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this article, benefits have been or will be received but are directed solely to a research fund, foundation, educational institution, or other non-profit organization with which one or more of the authors is associated. No funds were received in support of this study.

‡Department of Orthopaedics, Vancouver Hospital and Health Sciences Centre, Room 3114, 910 West 10th Avenue, Vancouver, British Columbia V5Z 4E3, Canada. The e-mail address for Dr. Masterson is ericlm@ndigo.ie. the e-mail address for Dr. Masri is masri@unixg.ubc.ca, and the e-mail address for Dr. Duncan is eduncan@unix.ubc.ca.

Microbiological Considerations

In most reports of periprosthetic infection, Staphylococcus aureus and Staphylococcus epidermidis are the most common infecting organisms, followed by a wide range of gram-positive and gram-negative bacteria. The importance of Staphylococcus epidermidis as a pathogen is well accepted and that organism should not be regarded as a contaminant from the skin, especially if it grows on culture on more than one occasion or in more than one broth.

Most staphylococci, with the exception of the strains designated as methicillin or oxacillin-resistant, are susceptible to cephalosporin. More than 95 per cent of the Staphylococcus aureus organisms encountered in our hospital are sensitive to oxacillin (and therefore to cephalosporin). However, at least 30 per cent of the Staphylococcus epidermidis isolates identified at our hospital are currently oxacillin-resistant. There is substantial regional variation in the sensitivity profile of Staphylococcus epidermidis. Methicillin-resistant Staphylococcus epidermidis has been identified as an important pathogen in patients who have an infection at the site of a total hip replacement⁴¹. Resistance to gentamicin has been associated with previous use of gentamicin-impregnated bone cement³⁹.

Staphylococcus species with resistance to vancomycin have not yet been encountered as a clinical problem, to our knowledge. There are concerns that chronic elution of vancomycin from antibiotic-impregnated bone cement could predispose to the emergence of a vancomycin-resistant Enterococcus in the bowel. However, the levels of vancomycin in serum following the use of vancomycin-loaded cement have been shown to be negligible⁵⁵, and an association between the use of vancomycin in cement and the isolation of vancomycin-resistant enterococci has not been demonstrated, to our knowledge. Vancomycin should not be used for the treatment of infections that can be treated adequately with alternative antibiotics.

Much interest recently has been focused on the ability of an infecting organism to produce a slime layer, or glycocalyx. This layer is made up of a variety of polysaccharides synthesized by the bacteria as well as a range of host molecules. The ability of the organism to produce a slime layer permits it to be divided into planktonic forms, which exist as individual free-floating cells, and sessile forms, which exist within a biofilm of glycocalyx. The production of a biofilm allows the organism to adhere to and survive on synthetic surfaces. Bacteria that exist within a biofilm are at least 500 times more resistant to antibiotics than the planktonic forms²⁰. They also are relatively resistant to complement activation and ingestion by neutrophils. Biofilms require a certain minimum time to form after the inoculation of the infecting organism. In vitro evidence has suggested that infections can be eradicated with antibiotics while the inoculated organism is still in a planktonic phase but not after a biofilm has formed⁵. This finding lends support to the use of débridement, administration of antibiotics, and retention of the prosthesis for the treatment of acute-onset infections in joints with solidly fixed components. Recent research has suggested that the efficacy of antibiotics in killing biofilm bacteria is greatly enhanced by the addition of a low electrical current^19,73. Possible therapeutic applications of electricity have yet to be explored.

Many species of Staphylococcus aureus and Staphylococcus epidermidis are slime producers. Most gram-negative organisms, with the notable exception of the Pseudomonas species, are poor slime producers. The eradication of pseudomonal infections also is complicated by slow rates of replication and a natural resistance to many antibiotics. There is little microbiological evidence to support contentions that other gram-negative organisms are especially difficult to eradicate, despite some clinical reports suggesting inferior results when the infecting organism was a gram-negative Bacillus^14,52,63. Lieberman et al., in a review of the results of a two-stage treatment protocol, were unable to find any association between infection with a gram-negative organism and the risk of recurrence of infection after treatment⁵¹. Tsukayama et al. recently reported the results of treatment of 106 periprosthetic hip infections in ninety-seven patients⁶⁹. In thirteen hips the infecting organism was a gram-negative Bacillus, and in all thirteen the infection was eradicated.

There is evidence that the material from which a component is made and the surface finish of the component may influence the ease with which infection may occur within the interstices of the prosthesis. Cordero et al., using an animal model, found that cobalt-chromium surfaces were more conducive to infection with Staphylococcus aureus than were titanium surfaces and that porous surfaces were more conducive to infection than were polished surfaces¹⁸. The lower prevalence of infection associated with titanium surfaces may be related to superior properties of osseointegration that allow the host tissues to adhere to the surface of the implant before any micro-organisms are able to adhere, elaborate glycocalyx, and cause a clinical yet indolent infection (this has been referred to as the "race for the surface"³⁵). The lower prevalence of infection associated with polished surfaces is probably a function of the smaller surface area for bacteria to adhere to and the shorter distances that host cells must travel in order to reach the surface of the component. In a series of in vitro experiments, Oga et al. found an increased prevalence of infection with coagulase-negative Staphylococcus in association with polymethylmethacrylate⁶⁰ and sintered hydroxyapatite surfaces⁵⁹, although impregnation of the polymethylmethacrylate with antibiotics appeared to inhibit bacterial adhesion⁵⁸.

A number of tests are available to determine the production of glycocalyx in laboratory cultures. However, the association between the production of glycocalyx by an organism and the development of an infection at the site of a total hip prosthesis is not sufficiently strong for the tests to have clear clinical relevance. Choosing between one and two-stage exchange procedures on the basis of production of a slime layer by the organism requires validation.

Classification of Periprosthetic Infections

Coventry, in 1975, described the natural history of infections associated with total hip arthroplasty²¹. Infection can be caused by contamination at the time of the operation. This type of infection can present acutely, usually within three weeks after the operation. It also can present in the form of an indolent, chronic, low-grade infection, which usually occurs at least eight weeks after the operation. The other mechanism of infection is hematogenous spread from a distant focus. This can happen at any time after the operation, and the presentation is similar to that of an acute infection.

Estrada et al. refined the classification of periprosthetic infections by the addition of a category to describe patients who had positive intraoperative cultures without other features of obvious infection²⁹. Those authors described postoperative infections as occurring either early (within one month after the operation) or late (more than one month after the operation). In addition, acute hematogenous infection may present at any stage in a hip joint that has been asymptomatic. Tsukayama et al. recently reported the results of treatment of 106 infections that were associated with total hip arthroplasty⁶⁹. The infections were treated with various protocols according to four clinical settings: positive intraoperative cultures, early postoperative infection, late chronic infection, and acute hematogenous infection. Infections that were diagnosed on the basis of positive cultures of specimens that had been obtained during a revision hip arthroplasty were treated with intravenous administration of antibiotics for six weeks without operative intervention, and a success rate of 90 per cent (twenty-eight of thirty-one) was reported. Early postoperative infections were treated with débridement, retention of the prosthesis, and administration of antibiotics; this protocol had a success rate of 71 per cent (twenty-five of thirty-five). Of the remaining ten infections in that group, eight were treated successfully with a subsequent exchange procedure. Late chronic infections were treated with use of a two-stage exchange protocol, and a success rate of 85 per cent (twenty-nine of thirty-four) was reported. Finally, acute hematogenous infections were treated with débridement, retention of the prosthesis, and intravenous administration of antibiotics; three of six infections were treated successfully with this protocol.

Operative Considerations in Revisions Performed because of Infection

The initial operative approach for the treatment of an infection at the site of a total hip prosthesis is identical regardless of whether the surgeon plans a definitive excision arthroplasty, a single-stage exchange, or a delayed exchange. In this regard, it is appropriate to emphasize a number of points of operative technique.

1. Old healed incisions should be used to gain access to the hip provided that the operative exposure is not compromised. This avoids the creation of unsightly and unnecessary so-called railway-track incisions, with the attendant risk of wound-edge necrosis. Closure of the wound at the end of the procedure is facilitated if active sinus tracts can be excised readily as part of the incision. Otherwise, sinus tracts should be irrigated thoroughly and cleared of debris and loose granulation tissue.

2. Antibiotics should be withheld until the hip-joint capsule has been incised and specimens of synovial tissue have been obtained for culture, even when the probable infecting organism has been identified by means of preoperative aspiration of the hip or culture of specimens from a draining sinus. This allows for confirmation of the infecting organism and helps to rule out the presence of a polyclonal infection. If the identity of the infecting organism is in doubt or is unusual, specimens also should be sent for Ziehl-Nielsen stains and mycobacterial cultures as well as for fungal studies. Patients who have clinical and radiographic evidence of chronic infection and who have received antibiotics orally or intravenously before referral are less likely to have a positive preoperative or intraoperative culture. In these instances, it is useful to perform a repeat aspiration of the hip after all antibiotics have been discontinued for a minimum of four weeks, provided that the patient's condition permits a delay in the definitive treatment. There may, however, be some patients for whom the cultures remain negative despite other features that are strongly suggestive of infection. It is our practice to manage these patients as if the hip were infected and to obtain intraoperative specimens of the periprosthetic tissue for culture and frozen-section analysis.

3. The choice of the operative approach should be based on the need to remove all foreign material and dead tissue, including bone, while at the same time avoiding devascularization of the tissues and creation of a new potential focus of infection. The importance of removing all particles of cement has been stressed^17,52, although some authors have found that retention of small quantities of cement did not adversely affect the clinical outcome^3,51. If the cement around the femoral component is loose, it may be possible to remove the cement from above without damaging the femur. However, if the cement remains solidly bonded to bone, extensive damage to the femur may result from attempts to remove the cement in a retrograde fashion and consideration should be given to exposing the femoral canal directly. This can be achieved readily with use of the extended trochanteric osteotomy as described by Younger et al.⁷⁷. We have been impressed by the ease with which solidly bonded cement can be removed with use of this technique and by the predictability of subsequent osseous union. If a so-called cortical window is used to gain access to distal cement, great care should be taken to ensure that the vastus lateralis muscle is not stripped from the window fragment and that the periosteal blood supply is maintained.

4. When all necrotic tissue and foreign material have been removed, the wound should be irrigated vigorously with copious amounts of saline solution in order to remove as much particulate matter as possible. Pulsed-lavage systems are very effective and should be used if available. In contrast to Weber and Lautenbach⁷², we have not been impressed by the value of continuous irrigation in the postoperative period other than as a recipe for an uncomfortable patient and a medical and nursing staff that is frustrated in its attempts to prevent the system from becoming blocked.

Treatment Protocols

Antibiotics without Operative Treatment

Antibiotics without operative intervention are most commonly used in the form of chronic suppressive therapy for periprosthetic infections when an operation is refused by the patient or is believed to be associated with an unacceptable risk³³. The infection is not eradicated but is controlled so that symptoms are minimized. Certain criteria must be fulfilled in order for a patient to be considered a suitable candidate for chronic suppressive therapy. Generally, these patients are considered medically unfit to have a major operation or, less commonly, they have refused operative treatment. In addition, the infecting organism must be known and must be sensitive to the chosen antibiotic. Finally, the antibiotic should be effective orally and should be well tolerated by the patient if reasonable compliance is to be expected. Side effects such as diarrhea or recurrent candidiasis usually result in the failure of treatment. The emergence of resistant strains as a result of prolonged single-agent therapy is another cause of failure of this form of treatment.

The newer fluoroquinolones have been shown to be effective in the treatment of implant-related infection caused by methicillin-susceptible Staphylococcus species²². The addition of rifampicin to antibiotic regimens also appears to be helpful⁷⁵. Drancourt et al. reported the results of a study on the use of oral ofloxacin with rifampicin for the treatment of infection with Staphylococcus associated with orthopaedic implants²⁴. Twenty-two hips that had a periprosthetic infection were included in the study population. Sensitivity to both antibiotics was a requirement for inclusion in the study, and antibiotics were continued orally for six months. The infection was eradicated in eight of the twelve joints that had a retained prosthesis after a follow-up of twelve to fifty-seven months. One failure of treatment was due to the patient's inability to tolerate the antibiotics, and another was due to the emergence of a resistant organism. Additional reports on this treatment protocol are necessary in order to determine if these results are maintained as the duration of follow-up increases.

Débridement with Retention of the Prosthesis

There is little argument about the necessity to remove a loose total hip prosthesis from a chronically infected joint. However, removal of a well fixed total hip implant that is associated with infection carries the risk of causing major damage to the remaining bone stock. It is therefore understandable that attempts have been made to define the circumstances in which the infection may be eradicated by débridement combined with systemic administration of antibiotics without removal of the prosthesis.

It is generally accepted that the results of débridement with retention of the prosthesis in patients who have a chronic infection are poor⁵⁶. This is in keeping with what we understand about the ability of infecting organisms to adhere to the surfaces of the implant and to survive within a slime layer that isolates the organism from host defense mechanisms and the effects of systemic antibiotics. However, we also know that the slime layer takes some time to form after inoculation and that there is a potential so-called window of opportunity while the infecting organism is still in its planktonic form. If the infection is treated intensively with adequate débridement and appropriate systemic antibiotics, eradication should be possible. Both postoperative and late hematogenous infections can present acutely, and it appears reasonable to treat both types of infection in this manner shortly after onset.

Difficulties with this approach revolve around the determination of the time of onset of the infection and the establishment of a cutoff time beyond which it is no longer reasonable to attempt to retain the implant. Additional difficulty arises from the inability to recognize dead infected tissues that will act as an ongoing nidus of infection.

Tsukayama et al. reported a 71 per cent rate of success with use of a protocol of operative débridement and intravenous administration of antibiotics to treat thirty-five early postoperative infections⁶⁹. They emphasized the importance of limiting this treatment method to infections that had developed less than one month postoperatively. Poor results were associated with implants that had been inserted without cement, leading those authors to suggest that such implants should be removed at the time of the débridement. The same authors reported success in eradicating three of six acute hematogenous infections⁶⁹. However, the small numbers of patients in that group precluded extensive analysis.

There are scant prospective data in the literature to guide the surgeon as to when an attempt should be made to retain the prosthesis. The primary difficulty appears to be the lack of accuracy with which acute infections can be distinguished from chronic ones. It is our practice to limit attempts at retention of the prosthesis to patients who have a solidly fixed implant and a very clear, short history of symptomatic infection, preferably with an identifiable cause such as a bacteremia resulting from a recent dental procedure. Patients in whom the distinction between acute and chronic infection cannot be made with confidence are managed as if they have a chronic infection.

Girdlestone Arthroplasty

A number of authors have reported the use of excision arthroplasty as a definitive procedure for the control of a periprosthetic infection rather than as the first stage in a staged reconstruction^{3,10,11,17,34,53}. The general consensus is that the procedure is highly effective in controlling infection and reducing pain; however, it usually is associated with a considerable loss of function. Patients who have had an excision arthroplasty walk poorly and almost always need walking aids. The absence of a fixed fulcrum for the abductor muscles results in a prominent lurching gait. Velocity and cadence are reduced, and energy expenditure is increased⁷¹. Limb-shortening may range from three to eleven centimeters but most typically ranges from four to six centimeters. This necessitates the use of external shoe-lifts that frequently are cosmetically unacceptable, especially to female patients.

Despite these drawbacks, excision arthroplasty may be the most appropriate definitive treatment for some patients, including those who are considered medically unfit to have an additional reconstructive procedure and those who are mentally impaired and may be unable to cooperate with the postoperative restrictions and the rehabilitation protocol after a complex reconstruction. A severe deficiency of bone stock also has been considered a contraindication to reimplantation⁵¹. However, initial encouraging results associated with the use of massive allografts suggest that a reconstruction can be performed successfully despite the poor bone stock^4,9. Furthermore, there is evidence to suggest that postoperative function is related to the level of resection of the proximal aspect of the femur, with worse results being seen in patients who have an extensive deficiency of femoral bone stock³⁴.

Excision arthroplasty is our treatment of choice for patients who have an infection at the site of a total hip prosthesis and an active history of intravenous drug abuse because such patients have a tendency toward poor compliance with postoperative instructions and a high risk of reinfection. Another group of patients for whom we consider excision arthroplasty to be the most appropriate treatment includes those who have major immunosuppression, especially after solid organ transplantation.

Single-Stage Exchange Arthroplasty

Interest in single-stage exchange arthroplasty was perhaps first aroused by the work of Buchholz and Engelbrecht, who used gentamicin-impregnated bone cement¹³. Buchholz et al. later reported a successful result in 77 per cent of 583 patients who were managed with a single-stage exchange for the treatment of infection; this rate increased to 90 per cent after subsequent exchange procedures¹⁴. During the course of that study, the amount of gentamicin in the cement was increased, erythromycin was temporarily added, and, toward the end of the study period, antibiotics were chosen on the basis of the sensitivity of the infecting organism. Systemic antibiotics were not used routinely. The duration of follow-up ranged from one to 131 months. The results after a longer duration of follow-up of patients from the same unit were later reported by Röttger⁶². The prosthesis had been retained in twenty-one of thirty-eight patients after a minimum duration of follow-up of ten years.

Carlsson et al., in 1978, reported on the use of gentamicin-impregnated bone cement in one and two-stage exchange arthroplasties performed because of infection¹⁵. Their protocol included the addition of 0.5 gram of gentamicin to each forty grams of bone cement and the use of systemic antibiotics. The exchange was completed during a single operative procedure in fifty-nine patients, and it was performed as a two-stage procedure in eighteen. The over-all rate of success was 78 per cent, and no significant difference was detected between the patients who had had a one-stage procedure and those who had had a two-stage procedure. It should be noted that twenty patients who had had a single-stage exchange were followed for less than one year and that antibiotics were administered for six months postoperatively.

The results after a longer duration of follow-up were later reported by Sanzén et al. in a study from the same center⁶⁵. The rate of success after the one-stage exchanges, at a minimum of two years, was 76 per cent (fifty-five of seventy-two procedures). However, aseptic loosening was noted in thirty (61 per cent) of forty-nine hips at five years.

The reported results of single-stage exchange arthroplasty were well summarized by Garvin and Hanssen³¹. They found that the cumulative success rate from sixteen reports of single-stage exchange arthroplasty performed with use of antibiotic-impregnated cement was 82 per cent (976 of 1189 hips), whereas the cumulative success rate from four reports of single-stage exchange arthroplasty performed without local delivery of antibiotics was 58 per cent (thirty-five of sixty hips). These data support the need for antibiotic-impregnated cement if a single-stage exchange is chosen. This recommendation also was supported by the results of single-stage exchange with antibiotic-impregnated cement as reported recently by Raut et al.⁶¹. In that study, 154 (84 per cent) of 183 patients were infection-free after a mean duration of follow-up of more than seven years. Almost one-third of the patients had an actively discharging sinus at the time of the revision, but this did not adversely affect the outcome. The protocol included the use of oral antibiotics for six weeks to three months.

The major advantage of a single-stage exchange procedure is self-evident. The avoidance of additional operative procedures is highly desirable for both the patient and society and is particularly important for patients who have several major medical problems, for whom the risks of additional procedures are cumulative. However, the potential benefits must be weighed against the slightly lower rates of eradication of infection that are observed after one-stage compared with two-stage procedures as well as against the difficulty of removing a solidly fixed cemented long or mid-length stem without destroying the remaining proximal femoral bone stock should the procedure fail to eradicate the infection. Furthermore, the insertion of an implant with cement is not appropriate in many revision procedures, particularly when bone stock in the proximal portion of the femur is deficient. Because one-stage exchange techniques require that the implant be inserted with antibiotic-impregnated cement, many patients cannot be managed with this technique. The need to insert the prosthesis with cement may be responsible for the high rates of aseptic loosening that have been reported for such patients⁶⁵.

Two-Stage Exchange Arthroplasty

In North America, periprosthetic infections of the hip are most commonly treated with a two-stage exchange arthroplasty, although the single-stage techniques remain popular in Europe. The principles of a two-stage exchange procedure include removal of the implant along with all cement containing infectious organisms and all dead or necrotic tissue, prolonged administration of antibiotics postoperatively, and eventual implantation of a new prosthesis. The popularity of this approach stems largely from reports of somewhat higher rates of eradication of infection compared with those associated with immediate-exchange protocols³¹. In a review of twelve reports of two-stage exchange procedures in which antibiotic-impregnated cement was used, Garvin and Hanssen found the cumulative rate of eradication of infection to be 91 per cent (385 of 423 hips)³¹. The rate for the nine studies in which antibiotic-impregnated cement was not used was 82 per cent (130 of 158 hips)³¹. These rates were somewhat higher than those in the reports of single-stage procedures³¹.

There are many variables even within two-stage exchange protocols. These include the type and duration of postoperative systemic antibiotic therapy, the timing of the reimplantation, the use of allograft bone in the reconstruction, and the choice of fixation (with or without cement). Additional variables include the use of antibiotic-loaded cement in the form of beads and the use of a temporary spacer device in the interim between the first and second stages.

The ideal duration and route of administration of antibiotic therapy have not been determined. Most protocols have included six weeks of intravenous administration of antibiotics^63,69. At least part of the advantage of the parenteral route probably stems from the more reliable administration of the antibiotic, usually by health-care workers. Adequate serum levels of many antibiotics can be achieved with use of the oral route, but compliance is always an issue when patients administer drugs to themselves. The appropriate dosage of antibiotics can be determined by measuring either bactericidal titers in serum⁵¹ or minimum inhibitory concentrations in culture media³¹. There is some evidence that the use of parenteral therapy for less than four weeks is associated with a higher rate of recurrence when the infection is caused by a more virulent organism⁵².

The interval between the first and second stages of a two-stage exchange procedure has varied widely, both between different reports and within individual reports. This interval has ranged from six days to more than six years⁵². Lieberman et al. reported the results of a protocol in which reimplantation was performed six weeks after an excision arthroplasty⁵¹. Their findings did not differ importantly from the results for patients in whom reimplantation was delayed for more than one year⁵². Our own protocol with use of the prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) includes four to six weeks of antibiotic therapy followed by repeat aspiration of the joint at a minimum of four weeks after discontinuation of the antibiotics²⁶. We proceed with reimplantation if the culture of the aspirate is negative and the clinical appearance, erythrocyte sedimentation rate, and C-reactive protein level are indicative of resolution of the infection. This approach minimizes the possibility of attempting a reconstruction in the presence of an unresolved infection.

There has been concern that the use of bone allograft for reconstruction after infection might be associated with a higher rate of recurrent infection because the allograft might act as a sequestrum. This concern is particularly pertinent given the frequency of major cavitary and segmental bone defects in patients who have an infection at the site of a total hip arthroplasty. Such major bone loss has been regarded by some authors as a contraindication to reimplantation after infection⁶³.

We are aware of only two reports that have dealt specifically with the use of allograft bone for reconstruction after infection. Berry et al. retrospectively reported on eighteen patients in whom various combinations of morselized and bulk allografts were used in the second stage of a two-stage exchange that was performed because of infection⁹. There were only two recurrent infections after a mean duration of follow-up of 4.2 years. Alexeeff et al. reported on eleven patients who had a revision with use of a massive structural allograft in the second stage of a two-stage exchange protocol⁴. There were no recurrent infections after a mean duration of follow-up of four years. All allografts united to host bone, and there was no major resorption of the graft apart from one small calcar graft that resorbed completely.

Most reports of exchange arthroplasty have described the results of reimplantation with use of components inserted with cement. To our knowledge, authors from only two centers have reported on large series of patients who had a revision total hip arthroplasty without cement after an infection. Nestor et al., in a report from the Mayo Clinic, described the results for thirty-four patients who had been managed with a two-stage exchange procedure with use of one of a variety of prostheses inserted without cement⁵⁷. Infection recurred in six patients (18 per cent) after a mean duration of follow-up of almost four years. Of the patients who did not have a recurrence of infection, six of twenty-eight had definite radiographic evidence of loosening and only fourteen of twenty-five were considered to have a satisfactory functional outcome. Those authors concluded that avoidance of the use of bone cement did not improve the rate of success.

A higher rate of success was reported recently by Lai et al., who described the results of two-stage exchange procedures that were performed with use of a variety of prostheses inserted without cement⁴⁶. They noted recurrent infection in five (13 per cent) of thirty-nine patients after a mean duration of follow-up of four years and reported a mean Harris hip score³⁷ of 91 points for the thirty-four remaining patients who did not have an infection.

Other Operative Options

Kostuik and Alexander reported on a series of fourteen patients who had had an arthrodesis of the hip, with use of a modified technique of the Association for the Study of Internal Fixation, for salvage of a failed total hip arthroplasty⁴³. Seven patients had a periprosthetic infection. The indications for the procedure were a young age, male gender, and strenuous functional demands. All hips eventually fused, and all patients were able to walk although they had a mean limb-length discrepancy of 4.6 centimeters.

Ablation of the limb also has been reported³⁰, but fortunately it is indicated only rarely.

Antibiotic-Loaded Cement and the Results with Use of the PROSTALAC System

The ability of thermostable antibiotics to elute from a bone-cement carrier has been widely documented in the literature^{2,6,8,12,23,28,38,42,45,48-50,54,64,67,70}. Therapeutic levels of tobramycin and vancomycin have been found in drainage fluid after they were used with cement between stages in the management of patients who had an infection at the site of a total hip arthroplasty²⁷. Tetracycline and chloramphenicol are not appropriate for use with bone cement because they are degraded by the exothermic curing reaction. The elution characteristics of Palacos bone cement (Merck, Darmstadt, Germany) are superior to those of other bone cements because Palacos cement has a higher surface porosity²⁸. The mechanical strength of cement is substantially weakened if large volumes of antibiotic powder⁴⁸ or antibiotics dissolved in liquid⁴⁹ are added. This is a concern only when the cement is being used for fixation of a prosthesis; it is not a problem when the cement is used solely as a vehicle for antibiotics between stages in an exchange procedure.

The use of acrylic cement as an antibiotic depot is associated with improved rates of eradication of infection after both one-stage and two-stage exchange arthroplasties³¹. In a two-stage exchange arthroplasty, the cement may be used both for the definitive reconstruction^32,51 and in the form of strings of beads inserted between stages^1,40.

Since 1986, we have been using an antibiotic-loaded implant between stages in a modified two-stage exchange protocol. This implant is known as the prosthesis of antibiotic-loaded acrylic cement; hence, the acronym PROSTALAC. The implant was designed to improve the patient's function between the first and second stages and to facilitate the definitive reconstruction by maintaining the soft tissues at their normal tension while providing the benefits of a local antibiotic depot.

The PROSTALAC includes a constrained acetabular component that is inserted with cement and a modular femoral component that consists of a stainless-steel endoskeleton surrounded by antibiotic-loaded cement. The femoral component is made intraoperatively with use of a series of molds. After thorough débridement and removal of all dead tissue and foreign material, the acetabular component is loosely cemented and fixation of the femoral component is achieved by means of a press-fit so that both components can be removed easily during the second stage without damaging the bone stock. A range of stem sizes and lengths is available to allow for the stabilization of hips with severe bone-stock deficiency. We most commonly use a combination of antibiotics consisting of 2.4 to 3.6 grams of tobramycin and 1.0 to 1.5 grams of vancomycin per package of bone cement. We avoid the use of wound-suction drains in order to encourage high levels of antibiotic within the infected tissues. Parenteral administration of antibiotics is continued postoperatively for four to six weeks. We proceed with definitive reconstruction if a culture of the hip aspirate, performed four weeks after the discontinuation of antibiotics, is negative and other indices suggest resolution of the infection. In our recent series of sixty-one patients, there was only one patient for whom the second stage of the exchange was delayed because of a positive culture of the hip aspirate. We believe that these organisms were contaminants because, in both cases, the organism that grew on culture was different from the initial infecting organism and the intraoperative cultures were negative. We have been impressed by the ease of exposure during the second stage as a result of appropriate soft-tissue tensioning by the temporary implant. Using this technique, we were able to eradicate infection in forty-five (94 per cent) of forty-eight patients at a minimum duration of follow-up of two years⁷⁶.

Treatment of Tuberculous Infections

Tuberculosis is a rare cause of periprosthetic infection; the reports that we are aware of consist only of isolated cases⁴⁴. A tuberculous infection may be diagnosed in the early postoperative period by means of a mycobacterial culture or a histological examination of specimens obtained at the time of a primary arthroplasty. Alternatively, the infection may present years after a primary arthroplasty as an unexpected pathogen in association with a loose prosthesis. There is some evidence, in case reports, that a solidly fixed prosthesis may be retained and that treatment can be successful with use of antituberculous chemotherapy alone⁶⁸. However, such treatment is unlikely to be successful in a patient who has a loose prosthesis; in such a situation, the prosthesis should be removed. There is little information in the literature to guide the surgeon as to the timing or advisability of reimplantation, although it seems reasonable to perform the procedure after completion of a full course of antituberculous chemotherapy, provided that the clinical, radiographic, and hematological indices suggest full resolution of the infection.

NOTE: The authors thank Mike Noble, M.D., F.R.C.P.(C), for his assistance in the preparation of this manuscript.

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