1 Orthopaedic Clinic and 2 Division of Infectious Diseases, Geneva University Hospital, 24 rue Micheli-du-Crest, 1211 Geneva 14, Switzerland; 3 Division of Infectious Diseases, Garches University Hospital, 104, Boulevard R. Poincaré, 92380 Garches, France
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Abstract |
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Keywords: total joint infection, exchange prosthesis, one-stage prosthetic reimplantation, two-stage prosthetic reimplantation
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Introduction |
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The treatment of infection following total joint arthroplasty involves surgery and antimicrobial therapy. Surgical alternatives include debridement and prosthesis retention; re-implantation with either a single- or two-stage exchange arthroplasty; arthrodesis (knee); and excision arthroplasty (shoulder, hip). There are no prospective trials comparing different combinations of surgical procedures. Antimicrobial therapy should always be combined with surgery. When used alone, as with chronic suppressive treatment of infection, antimicrobial therapy is rarely successful.
The duration of the infection is an important factor in determining optimal treatment. With an infection of greater than 1 month duration, it has been postulated that biofilm-associated bacterial disease has progressed to such a degree that cure with prosthetic retention is less achievable than with resection.2
As regards surgical procedures, two-stage re-implantation is considered the standard in the treatment of septic prosthetic joints, but is expensive, may result in large skeletal defects, long periods of hospitalization, severe functional impairment and occasionally death. This has stimulated re-visiting other surgical techniques and new concepts in antimicrobial therapy. The main difficulty in comparing reported studies in the literature is the wide variability concerning a number of specific variables, including: the host immune system;3 the type and route of infection; the surgical procedure; the bacteria cultured; and the antibiotics employed. We will review some of the leading microbiological and clinical studies published in the last decade that have led not only to a better understanding of the disease, but also to novel and more controversial therapeutic approaches.
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Surgical therapy: controversy between two-stage and one-stage revision |
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For these reasons, there is enthusiasm for a one-stage revision. The one-stage re-implantation technique involves the excision of all prosthetic components and infected tissue, and the implantation of new components during the same operation. It is applied mainly for hip prostheses. For other prosthetic joints (knee, shoulder, elbow), a two-stage exchange, with the use of antibiotic-loaded cement, is preferred.
Whereas a one-stage revision procedure appears to be much more attractive because it allows earlier mobility, it exposes the patient to the risk that remaining bacteria will lead to re-infection of the newly implanted prosthesis. This procedure is currently used in many centresmostly for hip prosthesiswith good results reported in 80% of patients. The consensus is that a one-stage revision should be used only if the following specific conditions are met: there is no need for a bone graft; no fistula is present; the met is not due to difficult-to-treat bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa; the debridement is extensive, such that an independent surgeon arriving mid-operation should not be able to determine that there was a pre-existing infection; and cement loaded with a targeted antibiotic will always be used. Commercially available cement can be obtained for a few antibiotics, usually aminoglycosides, clindamycin, colistin or erythromycin. Aminoglycosides are not ideal for infection resulting from MRSA, which are often resistant to such therapy.8 Many surgeons prepare the cementantibiotic mixture during surgery, with local recipes that have not undergone strict validation.
The microorganism should be cultivated before surgery by biopsy and/or aspiration cultures so that it may be treated with the appropriate pre-operative or intra-operative antibiotic regimen (which will expanded upon in the section Antimicrobial therapy). The optimal length of post-operative antibiotic therapy is not known. Controlled studies are mandatory to address the issue of one-stage versus two-stage revision, as well as to define the ideal duration of antibiotic therapy.
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Surgical therapy: definitive excision arthroplasty (hip) or arthrodesis (knee) |
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Is conservative surgical therapy possible? |
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A recent mathematical model has been performed on the clinical effectiveness of two different management strategiesprosthesis removal versus debridement and prosthesis retentionfor the infected, well-fixed, total hip arthroplasty in the elderly.12 This analysis considered that removal of a stable implant can be a difficult operation in itself, added to which is the subsequent morbidity of immobilization. Initial debridement and retention, on the other hand, may be associated with increased patient survival and have a favourable cost-effectiveness ratio for all patients. Debridement and retention were shown to increase life expectancy by 2.22.6 quality adjusted life months, and had a favourable cost-effectiveness ratio.
Other surgical alternatives, such as re-implantation with single-stage exchange, arthrodesis or definitive excision are not evaluated in this mathematical model.
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Antimicrobial therapy |
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Nevertheless, the addition of rifampicin to antibiotic regimens for treatment of prosthetic joint infection has been shown to be beneficial, and in addition it is believed that combination therapy is more effective in preventing the failure of treatment secondary to the emergence of resistant organisms. Penicillin-susceptible streptococcal prosthetic joint infection treated with prosthesis retention and intravenous penicillin, or once-daily ceftriaxone followed by oral amoxicillinrifampicin, appears to be an effective treatment modality.11 The main advantage of the combination of a quinolone plus rifampicin is their excellent bioavailability, allowing oral administration, with serum levels comparable to those obtained during intravenous therapy. In addition, both drugs display high levels of intracellular penetration and activity against intracellular Staphylococcus species.
Zimmerli and colleagues13 reported a double-blind, randomized, controlled clinical trial assessing the role of rifampicin in 33 patients with staphylococcal infection in a variety of orthopaedic implants, including eight following arthroplasty. All patients underwent surgical debridement and were randomized to long-term ciprofloxacin with or without rifampicin. The combination rifampicinciprofloxacin achieved a cure without removal of the implant (relapse after follow-up of 35 months: 0% in the ciprofloxacinrifampicin group versus 42% in the placebo and ciprofloxacin group). The authors did not explicitly outline the results for the total arthroplasty group. Nevertheless, these result are promising for the treatment of patients who are unable to have extensive surgery.
A different approach has been pursued by others. Drancourt et al.14 reported on a non-randomized trial comparing a combination of ofloxacin or fusidic acid and rifampicin in 46 patients with prosthetic infections caused by staphylococcus. Patients with an infected hip implant were treated for 6 months, with removal of any unstable prosthesis after 5 months treatment. Those with infected knee prostheses were treated for 9 months, with removal of the knee prosthesis after 6 months of therapy. Treatment was successful for 11 (55%) of 20 patients treated with rifampicin and fusidic acid and for 11 (50%) of the 22 treated with rifampicin and ofloxacin.
Unfortunately, the use of quinolones may be limited in the future as quinolone resistance continues to increase. High doses of oral co-trimoxazole led to a successful outcome in only six of 12 (50%) arthroplasty patients; three of the four failures occurred because of intolerance to the drug.15
Pseudomonas aeruginosa and MRSA prosthetic and bone infection remain difficult challenges, and two-step exchange revision remains the rule. Brouqui et al.16 utilized a combination of ceftazidime and ciprofloxacin, and achieved a cure in nine of nine patients with P. aeruginosa-infected osteosynthetic material, and four of five patients with hip and knee prostheses, without removing the implants. Ariza et al.17 have proposed that most failures in MRSA prosthetic infections are associated with hetero-resistance to vancomycin. For MRSA following surgery, continuous outpatient perfusion of vancomycin with steady-state plasma levels of 25 mg/L for several months, has been used with success.18 Teicoplanin administered once daily for very prolonged periods appears also to be efficacious.19 The duration of antibiotic therapy for the treatment of prosthetic infections is not clearly defined and ranges from 6 weeks to 6 months, with 6 weeks being the most common.
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Chronic suppressive therapy |
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Conclusions and challenges |
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Acknowledgements |
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We thank Richard Stern for technical assistance and for his critical review of the manuscript.
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Footnotes |
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References |
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Zimmerli, W., Widmer, A. F., Blatter M. et al. (1998). Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group. Journal of the American Medical Association 279, 153741.
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