Prosthetic Joint Infections: Bane of Orthopedists, Challenge for Infectious Disease Specialists

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1 INVITED ARTICLE CLINICAL PRACTICE Ellie J. C. Goldstein, Section Editor Prosthetic Joint Infections: Bane of Orthopedists, Challenge for Infectious Disease Specialists Joseph R. Lentino Section of Infectious Diseases, Medical Service, Edward Hines, Jr., VA Hospital, Hines, and Infectious Diseases, Department of Medicine, Loyola University Medical Center, Chicago, Illinois Prosthetic joint infections (PJIs) occur in of all primary hip or knee arthroplasties. The mortality rate attributed to PJIs may be as high as 2.5. Substantial morbidity is associated with a loss of mobility, although this is temporary. The costs associated with a single episode of PJI are $50,000 per episode, exclusive of lost wages. Risk factors that increase the occurrence of PJI include revision arthroplasty, time in the operating room, postoperative surgical site infection, and malignancy. Pain is the most consistent symptom. Staphylococcus species are the most common organisms isolated from PJI sites. Two-stage revision is superior to single-stage revision or to debridement with prosthesis retention. Long-term antibiotic suppression and/or arthrodesis are useful for patients too frail to undergo extensive surgery. Using an optimal approach, recurrent infection occurs in!10 of previously infected joints. Prosthetic joint infections (PJIs) of total hip arthroplasty (THA) or total knee arthroplasty (TKA) occur with an incidence of for primary THA or TKA, respectively, whereas revision THA or TKA carries a respective infection risk of 3.2 or 5.6 [1] (table 1). The estimated cost of treating an infected arthroplasty is 1$50,000 per episode [2]. The attendant mortality was estimated, in the 1970s and 1980s, to be between 2.7 and [2] in older patients. More current studies have estimated the mortality attendant to surgical intervention for PJI to be for 65-year-old patients and 2 7 for 80-year-old patients [3]. Fisman et al. [3] estimated a 2-fold increase in the probability of death during the 3 months after resection arthroplasty. The mortality reported since 1989 has ranged between 1 and 2.7 [4 10]. Berbari et al. [2] performed a large case-controlled prospective study of patients undergoing THA at the Mayo Clinic between 1969 and They reported that the 4 most significant factors predictive of PJI were (1) postoperative surgical site infection (OR, 35.9), (2) a National Nosocomial Infection Received 22 August 2002; accepted 17 January 2003; electronically published 14 April Reprints or correspondence: Dr. Joseph R. Lentino, Section of Infectious Diseases, Edward Hines, Jr. VA Hospital, 5th Ave. at Roosevelt Rd., Hines, IL (Joseph. Lentino@med.va.gov). Clinical Infectious Diseases 2003; 36: This article is in the public domain, and no copyright is claimed /2003/ Surveillance (NNIS) score 12.0 (OR, 3.9), (3) concurrent malignancy (OR, 3.1), and (4) prior THA (OR, 2.0). NNIS scores are calculated from 0 3 points, with 1 point each for anesthesia scores 13, operating room time 13 h, and wound class 3. The mean time for follow-up in this prospective study was 512 days. Despite the risks inherent in THA or TKA, both are much safer procedures now than in the past [11]. Four decades ago, 1 in 10 patients developed infection. Aggressive measures, including use of laminar air flow rooms, body exhaust suits, and judicious perioperative antibiotics, have reduced the risk of infection to 0.3 in THA and 0.5 in TKA. These results will be difficult, if not impossible, to improve. Clinically, pain is the single most frequent symptom and is often exacerbated by motion. Local warmth, tenderness, drainage, and effusions are helpful in diagnosing infection. They are not as universally present as is pain [1]. A normal erythrocyte sedimentation rate (ESR), along with a normal C-reactive protein level, would suggest a very low risk of infection [1]. The most frequently recovered isolates are Staphylococcus aureus and Staphylococcus epidermidis [2, 5 7, 12 16] in PJI infections. Table 2 presents data on the incidence of specific organisms recovered from infected THA or TKA. Gram-positive cocci predominate. Although there have been few evidencebased data to support a more aggressive surgical approach to infection with gram-negative bacilli, the impact of the recovered CLINICAL PRACTICE CID 2003:36 (1 May) 1157

2 Table 1. Risk factors for prosthetic joint infection in primary versus revision arthroplasty of the hip or knee. Arthroplasty procedure Primary Revision a Risk factor Rheumatoid arthritis Diabetes mellitus Poor nutritional status Obesity Concurrent UTI Steroid therapy Malignancy Postoperative surgical site infection NNIS 1 0 (see text) Prior joint surgery Prolonged operating room time Preoperative infection (of teeth or skin, or UTI) NOTE. NNIS, National Nosocomial Infection Surveillance score; UTI, urinary tract infection. a If done for infection. etiologic agent on the approach to management is substantial. There exists a bias, based on older studies, that gram-negative bacilli in a PJI most often require total removal of the prosthesis and a 2-stage revision, whereas some PJIs due to gram-positive cocci can be treated with debridement and retention of the prosthesis [12] or a 1-stage revision procedure [6, 7, 17]. Various maneuvers to enhance the recovery of an isolate from the infected prosthesis have been attempted. These include direct inoculation of blood-culture vials with intraoperatively recovered joint aspirate [] and immersion of the infected prosthesis into an anaerobic jar, followed by ultrasonography to loosen adherent organisms [19]. Histological evaluation of frozen section of intraoperatively obtained tissue from the prosthetic joint has been shown to have increased sensitivity and better negative predictive value than Gram stain alone in establishing infection [20]. In the current era, radiological evaluation includes not only plain x-ray and CT but MRI [21] and even positron emission tomography (PET) scans [22]. Table 3 reviews the radiological and nuclear medicine imaging techniques available or under study for their utility in diagnosing PJI [21 29]. With modifications, standard MRI can yield diagnostic-quality images, especially along the femoral component of THA. PET scan has a sensitivity of 90, a specificity of 89.3, and an accuracy of 89.5 in detecting THA infection. Its accuracy for TKA infection is 77.8 [22]. Table 3 should provide an overview of the developments within this area. The diagnosis of PJI requires clinical correlation. APPROACHES TO THERAPY FOR THA INFECTIONS The reader should note that the following is not an exhaustive review of the literature but represents my selections and reflects my opinions. Single-stage revision arthroplasties of the hip can be successfully performed with excellent outcomes. This approach has significant advantages that weigh in its favor: decreased duration of immobility, reduced cost, improved stability of the limb, and decreased patient morbidity [17]. However, to be successful, 1-stage exchanges require appropriate perioperative antibiotic treatment and meticulous operative techniques. Ure et al. [6] described 20 patients who had an average of 10 years free of infection in the postoperative period with the use of antibiotic-impregnated cement. It should be noted that a large number (45) of the patients had a coagulasenegative Staphylococcus species PJI. Streptococcus species and S. aureus were recovered from 25 of the patients. Perioperative antibiotics were administered parenterally for an average of 5 weeks (range, 2 weeks) and then orally for 4.7 months (range, months). These authors concluded that, with careful selection of patients, the 1-stage hip revision was as successful as a delayed exchange procedure. They specifically excluded patients who were immunosuppressed, had infection with known gram-negative or methicillin-resistant organisms, or had major skin, soft-tissue, or bone defects that made it impossible to obtain a closed wound or a stable implant. Miley Table 2. Microbial etiology of prosthetic joint infections. Procedure, infection type Percentage Total hip arthroplasty [2, 5 7] Staphylococcus aureus Coagulase-negative staphylococci Streptococci Gram-negative bacilli Anaerobic organisms Enterococcus Culture negative 1 12 Polymicrobial (mixed) Other 2 5 Total knee arthroplasty [12 16] Staphylococcus aureus Coagulase-negative staphylococci Streptococci Gram-negative bacilli Anaerobic organisms Enterococcus Culture negative Polymicrobial Other CID 2003:36 (1 May) CLINICAL PRACTICE

3 Table 3. joints. Radiological and nuclear medicine imaging of infected prosthetic Type of imaging Sensitivity, Specificity, PPV, NPV, Radiological X-ray ND ND ND ND CT ND ND ND ND MRI ND ND ND ND Nuclear medicine Tc bone scan Gallium scan ND ND 111 IN leukocyte scan Combined bone/wbcs Tc HMPAO leukocyte scan Tc antigranulocyte antibody scan In-IgG scan ND ND Tc-ciprofloxacin, knee ND ND Infection, hip ND ND ND ND FDG-PET scan, knee ND ND FDG-PET scan, hip ND ND NOTE. Data are from [17 25]. FDG, fluorodeoxyglucose; HMPAO, hexamethyl propyleneamine oxime; In, indinium; ND, no data available; NPV, negative predictive value; PET, positron emission tomography; PPV, positive predictive value; Tc, technetium. et al. [17], in an earlier report, evaluated 101 patients with an 87 success rate after 1-stage revision. They limited 1-stage revision arthroplasty to those patients who had infections with monomicrobial gram-positive organisms susceptible to a minimum of 3 antibiotics, no evidence for superinfection or draining sinus tracts, and relatively healthy surrounding soft tissue and femoral cortical bone. Patients who did not meet these inclusion criteria were treated with girdlestone resection. Finally, Jackson and Schmalzried [7] reviewed stage hip revisions with an average duration of follow-up of 4.8 years (range, years); 83 were deemed to be free of infection. Antibiotic-impregnated cement was used in 99 of the cases. Parenteral antibiotic use varied from 24 h to 8 weeks in length, and oral antibiotic use varied from none given to 8 months duration after parenteral therapy. This is one of the largest studies of this procedure. Factors predicting a successful outcome included an absence of wound complications after primary THA, good general health of the patient, methicillinsensitive staphylococcal or streptococcal infection, and an organism sensitive to the antibiotic mixed into the bone cement. Predictors of failure included polymicrobial infection, gramnegative organisms, and methicillin-resistant staphylococci. Two-stage THA revision was compared with 1-stage revision THA for infections caused by coagulase-negative staphylococci. [8]. Ninety-one patients with cemented prostheses and monomicrobial infection were evaluated for outcome after revision arthroplasty. Seventy-two patients had 1-stage revision, whereas 8 of 19 had a 2-stage revision. Although 83 of the patients with 1-stage revision were free of infection at a mean of 45 months, all 8 patients who had undergone the 2-stage procedure were had no infection after 21 months of follow-up. Problems with this study included the small number of patients who completed the 2-stage procedure and the short duration of follow-up. The authors found no differences in outcome of the patients who had undergone the 1-stage procedure on the basis of susceptibility of the isolate to gentamicin impregnated into the cement, presence or absence of sinus tract drainage, and elevated ESR (140 mm/h). Debridement with retention of infected THA was advocated by Fisman et al. [3] on the basis of a mathematical model of clinical and cost effectiveness. With the increasingly elderly population at risk for THA revision, the benefits of reduced morbidity, less immobilization, and rehabilitation make debridement with retention an attractive choice. However, there are 4 cardinal assumptions made in this model for it to be cost effective. First, patients must not have unstable prostheses or gram-negative infections. Second, all patients receive 6 weeks of antibiotics after debridement. Third, debridement occurs within 30 days of the onset of clinical symptoms. Fourth, to make this approach cost effective, enough older patients die before needing resection arthroplasty. There was an annual relapse rate of 30 with all infections, and, for those patients CLINICAL PRACTICE CID 2003:36 (1 May) 1159

4 with delayed debridement 130 days for S. aureus infection, the relapse rate was 80. Brandt et al. [9] performed a retrospective study of S. aureus PJI. The 1- and 2-year treatment failure rates (defined as a relapse of infection) were 54 and 69, respectively. A median of 4 procedures/patient was required to control the infection. Patients who had debridement delayed beyond 2 days after the onset of symptoms had a 12-fold (82 vs. 30) increased risk of failure at 1 year after surgery. Although their study was small, with 33 infected hips treated by debridement, there were 9 patients who remained free of infection, whereas the majority (24/33) either failed to respond or relapsed within 2 years. Long-term antibiotic suppression of infected THA without surgery can be successful in up to 60 of patients. Girdlestone resection of the hip is indicated for patients with severe bone loss, polymicrobial infection, virulent isolates, concurrent osteomyelitis, and unhealthy soft tissues. When a girdlestone resection becomes infected, long-term antibiotic administration is required to satisfactorily eradicate or suppress the infection. Long-term antibiotic suppression is an approach that should be reserved for the most medically fragile patients. There are no guidelines as to the duration or durability of such an approach. Drug toxicity, side effects, and potential antibiotic resistance are all possible consequences. Two-stage revision of infected THA is the procedure most often used in the United States. The majority of patients who present with PJI for revision THA do not meet the inclusion criteria for debridement and retention proposed by Fisman et al. [3]. Rather, polymicrobial infection, a lack of positive cultures from the infected joint, delay beyond 30 days from onset to presentation and loosened prostheses make that option unrealistic [30]. The majority of patients present with several months of pain, extended periods of infection, and consequent implant instability, making it more likely that a 1- or 2-stage implant exchange will be required. Success rates of can be achieved with 1-stage revision. Two-stage revision carries a 9 risk of reinfection or failure that is, it has a 91 success rate [31]. The importance of antibiotic-impregnated cement is lessened with the 2-stage procedure because of the interval of 6 weeks to 6 months during which time the patient can receive specific antimicrobial therapy. Cementless THA revision with reimplantation beyond 1 year after resection was associated with a 4-fold decrease in reinfection (27 vs. 7), compared with earlier reimplantation. The use of antibiotic-impregnated cement for THA improved the outcome. However, the study was smaller, with only 82 patients, and performed during an earlier era [10], when there was a more limited choice of antibiotics. Nonetheless, the 2-stage procedure remains the surgical option most frequently selected for the revision of an infected joint. APPROACHES TO THERAPY FOR TKA INFECTIONS In the case of 2-stage TKA revisions [30] success rates of are noted with follow-up periods of years. Mont et al. [13] prospectively compared 35 patients who underwent 2-stage TKA reimplantation after 6 weeks of antibiotics with 34 patients who had reimplantation deferred for an additional 4 weeks of antibiotic therapy, at which time a repeat culture of the joint was performed. They found that 3 of 34 patients for whom implant was delayed had positive cultures and required an additional 6 weeks of antibiotics; 1 patient, despite having a negative culture, had a recurrent infection. In comparison, among the first group of patients, who had TKA reimplantation after 6 weeks of antibiotic therapy, 5 (14) of 35 had recurrent infection. One way to look at these data is that, even with a 6-week-long course of therapy directed against the initial recovered pathogens, up to 9 (13) of 69 had recurrent infection. Similar results were reported by Goldman et al. [14] in an earlier study. Among the 60 patients they monitored for up to 7.5 years, 6 had had reinfection; 6 additional patients had aseptic loosening. Single-stage revision of infected TKA was noted by Bengston and Knutson [15] to have similar outcome to 2-stage procedures. Among 107 knees undergoing the procedure, 81 had clinical cure, regardless of the revision procedure selected. Goksan and Freeman [16] reported 1-stage revision to be reasonable, because only 1 of their patients developed a recurrent infection. Patients were monitored for up to 10 years after procedure. Rand and Bryan [32], in an earlier study, reported a 36 success rate 5 of 14 patients remained free of infection when reimplantation was performed within 14 days of infected TKA removal. Recently, Fansa et al. [33] found that the 2-stage procedure was superior to the 1-stage replacement in patients who underwent concurrent muscle-flap coverage. The reader should note that the data are very limited. Most patients in the above studies had infection with low-virulence organisms, such as coagulase-negative staphylococci. Debridement and retention of a TKA can be attempted by arthroscopic surgery. Proper selection of patients includes those with!7 days of symptoms and no radiological signs of osteitis or prosthetic loosening. Patients who are medically unstable or who are taking anticoagulation therapy can have a successful outcome with this approach. When combined with antibiotic suppression [34], 40 of patients do not require subsequent implant removal. Bengston and Knutson [15] did not find debridement and antibiotic therapy to be useful, resolving infection in only 37 (24) of 154 knees. Not all patients qualify for joint replacement. Windsor et al. [35] suggested that medically compromised patients with rheumatoid arthritis should instead have arthrodesis of the joint. In summary, there is no single approach that is best. Patient 1160 CID 2003:36 (1 May) CLINICAL PRACTICE

5 preference and health status need to be considered. Orthopedic surgeons assess the health of the infected bone and soft tissues. That consideration and the organism(s) recovered and their antibiotic susceptibility will dictate the approach to therapy. Infectious diseases specialists should advise surgeons on the optimal therapy, dosing, route of administration, and duration. We monitor these patients simultaneously and actively participate in their postoperative management. The diagnosis of PJI is often difficult, and treatment is prolonged, complicated, and expensive. Although its reported incidence is now!1 for all implanted joints [11], the occurrence of an episode of infection is a medical and surgical disaster for the individual patient. It is questionable whether randomized, prospective studies large enough to establish a difference in outcome between surgical approaches will ever be performed. We are, therefore, left to draw conclusions from small caseseries reports. Although 2-stage delayed reimplantation seems to be the most efficacious in terms of infection-free status for both THA and TKA infections, other approaches may be of benefit to individual patients. It seems clear that even debridement and retention may be successful under optimal conditions. References 1. Hanssen AD, Rand JA. Evaluation and treatment of infection at the site of a total hip or knee arthroplasty. AAOS Instruct Course Lect 1999; 48: Berbari EF, Hanssen AD, Duffy MC, et al. Risk factors for prosthetic joint infection: case-control study. Clin Infect Dis 1998; 27: Fisman DN, Reilly DT, Karchmer AW, Goldie SJ. Clinical effectiveness and cost-effectiveness of 2 management strategies for infected total hip arthroplasty in the elderly. Clin Infect Dis 2001; 32: Powers KA, Terpenning MS, Voice RA, Kauffman CA. Prosthetic joint infections in the elderly. Am J Med 1990; 88:5N Crockarell JR, Hanssen AD, Osmon DR, Morrey BF. Treatment of infection with debridement and retention of the components following hip arthroplasty. J Bone Joint Surg 1998; 80: Ure KJ, Amstutz HC, Nasser S, Schmalzried TP. Direct-exchange arthroplasty for the treatment of infection after total hip replacement. J Bone Joint Surg 1998; 80: Jackson WO, Schmalzried TP. Limited role of direct exchange arthroplasty in the treatment of infected total hip replacements. Clin Orthop 2000; 381: Hope PG, Kristinsson KG, Norman P, Elson RA. Deep infection of cemented total hip arthroplasties caused by coagulase-negative staphylococci. J Bone Joint Surg Br 1989; 71: Brandt CM, Sistruck WW, Duffy MC, et al. Staphylococcus aureus prosthetic joint infection treated with debridement and prosthesis retention. Clin Infect Dis 1997; 24: McDonald DJ, Fitzgerald RH Jr, Ilstrup DM. Two-stage reconstruction of a total hip arthroplasty because of infection. J Bone Joint Surg 1989; 71: Lidgren L. Joint prosthetic infections: a success story [editorial]. Acta Orthop Scand 2001; 72: Peersman G, Laskin R, Davis J, Peterson M. Infection in total knee replacement. Clin Orthop 2001; 392: Mont MA, Waldman BJ, Hungerford DS. Evaluation of preoperative cultures before second-stage reimplantation of a total knee prosthesis complicated by infection. J Bone Joint Surg Br 2000; 82: Goldman RT, Scuderi GR, Insall JN. 2-stage reimplantation for infected total knee replacements. Clin Orthop 1996; 331: Bengtson S, Knutson K. The infected knee arthroplasty. Acta Orthop Scand 1991; 62: Goksan SB, Freeman MAR. One-stage reimplantation for infected total knee arthroplasty. J Bone Joint Surg 1992; 74: Miley GD, Scheller, AD Jr, Turner R. Medical and surgical treatment of the septic hip with one-stage revision arthroplasty. Clin Orthop 1982; 170: Levine BR, Evans BG. Use of blood culture vial specimens in intraoperative detection of infection. Clin Orthop 2001; 382: Tunney MM, Patrick S, Gorman SP, et al. Improved detection of infection in hip replacements. J Bone Joint Surg Br 1998; 80: Spangehl MJ, Masri BA, O Connell JX, Duncan CP. Prospective analyses of preoperative and intraoperative investigations for the diagnosis of infection at the sites of two hundred and two revision total hip arthroplasties. J Bone Joint Surg Br 1999; 81: White LM, Kim JK, Mehta M, et al. Complications of total hip arthroplasty: MRI imaging initial experience. Radiology 2000; 215: Zhuang H, Duarte PS, Pourdehnad M, et al. The promising role of F-FDG PET in detecting infected lower limb prosthesis implants. J Nucl Med 2001; 42: Ivaneeviae V, Perka C, Hasart O, Sandrock D, Munz DL. Imaging of low-grade bone infection with a technetium-99m labeled monoclonal anti-nca-() Fab fragment in patients with previous joint surgery. Eur J Nucl Med Mol Imaging 2002; 29: Larikka MJ, Ahonen AK, Junila JA, Niemela O, Namalainen MM, Syrjala HP. Improved method for detecting knee replacement infections based on extended combined 99mTc-white blood cell/bone imaging. Nucl Med Commun 2001; 22: Yapar Z, Kibar M, Yapar AF, Togrul E, Kayaselcuk U, Sarpel Y. The efficacy of technetium-99m ciprofloxacin (infection) imaging in suspected orthopedic infection: a comparison with sequential bone/gallium imaging. Eur J Nucl Med 2001; 28: Joseph TN, Mujtaba M, Chen AL, et al. Efficacy of combined technetium-99m sulfur colloid/indium-111 leukocyte scans to detect infected total hip and total knee arthroplasties. J Arthroplasty 2001; 16: Spangehl MJ, Younger ASE, Masri BA, Duncan CP. Diagnosis of infection following hip arthroplasty. AAOS Instruct Course Lect 1998; 47: Weissman BN. Imaging of total hip replacement. Radiology 1997; 202: Eustace S, Shah B, Mason M. Imaging orthopedic hardware with an emphasis on hip prostheses. Orthop Clin North Am 1998; 29: Saleh K, Callaghan J, Gioe T, et al. Septic joint replacement: an orthopedic perspective [letter]. Clin Infect Dis 2002; 34: Robbins GM, Masri BA, Garbuz DS, Duncan CP. Primary total hip arthroplasty after infection. AAOS Instruct Course Lect 2001; 50: Rand JA, Bryan RS. Reimplantation for the salvage of an infected total knee arthroplasty. J Bone Joint Surg Am 1983; 65: Fansa H, Plogmeier K, Schenk K, Schneider W. Covering extensive soft tissue defects in infected knee endoprostheses by gastrocnemius flap [in German]. Chirurgie 1998; 69: Waldman BJ, Hostin E, Mont MA, Hungerford DS. Infected total knee arthroplasty treated by arthroscopic irrigation and debridement. J Arthroplasty 2000; 15: Windsor RE, Insall JN, Urs WK, Miller DV, Brause BD. Two-stage reimplantation for the salvage of total knee arthroplasty complicated by infection. J Bone Joint Surg Am 1990; 72: CLINICAL PRACTICE CID 2003:36 (1 May) 1161