Journal of Infection (2010) 61, 443e448

www.elsevierhealth.com/journals/jinf

REVIEW

Prosthetic joint infection: Recent developments in diagnosis and management

Maria Adriana Cataldo a, Nicola Petrosillo a, Michela Cipriani b, Roberto Cauda b, Evelina Tacconelli b,*
a 2nd Infectious Diseases Division, National Institute for Infectious Diseases, Lazzaro Spallanzani, Via Portuense, 292 00149 Rome, Italy b  Department of Infectious Diseases, Universita Cattolica, Largo F. Vito, 1 00168 Rome, Italy

Accepted 29 September 2010 Available online 7 October 2010

KEYWORDS
Prosthetic joint infection; Diagnosis; Therapy

Summary Over the past years there has been a signicant increase in the number of joint prosthesis replacements worldwide. The most serious complication of joint prosthesis is infection with an incidence of 1.5e2.5% for primary interventions and up to 20% for revision procedures. The mortality rate ranges between 1% and nearly 3%. The economic cost of this complication is up to $50,000 per patient and $250,000 million per year. A major issue in the management of prosthetic joint infection (PJI) is the relative difculty in making a diagnosis so to cause a signicant effect on the prognosis. Goals of the treatment are to eradicate infection, prevent its recurrence and preserve mechanical joint function. In this review we focus on the value of traditional and newer diagnostic tests and we discuss management and preventive strategies. European networks are needed to dene the best diagnostic and treatment strategies in order to reduce future challenge posed by PJIs. 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Over the past years there has been a signicant increase in the number of joint prosthesis replacements. In 2006 about 800,000 hip and knee arthroplasties were performed in the United States1 and 130,000 in England.2 Kurtz et al. formulated projections for the number of primary and revision total hip and knee arthroplasties that will be performed in the United States through 2030 and estimated an increase by 174%e572,000 for hip per year and by 673%e3.48 million

for knee prosthesis per year.3 The most serious complication of joint prosthesis is infection with an incidence of 1.5e2.5% for primary interventions and up to 20% for revision procedures.4 The mortality rate ranges between 1% and nearly 3%.4 The economic cost of this complication is up to $50,000 per patient and $250,000 million per year.5,6 In reason of the increase of life expectancy and of the predicted growth of the number of joint replacement procedures,

* Corresponding author. Tel.: 39 06 30154945; fax: 39 06 3054519. E-mail address: etacconelli@rm.unicatt.it (E. Tacconelli). 0163-4453/$36 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.jinf.2010.09.033

444 the next few years are likely to register a signicant increment in the number of prosthetic joint infections (PJIs) with a strong impact on countries health economic balance.

M.A. Cataldo et al. these parameters are high for up to two weeks after surgery.25 Recently, the role of procalcitonin in the diagnosis of deep implant infection in patients with a revision total knee or hip replacement has been evaluated. Procalcitonin levels (>0.3 ng/ml) were very specic (98%) but had a low sensitivity (33%).26 Blood cultures should be performed, although they are often negative due to the frequent use of empirical antimicrobial therapy.27 Deep samples of synovial uid and periprosthetic tissue cultures are more specic and accurate for detecting the etiologic agent. Unfortunately, deep cultures are uncommonly taken before starting antibiotics, thus false-negative cultures are possible. Culture of a supercial wound could be taken but it often represents bacterial skin colonisation. The use of polymerase-chain-reaction (PCR) assays may be helpful for a rapid and more sensitive microbiological diagnosis although ad hoc studies yielded controversial results.28e33 In a study comparing PCR and conventional culture techniques in the diagnosis of PJIs, signicantly higher sensitivity, accuracy and negative predictive values were reported for PCR versus cultures, with 83% concordance between the results of intraoperative culture and PCR detection of the causative bacteria.29 However, other studies reported lower PCR sensitivity (54%) and a large number of false positive results.30,32 Synovial uid white cell count and neutrophil differential may be a rapid way for differentiating PJI from aseptic failure.34 Major limits of these methods are related to the lack of cut-offs applicable to all types of prosthetic joint or to patients with underlying inammatory joint disease. Histopathology could add important information helping in the diagnosis of acute inammation.9 Recently, a sonication technique, used to sample biolm bacteria on the surface of removed hip and knee implants placed in solid containers, was clinically validated.35 A prospective trial compared culture of samples obtained by sonication of explanted hip and knee prostheses to dislodge adherent bacteria from the prosthesis with conventional culture of periprosthetic tissue for the microbiologic diagnosis of PJI. The sensitivities of periprosthetic tissue and sonicate-uid cultures signicantly differed (60.8% and 78.5%, respectively) while the specicities were of similar value (99.2% and 98.8%, respectively). Fourteen cases of PJIs were detected by sonicate-uid culture but not by prosthetic-tissue culture. The sensitivities of periprosthetic tissue and sonicate-uid culture signicantly differed also in patients receiving antimicrobial therapy within 14 days before surgery (45% and 75%, respectively).35 The main limitation of this technique is the difcult to identify bacterial species because of their variations in phenotypic appearance and biochemical reaction.36 Plain radiographs have low sensitivity and low specicity for the detection of PJI especially in early infection. Serial radiographs may be useful in monitoring bone changes. Computed tomography (CT) and magnetic resonance (MR) provide more specic information about normal and abnormal tissue but are associated with artefacts produced by prostheses. Bone scintigraphy with technetium-99-m labelled methylene diphosphonate is not specic for infection and remains abnormal from more than one year after prostheses implantation.37 The addition of gallium-67 improves the specicity up to 70e80%. Labelled-leukocyte imaging combined with bone marrow imaging with the use of technetium-99-m labelled sulphur colloid is, at the

Epidemiology
A common case denition for PJI has not yet been established, although there are widely accepted diagnostic criteria.7e9 Infections are usually classied in relation to the time of onset after surgery as early (rst 3 months after surgery), delayed (between 3 months and 2 years after surgery) or late (more than 2 years after surgery).10,11 PJIs occur more frequently in patients with a previous revision arthroplasty and in subjects with diabetes mellitus, rheumatoid arthritis, obesity, neoplasm, and immunosuppression.7,12 Surgical factors such as sterility, long operative time, use of antibiotic-impregnated cement are also determinant in the risk of infection.13e16 Microorganisms may reach the prosthesis at the time of implantation or later by haematogenous spread.7,17 The development of biolm has a strategic role in the pathogenesis of PJI. Microorganisms adhere to the implant and form a biolm in which they are protected from the host immune system and from most antibiotics.10 The most frequent etiologic agents are staphylococci, accounting for more than 50% of PJIs.10 Staphylococcus aureus is usually isolated in early infections whereas coagulase-negative staphylococci in late infections18 as well as Streptococci (9e10%), enterococci (3e7%) and anaerobes (2e4%).10 Gram-negative bacteria, mostly Pseudomonas aeruginosa, Enterobacter spp., Proteus spp., even tough relatively uncommon agents, have an important clinical impact because of the difculty in treatment.19,20 Interestingly, in a recent study, gram-negative organisms were involved in 15% of the episodes of PJIs.19 Compared to patients with infections due to gram-positive bacteria, those with gram-negative PJIs were older and developed infection earlier.19 Overall, about 20% of PJIs are polymicrobial and 7e11% are culture-negative.21,22 Unusual pathogens, such as Candida spp., Brucella spp. and mycobacteria have also been reported.23 A main concern in the recent years, has been the increase in reports of infections due to antibiotic-resistant bacteria. In a large surveillance on surgical site infection after orthopaedic interventions, 59% of the S. aureus isolates were methicillin-resistant. Salgado et al. observed that PJIs due to methicillin-resistant S. aureus (MRSA) have a higher risk of treatment failure than PJIs due to methicillin-susceptible S. aureus.24

Diagnosis
A major issue in the management of PJI is the relative difculty in making a diagnosis so to cause a signicant effect on the prognosis of PJI. Indeed, a delay in the antibiotic and surgical treatment has an important impact on the chance of saving the prosthesis and the joint function. The diagnosis of PJI is based on clinical signs, laboratory and microbiological tests, histopathology and imaging studies. Inammatory markers (C reactive protein, erythrocyte sedimentation rate, white blood cells count) determination is recommended but is not specic, particularly for early infection, since

Prosthetic joint infection moment, the most accurate imaging test.38 F-uorodeoxyglucose positron emission tomography (FDG-PET) has a sensitivity ranging from 28% to 91% and specicity from 9% to 97% in the diagnosis of PJIs.39 This variability depends on the different diagnostic criteria used. Recently, the role of scintigraphy with (99m) TC-labelled anti-granulocyte antibodies alone and in conjunction with SPECT/CT for diagnosing low-grade joint infection was assessed. The addition of SPECT with and without CT improved the utility of (99m) TC-labelled anti-granulocyte antibodies.40 Other imaging studies such as scintigraphy with anti-granulocyte monoclonal antibodies and combined PET and CT imaging are under investigation.

445 including those with infected orthopaedic devices, caused by resistant gram-positive cocci.49 Recently, Galdelman et al. reported that co-administration of linezolid and rifampicin resulted in a decrease in the area under the plasma concentration-time curve over the dosing interval and maximum concentration values for linezolid.50 The clinical signicance of this interaction is unknown. Daptomycin has activity against several gram-positive bacteria, including MRSA and vancomycin-resistant enterococci (VRE) and is able to kill also stationary phase bacteria in biolm. Its use has been investigated in orthopaedic infections and showed a cumulative cure rate of 81%.51 The analysis of outcomes in 62 patients with osteomyelitis from an ongoing, retrospective database of daptomycin use in the USA, the Cubicin Outcomes Registry and Experience (CORE), showed a success rate of 89% and of 100% in the subgroup with orthopaedic devices.52 The optimal dosage of daptomycin for bone and joint infections is still under evaluation, although published data showed a higher failure rate in patients receiving 4 mg/kg/day or less.52 In the USA a trial comparing the efcacy and safety of daptomycin at different dosage (6 mg/kg and 8 mg/kg) is ongoing. A possible role of tigecycline in treating orthopaedic infections is suggested by animal studies that showed good cure rates of MRSA osteomyelitis.53 The mean percentage of clinical isolates of MRSA cells killed in biolms was 57% after exposure to tigecycline.54 Human trials on the use of tigecycline in bone and joint infection are lacking. The ideal antimicrobial agents and the best duration of treatment for PJIs are still not dened and a very few randomised controlled trials have compared the efcacy of different antibiotics. Guidelines for the management of PJI are expected very soon from the Infectious Diseases Society of America, the British Orthopaedic Association and the British Infection Association. Choice of the antibiotic agent should be dependent on the type of bacteria and its sensitivity prole, patients characteristic and long term goals. Suggested therapy for methicillin-susceptible staphylococci is nafcillin or oxacillin followed by rifampicin plus ciprooxacin per os. Intravenous glycopeptides followed by oral therapy containing rifampicin associated with other antibiotics, according to the susceptibility prole, are recommended for the treatment of PJIs caused by MRSA. For the treatment of PJIs caused by a gram-negative bacteria, a cephalosporin, like ceftriaxone or ceftazidime, or a carbapenem eventually combined with an aminoglycoside could be used. For oral treatment quinolones and cotrimoxazole are good choices. In infections by Enterobacteriaceae the association quinolones plus rifampicin could also be used. To increase the rate of microorganisms eradication, the antibiotic treatment should be administered for a long time. In the majority of patients a surgical debridement or prosthetic joint removal is required. In patients undergoing debridement with retention of the prosthesis the antibiotic is generally prescribed for 3 or 6 months (in hip and knee prosthesis, respectively), whereas in patients undergoing a two-stage exchange the therapy is often administered for 4e6 weeks. In a recent retrospective study, antibiotic therapy appeared to be limited to a 6-week course, with one week of intravenous administration.55 Interestingly, oral treatment beyond six months did not enhance the cure rate.56

Antimicrobial therapy
Goals of the treatment of PJI are to eradicate infection, prevent its recurrence and preserve mechanical joint function. Drugs administered for PJIs should have bactericidal activity against slow-growing organisms in biolm and achieve high concentration into the bone. Among the oldest antibiotics, cefazolin, rifampicin, minocycline and cotrimoxazole should be considered. Recently, Zeller et al. reported that use of cefazolin by continuous infusion was effective in treating 93% of patients with bone and joint infections.41 Bone cefazolin concentrations were also determined in eight patients conrming high levels of penetration. Rifampicin is active against stationary phase bacteria in biolm present on implants. Its use is recommended for the treatment of PJIs due to staphylococci in combination with another antimicrobial agent active against these bacteria to avoid the development of resistance. The association with quinolones is the most widely used and its efcacy has been documented in several studies.42,43 A meta-analysis on clinical efcacy of antibiotic agents for bone and joint infections in adults, showed a trend towards improved, long-lasting infection control in favour of a rifampicineciprooxacin combination versus ciprooxacin monotherapy for the treatment of staphylococcal infections related to orthopaedic devices (absolute risk difference 29%).44 Cotrimoxazole frequently retains activity against multidrug-resistant staphylococci, is able to diffuse in bone tissue and is absorbed if administered by oral route. Due to these characteristics, it represents an attractive choice for the treatment of PJIs. High-dose of trimethoprimesulfamethoxazole has been used to treat MRSA implant infections with an overall cure rate at 6 years of 67%.45 Both cotrimoxazole and minocycline have been used in association with rifampicin.45,46 Newer antibiotics such as linezolid, tigecycline, daptomycin, although not approved for bone infections, are increasingly used. Linezolid is a bacteriostatic antibiotic, with excellent bioavailability by oral administration. The drug achieves a bone concentration above the MICs of the majority of gram-positive cocci, including multidrug-resistant strains, and, according to in vitro studies, is able to kill around half of clinical isolates of MRSA cells within biolms. Retrospective studies reported a success rate ranging from 80%46e100% of PJIs treated with linezolid.47,48 Prolonged oral therapy with the association of rifampicin/linezolid or rifampicin/cotrimoxazole were found to be equally effective in treating patients with bone and joint infection,

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Prevention
Antibiotic prophylaxis before the intervention of implantation of prosthesis has been proven to be effective in reducing the risk of subsequent infection. First or second generation cephalosporins are commonly recommended in orthopaedic surgery. In settings with a high prevalence of MRSA, glycopeptides are suggested.57 The use of antibiotic prophylaxis in patients with joint prostheses undergoing dental, genitourinary tract and gastrointestinal tract procedures is controversial. In a recent study, antibiotic prophylaxis in high-risk or low-risk dental procedures did not decrease the risk of subsequent total hip or knee infections.58 The American Association of Orthopaedic Surgeons recommends to consider the administration of antibiotic prophylaxis prior to any invasive procedure that may cause bacteraemia (dental, urologic and other surgical and medical procedures) in patients with total joint replacement, especially if one or more of the following risk factors are present: immunocompromised/ immunosuppressed patients, inammatory arthropathies, drug-induced immunosuppression, radiation-induced immunosuppression, patients with co-morbidities (e.g. diabetes, obesity, smoking), previous prosthetic joint infections, malnourishment, haemophilia, HIV infection, insulin-dependent diabetes, malignancy.59 Decolonisation with mupirocin of S. aureus nasal carriers has been proven to be efcacious in reducing bacterial infection in surgical patients.60 However, its efcacy in orthopaedic patients is still on debate. In a study including patients undergoing orthopaedic surgery, endogenous S. aureus infections occurred less frequently than in patients who received mupirocin prophylaxis.61 In a prospective observational study of patients undergoing elective total joint arthroplasty, postoperative S. aureus surgical site infections were not observed at 1-year follow-up in the group of S. aureus nasal carriers who received decolonisation regimen.62 A meta-analysis showed that preoperative intranasal mupirocin decreases the incidence of surgical site infection when used as prophylaxis in nongeneral surgery, including orthopaedic surgery.63 Pre-surgical screening for S. aureus is recommended in particular in hospital with endemic MRSA. Available data do not support wide application of rapid screening with molecular tests compared to conventional cultures.64

References
1. National Hospital Discharge Survey. Survey results and products. Available at. Atlanta: Center for Disease Control and Prevention, <http://www.cdc.gov/nchs/nhds_products.html>; 2009 [last access 14.09.10]. 2. UK National Joint Registry. Available at, <http://www. njrcentre.org.uk>. 3. Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 2007;89(4): 780e5. 4. Lentino JR. Prosthetic joint infections: bane of orthopedists, challenge for infectious disease specialists. Clin Infect Dis 2003;36(9):1157e61. 5. Zimmerli W. Infection and musculoskeletal conditions: prosthetic-joint-associated infections. Best Pract Res Clin Rheumatol 2006;20(6):1045e63. doi:10.1016/j.berh.2006.08.003. 6. Sculco TP. The economic impact of infected joint arthroplasty. Orthopedics 1995;18(9):871e3. 7. Berbari EF, Hanssen AD, Duffy MC, Steckelberg JM, Ilstrup DM, Harmsen WS, et al. Risk factors for prosthetic joint infection: case-control study. Clin Infect Dis 1998;27(5):1247e54. 8. Trampuz A, Zimmerli W. Prosthetic joint infections: update in diagnosis and treatment. Swiss Med Wkly 2005;135(17e18): 243e51. 9. Muller M, Morawietz L, Hasart O, Strube P, Perka C, Tohtz S. Diagnosis of periprosthetic infection following total hip arthroplastyeevaluation of the diagnostic values of pre- and intraoperative parameters and the associated strategy to preoperatively select patients with a high probability of joint infection. J Orthop Surg Res 2008;3:31. 10. Zimmerli W, Trampuz A, Ochsner PE. Prosthetic-joint infections. N Engl J Med 2004;351(16):1645e54. 11. Trampuz A, Widmer AF. Infections associated with orthopedic implants. Curr Opin Infect Dis 2006;19(4):349e56. 12. Hoekman P, Van de Perre P, Nelissen J, Kwisanga B, Bogaerts J, Kanyangabo F. Increased frequency of infection after open reduction of fractures in patients who are seropositive for human immunodeciency virus. J Bone Joint Surg Am 1991;73(5): 675e9. 13. Garibaldi RA, Cushing D, Lerer T. Risk factors for postoperative infection. Am J Med 1991;91(3B):158Se63S. 14. Hanssen AD, Rand JA. Evaluation and treatment of infection at the site of a total hip or knee arthroplasty. Instr Course Lect 1999;48:111e22. 15. Ilstrup DM, Nolan DR, Beckenbaugh RD, Coventry MB. Factors inuencing the results in 2,012 total hip arthroplasties. Clin Orthop Relat Res 1973;95:250e62. 16. Kendall RW, Duncan CP, Smith JA, Ngui-Yen JH. Persistence of bacteria on antibiotic loaded acrylic depots. A reason for caution. Clin Orthop Relat Res 1996;329:273e80. 17. Uckay I, Lubbeke A, Emonet S, Tovmirzaeva L, Stern R, Ferry T, et al. Low incidence of haematogenous seeding to total hip and knee prostheses in patients with remote infections. J Infect 2009 Nov;59(5):337e45. 10.1016/j.jinf.2009.08.015. 18. Moran E, Masters S, Berendt AR, McLardy-Smith P, Byren I, Atkins BL. Guiding empirical antibiotic therapy in orthopaedics: the microbiology of prosthetic joint infection managed by debridement, irrigation and prosthesis retention. J Infect 2007;55(1):1e7. doi:10.1016/j.jinf.2007.01.007. 19. Hsieh PH, Lee MS, Hsu KY, Chang YH, Shih HN, Ueng SW. Gramnegative prosthetic joint infections: risk factors and outcome of treatment. Clin Infect Dis 2009;49(7):1036e43. 20. Legout L, Senneville E, Stern R, Yazdanpanah Y, Savage C, Roussel-Delvalez M, et al. Treatment of bone and joint infections

Conclusions
Given the projected increase in the number of PJIs in the forthcoming years in most countries, a common action to reduce the associated morbidity and mortality is strongly encouraged in Europe. New multicenter European cohort studies are needed to explore risk factors and pathogenesis of infections after orthopaedic surgery. European networks set up to dene the best diagnostic and treatment strategies should be supported both at a national and international level. In particular, since the signicant impact on the quality of life of the elderly population of PJIs, future randomised clinical trials on prevention and treatment need to be designed to include this population.

Prosthetic joint infection

caused by gram-negative bacilli with a cefepimeeuoroquinolone combination. Clin Microbiol Infect 2006;12(10):1030e3. Sia IG, Berbari EF, Karchmer AW. Prosthetic joint infections. Infect Dis Clin North Am 2005;19(4):885e914. doi: 10.1016/j.idc.2005.07.010. Berbari EF, Marculescu C, Sia I, Lahr BD, Hanssen AD, Steckelberg JM, et al. Culture-negative prosthetic joint infection. Clin Infect Dis 2007 Nov 1;45(9):1113e9. Marculescu CE, Berbari EF, Cockerill 3rd FR, Osmon DR. Fungi, mycobacteria, zoonotic and other organisms in prosthetic joint infection. Clin Orthop Relat Res 2006;451:64e72. Salgado CD, Dash S, Cantey JR, Marculescu CE. Higher risk of failure of methicillin-resistant Staphylococcus aureus prosthetic joint infections. Clin Orthop Relat Res 2007;461:48e53. Bilgen O, Atici T, Durak K, Karaeminoullari O, Bilgen MS. C-reg active protein values and erythrocyte sedimentation rates after total hip and total knee arthroplasty. J Int Med Res 2001; 29(1):7e12. Bottner F, Wegner A, Winkelmann W, Becker K, Erren M, Gotze C. Interleukin-6, procalcitonin and TNF-alpha: markers of peri-prosthetic infection following total joint replacement. J Bone Joint Surg Br 2007;89(1):94e9. Pavoni GL, Giannella M, Falcone M, Scorzolini L, Liberatore M, Carlesimo B, et al. Conservative medical therapy of prosthetic joint infections: retrospective analysis of an 8-year experience. Clin Microbiol Infect 2004;10:831e7. Vandercam B, Jeumont S, Cornu O, Yombi JC, Lecouvet F,  Lefevre P, et al. Amplication-based DNA analysis in the diagnosis of prosthetic joint infection. J Mol Diagn 2008;10(6): 537e43. Gallo J, Kolar M, Dendis M, Loveckova Y, Sauer P, Zapletalova J, et al. Culture and PCR analysis of joint uid in the diagnosis of prosthetic joint infection. New Microbiol 2008;31(1):97e104. Panousis K, Grigoris P, Butcher I, Rana B, Reilly JH, Hamblen DL. Poor predictive value of broad-range PCR for the detection of arthroplasty infection in 92 cases. Acta Orthop 2005;76(3):341e6. De Man FH, Graber P, Luem M, Zimmerli W, Ochsner PE, Sendi P. Broad-range PCR in selected episodes of prosthetic joint infection. Infection 2009;37(3):292e4.  Fihman V, Hannouche D, Bousson V, Bardin T, Liote F, Raskine L, et al. Improved diagnosis specicity in bone and joint infections using molecular techniques. J Infect 2007;55: 510e7. doi:10.1016/j.jinf.2007.09.001. Dora C, Altwegg M, Gerber C, Bottger EC, Zbinden R. Evaluation of conventional microbiological procedures and molecular genetic techniques for diagnosis of infections in patients with implanted orthopedic devices. J Clin Microbiol 2008;46(2): 824e5. Parvizi J, Ghanem E, Sharkey P, Aggarwal A, Burnett RS, Barrack RL. Diagnosis of infected total knee: ndings of a multicenter database. Clin Orthop Relat Res 2008;466(11): 2628e33. Trampuz A, Piper KE, Jacobson MJ, Hanssen AD, Unni KK, Osmon DR, et al. Sonication of removed hip and knee prostheses for diagnosis of infection. N Engl J Med 2007;357(7): 654e63. Sendi P, Frei R, Maurer TB, Trampuz A, Zimmerli W, Graber P. Escherichia coli variants in periprosthetic joint infection: diagnostic challenges with sessile bacteria and sonication. J Clin Microbiol 2010;48(5):1720e5. Smith SL, Wastie ML, Forster I. Radionuclide bone scintigraphy in the detection of signicant complications after total knee joint replacement. Clin Radiol 2001;56(3):221e4. doi: 10.1053/crad.2000.0620. Love C, Tomas MB, Marwin SE, Pugliese PV, Palestro CJ. Role of nuclear medicine in diagnosis of the infected joint replacement. Radiographics 2001;21(5):1229e38.

447
39. Van der Bruggen W, Bleeker-Rovers CP, Boerman OC, Gotthardt M, Oyen WJ. PET and SPECT in osteomyelitis and prosthetic bone and joint infections: a systematic review. Semin Nucl Med 2010;40(1):3e15. doi:10.1053/j.semnuclmed. 2009.08.005. 40. Graute V, Feist M, Lehner S, Haug A, Muller PE, Bartenstein P, et al. Detection of low-grade prosthetic joint infections using (99m)Tc-antigranulocyte SPECT/CT: initial clinical results. Eur J Nucl Med Mol Imaging 2010;37(9):1751e9. 41. Zeller V, Durand F, Kitzis MD, Lhotellier L, Ziza JM, Mamoudy P, et al. Continuous cefazolin infusion to treat bone and joint infections: clinical efcacy, feasibility, safety, and serum and bone concentrations. Antimicrob Agents Chemother 2009;53(3):883e7. 42. Zimmerli W, Widmer AF, Blatter M, Frei R, Ochsner PE. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Foreign-Body Infection (FBI) Study Group. JAMA 1998;279(19):1537e41. 43. Berdal JE, Skr amm I, Mowinckel P, Gulbrandsen P, Bjrnholt JV. Use of rifampin and ciprooxacin combination therapy after surgical debridement in the treatment of early manifestation prosthetic joint infections. Clin Microbiol Infect 2005;11(10):843e5. 44. Stengel D, Bauwens K, Sehouli J, Ekkernkamp A, Porzsolt F. Systematic review and meta-analysis of antibiotic therapy for bone and joint infections. Lancet Infect Dis 2001;1(3):175e88. 45. Stein A, Bataille JF, Drancourt M, Curvale G, Argenson JN, Groulier P, et al. Ambulatory treatment of multidrug-resistant Staphylococcus-infected orthopedic implants with high-dose oral co-trimoxazole (trimethoprimesulfamethoxazole). Antimicrob Agents Chemother 1998;42(12):3086e91. 46. Trampuz A, Zimmerli W. New strategies for the treatment of infections associated with prosthetic joints. Curr Opin Investig Drugs 2005;6(2):185e90. 47. Bassetti M, Vitale F, Melica G, Righi E, Di Biagio A, Molfetta L, et al. Linezolid in the treatment of gram-positive prosthetic joint infections. J Antimicrob Chemother 2005;55(3):387e90. 48. Razonable RR, Osmon DR, Steckelberg JM. Linezolid therapy for orthopedic infections. Mayo Clin Proc 2004;79(9):1137e44. 49. Nguyen S, Pasquet A, Legout L, Beltrand E, Dubreuil L, Migaud H, et al. Efcacy and tolerance of rifampicinelinezolid compared with rifampicinecotrimoxazole combinations in prolonged oral therapy for bone and joint infections. Clin Microbiol Infect 2009;15(12):1163e9. 50. Gandelman K, Zhu T, Fahmi OA, Glue P, Lian K, Obach RS, et al. Unexpected effect of rifampin on the pharmacokinetics of linezolid: in silico and in vitro approaches to explain its mechanism. J Clin Pharmacol 2010 [Epub ahead of print]. 51. Falagas ME, Giannopoulou KP, Ntziora F, Papagelopoulos PJ. Daptomycin for treatment of patients with bone and joint infections: a systematic review of the clinical evidence. Int J Antimicrob Agents 2007 Sep;30(3):202e9. doi:10.1016/ j.ijantimicag.2007.02.012. 52. Sakoulas G. Clinical outcomes with daptomycin: a post-marketing, real-world evaluation. Clin Microbiol Infect 2009;15 (Suppl. 6):11e6. 53. Yin LY, Lazzarini L, Li F, Stevens CM, Calhoun JH. Comparative evaluation of tigecycline and vancomycin, with and without rifampicin, in the treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis in a rabbit model. J Antimicrob Chemother 2005;55(6):995e1002. 54. Smith K, Perez A, Ramage G, Gemmell CG, Lang S. Comparison of biolm-associated cell survival following in vitro exposure of meticillin-resistant Staphylococcus aureus biolms to the antibiotics clindamycin, daptomycin, linezolid, tigecycline and vancomycin. Int J Antimicrob Agents 2009;33(4):374e8. doi: 10.1016/j.ijantimicag.2008.08.029. 55. Bernard L, Legout L, Zurcher-Pfund L, Stern R, Rohner P, Peter R, et al. Six week of antibiotic treatment is sufcient following sur gery for septic arthroelasty. J Infect 2010;61(2):125e32.

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56. Mittal Y, Fehring TK, Hanssen A, Marculescu C, Odum SM, Osmon D. Two-stage reimplantation for periprosthetic knee infection involving resistant organisms. J Bone Joint Surg Am 2007;89(6):1227e31. 57. Bratzler DW, Houck PM. Surgical infection prevention Guideline Writers Workgroup. Antimicrobial prophylaxis for surgery: an advisory statement from the national surgical infection prevention Project. Am J Surg 2005;189(4):395e404. doi: 10.1016/j.amjsurg.2005.01.015. 58. Berbari EF, Osmon DR, Carr A, Hanssen AD, Baddour LM, Greene D, et al. Dental procedures as risk factors for prosthetic hip or knee infection: a hospital-based prospective case-control study. Clin Infect Dis 2010;50(1):8e16. doi: 10.1016/j.jinf.2010.05.005. 59. American Association of Orthopaedic Surgeons. Information statement: antibiotic prophylaxis for bacteremia in patients with joint replacements. Available at, www.aaos.org/about/ papers/advistmt/1033.asp; February 2009. 60. Bode LG, Kluytmans JA, Wertheim HF, Bogaers D, Vandenbroucke-Grauls CM, Roosendaal R, et al. Preventing surgical-

M.A. Cataldo et al.

site infections in nasal carriers of Staphylococcus aureus. N Engl J Med 2010;362(1):9e17. Kalmeijer MD, Coertjens H, van Nieuwland-Bollen PM, Bogaers-Hofman D, de Baere GA, Stuurman A, et al. Surgical site infections in orthopedic surgery: the effect of mupirocin nasal ointment in a double-blind, randomized, placebo-controlled study. Clin Infect Dis 2002;35(4):353e8. Rao N, Cannella B, Crossett LS, Yates Jr AJ, McGough 3rd R. A preoperative decolonization protocol for staphylococcus aureus prevents orthopaedic infections. Clin Orthop Relat Res 2008;466(6):1343e8. Kallen AJ, Wilson CT, Larson RJ. Perioperative intranasal mupirocin for the prevention of surgical-site infections: systematic review of the literature and meta-analysis. Infect Control Hosp Epidemiol 2005;26(12):916e22. Tacconelli E, De Angelis G, de Waure C, Cataldo MA, La Torre G, Cauda R. Rapid screening tests for meticillin-resistant Staphylococcus aureus at hospital admission: systematic review and meta-analysis. Lancet Infect Dis 2009;9(9): 546e54.

61.

62.

63.

64.