**6. Diagnostic approach**

It is important to accurately diagnose prosthetic-joint–associated infection because its management differs from that of other causes of arthroplasty failure. Although there is no universally accepted definition of this type of infection, the criteria listed in Table 3 have been applied in a number of studies.


Table 3. Criteria for the Diagnosis of a Prosthetic-Joint Infection.

therapy had failed were included in the study. SCVs have also been isolated from cases of infection of hip prostheses, and intracellular bacteria within host fibroblasts were identified

Clinically isolated SCVs with hemin auxotrophy, and defined *hemB* mutants, show enhanced intracellular persistence in a range of human cell types. The basis of this persistence is not established but may involve a number of possible mechanisms. *S. aureus hemB* mutants exhibit enhanced binding to fibrinogen and fibronectin, and transcribe and display more ClfA and FnBP on their surface, which may increase attachment and uptake by host cells. Transcriptional profiling of clinical and defined mutant SCVs reveals increased transcription of genes regulated by σB, including adhesin genes, and down-regulation of exoprotein and toxin genes. The effect of increased σB activity on MSCRAMM expression has been shown to correlate well with osteoblast invasion, adding weight to the argument that σB-mediated upregulation of adhesins increases host cell invasion, at least in vitro, and that increased invasion by SCVs may be partially dependent on this mechanism. It has been argued that reduced production of toxins, particularly haemolysins, by SCVs also

contributes to intracellular persistence by reducing the cytotoxic effect on host cells.

In a murine septic arthritis model, a defined stable *hemB* mutant, exhibiting the SCV phenotype, elicited more frequent and severe arthritis than the parental strain despite a reduced bacterial load in the kidney and joints. It has been argued that SCVs are therefore more virulent on a'per organism' basis and that enhanced protease production by *hemB*  mutants may partially explain this. It may be that in clinical infections relatively small numbers of SCVs with enhanced virulence survive within tissues, possibly intracellularly, for extended periods and cause persistent infections. Clinically isolated SCVs are able to revert to the parent phenotype, although to what extent this may play a role in infections, and whether *S. aureus* may 'switch' between states in different in vivo situations is currently

It is important to accurately diagnose prosthetic-joint–associated infection because its management differs from that of other causes of arthroplasty failure. Although there is no universally accepted definition of this type of infection, the criteria listed in Table 3 have

in one of the five instances.

unclear.

**6. Diagnostic approach** 

been applied in a number of studies.

Table 3. Criteria for the Diagnosis of a Prosthetic-Joint Infection.

Establishing the presence of acute infection or, in the presence of a draining sinus, chronic infection, is uncomplicated. In these situations, testing may be limited to that needed to establish the microbiologic diagnosis. Chronic infection manifested as localized joint pain alone poses more diagnostic difficulty, warranting additional testing. The criteria for interpreting laboratory and imaging findings in patients with a prosthetic joint are distinct from those applied in patients with a native joint. In addition to establishing the diagnosis, the identification of the involved organism or organisms and their antimicrobial susceptibility (i.e., on the basis of cultures of synovial fluid, periprosthetic tissue, the implant, or a combination of such cultures) is important in order to guide antimicrobial therapy.

**C-Reactive Protein**—In the absence of underlying inflammatory conditions, CRP measurement is the most useful preoperative blood test for detecting infection associated with a prosthetic joint. CRP testing has a sensitivity of 73 to 91% and a specificity of 81 to 86% for the diagnosis of prosthetic-knee infection with the use of a cutoff point of 13.5 mg per liter or more[68,69]. It has a sensitivity of 95% and a specificity of 62% for the diagnosis of prosthetichip infection with the use of a cutoff point of more than 5 mg per liter[70]. Although the CRP level and erythrocyte sedimentation rate are elevated after uncomplicated arthroplasty, the CRP level returns to the preoperative level within 2 months, whereas the erythrocyte edimentation rate may remain elevated for several months. A normal CRP level generally indicates an absence of infection, although false negative results may occur in patients who have been treated with antimicrobial agents or who have infection that is caused by low-virulenceorganisms such as *P. acnes*. Elevations in the peripheral -blood leukocyte count and levels of procalcitonin have low sensitivity for detecting infection.

**Imaging**—Plain radiography has low sensitivity and low specificity for detecting infection associated with a prosthetic joint[71]. Periprosthetic radiolucency, osteolysis, migration, or all of these features may be present on radiographs in patients with either infection or aseptic loosening of the prosthesis. Diagnostic studies with the use of computed tomography (CT) or magnetic resonance imaging (MRI) are hampered by artifacts produced by prostheses, although implants that are not ferromagnetic (i.e., titanium or tantalum) are associated with minimal MRI artifacts, and MRI scans of such implants provide good resolution for detecting soft-tissue abnormalities. Bone scans obtained after the administration of technetium-99m –labeled methylene diphosphonate are sensitive for detecting failed implants but nonspecific for detecting infection, and they may remain abnormal for more than a year after implantation.

Some studies suggest that combined bone and gallium-67 scans are more specific than bone scans alone. However, labeled-leukocyte imaging (e.g., leukocytes labeled with indium-111) combined with bone marrow imaging with the use of technetium -99m–labeled sulfur colloid is more accurate than bone imaging alone, combined bone and gallium-67 imaging, or labeledleukocyte and bone imaging when compared head to head, and it is considered the imaging test of choice when imaging is required[71]. 18F-fluorodeoxyglucose positronemission tomography (PET) has a sensitivity of 82% and a specificity of 87% for the detection of prosthetic-knee or prosthetic-hip infection, on the basis of pooled data from several studies, but it is not widely available[72]. Newer imaging strategies such as scintigraphy with antigranulocyte monoclonal antibodies and hybrid imaging (e.g., combined PET and CT) (see Fig. 3)are under investigation.

Staphylococcus Infection Associated with Arthroplasty 475

diagnose native-joint infection. Synovial-fluid culture has a sensitivity of 56 to 75% and a specificity of 95 to 100%, and to achieve optimal sensitivity and specificity, it should be performed by means of inoculation into a blood-culture bottle. If an organism of questionable clinical significance is isolated, repeat synovial-fluid aspiration for culture

**Histopathological Examination of Periprosthetic Tissue**—In patients in whom the diagnosis of prosthetic-joint–associated infection has not been established preoperatively, an intraoperative frozen section may be obtained to look for evidence of acute inflammation. In studies that used a polymorphonuclear-cell count ranging from more than 5 to 10 or more cells per high-power field as a positive test, sensitivity for infection ranged from 50 to 93%

**Intraoperative Microbiologic Testing**—Identification of the pathogen or pathogens is critical for choosing the antimicrobial regimen; if microbiologic testing has not been done preoperatively, specimens should be collected for microbiologic study at the time of surgery. Antimicrobial therapy should be discontinued at least 2 weeks before surgery, and perioperative antimicrobial coverage should be deferred until culture specimens have been collected. Cultures of sinus tract exudates should be avoided; these are often positive because

If periprosthetic tissue is obtained, collection of multiple periprosthetic-tissue specimens for aerobic and anaerobic bacterial culture is imperative because of the poor sensitivity of a single culture and to distinguish contaminants from pathogens. A study that used mathematical modeling to estimate yield based on the number of cultures concluded that to maximize accuracy, five or six specimens should be submitted for culture, and two or three

Periprosthetic-tissue cultures may be falsely negative because of previous antimicrobial therapy, leaching of antimicrobial agents from antimicrobial -impregnated cement, biofilm growth on the surface of the prosthesis (but not in the surrounding tissue), a low number of organisms in tissue, an inappropriate culture medium, an inadequate culture incubation time, or a prolonged time to transport the specimen to the laboratory. Because of poor sensitivity, neither intraoperative swab cultures nor Gram's staining of the periprosthetic tissue is recommended. Fungal cultures, mycobacterial cultures, or both may be considered (e.g., if bacterial cultures are negative in a patient with apparent infection), but they are not

Microorganisms form a biofilm on the prosthesis; therefore, if the prosthesis is removed, obtaining a sample from its surface is useful for microbiologic diagnosis. The implant is removed and transported to the laboratory in a sterile jar. After the addition of Ringer's solution, the container is vortexed and sonicated (frequency, 40 kHz; power density, 0.22 W per square centimeter) for 5 minutes in a bath sonicator, and the resultant fluid is cultured. This technique is more sensitive than and as specific as multiple periprosthetic-tissue cultures for diagnosing infection of a prosthetic hip, knee, or shoulder, provided that an appropriate cutoff for significant results is applied. This technique is particularly helpful in patients who have received previous antimicrobial therapy. In a study involving patients receiving antimicrobial agents within 2 weeks before surgery, the sensitivity of periprosthetic-tissue culture was 45%, whereas the sensitivity of sonicate-fluid culture was 75% (P<0.001). Sonication in bags is not recommended because of the potential for

should be considered. Previous antimicrobial treatment reduces the sensitivity.

and specificity ranged from 77 to 100%; the rate of interobserver agreement was 86%.

of microbial skin colonization and correlate poorly with cultures of surgical specimens.

culturepositive samples would be considered to be diagnostic.

routinely recommended.

contamination.

Fig. 3. Bone Scan, Labeled-Leukocyte Scan and Positron Emission Tomography/Computed Tomography Scan from a Patient with Prosthetic Joint Infection.

In Panel A, an anterior bone scan obtained after the administration of technetium-99m– labeled methylene diphosphonate shows diffusely increased activity around the femoral component of a left hip replacement, with foci of increased activity at the tip of the femoral component and around the tibia. In Panel B, a labeled leukocyte scan obtained after the administration of indium-111–labeled leukocytes shows accumulation of labeled leukocytes that is spatially congruent with the bone scan image shown in Panel A. In Panel C, 18Ffluoro-2-deoxyglucose positron emission tomography/computed tomography coronal and sagittal images show increased activity around the bone-prosthesis interface. Staphylococcus epidermidis and Finegoldia magna were isolated from the periprosthetic tissue. (Images courtesy of Carmen Vigil, M.D., and Jose Angel Richter, M.D., Department of Nuclear Medicine, University Hospital of Navarre, Pamplona, Spain.)

**Synovial-Fluid Studies**—If there is uncertainty about the diagnosis, the most useful preoperative diagnostic test is aspiration of joint synovial fluid for a total and differential cell count and culture. Aspiration should not be performed through overlying cellulitis. Hip aspiration may require imaging guidance. A synovial-fluid leukocyte count of more than 1.7×103 per cubic millimeter or a differential count with more than 65% neutrophils is consistent with prosthetic-knee infection. A synovial-fluid leukocyte count of more than 4.2×103 per cubic millimeter or more than 80% neutrophils is consistent with prosthetic-hip infection[73]. The leukocyte count cutoffs are dramatically lower than those used to

Fig. 3. Bone Scan, Labeled-Leukocyte Scan and Positron Emission Tomography/Computed

In Panel A, an anterior bone scan obtained after the administration of technetium-99m– labeled methylene diphosphonate shows diffusely increased activity around the femoral component of a left hip replacement, with foci of increased activity at the tip of the femoral component and around the tibia. In Panel B, a labeled leukocyte scan obtained after the administration of indium-111–labeled leukocytes shows accumulation of labeled leukocytes that is spatially congruent with the bone scan image shown in Panel A. In Panel C, 18Ffluoro-2-deoxyglucose positron emission tomography/computed tomography coronal and sagittal images show increased activity around the bone-prosthesis interface. Staphylococcus epidermidis and Finegoldia magna were isolated from the periprosthetic tissue. (Images courtesy of Carmen Vigil, M.D., and Jose Angel Richter, M.D., Department of

**Synovial-Fluid Studies**—If there is uncertainty about the diagnosis, the most useful preoperative diagnostic test is aspiration of joint synovial fluid for a total and differential cell count and culture. Aspiration should not be performed through overlying cellulitis. Hip aspiration may require imaging guidance. A synovial-fluid leukocyte count of more than 1.7×103 per cubic millimeter or a differential count with more than 65% neutrophils is consistent with prosthetic-knee infection. A synovial-fluid leukocyte count of more than 4.2×103 per cubic millimeter or more than 80% neutrophils is consistent with prosthetic-hip infection[73]. The leukocyte count cutoffs are dramatically lower than those used to

Tomography Scan from a Patient with Prosthetic Joint Infection.

Nuclear Medicine, University Hospital of Navarre, Pamplona, Spain.)

diagnose native-joint infection. Synovial-fluid culture has a sensitivity of 56 to 75% and a specificity of 95 to 100%, and to achieve optimal sensitivity and specificity, it should be performed by means of inoculation into a blood-culture bottle. If an organism of questionable clinical significance is isolated, repeat synovial-fluid aspiration for culture should be considered. Previous antimicrobial treatment reduces the sensitivity.

**Histopathological Examination of Periprosthetic Tissue**—In patients in whom the diagnosis of prosthetic-joint–associated infection has not been established preoperatively, an intraoperative frozen section may be obtained to look for evidence of acute inflammation. In studies that used a polymorphonuclear-cell count ranging from more than 5 to 10 or more cells per high-power field as a positive test, sensitivity for infection ranged from 50 to 93% and specificity ranged from 77 to 100%; the rate of interobserver agreement was 86%.

**Intraoperative Microbiologic Testing**—Identification of the pathogen or pathogens is critical for choosing the antimicrobial regimen; if microbiologic testing has not been done preoperatively, specimens should be collected for microbiologic study at the time of surgery. Antimicrobial therapy should be discontinued at least 2 weeks before surgery, and perioperative antimicrobial coverage should be deferred until culture specimens have been collected. Cultures of sinus tract exudates should be avoided; these are often positive because of microbial skin colonization and correlate poorly with cultures of surgical specimens.

If periprosthetic tissue is obtained, collection of multiple periprosthetic-tissue specimens for aerobic and anaerobic bacterial culture is imperative because of the poor sensitivity of a single culture and to distinguish contaminants from pathogens. A study that used mathematical modeling to estimate yield based on the number of cultures concluded that to maximize accuracy, five or six specimens should be submitted for culture, and two or three culturepositive samples would be considered to be diagnostic.

Periprosthetic-tissue cultures may be falsely negative because of previous antimicrobial therapy, leaching of antimicrobial agents from antimicrobial -impregnated cement, biofilm growth on the surface of the prosthesis (but not in the surrounding tissue), a low number of organisms in tissue, an inappropriate culture medium, an inadequate culture incubation time, or a prolonged time to transport the specimen to the laboratory. Because of poor sensitivity, neither intraoperative swab cultures nor Gram's staining of the periprosthetic tissue is recommended. Fungal cultures, mycobacterial cultures, or both may be considered (e.g., if bacterial cultures are negative in a patient with apparent infection), but they are not routinely recommended.

Microorganisms form a biofilm on the prosthesis; therefore, if the prosthesis is removed, obtaining a sample from its surface is useful for microbiologic diagnosis. The implant is removed and transported to the laboratory in a sterile jar. After the addition of Ringer's solution, the container is vortexed and sonicated (frequency, 40 kHz; power density, 0.22 W per square centimeter) for 5 minutes in a bath sonicator, and the resultant fluid is cultured. This technique is more sensitive than and as specific as multiple periprosthetic-tissue cultures for diagnosing infection of a prosthetic hip, knee, or shoulder, provided that an appropriate cutoff for significant results is applied. This technique is particularly helpful in patients who have received previous antimicrobial therapy. In a study involving patients receiving antimicrobial agents within 2 weeks before surgery, the sensitivity of periprosthetic-tissue culture was 45%, whereas the sensitivity of sonicate-fluid culture was 75% (P<0.001). Sonication in bags is not recommended because of the potential for contamination.

Staphylococcus Infection Associated with Arthroplasty 477

Fig. 4. Algorithm for the Treatment of Infection Associated with a Prosthetic joint

### **6.1 Treatment**

The goal of treatment is to cure the infection, prevent its recurrence, and ensure a pain-free, functional joint. This goal can best be achieved by a multidisciplinary team consisting of an orthopedic surgeon, an infectious-disease specialist, and a clinical microbiologist. On the basis of clinical experience, the use of antimicrobial agents alone, without surgical intervention, ultimately fails in most cases. Careful surgical débridement is critical. A general approach to surgical management is outlined in Figure 4; different centers and surgeons may use slightly different strategies. Chronic infections require resection arthroplasty either as a onstage exchange (i.e., removal of the infected prosthesis and reimplantation of a new prosthesis during the same surgical procedure) or a two-stage exchange (i.e., removal of the infected prosthesis and administration of systemic antimicrobial agents with subsequent implantation of a new prosthesis, usually between 6 weeks and 3 months after the first stage). Case series have suggested improved outcomes with a one-stage exchange when polymethylmethacrylate impregnated with one or more antimicrobial agents is used. A spacer impregnated with one or more antimicrobial agents may be used to maintain the leg at its correct length and to control infection during the prosthesis-free interval of a two-stage exchange. In a randomized trial involving patients with infection associated with hip arthroplasty, the use of a vancomycinloaded spacer (as compared with no spacer) resulted in a lower rate of recurrent infection (11% vs. 33%, P = 0.002)[74].

Patients who have had symptoms of infection for fewer than 3 weeks, who present with infection within 3 months after implantation or who have hematogenous infection, and who have a well-fixed, functioning prosthesis, without a sinus tract, and with an appropriate microbiologic diagnosis (Fig. 4) may be candidates for débridement and retention of the prosthesis. The addition of rifampin is recommended in cases of rifampin-susceptible staphylococcal infection. In a small, randomized trial comparing different antibiotic regimens in patients with staphylococcal infection of prosthetic knees or hips or osteosynthetic implants, salvage of the implant was successful in all 12 patients treated for 3 to 6 months with rifampin and ciprofloxacin, as compared with successful salvage in 7 of 12 patients treated with ciprofloxacin alone for 3 to 6 months (P = 0.02).

When unacceptable joint function is anticipated after surgery or the infection has been refractory to multiple surgical attempts at cure, resection arthroplasty with creation of a pseudarthrosis for hips (Girdlestone resection) or arthrodesis for knees may be considered. If the patient is not a candidate for surgery, antimicrobial suppression may be attempted; this approach is unlikely to cure infection, so the use of antimicrobial agents is often continued indefinitely.

In brief, information about antimicrobial susceptibility should be used to confirm the activity of any antimicrobial agent used for therapy. Data from randomized trials on the optimal duration of treatment are lacking. The therapeutic approach has to be selected in accordance with the mode of infection (NJI, PJI, RA), the expected or found pathogens, and their resistance. It should be remembered that the slowed growth of bacteria in a biofilm on surfaces of joint prosthesis may additionally reinforces antibiotic resistance. Responsible for such an increase against antibacterial substances are changes in cell wall synthesis, which limits the effect of beta-lactam antibiotics and glycopeptides, and the occurrence of bacterial variants with modifications of other metabolic activities, with implications for the action of quinolones, aminoglycosides, and tetracyclines. In principle, the spectrum of available antibiotics is limited by the specific pharmacokinetic requirements in the treatment of joint infections. This applies particularly to chronic infections and prosthesis infections.

The goal of treatment is to cure the infection, prevent its recurrence, and ensure a pain-free, functional joint. This goal can best be achieved by a multidisciplinary team consisting of an orthopedic surgeon, an infectious-disease specialist, and a clinical microbiologist. On the basis of clinical experience, the use of antimicrobial agents alone, without surgical intervention, ultimately fails in most cases. Careful surgical débridement is critical. A general approach to surgical management is outlined in Figure 4; different centers and surgeons may use slightly different strategies. Chronic infections require resection arthroplasty either as a onstage exchange (i.e., removal of the infected prosthesis and reimplantation of a new prosthesis during the same surgical procedure) or a two-stage exchange (i.e., removal of the infected prosthesis and administration of systemic antimicrobial agents with subsequent implantation of a new prosthesis, usually between 6 weeks and 3 months after the first stage). Case series have suggested improved outcomes with a one-stage exchange when polymethylmethacrylate impregnated with one or more antimicrobial agents is used. A spacer impregnated with one or more antimicrobial agents may be used to maintain the leg at its correct length and to control infection during the prosthesis-free interval of a two-stage exchange. In a randomized trial involving patients with infection associated with hip arthroplasty, the use of a vancomycinloaded spacer (as compared with no spacer) resulted in a lower rate of recurrent

Patients who have had symptoms of infection for fewer than 3 weeks, who present with infection within 3 months after implantation or who have hematogenous infection, and who have a well-fixed, functioning prosthesis, without a sinus tract, and with an appropriate microbiologic diagnosis (Fig. 4) may be candidates for débridement and retention of the prosthesis. The addition of rifampin is recommended in cases of rifampin-susceptible staphylococcal infection. In a small, randomized trial comparing different antibiotic regimens in patients with staphylococcal infection of prosthetic knees or hips or osteosynthetic implants, salvage of the implant was successful in all 12 patients treated for 3 to 6 months with rifampin and ciprofloxacin, as compared with successful salvage in 7 of 12

When unacceptable joint function is anticipated after surgery or the infection has been refractory to multiple surgical attempts at cure, resection arthroplasty with creation of a pseudarthrosis for hips (Girdlestone resection) or arthrodesis for knees may be considered. If the patient is not a candidate for surgery, antimicrobial suppression may be attempted; this approach is unlikely to cure infection, so the use of antimicrobial agents is often

In brief, information about antimicrobial susceptibility should be used to confirm the activity of any antimicrobial agent used for therapy. Data from randomized trials on the optimal duration of treatment are lacking. The therapeutic approach has to be selected in accordance with the mode of infection (NJI, PJI, RA), the expected or found pathogens, and their resistance. It should be remembered that the slowed growth of bacteria in a biofilm on surfaces of joint prosthesis may additionally reinforces antibiotic resistance. Responsible for such an increase against antibacterial substances are changes in cell wall synthesis, which limits the effect of beta-lactam antibiotics and glycopeptides, and the occurrence of bacterial variants with modifications of other metabolic activities, with implications for the action of quinolones, aminoglycosides, and tetracyclines. In principle, the spectrum of available antibiotics is limited by the specific pharmacokinetic requirements in the treatment of joint

infections. This applies particularly to chronic infections and prosthesis infections.

patients treated with ciprofloxacin alone for 3 to 6 months (P = 0.02).

**6.1 Treatment** 

infection (11% vs. 33%, P = 0.002)[74].

continued indefinitely.

Fig. 4. Algorithm for the Treatment of Infection Associated with a Prosthetic joint

Staphylococcus Infection Associated with Arthroplasty 479

hydrolysing a pentaglycine cross-bridge structure unique to the staphylococcal cell wall. As the cell wall cross-bridges of S. aureus are composed of a high proportion of pentaglycine, both proliferating and quiescent S. aureus cells are highly sensitive to lysostaphin. Lysostaphin kills meticillin-susceptible S. aureus (MSSA) and MRSA equally well and has been demonstrated to be a potent therapeutic agent for S. aureus infections in various animal studies. In the USA, two therapeutic products formulated with recombinant lysostaphin for topical use have entered clinical studies. And recombinant lysostaphin is

In patients undergoing débridement with retention of the prosthesis, 3-month courses of treatment for infection associated with hip prostheses and 6-month courses for infection associated with knee prostheses are often used. Oral therapy can be used if the agent has good oral bioavailability (e.g., quinolones, rimethoprim– sulfamethoxazole, and tetracyclines). In patients undergoing a two-stage exchange, systemic antimicrobial therapy is often administered for 4 to 6 weeks. Commercially available, preblended, polymethylmethacrylate impregnated with an antimicrobial agent is indicated for use in the second stage of a two-stage revision after elimination of active infection. Although it is not standard clinical practice, two studies involving a long period between the initial and second stages suggest that when a polymethylmethacrylate spacer impregnated with one or more antimicrobial agents or impregnated beads are used, the administration of systemic antimicrobial therapy for 2 weeks may be sufficient or systemic therapy may even be

In addition to good aseptic technique and procedures in the operating room, the administration of intravenous antimicrobial agents immediately before surgery minimizes the risk of infection. Cefazolin at a dose of 1 g (2 g if the patient weighs 80 kg) every 8 hours or cefuroxime at a dose of 1.5 g, followed by 750 mg every 8 hours is recommended routinely; vancomycin at a dose of 15 mg per kilogram every 12 hours (assuming normal renal function) is used in patients with a β-lactam allergy or MRSA colonization. Prophylaxis should begin within 60 minutes before surgical incision (within 120 minutes if vancomycin is used) and should be completed within 24 hours after the end of surgery. The

[1] National Hospital Discharge Survey: survey results and products. Atlanta: Centers for

[2] Lee K. Goodman S.B. Current state and future of joint replacements in the hip and knee.

[4] Nade S. Septic arthritis. Best. Pract. Res. Clin. Rheumatol. 2003;17:183–200. [PubMed:

[5] Stott N.S. Paediatric bone and joint infection. J. Orthop. Surg. (Hong Kong) 2001;9:83–90.

entire antimicrobial dose should be infused before inflation of a tourniquet[77].

Disease Control and Prevention; 2009 [Accessed July 24, 2009].

Expert Rev. Med. Devices 2008;5:383–393. [PubMed: 18452388] [3] Goldenberg D.L. Septic arthritis. Lancet 1998;351:197–202. [PubMed: 9449882]

http://www.cdc.gov/nchs/nhds/nhds\_products.htm

expected to be a potential alternative therapy for S. aureus infection[78]. For an overview of common substances and therapeutic regimes, see Table 4.

unnecessary[75,76].

**6.2 Prophylaxis** 

**7. References** 

12787520]

[PubMed: 12468850]


(all given dosages are for healthy adults of 70 kg with normal liver and kidney function)

Table 4. Antibiotics for therapy of infectious arthritis

Lysostaphin is a 27 kDa endopeptidase that was first isolated from a culture of Staphylococcus simulans by Schindler & Schuhardt. The enzyme kills the organism by hydrolysing a pentaglycine cross-bridge structure unique to the staphylococcal cell wall. As the cell wall cross-bridges of S. aureus are composed of a high proportion of pentaglycine, both proliferating and quiescent S. aureus cells are highly sensitive to lysostaphin. Lysostaphin kills meticillin-susceptible S. aureus (MSSA) and MRSA equally well and has been demonstrated to be a potent therapeutic agent for S. aureus infections in various animal studies. In the USA, two therapeutic products formulated with recombinant lysostaphin for topical use have entered clinical studies. And recombinant lysostaphin is expected to be a potential alternative therapy for S. aureus infection[78].

For an overview of common substances and therapeutic regimes, see Table 4.

In patients undergoing débridement with retention of the prosthesis, 3-month courses of treatment for infection associated with hip prostheses and 6-month courses for infection associated with knee prostheses are often used. Oral therapy can be used if the agent has good oral bioavailability (e.g., quinolones, rimethoprim– sulfamethoxazole, and tetracyclines). In patients undergoing a two-stage exchange, systemic antimicrobial therapy is often administered for 4 to 6 weeks. Commercially available, preblended, polymethylmethacrylate impregnated with an antimicrobial agent is indicated for use in the second stage of a two-stage revision after elimination of active infection. Although it is not standard clinical practice, two studies involving a long period between the initial and second stages suggest that when a polymethylmethacrylate spacer impregnated with one or more antimicrobial agents or impregnated beads are used, the administration of systemic antimicrobial therapy for 2 weeks may be sufficient or systemic therapy may even be unnecessary[75,76].

### **6.2 Prophylaxis**

478 Recent Advances in Arthroplasty

(all given dosages are for healthy adults of 70 kg with normal liver and kidney function)

Lysostaphin is a 27 kDa endopeptidase that was first isolated from a culture of Staphylococcus simulans by Schindler & Schuhardt. The enzyme kills the organism by

Table 4. Antibiotics for therapy of infectious arthritis

In addition to good aseptic technique and procedures in the operating room, the administration of intravenous antimicrobial agents immediately before surgery minimizes the risk of infection. Cefazolin at a dose of 1 g (2 g if the patient weighs 80 kg) every 8 hours or cefuroxime at a dose of 1.5 g, followed by 750 mg every 8 hours is recommended routinely; vancomycin at a dose of 15 mg per kilogram every 12 hours (assuming normal renal function) is used in patients with a β-lactam allergy or MRSA colonization. Prophylaxis should begin within 60 minutes before surgical incision (within 120 minutes if vancomycin is used) and should be completed within 24 hours after the end of surgery. The entire antimicrobial dose should be infused before inflation of a tourniquet[77].
