Orthopedics

Deep infection in the presence of an implant after open reduction and internal fixation (ORIF) is usually treated with removal of the implant, serial débridement procedures, lavage, intravenously administered antibiotics, and, in some cases, placement of antibiotic-impregnated beads. If infection occurs during the early stages of bone healing, stabilization of the fractures might be compromised after removal of the implant. Although antibiotic-impregnated beads offer local delivery of antibiotics, they do not provide structural support of the fracture site. The beads often are difficult to remove after in-growth of granulation tissue. In areas of subcutaneous bone, an antibiotic bead pouch might be preferred to an open wound. Published research regarding the use of antibiotic-coated plates during the acute or chronic stages of infection is scarce. Plates offer the versatility of fracture stabilization, and the addition of antibiotic cement to the plates might aid in eradication of infection without necessitating a second surgery for removal. The patients provided written informed consent for print and electronic publication of these case reports.

Technique

After removal of implants, we perform débridement of the soft tissues with a hydroscalpel (Versajet; Smith & Nephew, London, United Kingdom), mechanical débridement of bone, and curettage with high speed burr. The wound is then irrigated with pulse pressure lavage and a minimum of 3 L sterile normal saline. The extremity is re-prepped and re-draped; the entire surgical team’s gowns and gloves are changed; and new instrumentation, including cautery and suction equipment, is used. The cement is prepared with tobramycin (3.6 g) and vancomycin (1 g) per 40-g bag of cement. The plate is placed in silicon tubing, and the antibiotic-prepared cement is injected into the tubing and molded until dry. Care is taken to mold the locations of the screw holes by making incisions in the tubing at the appropriate locations. Screws are placed through the screw holes to ensure locking capability, and Kirschner wires are placed through temporary fixation holes (Figure 1). Once dry, the screws and wires are removed from the plate, and the cement-coated plate is removed from the tubing. The antibiotic-coated plate is applied to the fracture or osteotomy site and is seated with screws as appropriate (Figure 2). The wound is closed primarily. Wound drains or vacuum-assisted closure devices are not routinely used unless there is high risk for hematoma formation. The authors prefer to have high local concentrations of antibiotic in the surrounding tissues and wound.

Clinical Series

Case 1

A 31-year-old man fell from a ladder and sustained a bimalleolar ankle fracture-dislocation that was treated with ORIF. Three weeks after initial injury, the patient presented with an infected lateral wound with purulent discharge. He was taken to the operating room for initial débridement, irrigation, and fracture stabilization with an antibiotic-coated plate and tension-band wiring of the medial malleoli. He was discharged from the hospital on day 4 after admission. Cultures of the wound grew beta-hemolytic strep group G and coagulase-negative staphylococci in broth that was sensitive to oxacillin, vancomycin, and gentamycin. The patient was treated with a 6-week regimen of Unasyn (Roerig, New York, New York), developed bony union, and has been free of clinical signs of infection for 2 years (Figures 3, 4).

Case 2

A 27-year-old male carpenter fell from a height of 12 feet and sustained a fracture of the distal radius that was treated with external fixation. The proximal pin site became clinically infected and subsequently developed osteomyelitis. The patient had a draining wound with a fracture for 2 months. He underwent débridement with partial resection of the radius and placement of an antibiotic cement–coated plate and calcium phosphate bone-void filler impregnated with antibiotics. Pathology specimens were positive for osteomyelitis, and bone cultures showed methicillin-sensitive Staphylococcus aureus (MSSA). He received intravenously administered antibiotic therapy for 6 weeks after surgery. The patient has remained free of clinical signs of infection for more than 1 year and has achieved bony union (Figures 5A, 5B).

Case 3

A 44-year-old woman with insulin-dependent diabetes mellitus and venous stasis sustained a trimalleolar ankle fracture after a low-energy fall that was initially treated with ORIF. She underwent revision ORIF to treat a malunion 3 months after initial treatment. At 8 months, the patient developed a draining sinus communicating with the plate. Computed tomography revealed nonunion and indicated infection. The patient underwent resection of the osteomyelitis and repair of the fibular nonunion with an antibiotic-coated plate. Tissue cultures were positive for coagulase-negative staphylococcus, and pathology specimens were positive for osteomyelitis. She received postoperative antibiotics intravenously and 6 weeks of antibiotic therapy after discharge from the hospital. The patient has remained free of clinical signs of infection for more than 1 year and has achieved bony union (Figures 6, 7).

Case 4

A 48-year-old man sustained an open olecranon fracture in another country. The fracture was initially treated with 1 dose of intravenously administered antibiotics and 5 days of orally administered antibiotics. The patient returned to the United States and was treated with intravenously administered antibiotics for cellulitis of the elbow for 11 days before referral to our institution, where he underwent ORIF with placement of an antibiotic-coated plate and tension-band wiring. Soft-tissue and bone cultures had no growth. He received intravenously administered antibiotics for 6 weeks. At 5 months postoperatively, the plate was removed because of pain. The patient has remained free of clinical signs of infection for more than 1 year and has achieved bony union (Figures 8A-8C).

Discussion

Acute infections of fractures have recently been treated with success by Berkes and colleagues,¹ who reported a 71% union rate achieved with operative débridement, antibiotic suppression, and retention of fixation until fracture union occurs. The study by Berkes and colleagues¹ had a small patient population, and larger cohorts are needed to show more reliable results; however, this treatment maintains structural support for the fracture during healing but requires multiple trips to the operating room for débridements as well as the use of systemic intravenous antibiotic therapy.

A technique that was developed by the primary author (Janet D. Conway, MD) and has not been described in the literature allows for use of antibiotic cement–coated plates to treat early postoperative infections and osteomyelitic nonunions. This approach permits fracture stabilization and local delivery of high concentrations of broad-spectrum antibiotics and can reduce the number of débridement procedures required in the operating room. We present a technique that includes the use of antibiotic cement–coated plates to treat early postoperative infections associated with fractures and nonunions in order to provide eradication of infection and bony stabilization.

Our approach parallels the current theory that treating infection at a site of union is preferable to treating infection at a site of nonunion.¹ Fixation devices should remain in place until osseous union is achieved. With the addition of antibiotics to the plate, removal might not be necessary unless a device is loose, nonfunctional, or, ultimately, causing pain. Other options, such as external fixation, can be burdensome to patients and can be associated with other risks. One of our 4 patients required fixation removal because of pain at the elbow; however, even noncoated olecranon plates typically are removed because of pain after fracture healing. Antibiotic cement adds bulk to the construct and can become very prominent in areas of little soft-tissue coverage (Figure 9).

Studies, assessing variables that correlate with higher likelihood of failure for primary repairs, have shown that open fracture, use of an intramedullary nail, and smoking are the highest risk factors for infected nonunion.¹⁻⁴ Among our 4 patients, 3 were smokers and 1 originally had an open fracture. Smokers have been found to have a 37% higher nonunion rate and are 2 times more likely to develop wound infection and osteomyelitis.^1,5 More than 60% of the time, infections are caused by S aureus or coagulase-negative staphylococci.^1,5,6 In our study population, 3 of the 4 patients had coagulase-negative staphylococci grow in the cultures. Implants infected with S aureus or Candida require surgical removal. Those with less virulent coagulase-negative staphylococci might not necessitate removal; however, our population had had antibiotic therapy and continued draining sinus.⁵ Rightmire and colleagues⁷ reported that those who develop infection earlier than 16 weeks postoperatively have a 68% success rate and that smoking is a major risk factor for infection. Development of Pseudomonas in the wound has been shown to have a positive correlation with amputation.^1,2 Infection with Pseudomonas, smoking, and involvement of the femur, tibia, ankle, or foot tended to result in failure.^1,2 Being clinically free of signs of infection after 3 months offers a 50% cure rate, with 78% at 6 months and 95% after 1 year.²

When determining an antibiotic to use with the polymethylmethacrylate (PMMA) cement, many factors must be considered, including spectrum, heat stability, and elution characteristics.⁸ A synergistic effect has been seen with combinations of antibiotics (eg, vancomycin and tobramycin used together). Vancomycin concentrations increased by 103% and tobramycin by 68% when used together compared with their elution rates when used alone, showing passive opportunism.⁹ This will, in essence, increase concentrations of antibiotics at the site locally, which will increase the bacteriocidal potential but also create a larger antimicrobial spectrum.⁹

The authors used Cobalt Bone Cement (Biomet Orthopedics, Inc, Warsaw, Indiana) which been shown to have higher elution properties than Simplex P Bone Cement (Stryker, Kalamazoo, Michigan).^3,10 The majority of elution occurs in the first 3 to 5 days but can continue for weeks after implantation. We place the cement on the plate allowing for its retention, hoping to eliminate a second surgery for removal.⁸ We recommend 3.6 g of tobramycin, and 1 g of vancomycin per 40-g bag of PMMA.³ This dose has been shown to be safe in respect to renal toxicity, plus the entire dose is not administered in a single setting because only a small portion of the cement is used when coating the plate. We close all wounds primarily, and do not regularly use drains or vacuum-assisted closures to help prevent a decrease in the local concentration of the antibiotics.¹¹

Broad-spectrum antibiotics are used to coat the plate in order to cover as many microbial organisms as possible without knowing the final offending organism. In our experience, this current technique provides antibiotic delivery with bony stability, therefore eliminating the need for multiple sequential surgical procedures. This difficult patient problem does not occur with enough frequency to warrant a large randomized clinical trial. However, this technique has been effective in these cases and may be useful to orthopedic surgeons in the future.

Conclusion

Based on our experience, early aggressive débridement, coupled with broad-spectrum antibiotic cement–coated plate insertion, provides fracture stability and helps eradicate the infection with 1 surgical procedure.

Deep infection in the presence of an implant after open reduction and internal fixation (ORIF) is usually treated with removal of the implant, serial débridement procedures, lavage, intravenously administered antibiotics, and, in some cases, placement of antibiotic-impregnated beads. If infection occurs during the early stages of bone healing, stabilization of the fractures might be compromised after removal of the implant. Although antibiotic-impregnated beads offer local delivery of antibiotics, they do not provide structural support of the fracture site. The beads often are difficult to remove after in-growth of granulation tissue. In areas of subcutaneous bone, an antibiotic bead pouch might be preferred to an open wound. Published research regarding the use of antibiotic-coated plates during the acute or chronic stages of infection is scarce. Plates offer the versatility of fracture stabilization, and the addition of antibiotic cement to the plates might aid in eradication of infection without necessitating a second surgery for removal. The patients provided written informed consent for print and electronic publication of these case reports.

Technique

After removal of implants, we perform débridement of the soft tissues with a hydroscalpel (Versajet; Smith & Nephew, London, United Kingdom), mechanical débridement of bone, and curettage with high speed burr. The wound is then irrigated with pulse pressure lavage and a minimum of 3 L sterile normal saline. The extremity is re-prepped and re-draped; the entire surgical team’s gowns and gloves are changed; and new instrumentation, including cautery and suction equipment, is used. The cement is prepared with tobramycin (3.6 g) and vancomycin (1 g) per 40-g bag of cement. The plate is placed in silicon tubing, and the antibiotic-prepared cement is injected into the tubing and molded until dry. Care is taken to mold the locations of the screw holes by making incisions in the tubing at the appropriate locations. Screws are placed through the screw holes to ensure locking capability, and Kirschner wires are placed through temporary fixation holes (Figure 1). Once dry, the screws and wires are removed from the plate, and the cement-coated plate is removed from the tubing. The antibiotic-coated plate is applied to the fracture or osteotomy site and is seated with screws as appropriate (Figure 2). The wound is closed primarily. Wound drains or vacuum-assisted closure devices are not routinely used unless there is high risk for hematoma formation. The authors prefer to have high local concentrations of antibiotic in the surrounding tissues and wound.

Clinical Series

Case 1

A 31-year-old man fell from a ladder and sustained a bimalleolar ankle fracture-dislocation that was treated with ORIF. Three weeks after initial injury, the patient presented with an infected lateral wound with purulent discharge. He was taken to the operating room for initial débridement, irrigation, and fracture stabilization with an antibiotic-coated plate and tension-band wiring of the medial malleoli. He was discharged from the hospital on day 4 after admission. Cultures of the wound grew beta-hemolytic strep group G and coagulase-negative staphylococci in broth that was sensitive to oxacillin, vancomycin, and gentamycin. The patient was treated with a 6-week regimen of Unasyn (Roerig, New York, New York), developed bony union, and has been free of clinical signs of infection for 2 years (Figures 3, 4).

Case 2

A 27-year-old male carpenter fell from a height of 12 feet and sustained a fracture of the distal radius that was treated with external fixation. The proximal pin site became clinically infected and subsequently developed osteomyelitis. The patient had a draining wound with a fracture for 2 months. He underwent débridement with partial resection of the radius and placement of an antibiotic cement–coated plate and calcium phosphate bone-void filler impregnated with antibiotics. Pathology specimens were positive for osteomyelitis, and bone cultures showed methicillin-sensitive Staphylococcus aureus (MSSA). He received intravenously administered antibiotic therapy for 6 weeks after surgery. The patient has remained free of clinical signs of infection for more than 1 year and has achieved bony union (Figures 5A, 5B).

Case 3

A 44-year-old woman with insulin-dependent diabetes mellitus and venous stasis sustained a trimalleolar ankle fracture after a low-energy fall that was initially treated with ORIF. She underwent revision ORIF to treat a malunion 3 months after initial treatment. At 8 months, the patient developed a draining sinus communicating with the plate. Computed tomography revealed nonunion and indicated infection. The patient underwent resection of the osteomyelitis and repair of the fibular nonunion with an antibiotic-coated plate. Tissue cultures were positive for coagulase-negative staphylococcus, and pathology specimens were positive for osteomyelitis. She received postoperative antibiotics intravenously and 6 weeks of antibiotic therapy after discharge from the hospital. The patient has remained free of clinical signs of infection for more than 1 year and has achieved bony union (Figures 6, 7).

Case 4

A 48-year-old man sustained an open olecranon fracture in another country. The fracture was initially treated with 1 dose of intravenously administered antibiotics and 5 days of orally administered antibiotics. The patient returned to the United States and was treated with intravenously administered antibiotics for cellulitis of the elbow for 11 days before referral to our institution, where he underwent ORIF with placement of an antibiotic-coated plate and tension-band wiring. Soft-tissue and bone cultures had no growth. He received intravenously administered antibiotics for 6 weeks. At 5 months postoperatively, the plate was removed because of pain. The patient has remained free of clinical signs of infection for more than 1 year and has achieved bony union (Figures 8A-8C).

Discussion

Acute infections of fractures have recently been treated with success by Berkes and colleagues,¹ who reported a 71% union rate achieved with operative débridement, antibiotic suppression, and retention of fixation until fracture union occurs. The study by Berkes and colleagues¹ had a small patient population, and larger cohorts are needed to show more reliable results; however, this treatment maintains structural support for the fracture during healing but requires multiple trips to the operating room for débridements as well as the use of systemic intravenous antibiotic therapy.

A technique that was developed by the primary author (Janet D. Conway, MD) and has not been described in the literature allows for use of antibiotic cement–coated plates to treat early postoperative infections and osteomyelitic nonunions. This approach permits fracture stabilization and local delivery of high concentrations of broad-spectrum antibiotics and can reduce the number of débridement procedures required in the operating room. We present a technique that includes the use of antibiotic cement–coated plates to treat early postoperative infections associated with fractures and nonunions in order to provide eradication of infection and bony stabilization.

Our approach parallels the current theory that treating infection at a site of union is preferable to treating infection at a site of nonunion.¹ Fixation devices should remain in place until osseous union is achieved. With the addition of antibiotics to the plate, removal might not be necessary unless a device is loose, nonfunctional, or, ultimately, causing pain. Other options, such as external fixation, can be burdensome to patients and can be associated with other risks. One of our 4 patients required fixation removal because of pain at the elbow; however, even noncoated olecranon plates typically are removed because of pain after fracture healing. Antibiotic cement adds bulk to the construct and can become very prominent in areas of little soft-tissue coverage (Figure 9).

Studies, assessing variables that correlate with higher likelihood of failure for primary repairs, have shown that open fracture, use of an intramedullary nail, and smoking are the highest risk factors for infected nonunion.¹⁻⁴ Among our 4 patients, 3 were smokers and 1 originally had an open fracture. Smokers have been found to have a 37% higher nonunion rate and are 2 times more likely to develop wound infection and osteomyelitis.^1,5 More than 60% of the time, infections are caused by S aureus or coagulase-negative staphylococci.^1,5,6 In our study population, 3 of the 4 patients had coagulase-negative staphylococci grow in the cultures. Implants infected with S aureus or Candida require surgical removal. Those with less virulent coagulase-negative staphylococci might not necessitate removal; however, our population had had antibiotic therapy and continued draining sinus.⁵ Rightmire and colleagues⁷ reported that those who develop infection earlier than 16 weeks postoperatively have a 68% success rate and that smoking is a major risk factor for infection. Development of Pseudomonas in the wound has been shown to have a positive correlation with amputation.^1,2 Infection with Pseudomonas, smoking, and involvement of the femur, tibia, ankle, or foot tended to result in failure.^1,2 Being clinically free of signs of infection after 3 months offers a 50% cure rate, with 78% at 6 months and 95% after 1 year.²

When determining an antibiotic to use with the polymethylmethacrylate (PMMA) cement, many factors must be considered, including spectrum, heat stability, and elution characteristics.⁸ A synergistic effect has been seen with combinations of antibiotics (eg, vancomycin and tobramycin used together). Vancomycin concentrations increased by 103% and tobramycin by 68% when used together compared with their elution rates when used alone, showing passive opportunism.⁹ This will, in essence, increase concentrations of antibiotics at the site locally, which will increase the bacteriocidal potential but also create a larger antimicrobial spectrum.⁹

The authors used Cobalt Bone Cement (Biomet Orthopedics, Inc, Warsaw, Indiana) which been shown to have higher elution properties than Simplex P Bone Cement (Stryker, Kalamazoo, Michigan).^3,10 The majority of elution occurs in the first 3 to 5 days but can continue for weeks after implantation. We place the cement on the plate allowing for its retention, hoping to eliminate a second surgery for removal.⁸ We recommend 3.6 g of tobramycin, and 1 g of vancomycin per 40-g bag of PMMA.³ This dose has been shown to be safe in respect to renal toxicity, plus the entire dose is not administered in a single setting because only a small portion of the cement is used when coating the plate. We close all wounds primarily, and do not regularly use drains or vacuum-assisted closures to help prevent a decrease in the local concentration of the antibiotics.¹¹

Broad-spectrum antibiotics are used to coat the plate in order to cover as many microbial organisms as possible without knowing the final offending organism. In our experience, this current technique provides antibiotic delivery with bony stability, therefore eliminating the need for multiple sequential surgical procedures. This difficult patient problem does not occur with enough frequency to warrant a large randomized clinical trial. However, this technique has been effective in these cases and may be useful to orthopedic surgeons in the future.

Conclusion

Based on our experience, early aggressive débridement, coupled with broad-spectrum antibiotic cement–coated plate insertion, provides fracture stability and helps eradicate the infection with 1 surgical procedure.

Deep infection in the presence of an implant after open reduction and internal fixation (ORIF) is usually treated with removal of the implant, serial débridement procedures, lavage, intravenously administered antibiotics, and, in some cases, placement of antibiotic-impregnated beads. If infection occurs during the early stages of bone healing, stabilization of the fractures might be compromised after removal of the implant. Although antibiotic-impregnated beads offer local delivery of antibiotics, they do not provide structural support of the fracture site. The beads often are difficult to remove after in-growth of granulation tissue. In areas of subcutaneous bone, an antibiotic bead pouch might be preferred to an open wound. Published research regarding the use of antibiotic-coated plates during the acute or chronic stages of infection is scarce. Plates offer the versatility of fracture stabilization, and the addition of antibiotic cement to the plates might aid in eradication of infection without necessitating a second surgery for removal. The patients provided written informed consent for print and electronic publication of these case reports.

Technique

After removal of implants, we perform débridement of the soft tissues with a hydroscalpel (Versajet; Smith & Nephew, London, United Kingdom), mechanical débridement of bone, and curettage with high speed burr. The wound is then irrigated with pulse pressure lavage and a minimum of 3 L sterile normal saline. The extremity is re-prepped and re-draped; the entire surgical team’s gowns and gloves are changed; and new instrumentation, including cautery and suction equipment, is used. The cement is prepared with tobramycin (3.6 g) and vancomycin (1 g) per 40-g bag of cement. The plate is placed in silicon tubing, and the antibiotic-prepared cement is injected into the tubing and molded until dry. Care is taken to mold the locations of the screw holes by making incisions in the tubing at the appropriate locations. Screws are placed through the screw holes to ensure locking capability, and Kirschner wires are placed through temporary fixation holes (Figure 1). Once dry, the screws and wires are removed from the plate, and the cement-coated plate is removed from the tubing. The antibiotic-coated plate is applied to the fracture or osteotomy site and is seated with screws as appropriate (Figure 2). The wound is closed primarily. Wound drains or vacuum-assisted closure devices are not routinely used unless there is high risk for hematoma formation. The authors prefer to have high local concentrations of antibiotic in the surrounding tissues and wound.

Clinical Series

Case 1

A 31-year-old man fell from a ladder and sustained a bimalleolar ankle fracture-dislocation that was treated with ORIF. Three weeks after initial injury, the patient presented with an infected lateral wound with purulent discharge. He was taken to the operating room for initial débridement, irrigation, and fracture stabilization with an antibiotic-coated plate and tension-band wiring of the medial malleoli. He was discharged from the hospital on day 4 after admission. Cultures of the wound grew beta-hemolytic strep group G and coagulase-negative staphylococci in broth that was sensitive to oxacillin, vancomycin, and gentamycin. The patient was treated with a 6-week regimen of Unasyn (Roerig, New York, New York), developed bony union, and has been free of clinical signs of infection for 2 years (Figures 3, 4).

Case 2

A 27-year-old male carpenter fell from a height of 12 feet and sustained a fracture of the distal radius that was treated with external fixation. The proximal pin site became clinically infected and subsequently developed osteomyelitis. The patient had a draining wound with a fracture for 2 months. He underwent débridement with partial resection of the radius and placement of an antibiotic cement–coated plate and calcium phosphate bone-void filler impregnated with antibiotics. Pathology specimens were positive for osteomyelitis, and bone cultures showed methicillin-sensitive Staphylococcus aureus (MSSA). He received intravenously administered antibiotic therapy for 6 weeks after surgery. The patient has remained free of clinical signs of infection for more than 1 year and has achieved bony union (Figures 5A, 5B).

Case 3

A 44-year-old woman with insulin-dependent diabetes mellitus and venous stasis sustained a trimalleolar ankle fracture after a low-energy fall that was initially treated with ORIF. She underwent revision ORIF to treat a malunion 3 months after initial treatment. At 8 months, the patient developed a draining sinus communicating with the plate. Computed tomography revealed nonunion and indicated infection. The patient underwent resection of the osteomyelitis and repair of the fibular nonunion with an antibiotic-coated plate. Tissue cultures were positive for coagulase-negative staphylococcus, and pathology specimens were positive for osteomyelitis. She received postoperative antibiotics intravenously and 6 weeks of antibiotic therapy after discharge from the hospital. The patient has remained free of clinical signs of infection for more than 1 year and has achieved bony union (Figures 6, 7).

Case 4

A 48-year-old man sustained an open olecranon fracture in another country. The fracture was initially treated with 1 dose of intravenously administered antibiotics and 5 days of orally administered antibiotics. The patient returned to the United States and was treated with intravenously administered antibiotics for cellulitis of the elbow for 11 days before referral to our institution, where he underwent ORIF with placement of an antibiotic-coated plate and tension-band wiring. Soft-tissue and bone cultures had no growth. He received intravenously administered antibiotics for 6 weeks. At 5 months postoperatively, the plate was removed because of pain. The patient has remained free of clinical signs of infection for more than 1 year and has achieved bony union (Figures 8A-8C).

Discussion

Acute infections of fractures have recently been treated with success by Berkes and colleagues,¹ who reported a 71% union rate achieved with operative débridement, antibiotic suppression, and retention of fixation until fracture union occurs. The study by Berkes and colleagues¹ had a small patient population, and larger cohorts are needed to show more reliable results; however, this treatment maintains structural support for the fracture during healing but requires multiple trips to the operating room for débridements as well as the use of systemic intravenous antibiotic therapy.

A technique that was developed by the primary author (Janet D. Conway, MD) and has not been described in the literature allows for use of antibiotic cement–coated plates to treat early postoperative infections and osteomyelitic nonunions. This approach permits fracture stabilization and local delivery of high concentrations of broad-spectrum antibiotics and can reduce the number of débridement procedures required in the operating room. We present a technique that includes the use of antibiotic cement–coated plates to treat early postoperative infections associated with fractures and nonunions in order to provide eradication of infection and bony stabilization.

Our approach parallels the current theory that treating infection at a site of union is preferable to treating infection at a site of nonunion.¹ Fixation devices should remain in place until osseous union is achieved. With the addition of antibiotics to the plate, removal might not be necessary unless a device is loose, nonfunctional, or, ultimately, causing pain. Other options, such as external fixation, can be burdensome to patients and can be associated with other risks. One of our 4 patients required fixation removal because of pain at the elbow; however, even noncoated olecranon plates typically are removed because of pain after fracture healing. Antibiotic cement adds bulk to the construct and can become very prominent in areas of little soft-tissue coverage (Figure 9).

Studies, assessing variables that correlate with higher likelihood of failure for primary repairs, have shown that open fracture, use of an intramedullary nail, and smoking are the highest risk factors for infected nonunion.¹⁻⁴ Among our 4 patients, 3 were smokers and 1 originally had an open fracture. Smokers have been found to have a 37% higher nonunion rate and are 2 times more likely to develop wound infection and osteomyelitis.^1,5 More than 60% of the time, infections are caused by S aureus or coagulase-negative staphylococci.^1,5,6 In our study population, 3 of the 4 patients had coagulase-negative staphylococci grow in the cultures. Implants infected with S aureus or Candida require surgical removal. Those with less virulent coagulase-negative staphylococci might not necessitate removal; however, our population had had antibiotic therapy and continued draining sinus.⁵ Rightmire and colleagues⁷ reported that those who develop infection earlier than 16 weeks postoperatively have a 68% success rate and that smoking is a major risk factor for infection. Development of Pseudomonas in the wound has been shown to have a positive correlation with amputation.^1,2 Infection with Pseudomonas, smoking, and involvement of the femur, tibia, ankle, or foot tended to result in failure.^1,2 Being clinically free of signs of infection after 3 months offers a 50% cure rate, with 78% at 6 months and 95% after 1 year.²

When determining an antibiotic to use with the polymethylmethacrylate (PMMA) cement, many factors must be considered, including spectrum, heat stability, and elution characteristics.⁸ A synergistic effect has been seen with combinations of antibiotics (eg, vancomycin and tobramycin used together). Vancomycin concentrations increased by 103% and tobramycin by 68% when used together compared with their elution rates when used alone, showing passive opportunism.⁹ This will, in essence, increase concentrations of antibiotics at the site locally, which will increase the bacteriocidal potential but also create a larger antimicrobial spectrum.⁹

The authors used Cobalt Bone Cement (Biomet Orthopedics, Inc, Warsaw, Indiana) which been shown to have higher elution properties than Simplex P Bone Cement (Stryker, Kalamazoo, Michigan).^3,10 The majority of elution occurs in the first 3 to 5 days but can continue for weeks after implantation. We place the cement on the plate allowing for its retention, hoping to eliminate a second surgery for removal.⁸ We recommend 3.6 g of tobramycin, and 1 g of vancomycin per 40-g bag of PMMA.³ This dose has been shown to be safe in respect to renal toxicity, plus the entire dose is not administered in a single setting because only a small portion of the cement is used when coating the plate. We close all wounds primarily, and do not regularly use drains or vacuum-assisted closures to help prevent a decrease in the local concentration of the antibiotics.¹¹

Broad-spectrum antibiotics are used to coat the plate in order to cover as many microbial organisms as possible without knowing the final offending organism. In our experience, this current technique provides antibiotic delivery with bony stability, therefore eliminating the need for multiple sequential surgical procedures. This difficult patient problem does not occur with enough frequency to warrant a large randomized clinical trial. However, this technique has been effective in these cases and may be useful to orthopedic surgeons in the future.

Conclusion

Based on our experience, early aggressive débridement, coupled with broad-spectrum antibiotic cement–coated plate insertion, provides fracture stability and helps eradicate the infection with 1 surgical procedure.

Intravesicular instillation of bacillus Calmette-Guérin (BCG), an attenuated form of Mycobacterium bovis, is the most effective treatment for superficial bladder cancer.^1,2 Minor local reactions to this treatment, such as cystitis and hematuria, are common, but more severe systemic complications^3,4 have also been documented, including sepsis, pneumonitis, granulomatous hepatitis, vertebral osteomyelitis,^5,6 and rarely, total joint infection.^7-11

We present a case of M bovis infection of a total knee arthroplasty (TKA) after BCG immunotherapy for bladder cancer that was successfully treated with antitubercular chemotherapy and retention of implants. We include a review of the literature addressing this rare mode of infection. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 66-year-old man presented with a chief complaint of progressive left knee stiffness over several months. Five years earlier, he underwent uncemented left TKA. His knee was functioning well with active range of motion from 0° to 126°, and he had returned to strenuous cycling. One year after his TKA and 4 years prior to the onset of stiffness, he had been diagnosed with superficial transitional cell carcinoma of the bladder. His treatment included intravesicular BCG therapy weekly for 6 weeks followed by semi-annual maintenance therapy. 

Initial examination upon presentation with left knee stiffness showed a significant effusion and diminished range of motion but little discomfort. The patient denied fever, chills, night sweats, and weight loss. Radiographs were normal with good component positioning and normal-appearing bone-implant interfaces (Figures A, B). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell count (WBC) were within normal limits, and aspirate of the knee revealed no organisms. Based on these findings, the presumptive diagnosis was an adverse reaction to polyethylene wear. Because of persistent stiffness, the patient underwent an examination under anesthesia, arthroscopy, and major synovectomy with biopsy. Intraoperative findings included normal polyethylene but a marked hypertrophic synovitis and abnormal, semi-turbid fluid. The fluid WBC count was 5.35×10⁹/L but no organisms were isolated initially. Histologic samples showed chronic inflammation with patches of acute inflammation. Approximately 6 weeks after surgery, cultures became positive for acid-fast bacillus, which was identified as M bovis. 

Maintenance BCG therapy was discontinued, and antitubercular chemotherapy was initiated, consisting of 12 months of rifampin 600 mg daily and isoniazid 300 mg daily. Because symptoms significantly improved after arthroscopic incision and drainage and synovectomy, the TKA implants were maintained and symptoms closely monitored. Subsequent cultures and biopsies remained negative, and the patient continued to do well clinically with no residual stiffness. 

At 7½-year follow-up, there is no clinical evidence of infection, and the patient continues to enjoy a high level of function with no pain and no recurrent stiffness. He has returned to cycling, logging more than 40,000 miles. However, a recurrence of bladder cancer is being treated with mitomycin C and gemcitabine, alternative to BCG.

Discussion

Mycobacterial infection in total joint arthroplasty (TJA) is uncommon;¹²M bovis infection of joint arthroplasty after intravesicular BCG therapy is exceedingly rare. Joint infection is thought to be the result of dissemination of BCG throughout the bloodstream.¹³ 

A review of the literature of BCG infection of TJA after intravesicular therapy for bladder cancer revealed only 5 case reports (Table). The average age on presentation was 77 years, and all patients were men, with 4 total hip arthroplasties (THAs) and 1 TKA. The average time from index procedure to initial presentation was 7.8 years, and the average time from cancer diagnosis to initial presentation was 20 months. Patients received an average of 8.6 consecutive weeks of BCG treatments, and maintenance therapy was not noted in any of the published reports. The average duration of antitubercular therapy was 13 months, and it comprised either 2- or 3-agent therapy. All reported cases were treated with removal of primary implants in either a 1- or 2-stage fashion. To our knowledge, this is only the second case of BCG infection of TKA reported in the literature and the first report of successful treatment with retention of primary implants. 

There are several possible explanations for the success of a more conservative treatment approach in our patient. First, this TKA was uncemented. Second, BCG is an attenuated form of M bovis, which is itself a relatively less virulent species than M tuberculosis. Finally, mycobacterial species do not produce the biofilm that is seen in other bacterial arthroplasty infections, which typically necessitate removal of implants in cases of chronic infection.¹⁴ 

This case was unique because the patient lacked signs of infectious symptoms, there were normal inflammatory markers, and arthroscopy was necessary to aid in the diagnosis. The definitive diagnosis in this case was significantly delayed to attain a positive M bovis culture. Definitive treatment was provided by arthroscopy, implant salvage, and antitubercular chemotherapy only. The standard of care for an infected modular TKA normally involves revision of the polyethylene tibial insert with irrigation and débridement, or removal of components and insertion of new implants in a 1- or 2-stage procedure. Despite the unusual algorithm to reach a definitive diagnosis of an infected joint arthroplasty in this case, we do not recommend arthroscopic biopsy, washout, and antimicrobial therapy as definitive treatment for infected joint arthroplasty, and we continue to support the removal of infected components in a staged manner.

Conclusion

Joint replacement patients with bladder cancer represent a relatively small cohort. Based on current demographics and the increasing demand for joint arthroplasty, it is likely that this unique subset of patients will grow. No current standard of care exists for the treatment of these patients. One preventative measure is to consider alternative types of chemotherapy for bladder cancer treatment, such as mitomycin. Another potential solution would be administration of prophylactic doses of antitubercular agents concomitantly with intravesicular BCG, which would allow for the local effects of BCG immunotherapy while controlling the potential for systemic dissemination. The optimal dose range to achieve this dual effect is not known and is an area for research. 

It is important for both arthroplasty surgeons and urologists to be aware of this potential complication in order to appropriately counsel this unique subset of patients. Our case report is the first to demonstrate that a successful outcome can be obtained with retention of primary components. Through research and continued data acquisition, a more concrete standard of care can be established. Until then, we recommend a collaborative approach between informed parties to devise a patient-specific plan of care. 

Intravesicular instillation of bacillus Calmette-Guérin (BCG), an attenuated form of Mycobacterium bovis, is the most effective treatment for superficial bladder cancer.^1,2 Minor local reactions to this treatment, such as cystitis and hematuria, are common, but more severe systemic complications^3,4 have also been documented, including sepsis, pneumonitis, granulomatous hepatitis, vertebral osteomyelitis,^5,6 and rarely, total joint infection.^7-11

We present a case of M bovis infection of a total knee arthroplasty (TKA) after BCG immunotherapy for bladder cancer that was successfully treated with antitubercular chemotherapy and retention of implants. We include a review of the literature addressing this rare mode of infection. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 66-year-old man presented with a chief complaint of progressive left knee stiffness over several months. Five years earlier, he underwent uncemented left TKA. His knee was functioning well with active range of motion from 0° to 126°, and he had returned to strenuous cycling. One year after his TKA and 4 years prior to the onset of stiffness, he had been diagnosed with superficial transitional cell carcinoma of the bladder. His treatment included intravesicular BCG therapy weekly for 6 weeks followed by semi-annual maintenance therapy. 

Initial examination upon presentation with left knee stiffness showed a significant effusion and diminished range of motion but little discomfort. The patient denied fever, chills, night sweats, and weight loss. Radiographs were normal with good component positioning and normal-appearing bone-implant interfaces (Figures A, B). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell count (WBC) were within normal limits, and aspirate of the knee revealed no organisms. Based on these findings, the presumptive diagnosis was an adverse reaction to polyethylene wear. Because of persistent stiffness, the patient underwent an examination under anesthesia, arthroscopy, and major synovectomy with biopsy. Intraoperative findings included normal polyethylene but a marked hypertrophic synovitis and abnormal, semi-turbid fluid. The fluid WBC count was 5.35×10⁹/L but no organisms were isolated initially. Histologic samples showed chronic inflammation with patches of acute inflammation. Approximately 6 weeks after surgery, cultures became positive for acid-fast bacillus, which was identified as M bovis. 

Maintenance BCG therapy was discontinued, and antitubercular chemotherapy was initiated, consisting of 12 months of rifampin 600 mg daily and isoniazid 300 mg daily. Because symptoms significantly improved after arthroscopic incision and drainage and synovectomy, the TKA implants were maintained and symptoms closely monitored. Subsequent cultures and biopsies remained negative, and the patient continued to do well clinically with no residual stiffness. 

At 7½-year follow-up, there is no clinical evidence of infection, and the patient continues to enjoy a high level of function with no pain and no recurrent stiffness. He has returned to cycling, logging more than 40,000 miles. However, a recurrence of bladder cancer is being treated with mitomycin C and gemcitabine, alternative to BCG.

Discussion

Mycobacterial infection in total joint arthroplasty (TJA) is uncommon;¹²M bovis infection of joint arthroplasty after intravesicular BCG therapy is exceedingly rare. Joint infection is thought to be the result of dissemination of BCG throughout the bloodstream.¹³ 

A review of the literature of BCG infection of TJA after intravesicular therapy for bladder cancer revealed only 5 case reports (Table). The average age on presentation was 77 years, and all patients were men, with 4 total hip arthroplasties (THAs) and 1 TKA. The average time from index procedure to initial presentation was 7.8 years, and the average time from cancer diagnosis to initial presentation was 20 months. Patients received an average of 8.6 consecutive weeks of BCG treatments, and maintenance therapy was not noted in any of the published reports. The average duration of antitubercular therapy was 13 months, and it comprised either 2- or 3-agent therapy. All reported cases were treated with removal of primary implants in either a 1- or 2-stage fashion. To our knowledge, this is only the second case of BCG infection of TKA reported in the literature and the first report of successful treatment with retention of primary implants. 

There are several possible explanations for the success of a more conservative treatment approach in our patient. First, this TKA was uncemented. Second, BCG is an attenuated form of M bovis, which is itself a relatively less virulent species than M tuberculosis. Finally, mycobacterial species do not produce the biofilm that is seen in other bacterial arthroplasty infections, which typically necessitate removal of implants in cases of chronic infection.¹⁴ 

This case was unique because the patient lacked signs of infectious symptoms, there were normal inflammatory markers, and arthroscopy was necessary to aid in the diagnosis. The definitive diagnosis in this case was significantly delayed to attain a positive M bovis culture. Definitive treatment was provided by arthroscopy, implant salvage, and antitubercular chemotherapy only. The standard of care for an infected modular TKA normally involves revision of the polyethylene tibial insert with irrigation and débridement, or removal of components and insertion of new implants in a 1- or 2-stage procedure. Despite the unusual algorithm to reach a definitive diagnosis of an infected joint arthroplasty in this case, we do not recommend arthroscopic biopsy, washout, and antimicrobial therapy as definitive treatment for infected joint arthroplasty, and we continue to support the removal of infected components in a staged manner.

Conclusion

Joint replacement patients with bladder cancer represent a relatively small cohort. Based on current demographics and the increasing demand for joint arthroplasty, it is likely that this unique subset of patients will grow. No current standard of care exists for the treatment of these patients. One preventative measure is to consider alternative types of chemotherapy for bladder cancer treatment, such as mitomycin. Another potential solution would be administration of prophylactic doses of antitubercular agents concomitantly with intravesicular BCG, which would allow for the local effects of BCG immunotherapy while controlling the potential for systemic dissemination. The optimal dose range to achieve this dual effect is not known and is an area for research. 

It is important for both arthroplasty surgeons and urologists to be aware of this potential complication in order to appropriately counsel this unique subset of patients. Our case report is the first to demonstrate that a successful outcome can be obtained with retention of primary components. Through research and continued data acquisition, a more concrete standard of care can be established. Until then, we recommend a collaborative approach between informed parties to devise a patient-specific plan of care. 

Intravesicular instillation of bacillus Calmette-Guérin (BCG), an attenuated form of Mycobacterium bovis, is the most effective treatment for superficial bladder cancer.^1,2 Minor local reactions to this treatment, such as cystitis and hematuria, are common, but more severe systemic complications^3,4 have also been documented, including sepsis, pneumonitis, granulomatous hepatitis, vertebral osteomyelitis,^5,6 and rarely, total joint infection.^7-11

We present a case of M bovis infection of a total knee arthroplasty (TKA) after BCG immunotherapy for bladder cancer that was successfully treated with antitubercular chemotherapy and retention of implants. We include a review of the literature addressing this rare mode of infection. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 66-year-old man presented with a chief complaint of progressive left knee stiffness over several months. Five years earlier, he underwent uncemented left TKA. His knee was functioning well with active range of motion from 0° to 126°, and he had returned to strenuous cycling. One year after his TKA and 4 years prior to the onset of stiffness, he had been diagnosed with superficial transitional cell carcinoma of the bladder. His treatment included intravesicular BCG therapy weekly for 6 weeks followed by semi-annual maintenance therapy. 

Initial examination upon presentation with left knee stiffness showed a significant effusion and diminished range of motion but little discomfort. The patient denied fever, chills, night sweats, and weight loss. Radiographs were normal with good component positioning and normal-appearing bone-implant interfaces (Figures A, B). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and white blood cell count (WBC) were within normal limits, and aspirate of the knee revealed no organisms. Based on these findings, the presumptive diagnosis was an adverse reaction to polyethylene wear. Because of persistent stiffness, the patient underwent an examination under anesthesia, arthroscopy, and major synovectomy with biopsy. Intraoperative findings included normal polyethylene but a marked hypertrophic synovitis and abnormal, semi-turbid fluid. The fluid WBC count was 5.35×10⁹/L but no organisms were isolated initially. Histologic samples showed chronic inflammation with patches of acute inflammation. Approximately 6 weeks after surgery, cultures became positive for acid-fast bacillus, which was identified as M bovis. 

Maintenance BCG therapy was discontinued, and antitubercular chemotherapy was initiated, consisting of 12 months of rifampin 600 mg daily and isoniazid 300 mg daily. Because symptoms significantly improved after arthroscopic incision and drainage and synovectomy, the TKA implants were maintained and symptoms closely monitored. Subsequent cultures and biopsies remained negative, and the patient continued to do well clinically with no residual stiffness. 

At 7½-year follow-up, there is no clinical evidence of infection, and the patient continues to enjoy a high level of function with no pain and no recurrent stiffness. He has returned to cycling, logging more than 40,000 miles. However, a recurrence of bladder cancer is being treated with mitomycin C and gemcitabine, alternative to BCG.

Discussion

Mycobacterial infection in total joint arthroplasty (TJA) is uncommon;¹²M bovis infection of joint arthroplasty after intravesicular BCG therapy is exceedingly rare. Joint infection is thought to be the result of dissemination of BCG throughout the bloodstream.¹³ 

A review of the literature of BCG infection of TJA after intravesicular therapy for bladder cancer revealed only 5 case reports (Table). The average age on presentation was 77 years, and all patients were men, with 4 total hip arthroplasties (THAs) and 1 TKA. The average time from index procedure to initial presentation was 7.8 years, and the average time from cancer diagnosis to initial presentation was 20 months. Patients received an average of 8.6 consecutive weeks of BCG treatments, and maintenance therapy was not noted in any of the published reports. The average duration of antitubercular therapy was 13 months, and it comprised either 2- or 3-agent therapy. All reported cases were treated with removal of primary implants in either a 1- or 2-stage fashion. To our knowledge, this is only the second case of BCG infection of TKA reported in the literature and the first report of successful treatment with retention of primary implants. 

There are several possible explanations for the success of a more conservative treatment approach in our patient. First, this TKA was uncemented. Second, BCG is an attenuated form of M bovis, which is itself a relatively less virulent species than M tuberculosis. Finally, mycobacterial species do not produce the biofilm that is seen in other bacterial arthroplasty infections, which typically necessitate removal of implants in cases of chronic infection.¹⁴ 

This case was unique because the patient lacked signs of infectious symptoms, there were normal inflammatory markers, and arthroscopy was necessary to aid in the diagnosis. The definitive diagnosis in this case was significantly delayed to attain a positive M bovis culture. Definitive treatment was provided by arthroscopy, implant salvage, and antitubercular chemotherapy only. The standard of care for an infected modular TKA normally involves revision of the polyethylene tibial insert with irrigation and débridement, or removal of components and insertion of new implants in a 1- or 2-stage procedure. Despite the unusual algorithm to reach a definitive diagnosis of an infected joint arthroplasty in this case, we do not recommend arthroscopic biopsy, washout, and antimicrobial therapy as definitive treatment for infected joint arthroplasty, and we continue to support the removal of infected components in a staged manner.

Conclusion

Joint replacement patients with bladder cancer represent a relatively small cohort. Based on current demographics and the increasing demand for joint arthroplasty, it is likely that this unique subset of patients will grow. No current standard of care exists for the treatment of these patients. One preventative measure is to consider alternative types of chemotherapy for bladder cancer treatment, such as mitomycin. Another potential solution would be administration of prophylactic doses of antitubercular agents concomitantly with intravesicular BCG, which would allow for the local effects of BCG immunotherapy while controlling the potential for systemic dissemination. The optimal dose range to achieve this dual effect is not known and is an area for research. 

It is important for both arthroplasty surgeons and urologists to be aware of this potential complication in order to appropriately counsel this unique subset of patients. Our case report is the first to demonstrate that a successful outcome can be obtained with retention of primary components. Through research and continued data acquisition, a more concrete standard of care can be established. Until then, we recommend a collaborative approach between informed parties to devise a patient-specific plan of care. 

Surgical site infection after arthroplasty causes substantial morbidity and potential mortality. Prosthetic joint infection (PJI) ranges from simple superficial wound infection and cellulitis to deep subfascial infection that involves the prosthesis. Consistent use of prophylactic antibiotics has reduced postoperative hip and knee arthroplasty infections to rates of 0.25% to 2%.^1-4 Treatment of a patient with PJI commonly includes hospitalization, long-term intravenously administered antibiotics, resection arthroplasty, and staged reimplantation. The estimated cost of interventions reaches tens of millions of dollars annually in the United States and does not include the costs of psychosocial effects on patients and their families.^5,6

Betadine (povidone-iodine) is a widely used antiseptic for skin and mucous membrane wounds and has been shown to be effective for the prevention of PJI.⁷ Dilute Betadine solution has been proposed as an aid in treatment of PJI.⁸ At a minimum concentration of 5%, cytotoxicity has been observed in chicken tibia osteoblasts.⁹ A balance of the bactericidal and cytotoxic activities of Betadine, while maintaining its efficacy against resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), is optimized at dilutions between 0.5% and 4%.^10-14 We hypothesized that a dilute Betadine lavage of 3.5% would achieve a significant decrease in bacterial counts compared with an isolated saline lavage in an in vivo knee PJI model.

Materials and Methods

Animal Protocol

All surgical procedures were conducted according to the protocol approved by our institutional animal care and use committee. Using a power analysis and data obtained at our institution, we determined that 12 was the minimum number of animals needed to reach significance set at P < .05 and assuming a 50% decrease in colony-forming units (CFU) (SigmaStat Version 2.03; Aspire Software International, Ashburn, Virginia). Eight New Zealand White rabbits were used in our study; because significance was reached early, 12 were not needed. The average weight of the rabbits was 3.5 kg (weight range, 3.2-4.1 kg). All rabbits completed 1 week of acclimation before surgery.

Bacteria Preparation

A broth culture of methicillin-sensitive S aureus (MSSA) (ATCC 25923) was prepared 1 day before surgery. The bacteria were suspended in 5 mL of Trypticase Soy Broth (Becton Dickinson & Co, Franklin Lakes, New Jersey) and incubated at 37°C in a shaking incubator for 16 hours. The next day, the culture was centrifuged and irrigated twice with normal saline to remove the broth and prevent further growth. The bacteria were reconstituted in normal saline, and the concentration was standardized using a turbidity meter (LaMotte 2020e; LaMotte Co, Chestertown, Maryland), which correlated with 10⁶ CFU/100 µl plated on trypticase soy agar plates with 10% sheep blood (Fisher Scientific, Pittsburgh, Pennsylvania).

Surgical and Postoperative Procedures

Our procedure was based on the New Zealand White rabbit knee PJI model.¹⁵ General anesthesia was induced with ketamine and xylazine, and maintained with isoflurane inhalation via a nose cone mask. Rabbits were positioned supine, and bilateral knees were shaved, prepped, and draped in a sterile fashion.

A 2-cm longitudinal incision was made over the lateral knee, and arthrotomy was performed, exposing the lateral collateral ligament attachment at the lateral femoral condyle. Using a 4-mm drill bit, a defect was drilled obliquely into the lateral femoral condyle, anterior to the lateral collateral ligament attachment. This produced a defect in the non-weight-bearing, nonarticulating portion of the knee. A fully threaded 4×14-mm stainless steel screw (Synthes, West Chester, Pennsylvania) with a U-shaped ultrahigh-molecular-weight polyethylene washer (Synthes) was inserted into the defect. The joint capsule was closed with a running 3-0 Vicryl suture (Ethicon, Somerville, New Jersey). The knee joint was inoculated with 100 µL of the S aureus preparation using a 22-gauge needle. The skin was closed with a 4-0 Biosyn suture (Ethicon). The procedure was repeated on the contralateral knee (Figures 1A, 1B).

Seven days after the initial surgery, the rabbits were returned to the operating room and were anesthetized, positioned, and prepped for surgery as detailed above. Ceftriaxone (20 mg/kg of body weight) was intravenously administered to all rabbits for the treatment procedure. For each rabbit, a control knee and an experimental knee were randomly assigned. A longitudinal incision was made, exposing the previously placed implants. The screw was loosened slightly to remove the U-shaped polyethylene washer. Each knee then underwent lavage 2 times, for 90 seconds each time, with 3.5% dilute Betadine solution (experimental knee) or with normal saline (control knee). Because Pseudomonas contamination has been reported with povidone-iodine taken from unsterilized bottles,^16,17 packets of sterilized povidone-iodine (Aplicare; Clorox, Oakland, California) were used. After the irrigation was complete, a new sterile polyethylene washer was placed and the screw was tightened. The wound closure was repeated as detailed above.

Postoperative analgesia was provided based on a standard institutional animal care and use committee protocol. Rabbits were permitted full cage activity and nutrition ad libitum. Wound healing, body weight, and signs of distress were monitored daily.

Outcome Measures

Seven days after surgery, the rabbits were euthanized with administration of phenobarbital (100 mg/kg of body weight). Arterial blood samples were obtained from the auricular vein to ensure that the rabbits were not systemically infected. Using a sterile technique, the screw, polyethylene washer, lateral femoral condyle bone from the defect, and joint capsule were cultured. Harvested bone and soft tissues were weighed and immediately homogenized (PowerGen Model 35 Handheld Homogenizer; Thermo Fisher Scientific, Inc, Waltham, Massachusetts). Implants were sonicated (UBATH-Y; World Precision Instruments, Inc, Sarasota, Florida) in cold saline to obtain a sensitive culture.¹⁸

Bacterial quantification was determined by using trypticase soy agar plates after 24 hours of growth. Final CFU were calculated after serial dilutions and were standardized per gram of biopsied tissues.¹⁹ Members of the team were blinded to the treatment type.

Statistical Analysis

Statistical differences in mean bacterial burden were calculated independently for lateral condyle bone, joint capsule, polyethylene, and screws by conducting a Student t test.

Results

Treatment effect was higher than expected, and the study was terminated after 8 animals completed the protocol. All 8 rabbits tolerated the procedures well and were appropriately monitored during the postoperative period. No animals had signs of systemic infection or positive blood culture. All local cultures for screw, polyethylene washer, lateral femoral condyle defect, and joint capsule were positive.

Statistically significant decreases were shown in the bacterial burden of the Betadine-irrigated screws and the Betadine-irrigated polyethylene washers compared with the saline-irrigated controls. Betadine-irrigated screws grew an average of 7.16 × 10¹ CFU of S aureus/g, whereas screws from control knees grew an average of 1.45 × 10³ CFU/g (P = .0003) (Figure 2). Betadine-treated washers grew an average of 1.28 × 10³ CFU/g compared with 1.62 × 10⁴ CFU/g for control washers (P =. 04) (Figure 3).

A trend toward decreased bacterial counts was shown in Betadine-treated soft tissues compared with saline-treated soft tissues, but the difference did not reach statistical significance (P = .9). Biopsied joint capsule from knees treated with Betadine grew an average of 2.84 × 10⁴ CFU/g compared with an average of 3.16 × 10⁴ CFU/g in control-rabbit knees (Figure 4). Cultured lateral condyle from Betadine-treated knees had an average bacterial load of 3.22 × 10⁴ CFU/g compared with an average bacterial load of 1 × 10⁵ CFU/g in control knees (Figure 4).

Discussion

Knees irrigated with Betadine showed a significant (P = .0003) decrease in metal implant–related S aureus bacterial counts by 20-fold and a significant (P < .05) decrease in polyethylene implant–related counts by more than 10-fold. This arthroplasty model used Betadine lavage as a treatment adjunct with intravenously administered antibiotics and polyethylene exchange. Our 1-week interval after the index procedure classifies the infection as an acute postoperative arthroplasty infection (occurring less than 4 weeks postoperatively).

The gold standard treatment for these infections is irrigation and débridement with component retention.¹⁸ The success rate has been reported to be as high as 71%²⁰ but was closer to 44% in a study by Fridkin and colleagues,²¹ especially with more virulent bacteria. Staphylococcal species, higher American Society of Anesthesiologists scores, and frank pus around the prosthesis were markers of débridement failure in a recent study by Azzam and colleagues.¹⁸

The majority of postoperative joint arthroplasty infections are caused by S aureus, and the incidence of MRSA bacteria continues to rise.²² Community-acquired MRSA is increasing at an alarming rate and is now the predominant organism in skin and soft-tissue infections.²³ Organism resistance also occurs at a cellular level by the formation of a glycocalyx layer, or biofilm. This layer assists in changing the phenotypic properties of the organism and decreases the efficacy of antibiotics.²⁴ The self-produced layer of extracellular matrices, deoxyribonucleic acid, and polysaccharides attaches to inert material, preventing phagocytic action by neutrophils. In addition to antibacterial activity, povidone-iodine has antibiofilm activity against Staphylococcal species.²⁵ The active ingredient targets the gene that produces biofilm. This correlates to our study in which the largest decrease in bacterial counts was noted on the implants.

The use of Betadine lavage has shown some promise in vivo as well. A prospective randomized controlled trial²⁶ used 3.5% Betadine irrigation to prevent spine infection. No infections occurred in the Betadine group compared with a deep-infection rate of 2.9% in the control group. Brown and colleagues⁸ reviewed 1862 hip and knee arthroplasty cases before the use of Betadine lavage and 688 cases after the use of Betadine lavage and found a decrease in infection rate, from 0.97% to 0.15%. S aureus caused 13 of the 18 infections in the control group. These studies^8,26 used Betadine lavage for prophylaxis and prevention of deep spine and arthroplasty infection. Betadine lavage as a treatment adjunct for acute arthroplasty infection has not been studied clinically. It has the potential to increase isolated incision and débridement success and to improve component survivorship.

Our arthroplasty model mimics an intra-articular environment and accounts for an implant–polyethylene interface.¹⁵ Limitations of our study include the use of MSSA as opposed to MRSA. However, povidone-iodine has the same effects on both MSSA and MRSA.¹² We also treated our postoperative infection with 1 dose of antibiotics and not a course, although it should be noted that the single dose of ceftriaxone allowed us to isolate the independent effect of the Betadine lavage. A baseline level of infection severity could have been measured with cultures obtained at the time of irrigation and débridement. Also, a decrease in CFU does not directly correlate to a clinically significant outcome, such as a defined surgical site infection requiring intervention. Nevertheless, it is noteworthy that the decrease in bacterial counts on the stainless steel screws and polyethylene washers were maintained 1 week after the Betadine lavage.

Conclusion

Dilute Betadine lavage is a simple and inexpensive adjunct for the treatment of acute postoperative arthroplasty infection and may increase the rate of component retention. Additionally, the bactericidal and antibiofilm activities of Betadine may improve the effectiveness of systemic antibiotics. Further clinical investigation is warranted.

Surgical site infection after arthroplasty causes substantial morbidity and potential mortality. Prosthetic joint infection (PJI) ranges from simple superficial wound infection and cellulitis to deep subfascial infection that involves the prosthesis. Consistent use of prophylactic antibiotics has reduced postoperative hip and knee arthroplasty infections to rates of 0.25% to 2%.^1-4 Treatment of a patient with PJI commonly includes hospitalization, long-term intravenously administered antibiotics, resection arthroplasty, and staged reimplantation. The estimated cost of interventions reaches tens of millions of dollars annually in the United States and does not include the costs of psychosocial effects on patients and their families.^5,6

Betadine (povidone-iodine) is a widely used antiseptic for skin and mucous membrane wounds and has been shown to be effective for the prevention of PJI.⁷ Dilute Betadine solution has been proposed as an aid in treatment of PJI.⁸ At a minimum concentration of 5%, cytotoxicity has been observed in chicken tibia osteoblasts.⁹ A balance of the bactericidal and cytotoxic activities of Betadine, while maintaining its efficacy against resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), is optimized at dilutions between 0.5% and 4%.^10-14 We hypothesized that a dilute Betadine lavage of 3.5% would achieve a significant decrease in bacterial counts compared with an isolated saline lavage in an in vivo knee PJI model.

Materials and Methods

Animal Protocol

All surgical procedures were conducted according to the protocol approved by our institutional animal care and use committee. Using a power analysis and data obtained at our institution, we determined that 12 was the minimum number of animals needed to reach significance set at P < .05 and assuming a 50% decrease in colony-forming units (CFU) (SigmaStat Version 2.03; Aspire Software International, Ashburn, Virginia). Eight New Zealand White rabbits were used in our study; because significance was reached early, 12 were not needed. The average weight of the rabbits was 3.5 kg (weight range, 3.2-4.1 kg). All rabbits completed 1 week of acclimation before surgery.

Bacteria Preparation

A broth culture of methicillin-sensitive S aureus (MSSA) (ATCC 25923) was prepared 1 day before surgery. The bacteria were suspended in 5 mL of Trypticase Soy Broth (Becton Dickinson & Co, Franklin Lakes, New Jersey) and incubated at 37°C in a shaking incubator for 16 hours. The next day, the culture was centrifuged and irrigated twice with normal saline to remove the broth and prevent further growth. The bacteria were reconstituted in normal saline, and the concentration was standardized using a turbidity meter (LaMotte 2020e; LaMotte Co, Chestertown, Maryland), which correlated with 10⁶ CFU/100 µl plated on trypticase soy agar plates with 10% sheep blood (Fisher Scientific, Pittsburgh, Pennsylvania).

Surgical and Postoperative Procedures

Our procedure was based on the New Zealand White rabbit knee PJI model.¹⁵ General anesthesia was induced with ketamine and xylazine, and maintained with isoflurane inhalation via a nose cone mask. Rabbits were positioned supine, and bilateral knees were shaved, prepped, and draped in a sterile fashion.

A 2-cm longitudinal incision was made over the lateral knee, and arthrotomy was performed, exposing the lateral collateral ligament attachment at the lateral femoral condyle. Using a 4-mm drill bit, a defect was drilled obliquely into the lateral femoral condyle, anterior to the lateral collateral ligament attachment. This produced a defect in the non-weight-bearing, nonarticulating portion of the knee. A fully threaded 4×14-mm stainless steel screw (Synthes, West Chester, Pennsylvania) with a U-shaped ultrahigh-molecular-weight polyethylene washer (Synthes) was inserted into the defect. The joint capsule was closed with a running 3-0 Vicryl suture (Ethicon, Somerville, New Jersey). The knee joint was inoculated with 100 µL of the S aureus preparation using a 22-gauge needle. The skin was closed with a 4-0 Biosyn suture (Ethicon). The procedure was repeated on the contralateral knee (Figures 1A, 1B).

Seven days after the initial surgery, the rabbits were returned to the operating room and were anesthetized, positioned, and prepped for surgery as detailed above. Ceftriaxone (20 mg/kg of body weight) was intravenously administered to all rabbits for the treatment procedure. For each rabbit, a control knee and an experimental knee were randomly assigned. A longitudinal incision was made, exposing the previously placed implants. The screw was loosened slightly to remove the U-shaped polyethylene washer. Each knee then underwent lavage 2 times, for 90 seconds each time, with 3.5% dilute Betadine solution (experimental knee) or with normal saline (control knee). Because Pseudomonas contamination has been reported with povidone-iodine taken from unsterilized bottles,^16,17 packets of sterilized povidone-iodine (Aplicare; Clorox, Oakland, California) were used. After the irrigation was complete, a new sterile polyethylene washer was placed and the screw was tightened. The wound closure was repeated as detailed above.

Postoperative analgesia was provided based on a standard institutional animal care and use committee protocol. Rabbits were permitted full cage activity and nutrition ad libitum. Wound healing, body weight, and signs of distress were monitored daily.

Outcome Measures

Seven days after surgery, the rabbits were euthanized with administration of phenobarbital (100 mg/kg of body weight). Arterial blood samples were obtained from the auricular vein to ensure that the rabbits were not systemically infected. Using a sterile technique, the screw, polyethylene washer, lateral femoral condyle bone from the defect, and joint capsule were cultured. Harvested bone and soft tissues were weighed and immediately homogenized (PowerGen Model 35 Handheld Homogenizer; Thermo Fisher Scientific, Inc, Waltham, Massachusetts). Implants were sonicated (UBATH-Y; World Precision Instruments, Inc, Sarasota, Florida) in cold saline to obtain a sensitive culture.¹⁸

Bacterial quantification was determined by using trypticase soy agar plates after 24 hours of growth. Final CFU were calculated after serial dilutions and were standardized per gram of biopsied tissues.¹⁹ Members of the team were blinded to the treatment type.

Statistical Analysis

Statistical differences in mean bacterial burden were calculated independently for lateral condyle bone, joint capsule, polyethylene, and screws by conducting a Student t test.

Results

Treatment effect was higher than expected, and the study was terminated after 8 animals completed the protocol. All 8 rabbits tolerated the procedures well and were appropriately monitored during the postoperative period. No animals had signs of systemic infection or positive blood culture. All local cultures for screw, polyethylene washer, lateral femoral condyle defect, and joint capsule were positive.

Statistically significant decreases were shown in the bacterial burden of the Betadine-irrigated screws and the Betadine-irrigated polyethylene washers compared with the saline-irrigated controls. Betadine-irrigated screws grew an average of 7.16 × 10¹ CFU of S aureus/g, whereas screws from control knees grew an average of 1.45 × 10³ CFU/g (P = .0003) (Figure 2). Betadine-treated washers grew an average of 1.28 × 10³ CFU/g compared with 1.62 × 10⁴ CFU/g for control washers (P =. 04) (Figure 3).

A trend toward decreased bacterial counts was shown in Betadine-treated soft tissues compared with saline-treated soft tissues, but the difference did not reach statistical significance (P = .9). Biopsied joint capsule from knees treated with Betadine grew an average of 2.84 × 10⁴ CFU/g compared with an average of 3.16 × 10⁴ CFU/g in control-rabbit knees (Figure 4). Cultured lateral condyle from Betadine-treated knees had an average bacterial load of 3.22 × 10⁴ CFU/g compared with an average bacterial load of 1 × 10⁵ CFU/g in control knees (Figure 4).

Discussion

Knees irrigated with Betadine showed a significant (P = .0003) decrease in metal implant–related S aureus bacterial counts by 20-fold and a significant (P < .05) decrease in polyethylene implant–related counts by more than 10-fold. This arthroplasty model used Betadine lavage as a treatment adjunct with intravenously administered antibiotics and polyethylene exchange. Our 1-week interval after the index procedure classifies the infection as an acute postoperative arthroplasty infection (occurring less than 4 weeks postoperatively).

The gold standard treatment for these infections is irrigation and débridement with component retention.¹⁸ The success rate has been reported to be as high as 71%²⁰ but was closer to 44% in a study by Fridkin and colleagues,²¹ especially with more virulent bacteria. Staphylococcal species, higher American Society of Anesthesiologists scores, and frank pus around the prosthesis were markers of débridement failure in a recent study by Azzam and colleagues.¹⁸

The majority of postoperative joint arthroplasty infections are caused by S aureus, and the incidence of MRSA bacteria continues to rise.²² Community-acquired MRSA is increasing at an alarming rate and is now the predominant organism in skin and soft-tissue infections.²³ Organism resistance also occurs at a cellular level by the formation of a glycocalyx layer, or biofilm. This layer assists in changing the phenotypic properties of the organism and decreases the efficacy of antibiotics.²⁴ The self-produced layer of extracellular matrices, deoxyribonucleic acid, and polysaccharides attaches to inert material, preventing phagocytic action by neutrophils. In addition to antibacterial activity, povidone-iodine has antibiofilm activity against Staphylococcal species.²⁵ The active ingredient targets the gene that produces biofilm. This correlates to our study in which the largest decrease in bacterial counts was noted on the implants.

The use of Betadine lavage has shown some promise in vivo as well. A prospective randomized controlled trial²⁶ used 3.5% Betadine irrigation to prevent spine infection. No infections occurred in the Betadine group compared with a deep-infection rate of 2.9% in the control group. Brown and colleagues⁸ reviewed 1862 hip and knee arthroplasty cases before the use of Betadine lavage and 688 cases after the use of Betadine lavage and found a decrease in infection rate, from 0.97% to 0.15%. S aureus caused 13 of the 18 infections in the control group. These studies^8,26 used Betadine lavage for prophylaxis and prevention of deep spine and arthroplasty infection. Betadine lavage as a treatment adjunct for acute arthroplasty infection has not been studied clinically. It has the potential to increase isolated incision and débridement success and to improve component survivorship.

Our arthroplasty model mimics an intra-articular environment and accounts for an implant–polyethylene interface.¹⁵ Limitations of our study include the use of MSSA as opposed to MRSA. However, povidone-iodine has the same effects on both MSSA and MRSA.¹² We also treated our postoperative infection with 1 dose of antibiotics and not a course, although it should be noted that the single dose of ceftriaxone allowed us to isolate the independent effect of the Betadine lavage. A baseline level of infection severity could have been measured with cultures obtained at the time of irrigation and débridement. Also, a decrease in CFU does not directly correlate to a clinically significant outcome, such as a defined surgical site infection requiring intervention. Nevertheless, it is noteworthy that the decrease in bacterial counts on the stainless steel screws and polyethylene washers were maintained 1 week after the Betadine lavage.

Conclusion

Dilute Betadine lavage is a simple and inexpensive adjunct for the treatment of acute postoperative arthroplasty infection and may increase the rate of component retention. Additionally, the bactericidal and antibiofilm activities of Betadine may improve the effectiveness of systemic antibiotics. Further clinical investigation is warranted.

Surgical site infection after arthroplasty causes substantial morbidity and potential mortality. Prosthetic joint infection (PJI) ranges from simple superficial wound infection and cellulitis to deep subfascial infection that involves the prosthesis. Consistent use of prophylactic antibiotics has reduced postoperative hip and knee arthroplasty infections to rates of 0.25% to 2%.^1-4 Treatment of a patient with PJI commonly includes hospitalization, long-term intravenously administered antibiotics, resection arthroplasty, and staged reimplantation. The estimated cost of interventions reaches tens of millions of dollars annually in the United States and does not include the costs of psychosocial effects on patients and their families.^5,6

Betadine (povidone-iodine) is a widely used antiseptic for skin and mucous membrane wounds and has been shown to be effective for the prevention of PJI.⁷ Dilute Betadine solution has been proposed as an aid in treatment of PJI.⁸ At a minimum concentration of 5%, cytotoxicity has been observed in chicken tibia osteoblasts.⁹ A balance of the bactericidal and cytotoxic activities of Betadine, while maintaining its efficacy against resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA), is optimized at dilutions between 0.5% and 4%.^10-14 We hypothesized that a dilute Betadine lavage of 3.5% would achieve a significant decrease in bacterial counts compared with an isolated saline lavage in an in vivo knee PJI model.

Materials and Methods

Animal Protocol

All surgical procedures were conducted according to the protocol approved by our institutional animal care and use committee. Using a power analysis and data obtained at our institution, we determined that 12 was the minimum number of animals needed to reach significance set at P < .05 and assuming a 50% decrease in colony-forming units (CFU) (SigmaStat Version 2.03; Aspire Software International, Ashburn, Virginia). Eight New Zealand White rabbits were used in our study; because significance was reached early, 12 were not needed. The average weight of the rabbits was 3.5 kg (weight range, 3.2-4.1 kg). All rabbits completed 1 week of acclimation before surgery.

Bacteria Preparation

A broth culture of methicillin-sensitive S aureus (MSSA) (ATCC 25923) was prepared 1 day before surgery. The bacteria were suspended in 5 mL of Trypticase Soy Broth (Becton Dickinson & Co, Franklin Lakes, New Jersey) and incubated at 37°C in a shaking incubator for 16 hours. The next day, the culture was centrifuged and irrigated twice with normal saline to remove the broth and prevent further growth. The bacteria were reconstituted in normal saline, and the concentration was standardized using a turbidity meter (LaMotte 2020e; LaMotte Co, Chestertown, Maryland), which correlated with 10⁶ CFU/100 µl plated on trypticase soy agar plates with 10% sheep blood (Fisher Scientific, Pittsburgh, Pennsylvania).

Surgical and Postoperative Procedures

Our procedure was based on the New Zealand White rabbit knee PJI model.¹⁵ General anesthesia was induced with ketamine and xylazine, and maintained with isoflurane inhalation via a nose cone mask. Rabbits were positioned supine, and bilateral knees were shaved, prepped, and draped in a sterile fashion.

A 2-cm longitudinal incision was made over the lateral knee, and arthrotomy was performed, exposing the lateral collateral ligament attachment at the lateral femoral condyle. Using a 4-mm drill bit, a defect was drilled obliquely into the lateral femoral condyle, anterior to the lateral collateral ligament attachment. This produced a defect in the non-weight-bearing, nonarticulating portion of the knee. A fully threaded 4×14-mm stainless steel screw (Synthes, West Chester, Pennsylvania) with a U-shaped ultrahigh-molecular-weight polyethylene washer (Synthes) was inserted into the defect. The joint capsule was closed with a running 3-0 Vicryl suture (Ethicon, Somerville, New Jersey). The knee joint was inoculated with 100 µL of the S aureus preparation using a 22-gauge needle. The skin was closed with a 4-0 Biosyn suture (Ethicon). The procedure was repeated on the contralateral knee (Figures 1A, 1B).

Seven days after the initial surgery, the rabbits were returned to the operating room and were anesthetized, positioned, and prepped for surgery as detailed above. Ceftriaxone (20 mg/kg of body weight) was intravenously administered to all rabbits for the treatment procedure. For each rabbit, a control knee and an experimental knee were randomly assigned. A longitudinal incision was made, exposing the previously placed implants. The screw was loosened slightly to remove the U-shaped polyethylene washer. Each knee then underwent lavage 2 times, for 90 seconds each time, with 3.5% dilute Betadine solution (experimental knee) or with normal saline (control knee). Because Pseudomonas contamination has been reported with povidone-iodine taken from unsterilized bottles,^16,17 packets of sterilized povidone-iodine (Aplicare; Clorox, Oakland, California) were used. After the irrigation was complete, a new sterile polyethylene washer was placed and the screw was tightened. The wound closure was repeated as detailed above.

Postoperative analgesia was provided based on a standard institutional animal care and use committee protocol. Rabbits were permitted full cage activity and nutrition ad libitum. Wound healing, body weight, and signs of distress were monitored daily.

Outcome Measures

Seven days after surgery, the rabbits were euthanized with administration of phenobarbital (100 mg/kg of body weight). Arterial blood samples were obtained from the auricular vein to ensure that the rabbits were not systemically infected. Using a sterile technique, the screw, polyethylene washer, lateral femoral condyle bone from the defect, and joint capsule were cultured. Harvested bone and soft tissues were weighed and immediately homogenized (PowerGen Model 35 Handheld Homogenizer; Thermo Fisher Scientific, Inc, Waltham, Massachusetts). Implants were sonicated (UBATH-Y; World Precision Instruments, Inc, Sarasota, Florida) in cold saline to obtain a sensitive culture.¹⁸

Bacterial quantification was determined by using trypticase soy agar plates after 24 hours of growth. Final CFU were calculated after serial dilutions and were standardized per gram of biopsied tissues.¹⁹ Members of the team were blinded to the treatment type.

Statistical Analysis

Statistical differences in mean bacterial burden were calculated independently for lateral condyle bone, joint capsule, polyethylene, and screws by conducting a Student t test.

Results

Treatment effect was higher than expected, and the study was terminated after 8 animals completed the protocol. All 8 rabbits tolerated the procedures well and were appropriately monitored during the postoperative period. No animals had signs of systemic infection or positive blood culture. All local cultures for screw, polyethylene washer, lateral femoral condyle defect, and joint capsule were positive.

Statistically significant decreases were shown in the bacterial burden of the Betadine-irrigated screws and the Betadine-irrigated polyethylene washers compared with the saline-irrigated controls. Betadine-irrigated screws grew an average of 7.16 × 10¹ CFU of S aureus/g, whereas screws from control knees grew an average of 1.45 × 10³ CFU/g (P = .0003) (Figure 2). Betadine-treated washers grew an average of 1.28 × 10³ CFU/g compared with 1.62 × 10⁴ CFU/g for control washers (P =. 04) (Figure 3).

A trend toward decreased bacterial counts was shown in Betadine-treated soft tissues compared with saline-treated soft tissues, but the difference did not reach statistical significance (P = .9). Biopsied joint capsule from knees treated with Betadine grew an average of 2.84 × 10⁴ CFU/g compared with an average of 3.16 × 10⁴ CFU/g in control-rabbit knees (Figure 4). Cultured lateral condyle from Betadine-treated knees had an average bacterial load of 3.22 × 10⁴ CFU/g compared with an average bacterial load of 1 × 10⁵ CFU/g in control knees (Figure 4).

Discussion

Knees irrigated with Betadine showed a significant (P = .0003) decrease in metal implant–related S aureus bacterial counts by 20-fold and a significant (P < .05) decrease in polyethylene implant–related counts by more than 10-fold. This arthroplasty model used Betadine lavage as a treatment adjunct with intravenously administered antibiotics and polyethylene exchange. Our 1-week interval after the index procedure classifies the infection as an acute postoperative arthroplasty infection (occurring less than 4 weeks postoperatively).

The gold standard treatment for these infections is irrigation and débridement with component retention.¹⁸ The success rate has been reported to be as high as 71%²⁰ but was closer to 44% in a study by Fridkin and colleagues,²¹ especially with more virulent bacteria. Staphylococcal species, higher American Society of Anesthesiologists scores, and frank pus around the prosthesis were markers of débridement failure in a recent study by Azzam and colleagues.¹⁸

The majority of postoperative joint arthroplasty infections are caused by S aureus, and the incidence of MRSA bacteria continues to rise.²² Community-acquired MRSA is increasing at an alarming rate and is now the predominant organism in skin and soft-tissue infections.²³ Organism resistance also occurs at a cellular level by the formation of a glycocalyx layer, or biofilm. This layer assists in changing the phenotypic properties of the organism and decreases the efficacy of antibiotics.²⁴ The self-produced layer of extracellular matrices, deoxyribonucleic acid, and polysaccharides attaches to inert material, preventing phagocytic action by neutrophils. In addition to antibacterial activity, povidone-iodine has antibiofilm activity against Staphylococcal species.²⁵ The active ingredient targets the gene that produces biofilm. This correlates to our study in which the largest decrease in bacterial counts was noted on the implants.

The use of Betadine lavage has shown some promise in vivo as well. A prospective randomized controlled trial²⁶ used 3.5% Betadine irrigation to prevent spine infection. No infections occurred in the Betadine group compared with a deep-infection rate of 2.9% in the control group. Brown and colleagues⁸ reviewed 1862 hip and knee arthroplasty cases before the use of Betadine lavage and 688 cases after the use of Betadine lavage and found a decrease in infection rate, from 0.97% to 0.15%. S aureus caused 13 of the 18 infections in the control group. These studies^8,26 used Betadine lavage for prophylaxis and prevention of deep spine and arthroplasty infection. Betadine lavage as a treatment adjunct for acute arthroplasty infection has not been studied clinically. It has the potential to increase isolated incision and débridement success and to improve component survivorship.

Our arthroplasty model mimics an intra-articular environment and accounts for an implant–polyethylene interface.¹⁵ Limitations of our study include the use of MSSA as opposed to MRSA. However, povidone-iodine has the same effects on both MSSA and MRSA.¹² We also treated our postoperative infection with 1 dose of antibiotics and not a course, although it should be noted that the single dose of ceftriaxone allowed us to isolate the independent effect of the Betadine lavage. A baseline level of infection severity could have been measured with cultures obtained at the time of irrigation and débridement. Also, a decrease in CFU does not directly correlate to a clinically significant outcome, such as a defined surgical site infection requiring intervention. Nevertheless, it is noteworthy that the decrease in bacterial counts on the stainless steel screws and polyethylene washers were maintained 1 week after the Betadine lavage.

Conclusion

Dilute Betadine lavage is a simple and inexpensive adjunct for the treatment of acute postoperative arthroplasty infection and may increase the rate of component retention. Additionally, the bactericidal and antibiofilm activities of Betadine may improve the effectiveness of systemic antibiotics. Further clinical investigation is warranted.

The accuracy of using computed tomography (CT) to assess lumbar interbody fusion with titanium implants has been questioned in the past.^1-4 Reports have most often focused on older technologies using paired, threaded, smooth-surface titanium devices. Some authors have reported they could not confidently assess the quality of fusions using CT because of implant artifact.^1-3

When pseudarthrosis is suspected clinically, and imaging results are inconclusive, surgical explorations may be performed with mechanical stressing of the segment to assess for motion.^2,5-7 However, surgical exploration not only has the morbidity of another surgery but may not be conclusive. Direct exploration of an interbody fusion is problematic. In some cases, there may be residual normal springing motion through posterior elements, even in the presence of a solid interbody fusion, which can be confusing.⁵ Radiologic confirmation of fusion status is therefore preferred over surgical exploration. CT is the imaging modality used most often to assess spinal fusions.^8,9

A new titanium interbody fusion implant (Endoskeleton TA; Titan Spine, Mequon, Wisconsin) preserves the endplate and has an acid-etched titanium surface for osseous integration and a wide central aperture for bone graft (Figure 1). Compared with earlier titanium implants, this design may allow for more accurate CT imaging and fusion assessment. We conducted a study to determine the interobserver reliability of using CT to evaluate bone formation and other radiographic variables with this new titanium interbody device.

Materials and Methods

After receiving institutional review board approval for this study, as well as patient consent, we obtained and analyzed CT scans of patients after they had undergone anterior lumbar interbody fusion (ALIF) at L3–S1 as part of a separate clinical outcomes study.

Each patient received an Endoskeleton TA implant. The fusion cage was packed with 2 sponges (3.0 mg per fusion level) of bone morphogenetic protein, or BMP (InFuse; Medtronic, Minneapolis, Minnesota). In addition, 1 to 3 cm³ of hydroxyapatite/β-‌tricalcium phosphate (MasterGraft, Medtronic) collagen sponge was used as graft extender to fill any remaining gaps within the cage. Pedicle screw fixation was used in all cases.

Patients were randomly assigned to have fine-cut CT scans with reconstructed images at 6, 9, or 12 months. The scans were reviewed by 2 independent radiologists who were blinded to each other’s interpretations and the clinical results. The radiographic fusion criteria are listed in Tables 1 to 3. Interobserver agreement (κ) was calculated separately for each radiographic criterion and could range from 0.00 (no agreement) to 1.00 (perfect agreement).^10,11

Results

The study involved 33 patients (17 men, 16 women) with 56 lumbar spinal fusion levels. Mean age was 46 years (range, 23-66 years). Six patients (18%) were nicotine users. Seventeen patients were scanned at 6 months, 9 at 9 months, and 7 at 12 months. There were no significant differences in results between men and women, between nicotine users and nonusers, or among patients evaluated at 6, 9, or 12 months.

The radiologists agreed on 345 of the 392 data points reviewed (κ = 0.88). Interobserver agreement results for the fusion criteria are listed in Tables 1 and 3. Interobserver agreement was 0.77 for overall fusion grade, with the radiologists noting definite fusion (grade 5) in 80% and 91% of the levels (Table 1). Other radiographic criteria are listed in Tables 2 and 3. Interobserver agreement was 0.80 for degree of artifact, 0.95 for subsidence, 0.96 for both lucency and trabecular bone, 0.77 for anterior osseous bridging, and 0.95 for cystic vertebral changes.

Discussion

Radiographic analysis of interbody fusions is an important clinical issue. Investigators have shown that CT is the radiographic method of choice for assessing fusion.^8,9 Others have reported that assessing fusion with metallic interbody implants is more difficult compared with PEEK (polyether ether ketone) or allograft bone.^3,4,5,12

Heithoff and colleagues^1,2 reported on difficulties they encountered in assessing interbody fusion with titanium implants, and their research has often been cited. The authors concluded that they could not accurately assess fusion in these cases because of artifact from the small apertures in the cages and metallic scatter. Their study was very small (8 patients, 12 surgical levels) and used paired BAK (Bagby and Kuslich) cages (Zimmer, Warsaw, Indiana).

Recently, a unique surface technology, used to manufacture osseointegrative dental implants, has been adapted for use in the spine.^13-15 Acid etching modifies the surface of titanium to create a nano-scale (micron-level) alteration. Compared with PEEK and smooth titanium, acid-etched titanium stimulates a better osteogenic environment.^16,17 As this technology is now used clinically in spinal surgery, we thought it important to revisit the issue of CT analysis for fusion assessment with the newer titanium implants.

Artifact

The results of our study support the idea that the design of a titanium interbody fusion implant is important to radiographic analysis. The implant studied has a large open central aperture that appears to generate less artifact than historical controls (paired cylindrical cages) have.^1-4 Other investigators have reported fewer problems with artifact in their studies of implants incorporating larger openings for bone graft.^6,18 The radiologists in the present study found no significant problems with artifact. Less artifact is clinically important, as the remaining fusion variables can be more clearly visualized (Table 2, Figure 2).

Anterior Osseous Bridging, Subsidence, Lysis

In this study, the bony endplates were preserved. The disc and endplate cartilage was removed without reaming or drilling. Endplate reaming most likely contributes to subsidence and loss of original fixation between implant and bone interface.^1,4,12 Some authors have advocated recessing the cages deeply and then packing bone anteriorly to create a “sentinel fusion sign.”^1,2,6 Deeply seating interbody implants, instead of resting them more widely on the apophyseal ring of the vertebral endplate, may also lead to subsidence.^4,12 The issue of identifying a sentinel fusion sign is relevant only if the surgeon tries to create one. In the present study, the implant used was an impacted cage positioned on the apophyseal perimeter of the disc space, just slightly recessed, so there was no attempt to create a sentinel fusion sign, as reflected in the relatively low scores on anterior osseous bridging (48%, 52%).

Subsidence and peri-implant lysis are pathologic variables associated with motion and bone loss. Sethi and colleagues¹⁹ noted a high percentage of endplate resorption and subsidence in cases reviewed using PEEK or allograft spacers paired with BMP-2. Although BMP-2 was used in the present study, we found very low rates of subsidence (0%, 5%) and no significant peri-implant lucencies (2%, 4%) (Figure 2). Interobserver agreement for these variables was high (0.95, 0.96). We hypothesize that the combination of endplate-sparing surgical technique and implant–bone integration contributed to these results.

Trabecular Bone and Fusion Grade

The primary radiographic criterion for solid interbody fusion is trabecular bone throughout the cage, bridging the vertebral bodies. In our study, the success rates for this variable were 96% and 100%, and there was very high interobserver agreement (0.96) (Figure 3). This very high fusion rate may preclude detecting subtle differences in interobserver agreement, but to what degree, if any, is unknown. Other investigators have effectively identified trabecular bone across the interspace and throughout the cages.^6,18 The openings for bone formation were larger in the implants they used than in first-generation fusion cages but not as large as the implant openings in the present study. Larger openings may correlate with improved ability to visualize bridging bone on CT.

Radiologists and surgeons must ultimately arrive at a conclusion regarding the likelihood a fusion has occurred. Our radiologists integrated all the separate radiologic variables cited here, as well as their overall impressions of the scans, to arrive at a final grade regarding fusion quality (Figures 3, 4). Although this category provides the most interpretive latitude of all the variables examined, the results demonstrate high interobserver reliability. Agreement to exactly the same fusion grade was 0.77, and agreement to within 1 category grade was 0.95.

This study had several limitations. Surgical explorations were not clinically indicated and were not performed. There were no suspected nonunions or hardware complications, two of the most common indications for exploration. In addition, this study was conducted not to determine specific accuracy of CT (compared with surgery exploration) for fusion assessment but to assess interobserver reliability. The clinical success rates for this population were high, and no patient required revision surgery for suspected pseudarthrosis. To assess the true accuracy of CT for fusion assessment, one would have to subject patients to follow-up exploratory surgery to test fusions mechanically.

Another limitation is the lack of a single industry-accepted radiographic fusion grading system. Fusion criteria are not standardized across all studies. Our radiologists have extensive research experience and limit their practices to neuromuscular radiology with a concentration on the spine. The radiographic criteria cited here are the same criteria they use in clinical practice, when reviewing CT scans for clinicians. Last, there was no control group for direct comparison against other cages. Historical controls were cited. This does not adversely affect the conclusions of this investigation.

Conclusion

Clinicians have been reluctant to rely on CT with titanium devices because of concerns about the accuracy of image interpretations. The interbody device used in this study demonstrated minimal artifact and minimal subsidence, and trabecular bone was easily identified throughout the implant in the majority of cases reviewed. We found high interobserver agreement scores across all fusion criteria. Although surgical exploration remains the gold standard for fusion assessment, surgeons should have confidence in using CT with this titanium implant.

The accuracy of using computed tomography (CT) to assess lumbar interbody fusion with titanium implants has been questioned in the past.^1-4 Reports have most often focused on older technologies using paired, threaded, smooth-surface titanium devices. Some authors have reported they could not confidently assess the quality of fusions using CT because of implant artifact.^1-3

When pseudarthrosis is suspected clinically, and imaging results are inconclusive, surgical explorations may be performed with mechanical stressing of the segment to assess for motion.^2,5-7 However, surgical exploration not only has the morbidity of another surgery but may not be conclusive. Direct exploration of an interbody fusion is problematic. In some cases, there may be residual normal springing motion through posterior elements, even in the presence of a solid interbody fusion, which can be confusing.⁵ Radiologic confirmation of fusion status is therefore preferred over surgical exploration. CT is the imaging modality used most often to assess spinal fusions.^8,9

A new titanium interbody fusion implant (Endoskeleton TA; Titan Spine, Mequon, Wisconsin) preserves the endplate and has an acid-etched titanium surface for osseous integration and a wide central aperture for bone graft (Figure 1). Compared with earlier titanium implants, this design may allow for more accurate CT imaging and fusion assessment. We conducted a study to determine the interobserver reliability of using CT to evaluate bone formation and other radiographic variables with this new titanium interbody device.

Materials and Methods

After receiving institutional review board approval for this study, as well as patient consent, we obtained and analyzed CT scans of patients after they had undergone anterior lumbar interbody fusion (ALIF) at L3–S1 as part of a separate clinical outcomes study.

Each patient received an Endoskeleton TA implant. The fusion cage was packed with 2 sponges (3.0 mg per fusion level) of bone morphogenetic protein, or BMP (InFuse; Medtronic, Minneapolis, Minnesota). In addition, 1 to 3 cm³ of hydroxyapatite/β-‌tricalcium phosphate (MasterGraft, Medtronic) collagen sponge was used as graft extender to fill any remaining gaps within the cage. Pedicle screw fixation was used in all cases.

Patients were randomly assigned to have fine-cut CT scans with reconstructed images at 6, 9, or 12 months. The scans were reviewed by 2 independent radiologists who were blinded to each other’s interpretations and the clinical results. The radiographic fusion criteria are listed in Tables 1 to 3. Interobserver agreement (κ) was calculated separately for each radiographic criterion and could range from 0.00 (no agreement) to 1.00 (perfect agreement).^10,11

Results

The study involved 33 patients (17 men, 16 women) with 56 lumbar spinal fusion levels. Mean age was 46 years (range, 23-66 years). Six patients (18%) were nicotine users. Seventeen patients were scanned at 6 months, 9 at 9 months, and 7 at 12 months. There were no significant differences in results between men and women, between nicotine users and nonusers, or among patients evaluated at 6, 9, or 12 months.

The radiologists agreed on 345 of the 392 data points reviewed (κ = 0.88). Interobserver agreement results for the fusion criteria are listed in Tables 1 and 3. Interobserver agreement was 0.77 for overall fusion grade, with the radiologists noting definite fusion (grade 5) in 80% and 91% of the levels (Table 1). Other radiographic criteria are listed in Tables 2 and 3. Interobserver agreement was 0.80 for degree of artifact, 0.95 for subsidence, 0.96 for both lucency and trabecular bone, 0.77 for anterior osseous bridging, and 0.95 for cystic vertebral changes.

Discussion

Radiographic analysis of interbody fusions is an important clinical issue. Investigators have shown that CT is the radiographic method of choice for assessing fusion.^8,9 Others have reported that assessing fusion with metallic interbody implants is more difficult compared with PEEK (polyether ether ketone) or allograft bone.^3,4,5,12

Heithoff and colleagues^1,2 reported on difficulties they encountered in assessing interbody fusion with titanium implants, and their research has often been cited. The authors concluded that they could not accurately assess fusion in these cases because of artifact from the small apertures in the cages and metallic scatter. Their study was very small (8 patients, 12 surgical levels) and used paired BAK (Bagby and Kuslich) cages (Zimmer, Warsaw, Indiana).

Recently, a unique surface technology, used to manufacture osseointegrative dental implants, has been adapted for use in the spine.^13-15 Acid etching modifies the surface of titanium to create a nano-scale (micron-level) alteration. Compared with PEEK and smooth titanium, acid-etched titanium stimulates a better osteogenic environment.^16,17 As this technology is now used clinically in spinal surgery, we thought it important to revisit the issue of CT analysis for fusion assessment with the newer titanium implants.

Artifact

The results of our study support the idea that the design of a titanium interbody fusion implant is important to radiographic analysis. The implant studied has a large open central aperture that appears to generate less artifact than historical controls (paired cylindrical cages) have.^1-4 Other investigators have reported fewer problems with artifact in their studies of implants incorporating larger openings for bone graft.^6,18 The radiologists in the present study found no significant problems with artifact. Less artifact is clinically important, as the remaining fusion variables can be more clearly visualized (Table 2, Figure 2).

Anterior Osseous Bridging, Subsidence, Lysis

In this study, the bony endplates were preserved. The disc and endplate cartilage was removed without reaming or drilling. Endplate reaming most likely contributes to subsidence and loss of original fixation between implant and bone interface.^1,4,12 Some authors have advocated recessing the cages deeply and then packing bone anteriorly to create a “sentinel fusion sign.”^1,2,6 Deeply seating interbody implants, instead of resting them more widely on the apophyseal ring of the vertebral endplate, may also lead to subsidence.^4,12 The issue of identifying a sentinel fusion sign is relevant only if the surgeon tries to create one. In the present study, the implant used was an impacted cage positioned on the apophyseal perimeter of the disc space, just slightly recessed, so there was no attempt to create a sentinel fusion sign, as reflected in the relatively low scores on anterior osseous bridging (48%, 52%).

Subsidence and peri-implant lysis are pathologic variables associated with motion and bone loss. Sethi and colleagues¹⁹ noted a high percentage of endplate resorption and subsidence in cases reviewed using PEEK or allograft spacers paired with BMP-2. Although BMP-2 was used in the present study, we found very low rates of subsidence (0%, 5%) and no significant peri-implant lucencies (2%, 4%) (Figure 2). Interobserver agreement for these variables was high (0.95, 0.96). We hypothesize that the combination of endplate-sparing surgical technique and implant–bone integration contributed to these results.

Trabecular Bone and Fusion Grade

The primary radiographic criterion for solid interbody fusion is trabecular bone throughout the cage, bridging the vertebral bodies. In our study, the success rates for this variable were 96% and 100%, and there was very high interobserver agreement (0.96) (Figure 3). This very high fusion rate may preclude detecting subtle differences in interobserver agreement, but to what degree, if any, is unknown. Other investigators have effectively identified trabecular bone across the interspace and throughout the cages.^6,18 The openings for bone formation were larger in the implants they used than in first-generation fusion cages but not as large as the implant openings in the present study. Larger openings may correlate with improved ability to visualize bridging bone on CT.

Radiologists and surgeons must ultimately arrive at a conclusion regarding the likelihood a fusion has occurred. Our radiologists integrated all the separate radiologic variables cited here, as well as their overall impressions of the scans, to arrive at a final grade regarding fusion quality (Figures 3, 4). Although this category provides the most interpretive latitude of all the variables examined, the results demonstrate high interobserver reliability. Agreement to exactly the same fusion grade was 0.77, and agreement to within 1 category grade was 0.95.

This study had several limitations. Surgical explorations were not clinically indicated and were not performed. There were no suspected nonunions or hardware complications, two of the most common indications for exploration. In addition, this study was conducted not to determine specific accuracy of CT (compared with surgery exploration) for fusion assessment but to assess interobserver reliability. The clinical success rates for this population were high, and no patient required revision surgery for suspected pseudarthrosis. To assess the true accuracy of CT for fusion assessment, one would have to subject patients to follow-up exploratory surgery to test fusions mechanically.

Another limitation is the lack of a single industry-accepted radiographic fusion grading system. Fusion criteria are not standardized across all studies. Our radiologists have extensive research experience and limit their practices to neuromuscular radiology with a concentration on the spine. The radiographic criteria cited here are the same criteria they use in clinical practice, when reviewing CT scans for clinicians. Last, there was no control group for direct comparison against other cages. Historical controls were cited. This does not adversely affect the conclusions of this investigation.

Conclusion

Clinicians have been reluctant to rely on CT with titanium devices because of concerns about the accuracy of image interpretations. The interbody device used in this study demonstrated minimal artifact and minimal subsidence, and trabecular bone was easily identified throughout the implant in the majority of cases reviewed. We found high interobserver agreement scores across all fusion criteria. Although surgical exploration remains the gold standard for fusion assessment, surgeons should have confidence in using CT with this titanium implant.

The accuracy of using computed tomography (CT) to assess lumbar interbody fusion with titanium implants has been questioned in the past.^1-4 Reports have most often focused on older technologies using paired, threaded, smooth-surface titanium devices. Some authors have reported they could not confidently assess the quality of fusions using CT because of implant artifact.^1-3

When pseudarthrosis is suspected clinically, and imaging results are inconclusive, surgical explorations may be performed with mechanical stressing of the segment to assess for motion.^2,5-7 However, surgical exploration not only has the morbidity of another surgery but may not be conclusive. Direct exploration of an interbody fusion is problematic. In some cases, there may be residual normal springing motion through posterior elements, even in the presence of a solid interbody fusion, which can be confusing.⁵ Radiologic confirmation of fusion status is therefore preferred over surgical exploration. CT is the imaging modality used most often to assess spinal fusions.^8,9

A new titanium interbody fusion implant (Endoskeleton TA; Titan Spine, Mequon, Wisconsin) preserves the endplate and has an acid-etched titanium surface for osseous integration and a wide central aperture for bone graft (Figure 1). Compared with earlier titanium implants, this design may allow for more accurate CT imaging and fusion assessment. We conducted a study to determine the interobserver reliability of using CT to evaluate bone formation and other radiographic variables with this new titanium interbody device.

Materials and Methods

After receiving institutional review board approval for this study, as well as patient consent, we obtained and analyzed CT scans of patients after they had undergone anterior lumbar interbody fusion (ALIF) at L3–S1 as part of a separate clinical outcomes study.

Each patient received an Endoskeleton TA implant. The fusion cage was packed with 2 sponges (3.0 mg per fusion level) of bone morphogenetic protein, or BMP (InFuse; Medtronic, Minneapolis, Minnesota). In addition, 1 to 3 cm³ of hydroxyapatite/β-‌tricalcium phosphate (MasterGraft, Medtronic) collagen sponge was used as graft extender to fill any remaining gaps within the cage. Pedicle screw fixation was used in all cases.

Patients were randomly assigned to have fine-cut CT scans with reconstructed images at 6, 9, or 12 months. The scans were reviewed by 2 independent radiologists who were blinded to each other’s interpretations and the clinical results. The radiographic fusion criteria are listed in Tables 1 to 3. Interobserver agreement (κ) was calculated separately for each radiographic criterion and could range from 0.00 (no agreement) to 1.00 (perfect agreement).^10,11

Results

The study involved 33 patients (17 men, 16 women) with 56 lumbar spinal fusion levels. Mean age was 46 years (range, 23-66 years). Six patients (18%) were nicotine users. Seventeen patients were scanned at 6 months, 9 at 9 months, and 7 at 12 months. There were no significant differences in results between men and women, between nicotine users and nonusers, or among patients evaluated at 6, 9, or 12 months.

The radiologists agreed on 345 of the 392 data points reviewed (κ = 0.88). Interobserver agreement results for the fusion criteria are listed in Tables 1 and 3. Interobserver agreement was 0.77 for overall fusion grade, with the radiologists noting definite fusion (grade 5) in 80% and 91% of the levels (Table 1). Other radiographic criteria are listed in Tables 2 and 3. Interobserver agreement was 0.80 for degree of artifact, 0.95 for subsidence, 0.96 for both lucency and trabecular bone, 0.77 for anterior osseous bridging, and 0.95 for cystic vertebral changes.

Discussion

Radiographic analysis of interbody fusions is an important clinical issue. Investigators have shown that CT is the radiographic method of choice for assessing fusion.^8,9 Others have reported that assessing fusion with metallic interbody implants is more difficult compared with PEEK (polyether ether ketone) or allograft bone.^3,4,5,12

Heithoff and colleagues^1,2 reported on difficulties they encountered in assessing interbody fusion with titanium implants, and their research has often been cited. The authors concluded that they could not accurately assess fusion in these cases because of artifact from the small apertures in the cages and metallic scatter. Their study was very small (8 patients, 12 surgical levels) and used paired BAK (Bagby and Kuslich) cages (Zimmer, Warsaw, Indiana).

Recently, a unique surface technology, used to manufacture osseointegrative dental implants, has been adapted for use in the spine.^13-15 Acid etching modifies the surface of titanium to create a nano-scale (micron-level) alteration. Compared with PEEK and smooth titanium, acid-etched titanium stimulates a better osteogenic environment.^16,17 As this technology is now used clinically in spinal surgery, we thought it important to revisit the issue of CT analysis for fusion assessment with the newer titanium implants.

Artifact

The results of our study support the idea that the design of a titanium interbody fusion implant is important to radiographic analysis. The implant studied has a large open central aperture that appears to generate less artifact than historical controls (paired cylindrical cages) have.^1-4 Other investigators have reported fewer problems with artifact in their studies of implants incorporating larger openings for bone graft.^6,18 The radiologists in the present study found no significant problems with artifact. Less artifact is clinically important, as the remaining fusion variables can be more clearly visualized (Table 2, Figure 2).

Anterior Osseous Bridging, Subsidence, Lysis

In this study, the bony endplates were preserved. The disc and endplate cartilage was removed without reaming or drilling. Endplate reaming most likely contributes to subsidence and loss of original fixation between implant and bone interface.^1,4,12 Some authors have advocated recessing the cages deeply and then packing bone anteriorly to create a “sentinel fusion sign.”^1,2,6 Deeply seating interbody implants, instead of resting them more widely on the apophyseal ring of the vertebral endplate, may also lead to subsidence.^4,12 The issue of identifying a sentinel fusion sign is relevant only if the surgeon tries to create one. In the present study, the implant used was an impacted cage positioned on the apophyseal perimeter of the disc space, just slightly recessed, so there was no attempt to create a sentinel fusion sign, as reflected in the relatively low scores on anterior osseous bridging (48%, 52%).

Subsidence and peri-implant lysis are pathologic variables associated with motion and bone loss. Sethi and colleagues¹⁹ noted a high percentage of endplate resorption and subsidence in cases reviewed using PEEK or allograft spacers paired with BMP-2. Although BMP-2 was used in the present study, we found very low rates of subsidence (0%, 5%) and no significant peri-implant lucencies (2%, 4%) (Figure 2). Interobserver agreement for these variables was high (0.95, 0.96). We hypothesize that the combination of endplate-sparing surgical technique and implant–bone integration contributed to these results.

Trabecular Bone and Fusion Grade

The primary radiographic criterion for solid interbody fusion is trabecular bone throughout the cage, bridging the vertebral bodies. In our study, the success rates for this variable were 96% and 100%, and there was very high interobserver agreement (0.96) (Figure 3). This very high fusion rate may preclude detecting subtle differences in interobserver agreement, but to what degree, if any, is unknown. Other investigators have effectively identified trabecular bone across the interspace and throughout the cages.^6,18 The openings for bone formation were larger in the implants they used than in first-generation fusion cages but not as large as the implant openings in the present study. Larger openings may correlate with improved ability to visualize bridging bone on CT.

Radiologists and surgeons must ultimately arrive at a conclusion regarding the likelihood a fusion has occurred. Our radiologists integrated all the separate radiologic variables cited here, as well as their overall impressions of the scans, to arrive at a final grade regarding fusion quality (Figures 3, 4). Although this category provides the most interpretive latitude of all the variables examined, the results demonstrate high interobserver reliability. Agreement to exactly the same fusion grade was 0.77, and agreement to within 1 category grade was 0.95.

This study had several limitations. Surgical explorations were not clinically indicated and were not performed. There were no suspected nonunions or hardware complications, two of the most common indications for exploration. In addition, this study was conducted not to determine specific accuracy of CT (compared with surgery exploration) for fusion assessment but to assess interobserver reliability. The clinical success rates for this population were high, and no patient required revision surgery for suspected pseudarthrosis. To assess the true accuracy of CT for fusion assessment, one would have to subject patients to follow-up exploratory surgery to test fusions mechanically.

Another limitation is the lack of a single industry-accepted radiographic fusion grading system. Fusion criteria are not standardized across all studies. Our radiologists have extensive research experience and limit their practices to neuromuscular radiology with a concentration on the spine. The radiographic criteria cited here are the same criteria they use in clinical practice, when reviewing CT scans for clinicians. Last, there was no control group for direct comparison against other cages. Historical controls were cited. This does not adversely affect the conclusions of this investigation.

Conclusion

Clinicians have been reluctant to rely on CT with titanium devices because of concerns about the accuracy of image interpretations. The interbody device used in this study demonstrated minimal artifact and minimal subsidence, and trabecular bone was easily identified throughout the implant in the majority of cases reviewed. We found high interobserver agreement scores across all fusion criteria. Although surgical exploration remains the gold standard for fusion assessment, surgeons should have confidence in using CT with this titanium implant.