Dean T. Tsukayama

Infection after total hip arthroplasty. A study of the treatment of one hundred and six infections.

We evaluated the results of treatment for ninety-seven patients (106 infections in ninety-eight hips) who had had either an infection after a total hip arthroplasty or positive intraoperative cultures of specimens obtained during revision of a total hip arthroplasty for presumed aseptic loosening. The patients were managed according to various protocols on the basis of the clinical setting (positive intraoperative cultures, early postoperative infection, late chronic infection, or acute hematogenous infection). Aerobic gram-positive cocci accounted for 109 (74 per cent) of the 147 microbial isolates; gram-negative bacilli, for twenty-one (14 per cent); and anaerobes, for twelve (8 per cent). The white blood-cell count and erythrocyte sedimentation rate were elevated in association with seventeen (16 per cent) and sixty-seven (63 per cent) of the 106 infections, respectively. The mean duration of follow-up was 3.8 years (range, 0.3 to eleven years). A good result was noted after the initial treatment of twenty-eight (90 per cent) of the thirty-one infections that had been diagnosed on the basis of positive intraoperative cultures at the time of the revision, twenty-five (71 per cent) of the thirty-five early postoperative infections, twenty-nine (85 per cent) of the thirty-four late chronic infections, and three of the six acute hematogenous infections. Of the twenty-one infections for which the initial therapy failed, twelve eventually were eradicated after additional treatment and the hip had a functional prosthesis at the time of follow-up. Of the ninety-seven infections that were treated successfully (there was a functional retained or exchange prosthesis in place at the time of the most recent follow-up and infection had not recurred at least two years after the discontinuation of antibiotic therapy), nine were associated with subsequent aseptic loosening of the prosthesis. The factors associated with recurrent infection were retained bone cement, the number of previous operations, potential immunocompromise, and early postoperative infection after arthroplasty without cement.

Infection after total knee arthroplasty. A retrospective study of the treatment of eighty-one infections.

BACKGROUND The clinical presentation of an infection at the site of a total knee arthroplasty can be used as a guide to treatment, including the decision as to whether the prosthesis should be retained or removed. We reviewed the results of treatment of infection after total knee arthroplasty to evaluate the effectiveness of four treatment protocols based on the clinical setting of the infection. METHODS We retrospectively evaluated the results of treatment of eighty-one infections in seventy-six consecutive patients who either had an infection after a total knee arthroplasty or had multiple positive intraoperative cultures of specimens of periprosthetic tissue obtained during a revision total knee arthroplasty performed because of presumed aseptic loosening. The patients were managed according to one of four protocols. Five infections in five patients who had positive intraoperative cultures were treated with antibiotic therapy alone. Twenty-three early postoperative infections in twenty-one patients were treated with débridement, antibiotic therapy, and retention of the prosthesis. Twenty-nine late chronic infections in twenty-eight patients were treated with a delayed-exchange arthroplasty after a course of antibiotics. Seven acute hematogenous infections in six patients were treated with débridement, antibiotic therapy, and retention of the prosthesis. Seventeen infections in seventeen patients were not treated according to one of the four protocols. Sixteen late chronic infections were treated either with an arthrodesis (five infections) or with débridement, antibiotic therapy, and retention of the prosthesis (eleven infections). One acute hematogenous infection was treated with resection arthroplasty because of life-threatening sepsis. RESULTS The mean duration of follow-up was 4.0 years (range, 0.3 to 14.0 years). Eleven patients who had an arthrodesis, a resection arthroplasty, or an above-the-knee amputation after less than two years of follow-up were included in the study as individuals who had a failure of treatment. In the group of patients who were managed according to protocol, the initial course of treatment was successful for all five infections that were diagnosed on the basis of positive intraoperative cultures, five of the ten deep early infections, all thirteen superficial early infections, twenty-four of the twenty-nine late chronic infections, and five of the seven acute hematogenous infections. Only one of eleven prostheses in patients who had a late chronic infection that was not treated according to protocol was successfully retained after débridement. CONCLUSIONS Our treatment protocols, which were based on the clinical setting of the infection, were successful for most patients. A major factor associated with treatment failure was a compromised immune status. Bone loss and necrosis of the soft tissues around the joint also complicated the treatment of these infections.

Diagnosis and Management of Infection After Total Knee Arthroplasty

The key to successful management of an infection at the site of a total knee arthroplasty is an early and accurate diagnosis that allows prompt treatment. Therefore, it is critical that every patient with pain at the site of a total knee arthroplasty is assessed for the presence of infection1. The usual presentation is characterized by constant pain, warmth, and effusion. Erythema is unusual. It is important to elicit the history of the perioperative course that followed the primary total knee replacement: Did the original wound heal without delay? Was there any postoperative drainage? A complete history ( Table I), physical examination, plain radiographs, and other diagnostic studies discussed below are critical to confirm the diagnosis of infection and to rule out other causes of knee pain2. View this table: TABLE I: Risk Factors for Infection Following Total Knee Arthroplasty Aspiration of the affected knee should be among the first diagnostic tests performed3-5. If the first aspirate is negative but a suspicion of infection remains, then at least two additional aspirations should be performed. Any current antibiotic therapy should be sdiscontinued for a minimum of ten days, and the aspiration should then be repeated. The aspirate should be sent for aerobic, anaerobic, and fungal cultures, and a white blood-cell count with differential should be performed. Blood tests should include determination of the erythrocyte sedimentation rate and the C-reactive protein level. The results of aspiration of the knee must be correlated with the results of the physical examination and radiographs for complete assessment of the possibility of infection6. Radionucleotide studies, particularly bisphosphonate scans in conjunction with indium-labeled leukocyte scans, may contribute to a proper diagnosis. A normal radionucleotide scan suggests that loosening or infection is not the likely cause of pain. It must be remembered, however, …

Titanium, chromium and cobalt ions modulate the release of bone-associated cytokines by human monocytes/macrophages in vitro

Osteolysis has become a major cause of aseptic loosening in total joint arthroplasty (TJA). Titanium, cobalt and chromium are commonly used in orthopaedic implants (e.g. joint prostheses). The release of bone-associated cytokines has been associated with the development of osteolysis in patients with prostheses. We evaluated the effects of these metals on the release of bone-associated cytokines (IL-1 beta, IL-6, TNF-alpha and TGF-beta 1) by human blood monocytes/macrophages and monocyte-like U937 cells upon lipopolysaccharide (LPS) stimulation, the cell proliferation, and their cytotoxic effects on these cells in vitro. We found that the release of IL-1 beta was enhanced by titanium, chromium and cobalt, the release of TNF-alpha was enhanced by titanium and chromium, and the release of IL-6 was enhanced by titanium. All three metal ions inhibited the release of TGF-beta 1. We also found that titanium and chromium, but not cobalt, enhanced blood monocyte/macrophage proliferation in response to LPS while only titanium enhanced U937 cell proliferation in response to LPS. The metals in concentrations ranging from 0.01 to 100 ngml-1 did not stimulate the cells to secrete detectable cytokines in the absence of LPS. Furthermore, a 4-h pre-exposure of blood monocytes/macrophages or U937 cells to the metals did not alter cytokine release when the metals were removed from the media prior to the addition of LPS. Similarly, a 4-h pre-exposure of blood monocytes/macrophages or U937 cells to LPS did not alter cytokine release when LPS was removed from the media prior to the addition of the metals. The metals did not reduce cell viability and induce cell injury after 72h incubation with the cells. The data suggest that the three metals at clinically relevant concentrations modulated cytokine expression, whereas they did not induce any cytotoxic effects. A metal-induced enhancement of bone-resorbing cytokine release with a concomitant inhibition of bone-forming cytokine release may be an important factor in the development of osteolysis, which can severely compromise the outcome of TJA.

Update on the management of open fractures of the tibial shaft.

A retrospective study of 133 open tibial fractures in 129 patients treated at the Hennepin County Medical Center between 1986 and 1993 was done. The results of the treatment protocol in this patient group is presented and the current classification schemes, prevention of infection, debridement, antibiotics, soft tissue reconstruction, fracture stabilization methods, bone grafting, and exchange nailing are discussed. Recent studies that have documented interobserver disagreement in the classification of open fractures underscore the difficulties encountered in the initial assessment and treatment of open tibial shaft fractures. Despite repetitive and aggressive debridement, a certain number of fractures will remain contaminated and become infected. Infection after these severe injuries is probably multifactorial, and its prevention requires that the surgeon diligently adhere to the imperatives of open fracture care.

Pathophysiology of posttraumatic osteomyelitis.

Understanding the pathophysiology of posttraumatic osteomyelitis is crucial as researchers attempt to meet the challenge of developing more effective strategies for the management and prevention of this infection. Some aspects of pathogenesis have been well described, including the important roles of the extent of soft tissue injury, bacterial attachment to necrotic bone and fixation devices, and bacterial contamination at the time of injury. More recently, the importance of early wound coverage in preventing osteomyelitis has been emphasized. Now some of the cellular interactions that promote infection and tissue damage are beginning to be understood. Trauma can have deleterious effects on host response to infection through its activation of certain cytokines. These cytokines, mainly produced by cells of the immune system, regulate the action of polymorphonuclear leukocytes, macrophages, and lymphocytes. Bacteria have been shown to use diverse tactics to initiate and maintain infection that lead to host defense impairment, decreased efficacy of antibiotics, and direct tissue damage. New insights into the pathophysiology of osteomyelitis may lead to the innovative therapeutic approaches needed to improve the standard of care for this infection.

Suppressive antibiotic therapy in chronic prosthetic joint infections.

Thirteen patients with chronic total joint infections (eight knees, five hips) were treated with suppressive antibiotic therapy and retention of the prosthesis following surgical debridement and 4 to 6 weeks of intravenous antibiotic therapy. These patients faced poor functional outcome after prosthesis removal. After a mean follow up of 37.6 months (range: 24 to 55), only three patients have retained their prostheses. Ten patients required prosthesis removal for recurrent infection a mean of 21.6 months (range: 6 to 48) after starting suppressive therapy. In addition, 38% of patients experienced adverse effects which led to changes in the antibiotic regimen. Suppressive antibiotic therapy in the treatment of chronic prosthesis infections has limited clinical efficacy and is associated with a substantial risk of adverse effects.

Prosthetic metals interfere with the functions of human osteoblast cells in vitro.

The release of metals from total joint prostheses may contribute to periprosthetic bone loss manifested as osteolysis. The effects of titanium, cobalt, and chromium on human osteogenic sarcoma cells (osteoblastlike cells) were investigated in vitro. Titanium, cobalt, and chromium at concentrations of 1, 10, and 100 ng/ml did not cause any changes in the cell growth, viability, and injury after 72-hour incubation with the cells. Titanium, cobalt, and chromium at concentrations ranging from 0.01 to 100 ng/ml significantly enhanced the release of interleukin-1β and tumor necrosis factor-α by lipopolysaccharide stimulated human osteogenic sarcoma cells, whereas they did not alter the release of transforming growth factor-β1. Cobalt at concentrations ranging from 0.1 to 100 ng/ml significantly enhanced the release of interleukin-6, but titanium and chromium did not. Cobalt and chromium at concentrations of 10 and 100 ng/ml significantly inhibited the release of osteocalcin by human osteogenic sarcoma cells, whereas titanium had no effect. Titanium, cobalt, and chromium at concentrations of 10 and 100 ng/ml significantly inhibited the synthesis of Type I collagen by human osteogenic sarcoma cells. Cobalt and chromium inhibited the cell proliferation in response to lipopolysaccharide stimulation, whereas titanium did not. The data presented in this article suggest that the metal induced disregulation of cytokine release and osteoblast dysfunction may play an important role in the induction of osteolysis in patients with total joint arthroplasties.

Inhibition of T and B cell proliferation by titanium, cobalt, and chromium: role of IL-2 and IL-6.

The mechanism by which an increased risk of prosthetic infection is induced in patients with total joint arthroplasties is poorly understood. The adverse effects of metallic corrosion products of a prosthesis on host defense mechanisms, particularly immune response and release of immunoregulatory cytokines, remain largely unknown. Titanium, cobalt, and chromium are the materials most often used for joint implantation. Therefore, this study was aimed at investigating the cytotoxicity of titanium, cobalt, and chromium and whether these metals affect T and B cell proliferation and the release of cytokines by human peripheral blood mononuclear cells (PBMC) in vitro. Metal cytotoxicity was not observed judging by cell viability and cell injury after PBMC was extensively exposed to the metals. Phytohemagglutinin (PHA)-induced T cell proliferation and lipopolysaccharide-induced B cell proliferation were significantly inhibited by titanium, chromium, and cobalt. The release of IL-2 and IL-6 by PHA-stimulated PBMC was significantly inhibited by titanium, chromium, and cobalt. Titanium did not alter IFN-gamma production, whereas chromium and cobalt significantly reduced IFN-gamma release by PHA-stimulated PBMC. The addition of IL-2 and IL-6 significantly restored the metal-induced inhibition of T cell and B cell proliferation, respectively. This study sheds light on how the metals impair immune response and cytokine release, suggesting that patients with an extensive exposure to the metals may develop immune dysfunctions. The compromised immune response induced by the metals might significantly contribute to an increased risk of infection in patients with joint prostheses.

Effect of time of onset and depth of infection on the outcome of total knee arthroplasty infections.

The treatment results of 24 infected total knee arthroplasties with a minimum follow-up period of two years are presented. The most common pathogens were coagulase-positive staphylococci (50%), coagulase-negative staphylococci (29.2%), and enterococci (12.5%). Eleven patients with early postoperative infections (occurring within one month of prosthesis implantation) were treated with debridement, retention of the prosthesis, and intravenous antibiotics. Treatment was successful in all five patients with superficial infections not extending into the joint. In six patients with deep infections, treatment was successful in only two (33%), despite a longer course of antibiotic therapy (four to six weeks) and the use of tobramycin-impregnated polymethylmethacrylate beads. Three patients continued to have recurrent drainage, and one patient was subsequently successfully treated with a delayed exchange arthroplasty. Thirteen patients were diagnosed with late infections. One patient with a late, superficial infection and another with an acute (hematogenous seeding), deep infection were successfully managed with debridement and intravenous antibiotics. Prosthesis removal was not required. Eleven patients presented with late, deep infections. Of three patients who were treated without removal of the prosthesis, infection was arrested in only one. The remaining eight patients were treated with debridement, intravenous antibiotics, tobramycin-impregnated polymethylmethacrylate beads, and delayed exchange arthroplasty. The median interval to reimplantation was eight weeks (range, seven to 25 weeks). Treatment was successful in six cases (75%). The overall success rate in the treatment of total knee arthroplasty infections was 71%. In 19 patients with deep infections, treatment success was seen in 78% of patients treated with delayed exchange arthroplasty, but this value was only 40% in patients who were not treated with prosthesis removal. All superficial infections (n = 6) were successfully treated without removal of the prosthesis.