Opioid peptides rapidly stimulate superoxide production by human polymorphonuclear leukocytes and macrophages.

Opioid peptides found in the general circulation can modulate several functions of phagocytic cells that are related to their microbicidal and cytotoxic activity. Since reactive oxygen species are crucial to these activities, the affect of opioid peptides on superoxide (O-2) generation was evaluated with the use of lucigenin-enhanced chemiluminesence (CL). beta-Endorphin and dynorphin stimulate the production of O-2 in human polymorphonuclear leukocytes (PMN) and peritoneal macrophages (PMO) at peptide concentrations that prevail systemically (10(-14)-10(-12)M). There is an inverse dose-response relation for PMN but not PMO. The effect is rapid and sustained in PMN (peak CL at 2-4 min, duration greater than 15 min), whereas it is rapid but brief in PMO (peak 1 min, duration less than 3 min). Naloxone inhibits CL responses by greater than 75% in both cell types.

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.

Enterococcus faecium resistant to ampicillin and gentamicin.

Thirty ampicillin-resistant enterococci were isolated from clinical specimens at our institution, 28 of these over a six month period. All were identified as Enterococcus faecium with an MIC(90) to ampicillin ond penicillin of 32 and 128 mug/ml, respectively. These isolates were also resistant to imipenem, ampicillin-sulbactam, and amoxicillin-clavulanic acid, but susceptible to vancomycin. Only 10%% were resistant to gentamicin at 2 000 mug/ml, but bactericidad synergy could not be demonstrated against any of these isolates using the combination of gentamicin added to either penicillin or vancomycin. No beta-lactamase activity was detected by the nitrocephin test, or by the addition of clavulanic acid or sulbactam. Plasmid analysis revealed a band common to 29 of 30 ampicillin-resistant E. faecium, which was not present in two ampicillin-sensitive E. faecium or in any of twenty E. faecalis. The limited number of options available to treat these isolates of E. faecium simultaneously resistant to multiple antibiotics and resistant to the bactericidad synergy of gentamicin underscores the need to develop new strategies in the prevention and treatment of enterococcal infections.

The evolution of Pseudomonas aeruginosa during antibiotic rotation in a medical intensive care unit: the RADAR-trial.

Bacterial spread between patients may contribute to the high prevalence of antibiotic-resistant pathogens within ICUs. The aim of this study was to evaluate the fate of Pseudomonas aeruginosa during the different antibiotic regimens. Susceptibility patterns and genotyping were performed to determine whether there was a predominant clone and to track the spread of resistant strains within the unit. Twenty-eight different ribotypes were found among 82 Pseudomonas isolates. Four ribotypes accounted for 42 (51%) isolates and were designated the "major clones" occurring throughout multiple cycles. The ribotypes with multiple occurrences were more resistant to antibiotics than ribotypes that appeared only once. The correlation of antibiotic use with antibiotic resistance and the finding of a large number of ribotypes suggested that de novo development of antibiotic resistance is a likely event in P. aeruginosa. In addition, ribotypes associated with antibiotic resistance appeared to have a survival advantage and can become frequent colonizers in the ICU.

Prosthetic metals impair murine immune response and cytokine release in vivo and in vitro.

This study was designed to investigate whether prosthetic metals adversely affect immune responses and the release of immunoregulatory cytokines in vivo and in vitro. Titanium and cobalt-chromium alloy were injected into the peritoneal cavity of female mice. At 5, 8, and 12 weeks after the injection, the levels of cobalt and chromium in the blood were significantly increased compared with the levels in control mice; the level of titanium was not significantly changed until 12 weeks. The release of interleukin-2 was significantly inhibited by cobalt-chromium particles after 3 weeks; titanium particles did not have the same effect until 8 and 12 weeks. The release of interleukin-4 was significantly inhibited by cobalt-chromium particles after 3 weeks but was not significantly inhibited by titanium particles until 12 weeks. The release of interferon-gamma was significantly inhibited by cobalt-chromium particles only at 12 weeks and was not inhibited by titanium particles. The proliferation of T cells was significantly inhibited by cobalt-chromium particles at 3 weeks and by titanium particles at 8 and 12 weeks, and the proliferation of B cells was significantly inhibited by cobalt-chromium particles after 3 weeks but was not inhibited by titanium particles. The production of immunoglobulin by lipopolysaccharide-stimulated B cells was also significantly reduced by cobalt-chromium particles after 3 weeks and by titanium particles at 8 and 12 weeks. The cytokine release by lymphocytes, proliferation of T and B cells, and immunoglobulin production by B cells were also significantly inhibited by titanium and cobalt-chromium particles, as well as by titanium, cobalt, and chromium ions in vitro, whereas these metals are not cytotoxic to murine lymphocytes in vitro. The data indicate that the metal-induced immunosuppression may be another important factor in the development of implant-associated infection in patients with a prosthesis.

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.

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.

The effect of anaerobiosis on antistaphylococcal antibiotics.

The activity of eight antimicrobial agents which might be used in the treatment of staphylococcal osteomyelitis was tested under anaerobic conditions similar to those found in chronically infected bone. An agar-dilution method was employed to determine the minimum inhibitory concentrations of tobramycin, vancomycin, teicoplanin, ciprofloxacin, clindamycin, ceftriaxone, ticarcillin-clavulanic acid, and amoxicillin-clavulanic acid against 25 coagulase-positive and 25 coagulase-negative staphylococcal strains. The activity of tobramycin against coagulase-positive staphylococci, and of amoxicillin-clavulanic acid and ticarcillin-clavulanic acid against coagulase-negative staphylococci was markedly decreased with anaerobiosis. Vancomycin, teicoplanin, and ciprofloxacin were active against coagulase-positive and coagulase-negative staphylococci under both aerobic and anaerobic conditions. It was also found that antibiotic concentrations comparable to the high levels which might be achieved with local antibiotic therapy of osteomyelitis were not sufficient to overcome the level of resistance (100 micrograms/ml) of staphylococci which were not susceptible to tobramycin, clindamycin, ceftriaxone, and ticarcillin-clavulanic acid.

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of extra-pulmonary tuberculosis.

SETTING: The incidence of extra-pulmonary tuberculosis (EPTB) is surprisingly high among certain subgroups of patients in industrialized countries. Diagnosis is often difficult and can require costly invasive workup. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a safe, minimally invasive, accurate, out-patient diagnostic modality for assessing mediastinal and abdominal lymphadenopathy and masses. OBJECTIVE: To evaluate the usefulness of EUS-FNA for diagnosing EPTB. DESIGN: Retrospective 6-year review, including all patients who had evidence of lymphadenopathy or mass on computed tomography scan accessible by EUS and consideration of tuberculosis (TB) in the differential diagnosis. RESULTS: Of 81 potential patients, a total of 20 cases with EPTB diagnosed by EUS-FNA were identified. Necrotizing granulomas had a 58% likelihood of TB vs. 14% for other cytologic findings (P < 0.0001); necrosis was also predictive, with a 44% likelihood of TB vs. 19% (P < 0.0225). EUS-FNA cytology was diagnostic for TB when an African-born patient had necrotizing granulomas (P < 0.0001), and was highly suggestive with necrosis alone (P < 0.0514). Non-necrotizing granulomas were not predictive of TB and an alternative diagnosis was more likely, including sarcoidosis and cancer. CONCLUSION: EUS-FNA is a useful diagnostic modality that should be used early in the diagnostic workup of suspected EPTB.

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.

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Fibrin glue-antibiotic suspension in the prevention of prosthetic graft infection.

UNLABELLED: The following study was done to assess whether fibrin glue-antibiotic suspension (FGAS) can prevent infection of a PTFE vascular graft in a contaminated wound. METHODS: FGAS was made by combining cryoprecipitate with a mixture of bovine thrombin, aminocaproic acid, and tobramycin (5 mg/cc thrombus). Antibiotic activity was documented by in vitro kinetics which revealed initial elutions to be greater than 8,000 mu gm/cc and elutions at 4 days to be greater than 2 mcg/cc. Twelve dogs had a 1-cm section of infrarenal aorta replaced with a PTFE graft that had been bathed in a 2-cc solution of E. coli 3 x 10(8) CFU/ml and S. aureus 3 x 10(8) CFU/ml. Both organisms were sensitive to tobramycin and cefonicid. Dogs were divided into three groups of four. Group I had a contaminated PTFE graft placed and no further therapy. Group II had a contaminated PTFE graft placed and sealed with fibrin glue. Group III had a contaminated PTFE graft placed and sealed with FGAS. All three groups received daily IV cefonicid. RESULTS: Group I: Four of four dogs were reoperated on the fourth day for suspected sepsis and all four had pseudoaneurysms (one ruptured). Three of four were culture positive for S. aureus and two of four positive for E. coli. Group II: Four of four died of anastomotic disruption by the third day. Four of four were culture positive for S. aureus and E. coli. Group III: All four dogs survived and were sacrificed on Day 17: all anastomoses were normal. Animal survival was significantly associated with the treatment given (p = 0.0025). Three of four tissue cultures of the grafts were weakly positive for S. aureus and one of four for E. coli and Pseudomonas. Serum tobramycin levels were negligible at 12, 24, 72, and 96 hours. CONCLUSIONS: The data show that FGAS was associated with a reduction in vascular graft infection and pseudoaneurysm formation after exposure to a standardized bacterial inoculum. Whether complete eradication of all organisms can be achieved with higher doses of tobramycin is as yet undetermined.

Beta-endorphin stimulates human polymorphonuclear leukocyte superoxide production via a stereoselective opiate receptor.

Opioid peptides have been shown to modulate the function of cells associated with host defense. Both opiate and nonopiate receptor mechanisms have been shown to mediate cell responses to these peptides. In this study we used a ferricytochrome C reduction microassay to measure superoxide (O2-) production by human polymorphonuclear leukocytes after stimulation with beta-endorphin (beta-END). beta-END was found to stimulate O2- release at concentrations from 10(-14) to 10(-8) M; the peak response occurred at 10(-12) M. A microassay based on the horseradish peroxidase-mediated oxidation of phenol red was used to demonstrate the production of hydrogen peroxide H2O2, by beta-END at 10(-12) M. The accumulation of H2O2 was reduced by the inhibitor, nitroprusside, and by the converting enzyme, catalase. The accumulation of O2- in response to the potent chemotactic peptide formyl-methionine-leucine-phenylalanine was studied and a distinctly different dose-response profile with a peak response at 10(-8) M was observed. Because beta-END can apparently bind to and activate cellular functions by nonopiate receptors, N-acetyl-beta-END was tested. At doses between 10(-14) and 10(-8) M, it failed to effect O2- accumulation. Moreover, (-)-naloxone 10(-12) M was shown to completely abolish the stimulatory effect of equimolar beta-END whereas (+)-naloxone was entirely ineffective. At 10(-8) M both stereoisomers also failed to inhibit formyl-methionine-leucine-phenylalanine 10(-8) M. Thus, at the picomolar concentration present in the human systemic circulation, beta-END activates oxygen metabolism by polymorphonuclear leukocytes through stereoselective, naloxone-sensitive opiate receptors.

Uptake and activity of rifapentine in human peritoneal macrophages and polymorphonuclear leukocytes.

Rifapentine uptake by human peritoneal macrophages and polymorphonuclear leukocytes was evaluated and its activity against intracellular Staphylococcus aureus and Staphylococcus epidermidis in both types of phagocytes was compared to that of rifampin, teicoplanin and clindamycin. Uptake of radiolabeled rifapentine by peritoneal macrophages (intracellular/extracellular ratio 61.4 +/- 5.8) and polymorphonuclear leukocytes (intracellular/extracellular ratio 87.6 +/- 3.9) was significantly higher than that of teicoplanin (intracellular/extracellular ratio 40.8 +/- 3.6 and 52.3 +/- 3.2 respectively) and clindamycin (intracellular/extracellular ratio 6.9 +/- 0.4 and 8.3 +/- 0.5 respectively). Rifapentine and rifampin showed the highest activity against intracellular staphylococci in both peritoneal macrophages and polymorphonuclear leukocytes. Clindamycin also showed efficient intracellular activity. In contrast, teicoplanin, which achieved high cellular levels with both types of phagocytes, failed to produce a significant reduction in viable intraphagocytic Staphylococcus epidermidis. On the basis of these findings it is suggested that rifapentine may play a future role in the treatment of certain types of staphylococcal infection.

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-1 beta and tumor necrosis factor-alpha by lipopolysaccharide stimulated human osteogenic sarcoma cells, whereas they did not alter the release of transforming growth factor-beta 1. 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.

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.