Steve Wen-Neng Ueng

Gram-negative Prosthetic Joint Infections: Risk Factors and Outcome of Treatment

BACKGROUND Little information is available regarding the demographic characteristics and outcomes of patients with prosthetic joint infection (PJI) resulting from gram-negative (GN) organisms, compared with patients with PJI resulting from gram-positive (GP) organisms. METHODS We performed a retrospective cohort analysis of all cases of PJI that were treated at our institution during the period from 2000 through 2006. RESULTS GN microorganisms were involved in 53 (15%) of 346 first-time episodes of PJI, and Pseudomonas aeruginosa was the most commonly isolated pathogen (21 [40%] of the 53 episodes). Patients with GN PJI were older (median age, 68 vs. 59 years; P<.001) and developed infection earlier (median joint age, 74 vs. 109 days; P<.001) than those with GP PJI. Of the 53 episodes of GN PJI, 27 (51%) were treated with debridement, 16 (30%) with 2-stage exchange arthroplasty, and 10 (19%) with resection arthroplasty. Treating GN PJI with debridement was associated with a lower 2-year cumulative probability of success than treating GP PJI with debridement (27% vs. 47% of episodes were successfully treated; P=.002); no difference was found when a PJI was treated with 2-stage exchange or resection arthroplasty. A longer duration of symptoms before treatment with debridement was associated with treatment failure for GN PJI, compared with for GP PJI (median duration of symptoms, 11 vs. 5 days; P=.02). CONCLUSIONS GN PJI represents a substantial proportion of all occurrences of PJI. Debridement alone has a high failure rate and should not be attempted when the duration of symptoms is long. Resection of the prosthesis, with or without subsequent reimplantation, as a result of GN PJI is associated with a favorable outcome rate that is comparable to that associated with PJI due to GP pathogens.

Sustainable release of vancomycin, gentamicin and lidocaine from novel electrospun sandwich-structured PLGA/collagen nanofibrous membranes.

This study investigated the in vitro release of vancomycin, gentamicin, and lidocaine from novel electrospun sandwich-structured polylactide-polyglycolide (PLGA)/collagen nanofibrous membranes. For the electrospinning of biodegradable membranes, PLGA/collagen and PLGA/vancomycin/gentamicin/lidocaine were separately dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). They were then electrospun into sandwich structured membranes, with PLGA/collagen for the surface layers and PLGA/drugs for the core layer. After electrospinning, an elution method and HPLC assay were employed to characterize the in vitro release rates of the pharmaceutics over a 30-day period. The experiment showed that biodegradable nanofibrous membranes released high concentrations of vancomycin and gentamicin (well above the minimum inhibition concentration) for 4 and 3 weeks, respectively, and lidocaine for 2 weeks. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity of vancomycin and gentamicin ranged from 30% to 100% and 37% to 100%, respectively. In addition, results indicated that the nanofibrous membranes were functionally active in responses in human fibroblasts. By adopting the electrospinning technique, we will be able to manufacture biodegradable biomimetic nanofibrous extracellular membranes for long-term drug delivery of various pharmaceuticals.

Closed management and percutaneous fixation of unstable proximal humerus fractures.

BACKGROUND In dealing with displaced proximal humerus fractures, there is still much controversy in treatment modalities. The latest investigations emphasize the concept of minimal exposure and rigid fixation. METHODS The technique of closed reduction and percutaneous fixation with cannulated screws and k-pins was performed on 19 patients with two- and three-part proximal humerus fractures. The outcomes were evaluated with a mean follow-up of 21 months. RESULTS All except one case had a solid union of the fracture. Sixteen of 19 patients (84%) acquired good or excellent results according to Neers classification. No further collapse or avascular necrosis was found. CONCLUSION The method of closed reduction and percutaneous fixation, although technically demanding, yields satisfactory results in displaced proximal humerus fracture. Cannulated screws provided rigid fixation that was the underlying tenet for early functional retrieval.

Management of femoral diaphyseal infected nonunion with antibiotic beads local therapy, external skeletal fixation, and staged bone grafting

BACKGROUND Fifteen patients with femoral shaft fractures complicated by infected nonunions were treated with a two-stage protocol. METHODS In the first stage, radical debridement was performed along with antibiotic bead chains local therapy and external skeletal fixation. In the second stage, the debrided nonunion site was repaired with bone grafting and the external skeletal fixator was used until bony union was achieved. The time between the first and second stages of treatment was 2 to 6 weeks. The debrided bone defects ranged from 0.5 to 15 cm. Autogenous iliac cancellous bone grafting was performed in 11 patients, and microvascularized osteoseptocutaneous fibular transfer was performed in 4 patients. RESULTS Wound healing and bone union were achieved in all 15 cases. The duration of external fixation of these patients ranged from 7 to 15 months, with an average of 9 months. Minor pin-track infection was seen in seven patients. Postoperative infection after the second-stage bone grafting occurred in three patients. These three infections were arrested by limited debridement along with 2 to 4 weeks of parenteral antibiotic therapy. In one case, stress fracture occurred at 11 months after microvascularized fibular transfer; this was managed with another 5 months of external skeletal fixation. With an aggressive physical therapy program, 10 patients achieved nearly full range of knee motion and 5 patients had relevant knee flexion deficits. The follow-up averaged 58 months (range, 40-76 months); no recurrence of osteomyelitis was observed even at 76 months. CONCLUSION We have found that our two-stage treatment with antibiotic beads local therapy, definitive external skeletal fixation, and staged bone grafting is an acceptable treatment protocol for the management of femoral diaphyseal infected nonunion. It results in rapid recovery from osteomyelitis and a predictable recovery from nonunion.

Antibiotic-impregnated autogenic cancellous bone grafting is an effective and safe method for the management of small infected tibial defects: a comparison study.

OBJECTIVE Bone grafting plays an important role in reconstructing infected tibial nonunions. The effects of antibiotic-impregnated bone grafting in infection elimination and bone incorporation was reported in this retrospective study. METHODS Ninety-six patients treated for infected tibial nonunions were evaluated. These patients were managed with local antibiotic bead therapy and staged antibiotic-impregnated autogenous cancellous bone graft or pure autogenous cancellous bone graft. Patients were randomized to antibiotic-impregnated bone grafting or bone grafting-only groups on the basis of whether the admission date was odd or even. Patients were divided into two groups (antibiotic-impregnated bone grafting group and pure cancellous bone grafting group), according to the procedure used in preparing the bone grafts. The antibiotic-impregnated bone grafting group included 37 men and 9 women whose average age was 36 years (range, 17 to 72 years). The average follow-up period was 4.8 years. By using the Cierny-Mader staging classification of chronic osteomyelitis, 32 of 46 patients (70%) were stage 4A, and 14 of 36 patients (30%) were stage 4B. The pure cancellous bone grafting group included 39 men and 11 women whose average age was 37 years (range, 18 to 72 years). The average follow-up period was 4.5 years (range, 4 to 6 years). Thirty-nine of 50 patients (78%) were stage 4A, and 11 of 50 patients (22%) were stage 4B. The bone defects in both groups ranged from 2 to 4 cm. RESULTS Wound healing and bony union were achieved in the antibiotic-impregnated bone grafting group. Only two patients had recurrent infections. The infection arrest rate was 95.6%. However, 9 of 50 patients in the pure cancellous bone grafting group had recurrent infections. The infection arrest rate was 82%. The antibiotic-impregnated bone grafting group had significantly superior results (95.6% vs. 82% chi2 test, p < 0.05) in infection elimination than the pure cancellous bone grafting group. CONCLUSION After 4 to 6 years of follow-up, our results suggest that the use of impregnating antibiotics have no adverse effects on autogenic cancellous bone graft incorporation and could help to eliminate infection effectively.

Effect of intermittent cigarette smoke inhalation on tibial lengthening : Experimental study on rabbits

We investigated the effect of intermittent cigarette smoke inhalation on the bone healing of tibial lengthening in rabbits. Thirty-eight male rabbits were divided into two groups of 19 animals each. The first group went through intermittent cigarette smoke inhalation, and the second group did not go through intermittent cigarette smoke inhalation. Each animals right tibia was lengthened 5 mm using an uniplanar lengthening device. Five animals of each group were killed at 4, 6, and 8 weeks postoperatively for biomechanical testing, and one animal of each group was killed at 2, 4, 6, and 8 weeks postoperatively for histologic study. Using the contralateral nonoperated tibia as an internal control, we found that torsional strength of the lengthened tibia of the smoke inhalation group was decreased significantly compared with the non-smoke inhalation group. The mean percent of maximal torque at 4, 6, and 8 weeks were 22.0, 66.3, and 78.6%, respectively, in the smoke inhalation group, whereas the mean percent of maximal torque were 48.0, 84.1, and 90.8% %, respectively, in non-smoke inhalation group (one-tailed t test, p < 0.01, p < 0.01, and p < 0.05 at 4, 6, and 8 weeks, respectively). Our histologic observations revealed that the granulation tissue resorption, bone formation, and remodeling were delayed in smoke inhalation group. The results of this study suggest that intermittent inhalation of cigarette smoke delays, but does not prevent, the bone healing in tibial lengthening.

Bone healing of tibial lengthening is enhanced by hyperbaric oxygen therapy: a study of bone mineral density and torsional strength on rabbits.

We investigated the effect of intermittent hyperbaric oxygen (HBO) therapy on the bone healing of tibial lengthening in rabbits. Twelve male rabbits were divided into two groups of six animals each. The first group went through 2.5 atmospheres absolute of hyperbaric oxygenation for 2 hours daily, and the second group did not go through hyperbaric oxygenation. Each animals right tibia was lengthened 5 mm using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all of the animals at 1 day before operation and at 3, 4, 5, and 6 weeks after operation. All of the animals were killed at 6 weeks postoperatively for biomechanical testing. Using the preoperative BMD as an internal control, we found that the BMD of the HBO group was increased significantly compared with the non HBO group. The mean %BMD at 3, 4, 5, and 6 weeks were 69.5%, 80.1%, 87.8%, and 96.9%, respectively, in HBO group, whereas the mean %BMD were 51.6%, 67.7%, 70.5%, and 79.2%, respectively, in non-HBO group (two tailed t test, p < 0.01, p < 0.01, p < 0.01, and p < 0.01 at 3, 4, 5, and 6 weeks, respectively). Using the contralateral nonoperated tibia as an internal control, we found that torsional strength of lengthened tibia of the HBO group was increased significantly compared with the non-HBO group. The mean percent of maximal torque was 88.6% in HBO group at 6 weeks, whereas the mean percent of maximal torque was 76.0% in non-HBO group (two-tailed t test, p < 0.01). The results of this study suggest that the bone healing of tibial lengthening is enhanced by intermittent hyperbaric oxygen therapy.

Bone healing of tibial lengthening is delayed by cigarette smoking : Study of bone mineral density and torsional strength on rabbits

OBJECTIVE We investigated the effect of intermittent cigarette smoke inhalation on the bone healing of tibial lengthening in rabbits. METHODS Twelve male rabbits were divided into two groups of six animals each. The first group underwent intermittent cigarette smoke inhalation, and the second group did not undergo intermittent cigarette smoke inhalation. Each animals right tibia was lengthened 5 mm by using an uniplanar lengthening device. Bone mineral density (BMD) study was performed for all of the animals 1 day before operation and 3, 4, 5, and 6 weeks after operation. All of the animals were killed 6 weeks postoperatively for biomechanical testing. RESULTS By using the preoperative BMD as an internal control, we found that the BMD of the smoke-inhalation group was decreased significantly compared with the non-smoke-inhalation group. The mean %BMD at 3, 4, 5, and 6 weeks were 49.9%, 61.2%, 65.9%, and 71.0%, respectively, in the smoke-inhalation group, whereas the mean %BMD were 54.9%, 71.8%, 76.4%, and 82.0%, respectively, in the non-smoke-inhalation group (two-tailed t test, p > 0.05, p < 0.01, p < 0.01 and p < 0.01 at 3, 4, 5, and 6 weeks, respectively). By using the contralateral nonoperated tibia as internal control, we found that torsional strength of the smoke-inhalation group was decreased significantly compared with the non-smoke-inhalation group. The mean percentage of maximal torque was 63.8% in the smoke-inhalation group, whereas the mean percentage of maximal torque was 77.1% in the non-smoke-inhalation group (two tailed t test, p < 0.01). CONCLUSION This study suggests that cigarette smoking delays the mineralization during the bone healing process of distraction osteogenesis and, thus, decreases the mechanical strength of the regenerating bone.

Development of a biodegradable antibiotic delivery system.

Antibiotic beads have been used as a drug delivery system for the treatment of various surgical infections. In this study, the copolymer 50:50 poly(DL-lactide):co-glycolide was mixed with vancomycin powder and hot compressing molded at 55 degrees C to form five types of biodegradable antibiotic beads. The beads were placed in 1 mL of phosphate buffered saline and incubated at 37 degrees C. The phosphate buffered saline was changed daily, and the removed buffer solutions were stored at -70 degrees C until the antibiotic concentration in each sample was determined by high performance liquid chromatography system assay. The concentration of vancomycin in each sample was well above the breakpoint sensitivity concentration (the antibiotic concentration at the transition point between bacterial killing and resistance to the antibiotic) for more than 32 days. The release was most marked during the first 48 hours. All copolymer 50:50 poly(DI lactide):co-glycolide biodegradable beads released high concentrations of the antibiotics in vitro for the time needed to treat bone infections (4 to 6 weeks). The diameter of the sample inhibition zone ranged from 6.5 mm to 10 mm, and the relative activity of vancomycin ranged from 12.5% to 100%. Copolymers with low heat of formation temperatures are required for making a controlled release system to prevent antibiotic decomposition, which occurs when using the hot compressing molded method. The rate and duration of release from the antibiotic beads can be adjusted by varying the diameter of the beads. This offers a convenient method to adjust the release rate to meet the specific antibiotic requirements for different patients.

In Vitro Activities of Daptomycin-, Vancomycin-, and Teicoplanin-Loaded Polymethylmethacrylate against Methicillin-Susceptible, Methicillin-Resistant, and Vancomycin-Intermediate Strains of Staphylococcus aureus

ABSTRACT The objective of this study was to evaluate the antibacterial effects of polymethylmethacrylate (PMMA) bone cements loaded with daptomycin, vancomycin, and teicoplanin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-intermediate Staphylococcus aureus (VISA) strains. Standardized cement specimens made from 40 g PMMA loaded with 1 g (low-dose), 4 g (middle-dose) or 8 g (high-dose) antibiotics were tested for elution characteristics and antibacterial activities. The patterns of release of antibiotics from the cement specimens were evaluated using in vitro broth elution assay with high-performance liquid chromatography. The activities of broth elution fluid against different Staphylococcus aureus strains (MSSA, MRSA, and VISA) were then determined. The antibacterial activities of all the tested antibiotics were maintained after being mixed with PMMA. The cements loaded with higher dosages of antibiotics showed longer elution periods. Regardless of the antibiotic loading dose, the teicoplanin-loaded cements showed better elution efficacy and provided longer inhibitory periods against MSSA, MRSA, and VISA than cements loaded with the same dose of vancomycin or daptomycin. Regarding the choice of antibiotics for cement loading in the treatment of Staphylococcus aureus infection, teicoplanin was superior in terms of antibacterial effects.