Background and purpose Late infections after total hip arthroplasty are still a problem. Treatment procedures include resection arthroplasty with implantation of antibiotic-loaded beads or implantation of an antibiotic-impreganted spacer. However, little is known about antibiotic elution from bone cement beyond the first 2–3 postoperative days in humans.Methods 17 hip spacers (80g PMMA, 1g gentamicin, and 4 g vancomycin) and 11 chains (40 g PMMA, 0.5 g gentamicin, and 2 g vancomycin) in 28 patients were studied. The release of both agents was measured in the drainage fluid on a daily basis. The drains were left in situ until less than 50 mL was produced per day. The elution of both antibiotics was determined by fluorescence polarization immunoassay. Systemic antibiotics were given postoperatively according to antibiogram. If possible, no gentamicin or vancomycin was given.Results Peak mean concentrations from beads and spacers were reached for gentamicin (1,160 (12–371) µg/mL and 21 (0.7–39) µg/mL, respectively) and for vancomycin (80 (21–198) µg/mL and 37 (3.3–72) µg/mL) on day 1. The last concentrations to be determined were 3.7 µg/mL gentamicin and 23 µg/mL vancomycin in the beads group after 13 days, and 1.9 µg/mL gentamicin and 6.6 µg/mL vancomycin in the spacer group after 7 days. Between the fifth and seventh day, an intermittent increase in elution of vancomycin from both beads and spacers and of gentamicin from spacers was noticed. No renal or hepatic dysfunction was observed.Interpretation Beads showed higher elution characteristics in vivo than the spacers due to their larger surface area; however, a great amount of inter-subject variability was seen for both beads and spacers. The inferior elution properties of spacers emphasize the importance of additional systemic antibiotics for this treatment procedure during the postoperative period. Future studies should clarify whether the dose of antibiotics or length of antibiotic therapy may be reduced in the case of bead implantation, without jeopardizing the control of infection.

Previously we reported that stable transfection of human UDP-glucose pyrophosphorylase (hUGP2) rescued galactose-1-phosphate uridyltransferase (GALT)-deficient yeast from "galactose toxicity." Here we test in human cell lines the hypothesis that galactose toxicity was caused by excess accumulation of galactose-1-phosphate (Gal-1-P), inhibition of hUGP2, and UDP-hexose deficiency. We found that SV40-transformed fibroblasts derived from a galactosemic patient accumulated Gal-1-P from 1.2+/-0.4 to 5.2+/-0.5 mM and stopped growing when transferred from 0.1% glucose to 0.1% galactose. Control fibroblasts accumulated little Gal-1-P and continued to grow. The GALT-deficient cells had 157+/-10 micromoles UDP-glucose/100 g protein and 25+/-5 micromoles UDP-galactose/100 g protein when grown in 0.1% glucose. The control cells had 236+/-25 micromoles UDP- glucose/100 g protein and 82+/-10 micromoles UDP-galactose/100 g protein when grown in identical medium. When we transfected the GALT-deficient cells with either the hUGP2 or GALT gene, their UDP-glucose content increased to 305+/-28 micromoles/100 g protein (hUGP2-transfected) and 210+/-13 micromoles/100 g protein (GALT-transfected), respectively. Similarly, UDP-galactose content increased to 75+/-12 micromoles/100 g protein (hUGP2-transfected) and 55+/-9 micromoles/100 g protein (GALT-transfected), respectively. Though the GALT-transfected cells grew in 0.1% galactose with little accumulation of Gal-1-P (0.2+/-0.02 mM), the hUGP2-transfected cells grew but accumulated some Gal-1-P (3.1+/-0.4 mM). We found that 2.5 mM Gal-1-P increased the apparent KM of purified hUGP2 for glucose-1-phosphate from 19.7 microM to 169 microM, without changes in apparent Vmax. The Ki of the reaction was 0.47 mM. Gal-1-P also inhibited UDP-N-acetylglucosamine pyrophosphorylase, which catalyzes the formation of UDP-N-acetylglucosamine. We conclude that intracellular concentrations of Gal-1-P found in classic galactosemia inhibit UDP-hexose pyrophosphorylases and reduce the intracellular concentrations of UDP-hexoses. Reduced Sambucus nigra agglutinin binding to glycoproteins isolated from cells with increased Gal-1-P is consistent with the resultant inhibition of glycoprotein glycosylation.

The aim of this retrospective study was to identify and evaluate complications after hip spacer implantation other than reinfection and/or infection persistence.Between 1999 and 2008, 88 hip spacer implantations in 82 patients have been performed. There were 43 male and 39 female patients at a mean age of 70 [43 - 89] years. The mean spacer implantation time was 90 [14-1460] days. The mean follow-up was 54 [7-96] months. The most common identified organisms were S. aureus and S. epidermidis. In most cases, the spacers were impregnated with 1 g gentamicin and 4 g vancomycin / 80 g bone cement.The overall complication rate was 58.5 % (48/82 cases). A spacer dislocation occurred in 15 cases (17 %). Spacer fractures could be noticed in 9 cases (10.2 %). Femoral fractures occurred in 12 cases (13.6 %). After prosthesis reimplantation, 16 patients suffered from a prosthesis dislocation (23 %). 2 patients (2.4 %) showed allergic reactions against the intravenous antibiotic therapy. An acute renal failure occurred in 5 cases (6 %). No cases of hepatic failure or ototoxicity could be observed in our collective. General complications (consisting mostly of draining sinus, pneumonia, cardiopulmonary decompensation, lower urinary tract infections) occurred in 38 patients (46.3 %).Despite the retrospective study design and the limited possibility of interpreting these findings and their causes, this rate indicates that patients suffering from late hip joint infections and being treated with a two-stage protocol are prone to having complications. Orthopaedic surgeons should be aware of these complications and their treatment options and focus on the early diagnosis for prevention of further complications. Between stages, an interdisciplinary cooperation with other facilities (internal medicine, microbiologists) should be aimed for patients with several comorbidities for optimizing their general medical condition.

The antibiotic release from and the bacteria growth inhibition by antibiotic-loaded acrylic bone cement hip spacers were studied. The cement used was Palacos R, and it was loaded with either one antibiotic powder (gentamicin, vancomycin, teicoplanin, or synercid) [monoantibiotic case] or two antibiotic powders (gentamicin + vancomycin or gentamicin + teicoplanin) [biantibiotic case] and then tested against Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, and methicillin-resistant Staphylococcus aureus (MRSA). Antibiotic elution and bacteria growth were measured every 24 h simultaneously by fluorescence polarization immunoassay and photometrically, respectively. The gentamicin + vancomycin combination achieved the longest growth inhibition on S. epidermidis and MRSA (mean of 20 and 14 days, respectively). Gentamicin + teicoplanin-loaded spacers were capable of inhibiting growth on E. faecalis and S. aureus for the longest period (11 and 16 days, respectively). The highest concentrations of gentamicin and vancomycin could be assayed during the first 4 days. Teicoplanin concentrations could be detected only during the first 72 h, synercid was not detected at all, possibly because of the limitation of the detection technique used. A greater percentage of the gentamicin was released than of the vancomycin. The aminoglycosid-glycopeptid combination showed a synergistic effect on the release of gentamicin, but not on vancomycin or teicoplanin. Biantibiotic-impregnated hip spacers proved to be superior to monoantibiotic ones. Because of important differences between the conditions used for the present tests and the in vivo environment, any recommendation with regard to the use of monoantibiotic- and biantibiotic-loaded acrylic bone cement spacers must await the results of further investigations.

The antimicrobial properties and the elution characteristics of gentamicin-vancomycin-loaded hip spacers were studied in vivo and in vitro. Vancomycin elution was greater than gentamicin elution. The antibiotic concentrations in vivo were less than those in vitro. Not dependent on implantation duration, growth inhibition by spacers in vitro was observed for 2 weeks. The reason for protracted wound healing cannot be insufficient antibiotic release.