Jens Kelm

Antibiotic-impregnated PMMA hip spacers: Current status.

The infection rate after primary hip arthroplasty lies at 1–2%. In the past few years, a two-stage protocol with the implantation of an antibiotic-loaded spacer has become a popular procedure in the treatment of infected hip joint arthroplasties. In this review, we pay special attention to the elution characteristics of the spacers, their mechanical stability and the clinical response. We conclude that hip spacers are an effective method in the treatment of hip joint infections, with success rates of over 90%.

Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo

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.

Persistence of bacterial growth on antibiotic-loaded beads: Is it actually a problem?

Background and purpose Implantation of antibiotic-loaded beads is used for orthopedic infections. However, recent in vitro reports have emphasized that bacteria can persist on—or even colonize—antibiotic-impregnated bone cement. We therefore assessed whether bacterial adherence and growth could be determined on gentami-cin- and gentamicin-vancomycin-loaded beads that had been removed after eradication of infection. Material and methods We bacteriologically examined 18 chains of antibiotic-loaded beads (11 gentami-cin-loaded, 7 gentamicin-vancomycin-loaded) that had been implanted because of orthopedic infections. Among the causative agents, Staphylococcus epidermidis, Staph-ylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) were the most frequent organisms identified. Results In 4 cases (3 with S. epidermidis and one with MRSA), we found that there was persistence of bacterial growth on the beads. S. epidermidis strains persisted only on gentamicin-loaded beads, while MRSA could grow on gentamicin-vancomycin-impregnated cement. In one case, the emergence of a gentamicin-resistant S. epidermidis strain was observed despite the fact that preoperative samples of S. epidermidis from this patient had been susceptible to the antibiotic. Interpretation Persistence of bacterial growth on bone cement remains a hazardous problem in orthopedic surgery. Adherence of bacteria to cement can lead to emergence of bacterial resistance to antibiotics and might result in clinical recurrence of infection.

Enhancement of antibiotic elution from acrylic bone cement

Antibiotic-loaded acrylic bone cement is a well-established tool in the prophylaxis and treatment of orthopedic infections. Numerous studies about its pharmacokinetic properties have demonstrated that only a small part of the incorporated antibiotic amounts can be released, mostly over the first 8-10 weeks. Therefore, in the past 10 years, several attempts have been made for enhancement of the drug elution from bone cement. This article reviews this experience and pays special attention on biantibiotic combinations, additives other than antimicrobial agents, as well as the effect of ultrasound on the antibiotic elution characteristics.

Rupture of the anterior tibial tendon: three clinical cases, anatomical study, and literature review.

Background: We report three cases of anterior tibial tendon ruptures and the results of an anatomical study in regard to the tendons insertion site and a literature review. Methods: Three patients were referred to our hospital with anterior tibial tendon ruptures. In the anatomical study, 53 feet were dissected, looking in particular for variants of the bony insertion of the tendon. Results: Two patients had surgical treatment (one primary repair and one semimembranosus tendon graft) and one conservative treatment. After a mean followup of 14 weeks all patients had satisfactory outcomes. In the anatomical study, we noted three different insertion sites: in 36 feet the tendon inserted into the medial side of the cuneiform and the base of the first metatarsal bone and in 13 feet only into the medial side of the cuneiform bone. In the remaining four feet the tendon inserted into the cuneiform and the first metatarsal bone, but an additional tendon was noted taking its origin from the anterior tibial tendon near its insertion into the medial cuneiform and attaching to the proximal part of the first metatarsal. Conclusions: According to literature, surgical repair is the treatment of choice for acute ruptures and for patients with high activity levels. For chronic ruptures and patients with low demands, conservative management may lead to an equally good outcome. Knowledge of the anatomy in this region may be helpful for diagnosis and for the interpretation of intraoperative findings and choosing the most appropriate surgical procedure.

Fungal periprosthetic hip and knee joint infections clinical experience with a 2-stage treatment protocol.

Fungal periprosthetic joint infections are a rare entity in orthopedic surgery, and there exist no guidelines according to which these infections can be successfully managed. Between 2004 and 2009, 7 patients with fungal periprosthetic joint infections (4 total hip arthroplasties and 3 total knee arthroplasties) have been treated with a 2-stage protocol and implantation of antibiotic-loaded cement spacers. Most of the infection was caused by Candida species. Systemic antifungal agents were administered for 6 weeks in 6 cases and 6 months in 1 case. The mean spacer implantation time was 12 weeks. At a mean follow-up of 28 months (5-70 months), no persistence of infection or reinfection could be observed. A 2-stage treatment protocol with implantation of an antibiotic-loaded cement spacer is an efficient option in the treatment of fungal periprosthetic infections.

In Vivo and In Vitro Studies of Antibiotic Release from and Bacterial Growth Inhibition by Antibiotic-Impregnated Polymethylmethacrylate Hip Spacers

ABSTRACT 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.

Antimicrobial properties and elution kinetics of linezolid-loaded hip spacers in vitro

Bacterial adhesion to and -persistence on antibiotic-loaded bone cement is an increasing problem. New antibiotics with good antimicrobial and pharmacokinetic properties (e.g. linezolid) may be the solution to this problem; however, few data concerning linezolid-loaded acrylic cement are currently available. Ten gentamicin-linezolid-loaded hip spacers (1 g gentamicin/2.4 g linezolid/80 g PMMA; five spacers including a metallic endoskeleton, five with no metallic components) were tested in vitro against a strain of methicillin-resistant Staphylococcus aureus with regard to antibiotic release and bacteria growth inhibition. Daily, the antibiotic elution was determined by high liquid performance chromatography (linezolid) and fluorescence polarization immunoassay (gentamicin), the bacteria growth inhibition photometrically at 546 nm. All spacers demonstrated growth inhibition for 8 days. Peak average concentrations were reached for both agents on day 1 (gentamicin-35.10 mug/mL [24.10-52.52], linezolid-36.28 mug/mL [22.87-71.76]). After 8 days, 0.97% [0.93-1.05%] of the initial amount of linezolid and 3.13% [2.85-3.31%] of gentamicin were meanly released from spacers containing a metallic endoskeleton. In those containing of simple cement these values were 1.22% [0.91-1.59%] and 2.67% [2.12-2.73%], respectively. Linezolid demonstrated acceptable elution kinetics from bone cement; however, further experimental research and animal studies should clarify any possible side effect of linezolid-loaded cement media before definitive use in the clinical practice.

The "glove" technique: a modified method for femoral fixation of antibiotic-loaded hip spacers.

In the past few years hip spacers have become popular in the treatment of infected total hip arthroplasties (THAs), with reported infection eradication rates of > 90% (Anagnostakos et al. 2006). Two methods have been described for femoral fixation of a hip spacer. The spacer stem can be inserted into the femur either by a “press-fit” method, or by cementing onto the proximal femur (Anagnostakos et al. 2006). It is unclear which of these two methods provides superior fixation and thus acts better in the prevention of a spacer dislocation. In this report, we introduce a new technique for femoral fixation of an antibiotic-impregnated hip spacer. Surgical technique In our department, we produce hip spacers by means of a two-parted mold (Figure 1). The mold consists of polyoxymethylene (POM). A special mold is also available for acetabular defects (Figure 2). For clinical use, Refobacin-Palacos (0.5 g gentamicin/40 g cement) as bone cement has been shown to have elution characteristics that are better than those of other bone cements (Anagnostakos et al. 2006). For the spacer prosthesis and the acetabular component, production of 80 g and 40 g of polymethylmethacrylate (PMMA), respectively, is required. Depending on the identity of the causative pathogen and its sensitivity profile, we sometimes load the bone cement with a second antibiotic. In cases of an unidentified bacterium preoperatively or if the infection was revealed during an operation for presumed aseptic conditions, we routinelly use the combination of 1 g gentamicin/4 g vancomycin/80 g PMMA. Each spacer has a head diameter of 50 mm, a stem length of 10 cm, and a total surface area of 13,300 mm2. The acetabular component has an inside/outside diameter of 53/56 mm and a total surface area of 4,410 mm2. When there is to be a combination of antibiotics, the second antibiotic is added manually to the Refobacin-Palacos powder. After thorough mixing, the cement’s liquid monomer is added. After attaining a doughy state, the cement is then poured into the two halves of the spacer mold. The halves are then clamped together. After 15 min, they are opened again and the molded spacer is removed. Figure 1. Mold, consisting of polyoxymethylene (POM), for standardized production of hip spacers. Each spacer has a head diameter of 50 mm, a stem length of 10 cm, and a total surface area of 13,300 mm2. Figure 2. Mold for production of the acetabular component. The component has an inside/outside diameter of 53/56 mm and a total surface area of 4,410 mm2. For femoral fixation of the spacer stem, we have developed the “glove” technique. A sterile glove is placed in the proximal femur, and the fingers are bound together with a vicryl suture. After preparing the same mixture as used for the spacer (40 g), the doughy bone cement is now introduced into the glove (Figure 3). Afterwards, the intraoperatively prepared spacer is inserted into the cement-filled glove (Figure 4). Figure 3. The antibiotic-loaded bone cement, consisting of the same mixture as the spacer, is introduced into the glove. Figure 4. Insertion of the hip spacer into the cement-filled glove. The entire construction is removed after a minimum of 2 min, yielding a spacer that is a nearly exact anatomical copy of the proximal femoral part (Figure 5). There is no risk that the spacer-glove complex will get stuck in the femur, as long as it is removed after 2 min—before the heat of polymerization has started. Figure 5. After removal of the glove, the cement mantle around the stem of the spacer shows an almost exact anatomical copy of the proximal part of the femur. The glove is removed from the cement mantle around the spacer’s stem. Following the reinsertion of the stem (Figure 6), the remaining doughy cement is used for punctual fixation onto the femoral resection surface. After the cement has hardened, the spacer is reduced (Figure 7). For implantation of an acetabular spacer, this is normally cemented. We do not consider that it is necessary to use the glove technique also for the acetabular component because if a dislocation occurs, this happens on the femoral side. To our knowledge, there have been no reports about dislocation of an acetabular spacer and we have not seen any such case in our department. Figure 6. Reinsertion of the spacer into the femur. Figure 7. Articulating hip spacer fixed according to the “glove technique” in situ. Discussion The major factors that may influence the risk of dislocation of a hip spacer include the spacer’s geometry and its cervicodiaphyseal angle, the means of production (manually shaped vs. standard fit), the method of fixation to the proximal femur, and residual bone deficits of the acetabulum—to which the shape or size of the spacer cannot adapt. Despite the wide use of hip spacers and an estimated dislocation rate of 10–20%, there is no consensus on the ideal femoral fixation method. There is controversial data in the literature regarding hip spacer dislocations. Leunig et al. (1998) reported dislocations of the hip in 5 of 12 patients after implantation of a hand-made spacer. The authors showed that with regard to the geometry a relatively small spacer femoral neck/head ratio should be aimed for ( 57 mm). Magnan et al. (2001) and Duncan et al. (1993) described 1/10 and 3/13 dislocations, respectively, after implantation of a standardized spacer. On the contrary, Ries and Jergesen (1999), Koo et al. (2001), Shin et al. (2002), and Takahira et al. (2003) did not observe any spacer dislocation in their respective series. Despite the fact that there have been numerous reports about dislocations after hip spacer implantation, the precise method of fixation is often not well and accurately described in the literature. Although a proximal cementation of the spacer to the femur might preserve leg length and prevent any rotation compared to the “press-fit” method, there have been no studies showing which one of the two methods is superior. However, one possible disadvantage of normal cementation of a hip spacer may be that the cement can leach through the pre-drilled femoral canal so that difficulties can occur at the spacer explantation later, due to the cement removal. The “glove” technique allows spacer explantation in one piece without cement debris, thus reducing both mechanical complications and operating time. Over the past 7 years, we have observed that the “glove” technique gives a lower dislocation rate than the “press-fit” method, and that it allows a shorter reimplantation time compared with the “normal” cementation because no cement debris has to be removed from the femoral canal (unpublished data). Based on these observations, this technique has become a standard procedure in our department. Moreover, another advantage is that this technique can also be used for other, commercially available hip spacers such as the Spacer G or those made by using the Biomet silicon molds.

Two-stage treatment protocol for isolated septic acetabular cup loosening.

The aim of this study was to evaluate the treatment of isolated septic acetabular cup loosening without involvement of the prosthesis stem by insertion of an antibiotic-loaded spacer head and stem retention. Between 1999 and 2008, 13 patients (5 men, 8 women, mean age 69 years) were treated according to this regimen. S. epidermidis and S. aureus were the two most commonly identified pathogens. In 12 cases the polymethylmethacrylate spacers were impregnated with 0.5 g gentamicin + 2 g vancomycin per 40 g bone cement, except in one patient with vancomycin allergy, in whom 0.5 g gentamicin + 0.4 g teicoplanin were used. The spacers acted as hemiarthroplasties. The mean spacer head implantation time was 88 (35–270) days. At a mean follow-up of 55 (12–83) months, infection eradication was achieved in 11 out of 12 cases (91.6%). Complications included a draining sinus, and one spacer and one definitive prosthesis dislocation. One patient died after reimplantation due to cardiopulmonary decompensation.