Comprehensive meta-analysis of antibiotic-impregnated bone cement versus plain bone cement in primary total knee arthroplasty for preventing periprosthetic joint infection

PurposeAntibiotic-loaded bone cement (ALBC) was usually used to prevent periprosthetic joint infection (PJI) in primary total knee arthroplasty (PTKA), but whether to use ALBC or plain bone cement in PTKA remains unclear. We aimed to compare the occurrence rate of PJI using two different cements, and to investigate the efficacy of different antibiotic types and doses administered in preventing surgical site infection (SSI) with ALBC.MethodsThe availability of ALBC for preventing PJI was evaluated by using a systematic review and meta-analysis referring to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Existing articles until December 2021 involving PTKA patients with both ALBC and plain bone cement cohorts were scanned by searching “total knee arthroplasty”, “antibiotic-loaded cement”, “antibiotic prophylaxis”, “antibiotic-impregnated cement” and “antibiotic-laden cement” in the database of PubMed/MEDLINE, Embase, Web of Science and the Cochrane Library. Subgroup analysis included the effectiveness of different antibiotic types and doses in preventing SSI with ALBC. The modified Jadad scale was employed to score the qualities of included articles.ResultsEleven quantitative studies were enrolled, including 34,159 knees undergoing PTKA. The meta-analysis results demonstrated that the use of prophylactic ALBC could significantly reduce the prevalence of deep incisional SSI after PTKA, whereas there was no significant reduction in the rate of superficial incisional SSI. Moreover, gentamicin-loaded cement was effective in preventing deep incisional SSI, and the use of high-dose ALBC significantly reduced the rate of deep incisional SSI after PTKA. Besides, no significant adverse reactions and complications were stated during the use of ALBC in PTKA.ConclusionThe preventive application of ALBC during PTKA could reduce the rates of deep PJI. Furthermore, bone cement containing gentamicin and high-dose ALBC could even better prevent deep infection after PTKA. However, the existing related articles are mostly single-center and retrospective studies, and further high-quality ones are needed for confirmation.     

How do porosity-inducing techniques affect antibiotic elution from bone cement? An in vitro comparison between hydrogen peroxide and a mechanical mixer

Background Increasing the porosity of an antibiotic-loaded cement spacer increases the antibiotic elution, but the correlation between porosity and antibiotic elution is not well documented. The purposes of this study was to attempt new porosity-increasing methods and to investigate the correlation between antibiotic elution and both total and surface porosity. Materials and methods Five types of antibiotic-loaded bone cement (ALBC) using 2 g cefazolin and 40 g cement were prepared. Other than manual mixing, hydrogen peroxide was used as a foaming agent and a mixing drill piece was used as a mechanical device to try to induce porosity when mixing the cement. Elution of antibiotic into phosphate-buffered saline was measured from 1 h to 1 week. Surface porosity was calculated from density values which were measured with a density kit and an electronic balance, while total porosity was quantified using micro-computed tomography. Results When a mixing drill piece was used to induce porosity, we observed a significant increasin antibiotic elution compared to a manually mixed ALBC. On the other hand, hydrogen peroxide reduced the elution significantly. Mild correlation between the total amount of cluted in 1 week antibiotic elution and total porosity was observed. Conclusions In terms of improving elution, the mixing drill piece seemed to be efficient. A relationship between surface porosity and elution efficacy was not observed.     

Antibiotic elution from acrylic bone cement loaded with high doses of tobramycin and vancomycin

Two‐stage revision treatment of prosthetic joint infection (PJI) frequently employs the use of a temporary bone cement spacer loaded with multiple antibiotic types. Tobramycin and vancomycin are commonly used antibiotics in cement spacers, however, there is no consensus on the relative concentrations and combinations that should be used. Therefore, the purpose of this study was to investigate the influence of dual antibiotic loading on the total antibiotic elution and compressive mechanical properties of acrylic bone cement. Varying concentrations of tobramycin (0–3 g) and vancomycin (0–3 g) were added either alone or in combination to acrylic cement (Palacos R), resulting in 12 experimental groups. Samples were submerged in 37°C saline for 28 d and sampled at specific time points. The collected eluent was analyzed to determine the cumulative antibiotic release. In addition, the cement's compressive mechanical properties and porosity were characterized. Interestingly, the cement with the highest concentration of antibiotics did not possess the best elution properties. Cement samples containing both 3 g of tobramycin and 2 g vancomycin demonstrated the highest cumulative antibiotic release after 28 d, which was coupled with a significant decrease in the mechanical properties and an increased porosity. The collected data also suggests that tobramycin elutes more effectively than vancomycin from cement. In conclusion, this study demonstrates that high antibiotic loading in cement does not necessarily lead to enhanced antibiotic elution. Clinically this information may be used to optimize cement spacer antibiotic loading so that both duration and amount of antibiotics eluted are optimized. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1078–1085, 2018.

     

Use and duration of antibiotic prophylaxis and the rate of urinary tract infection after radical cystectomy for bladder cancer: Results of a multicentric series

Objectives

To assess the rate of urinary tract infection (UTI), the characteristics of the bacterial aetiological agents involved, the type and duration of antibiotics used, and the clinical risk factors of UTI in a multi-institutional cohort of patients who had undergone radical cystectomy (RC).

Vancomycin prophylaxis for revision hip arthroplasty in penicillin and cephalosporin sensitive patients: Is dose adjustment necessary in accordance with blood loss and fluid replacement?

ObjectiveThe aims of this study were (1) to investigate the changes in the serum concentration of prophylactically administrated vancomycin in the perioperative period of revision hip arthroplasty in penicillin/cephalosporin-allergic patients, (2) to assess whether the postoperative re-administration of vancomycin is needed, and (3) to determine the relationships of vancomycin serum concentration with blood loss, body weight, and fluid replacement in such patients.MethodsThis study consisted of 29 patients (20 females, 9 males; mean age=63.3 years; age range=45–79 years) with a history of penicillin/cephalosporin allergy undergoing revision hip arthroplasty secondary to aseptic loosening or periprosthetic fractures. Serum vancomycin levels were measured (1) before administration of vancomycin, (2) at the time of skin incision, (3) every 1,5 hours thereafter until the end of the operation, (4) during the skin closure, and (5) after three and 12 hours from the initial dosage. Data regarding body weight, amounts of intraoperative blood loss, fluid and blood replacements and postoperative wound drainage were recorded.ResultsThe average blood loss, fluid replacement, and drain volume were 1280.3±575.8 (500–2700) mL, 2922.6±768.8 (1700–4600) mL, and 480.2±163.7 (200–850) mL, respectively. The mean levels of serum vancomycin were 46.3±21.8 (14.1–80.7) mg/L at the time of skin incision, 17.9±4.7 (9.4–30.9) and 9.8±2.2 (4.3–13.8) mg/L after 1.5 and 3 hours from the beginning of the surgery and 5.1±1.1 (2.9–6.8)mg/L after 12th hour postoperatively. The measured vancomycin levels were below the effective serum concentrations (< 5 mg/L) for 18 patients at 12 hours the administration of the first dose. A moderate level negative correlation between the blood loss/body weight ratio and vancomycin levels was found (p=0.004, r=−0.493). Predictive ROC curve analysis resulted in determining a blood loss volume higher than 1150 ml and a blood loss/body weight ratio higher than 18,5 is significant to estimate the vancomycin level below the minimum effective serum level at 12th hour postoperatively (AUC=0.793±0.16, p=0.009, AUC=0.753) 26±0.12, p=0.025, respectively).ConclusionEvidence from this study has indicated vancomycin concentration at 12th hour is below the effective level in most patients. Thus, earlier repetitive infusion of vancomycin seems to be necessary in penicillin/cephalosporin-allergic patients undergoing revision hip arthroplasty, especially in those with high blood loss.Level of EvidenceLevel III, Therapeutic Study     

Use of antibiotic cement rod to treat intramedullary infection after nailing: preliminary study in 19 patients

The treatment of intramedullary infections after nailing usually includes removal of the nail, debridement, and, in some cases, insertion of antibiotic-impregnated cement beads. We use this self-made antibiotic cement rod to treat intramedullary infections. Compared with the beads, it provides some limited mechanical support and can be preserved in the canal for a long time. We reviewed 19 infected patients who underwent removal of the nails, excision of sinus tracks, debridement of the canal and insertion of the rods. No recurrent infection occurred in 18 cases and 11 cases achieved bone healing, 6 cases achieved partial union. One patient had nonunion and one patient underwent amputation because of severe primary trauma and long-term infection. The rod was removed between 35 and 123 days after implantation. We conclude that the antibiotic cement rods could be a relatively effective, simple and inexpensive method of treating intramedullary infections after nailing.     

An articulated antibiotic spacer used for infected total knee arthroplasty: a comparative in vitro elution study of Simplex and Palacos bone cements.

For the staged management of infected total knee arthroplasty (TKA), antibiotic laden polymethylmethacrylate (PMMA) spacers have been recommended. Antibiotic-impregnated PMMA spacers target drug delivery, achieving high local levels while limiting the potential for host toxicity associated with parenteral antimicrobial therapy. This study examined the elution characteristics of an articulating PMMA TKA spacer that has been useful clinically. Tobramycin and vancomycin are both active against many organisms leading to joint infections. We used various combined antibiotic concentrations (maintaining a relative ratio of 55% tobramycin to 45% vancomycin w/w), and then assayed the elution profile of the TKA spacer in vitro. Additionally, the elution qualities of two brands of bone cement, Simplex and Palacos, were compared. Briefly, three groups of PMMA spacers, impregnated with different antibiotic loads, were fashioned from a mold replicating a femoral TKA component. The entire spacer surface area was immersed in sterile phosphate buffered saline (PBS) in a 1:6 ratio of grams of cement to milliliters of PBS and incubated at 37 degrees C for 24 h. After 24 h, aliquot eluates were taken, the PBS discarded, and replaced with fresh, sterile PBS. PBS was changed daily and an aliquot was taken at least weekly for nine weeks. Eluate samples were stored at -70 degrees C until assayed. Each spacer eluate sample's antibiotic concentration was determined by disc diffusion bioassay against Bacillus subtilis. Mean zone inhibition diameters were extrapolated from the standard curve to yield micrograms per milliliter of antibiotic in PBS. In all groups the Palacos spacers demonstrated higher elution levels, above the MIC for the organism used, for a longer period of time than those made with Simplex. Based on the observed elution profiles, antibiotic-impregnated Palacos bone cement may offer a more effective vehicle for local drug delivery during staged treatment of infected TKA.     

High concentration and bioactivity of vancomycin and aztreonam eluted from Simplex cement spacers in two-stage revision of infected hip implants: a study of 46 patients at an average follow-up of 107 days.

This study investigated the release of antibiotics in vivo, from an articulating polymethylmethacrylate (PMMA) spacer used in two-stage revision arthroplasty of infected hip implants. Forty-six patients who underwent two-stage revision hip arthroplasty for infections were managed with an interim PMMA spacer loaded with a high dose of vancomycin and aztreonam. Serum and aliquots of drainage collected after the first-stage surgery, and joint fluid obtained at the time of the second-stage surgery were analyzed for antibiotic concentrations by high performance liquid chromatography and bioactivity by tube dilution bioassay. Following implantation, the highest levels of antibiotics were measured in aliquots of drainage on the first day (vancomycin: 1538.0 +/- 243.6 microg/mL; aztreonam: 1003.5 +/- 323.5 microg/mL), decreasing to 571.9 +/- 169.4 microg/mL for vancomycin and 313.6 +/- 88.3 microg/mL for aztreonam after 7 days. Antibiotic concentrations in serum were very low (vancomycin: 0.58 +/- 0.2 microg/mL, range: 0.1-1.6 microg/mL; aztreonam: 0.46 +/- 0.3 microg/mL, range: 0.1-0.9 microg/mL at 24 h) and there was no systemic adverse effect. At a mean 107 days after the first-stage surgery, the concentrations of antibiotics in joint fluid were well above the minimal inhibitory concentration of most common microorganisms. The released antibiotics were bioactive against the test organisms. Based on the observed results, we confirmed the safety and effectiveness of in vivo drug delivery from antibiotic-impregnated PMMA hip spacers.