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Keywords = Copal G+V

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13 pages, 1092 KiB  
Article
In Vivo Antibiotic Elution and Inflammatory Response During Two-Stage Total Knee Arthroplasty Revision: A Microdialysis Pilot Study
by Julika Johanna Behrens, Alexander Franz, Frank Alexander Schildberg, Markus Rudowitz, Stefan Grote and Frank Sebastian Fröschen
Antibiotics 2025, 14(8), 742; https://doi.org/10.3390/antibiotics14080742 - 24 Jul 2025
Viewed by 308
Abstract
Introduction: Two-stage revision with an antibiotic-loaded, temporary static cement spacer is a common treatment for periprosthetic joint infection (PJI) of the knee. However, limited data exists on in vivo antibiotic elution kinetics after spacer implantation. This pilot study uses the technique of [...] Read more.
Introduction: Two-stage revision with an antibiotic-loaded, temporary static cement spacer is a common treatment for periprosthetic joint infection (PJI) of the knee. However, limited data exists on in vivo antibiotic elution kinetics after spacer implantation. This pilot study uses the technique of microdialysis (MD) to collect intra-articular knee samples. The aim was to evaluate MD as an intra-articular sampling method to detect spacer-eluted antibiotics within 72 h after surgery and to determine whether they show specific elution kinetics. Methods: Ten patients (six male, four female; age median 71.5 years) undergoing two-stage revision for knee PJI were included. A MD catheter was inserted into the joint during explantation of the infected inlying implant and implantation of a custom-made static spacer coated with COPAL cement (0.5 g gentamicin (G) and 2 g vancomycin (V)). Over 72 h postoperatively, samples were collected and analyzed for spacer-eluted antibiotics, intravenously administered antibiotics (e.g., cefazolin and cefuroxime), metabolic markers (glucose and lactate), and Interleukin-6 (IL-6). Local and systemic levels were compared. Results: All catheters were positioned successfully and well tolerated for 72 h. Antibiotic concentrations in MD samples peaked within the first 24 h (G: median 9.55 µg/mL [95% CI: 0.4–17.36]; V: 37.57 µg/mL [95% CI: 3.26–81.6]) and decreased significantly over 72 h (for both p < 0.05, G: 4.27 µg/mL [95% CI: 2.26–7.2]; V: 9.69 µg/mL [95% CI: 3.86–24]). MD concentrations consistently exceeded blood levels (p < 0.05), while intravenously administered antibiotics showed higher blood concentrations. Glucose in MD samples decreased from 17.71 mg/dL to 0.89 mg/dL (p < 0.05). IL-6 and lactate concentrations showed no difference between MD and blood samples. Conclusions: Monitoring antibiotics eluted by a static spacer with intra-articular MD for 72 h is feasible. Gentamicin and vancomycin levels remained above the minimal inhibitory concentration. Differentiating infection from surgical response using metabolic and immunological markers remains challenging. Prolonged in vivo studies with MD are required to evaluate extended antibiotic release in two-stage exchanges. Full article
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18 pages, 2298 KiB  
Article
High and Low Dosage of Vancomycin in Polymethylmethacrylate Cements: Efficacy and Mechanical Properties
by Jeffrey W. Kwong, Michael Abramowicz, Klaus Dieter Kühn, Christian Foelsch and Erik N. Hansen
Antibiotics 2024, 13(9), 818; https://doi.org/10.3390/antibiotics13090818 - 28 Aug 2024
Cited by 6 | Viewed by 1671
Abstract
Introduction: Prosthetic joint infections (PJIs) are difficult to treat and represent a significant burden to the healthcare system. Two-stage revision surgery with placement of an antibiotic-loaded cement spacer is currently the gold standard for treatment in the United States for late-onset infections. We [...] Read more.
Introduction: Prosthetic joint infections (PJIs) are difficult to treat and represent a significant burden to the healthcare system. Two-stage revision surgery with placement of an antibiotic-loaded cement spacer is currently the gold standard for treatment in the United States for late-onset infections. We evaluate the efficacy of varying doses of vancomycin added to antibiotic-containing acrylic cement spacers and discuss the biomechanical and antimicrobial properties of using high versus low doses of vancomycin in cement spacers in the hip and knee. Materials and Methods: Commercially available Copal cement containing either gentamicin and clindamycin (G + C) or gentamicin and vancomycin (G + V) was prepared with the manual addition of low (2 g) and high (6 g) doses of vancomycin. In vitro mechanical testing was then carried out according to ISO 5833 and DIN 53435, as well as inhibition zone assays against common PJI pathogens. Additionally, inhibition zone assays were conducted on two commercially available prefabricated spacers containing gentamicin: Copal Exchange G and Cemex Spacer-K. Results: In biomechanical testing, Copal G + V with the addition of 6 g of vancomycin failed to meet the ISO standard. Copal G + C and Copal G + V with low and high dosages of vancomycin were all effective against the tested pathogens and displayed constant efficacy for a duration of 42 days. High doses of vancomycin showed significantly lower mechanical stability. Moreover, Copal Exchange G showed significantly larger inhibition zones across 42 days. Discussion: While higher concentrations of vancomycin appear to improve the antimicrobial efficacy of cement, they also reduce its mechanical stability. Despite its smoother surface, the Copal Exchange G spacer exhibits large inhibition zones after 1 day and maintains consistently large inhibition zones over 6 weeks. Thus, it may be preferred for use in two-stage revision surgery. Conclusion: Copal Exchange G is more effective than Cemex Spacer K against S. aureus and E. coli. The manual addition of vancomycin to cement containing double antibiotics is very effective. The influence on ISO compression is low, the ISO bending modulus is increased, and ISO bending, DIN bending, and DIN impact, are reduced. Full article
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12 pages, 3002 KiB  
Article
Impact of Manual Addition of Vancomycin to Polymethylmethacrylate (PMMA) Cements
by Clemens Kittinger, Michael Eder-Halbedl and Klaus Dieter Kühn
Antibiotics 2024, 13(8), 721; https://doi.org/10.3390/antibiotics13080721 - 1 Aug 2024
Cited by 1 | Viewed by 1359
Abstract
(1) Background: The addition of antibiotics to bone cements is a common practice in the treatment of periprosthetic joint infections. In revision cases, the amount and type of antibiotic is often insufficient and additional antibiotics must be added. The addition, however, changes the [...] Read more.
(1) Background: The addition of antibiotics to bone cements is a common practice in the treatment of periprosthetic joint infections. In revision cases, the amount and type of antibiotic is often insufficient and additional antibiotics must be added. The addition, however, changes the product itself, and the surgeon becomes the “manufacturer” of the bone cement. PMMAe wished to clarify whether the admixture of antibiotics changes the mechanical stability of the bone cements used and if the added antibiotics were still functional and released in sufficient quantities. (2) Methods: We compared two industrially manufactured vancomycin-containing PMMA cements; the low-viscous VancogenX® (TECRES, Sommacampagna, Italy) and the high-viscous Copal® G+V (Heraeus Medical GmbH, Wehrheim, Germany), with two PMMA cements loaded with aminoglycosides, to which 2.0 g of vancomycin (Hexal CT1631) were manually added—the high-viscous Smartset® GHV and the medium-viscous Antibiotic Simplex with Tobramycin (antibiotic Simplex® T). Test specimens of the bone cements were used to determine mechanical stability (bending strength and bending module), and the release of the antibiotics was determined by HLPC and modified Kirby–Bauer assays. (3) Results: All tested bone cements showed an initial high release within the first hours. Repeated testing after 24 h showed a reduced efficacy of VancogenX® and Smartset® GHV in Kirby–Bauer assays. Long-time release over days showed a release of functional antimicrobial active ingredients over this period of time in anti-microbial assays, but no activity of VancogenX® from day 21 onward. No significant differences in the ISO bending modules could be detected, but in contrast to the bending module, the ISO bending strength was substantially reduced by 10–15 mPal in comparison to both cements of the reference group. The Simplex®T met just the ISO 5833; the Smartset® GHV did not after adding vancomycin. (4) Conclusions: In conclusion, the manual addition of 2 g of vancomycin to 40 g of PMMA powder is recommended for the treatment of methicillin-resistant staphylococci. Vancomycin is released over a period of 42 days with concentrations above the MIC for typical staphylococci. The mechanical properties of the PMMA just met, or did not fulfill, ISO mechanical specification. Copal® G+V showed a better elution than VancogenX® over time. Full article
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14 pages, 3106 KiB  
Article
Development of a Galleria mellonella Infection Model to Evaluate the Efficacy of Antibiotic-Loaded Polymethyl Methacrylate (PMMA) Bone Cement
by You Zhao, Gopala Krishna Mannala, Raphaëlle Youf, Markus Rupp, Volker Alt and Martijn Riool
Antibiotics 2024, 13(8), 692; https://doi.org/10.3390/antibiotics13080692 - 25 Jul 2024
Cited by 1 | Viewed by 1887
Abstract
Prosthetic joint infections (PJIs) can have disastrous consequences for patient health, including removal of the device, and placement of cemented implants is often required during surgery to eradicate PJIs. In translational research, in vivo models are widely used to assess the biocompatibility and [...] Read more.
Prosthetic joint infections (PJIs) can have disastrous consequences for patient health, including removal of the device, and placement of cemented implants is often required during surgery to eradicate PJIs. In translational research, in vivo models are widely used to assess the biocompatibility and antimicrobial efficacy of antimicrobial coatings and compounds. Here, we aim to utilize Galleria mellonella implant infection models to assess the antimicrobial activity of antibiotic-loaded bone cement (ALBC) implants. Therefore, we used commercially available bone cement loaded with either gentamicin alone (PALACOS R+G) or with a combination of gentamicin and vancomycin (COPAL G+V), compared to bone cement without antibiotics (PALACOS R). Firstly, the in vitro antimicrobial activity of ALBC was determined against Staphylococcus aureus. Next, the efficacy of ALBC implants was analyzed in both the G. mellonella hematogenous and early-stage biofilm implant infection model, by monitoring the survival of larvae over time. After 24 h, the number of bacteria on the implant surface and in the tissue was determined. Larvae receiving dual-loaded COPAL G+V implants showed higher survival rates compared to implants loaded with only gentamicin (PALACOS R+G) and the control implants without antibiotics (PALACOS R). In conclusion, G. mellonella larvae infection models with antibiotic-loaded bone cements are an excellent option to study (novel) antimicrobial approaches. Full article
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15 pages, 641 KiB  
Article
Effect of Multiantibiotic-Loaded Bone Cement on the Treatment of Periprosthetic Joint Infections of Hip and Knee Arthroplasties—A Single-Center Retrospective Study
by Benedikt Paul Blersch, Florian Hubert Sax, Moritz Mederake, Sebastian Benda, Philipp Schuster and Bernd Fink
Antibiotics 2024, 13(6), 524; https://doi.org/10.3390/antibiotics13060524 - 3 Jun 2024
Cited by 4 | Viewed by 2116
Abstract
Background: Two-stage septic revision is the prevailing method for addressing late periprosthetic infections. Using at least dual-antibiotic-impregnated bone cement leads to synergistic effects with a more efficient elution of individual antibiotics. Recent data on the success rates of multiantibiotic cement spacers in two-stage [...] Read more.
Background: Two-stage septic revision is the prevailing method for addressing late periprosthetic infections. Using at least dual-antibiotic-impregnated bone cement leads to synergistic effects with a more efficient elution of individual antibiotics. Recent data on the success rates of multiantibiotic cement spacers in two-stage revisions are rare. Methods: We conducted a retrospective follow-up single-center study involving 250 patients with late periprosthetic hip infections and 95 patients with prosthetic knee infections who underwent septic two-stage prosthesis revision surgery between 2017 and 2021. In accordance with the antibiotic susceptibility profile of the microorganisms, a specific mixture of antibiotics within the cement spacer was used, complemented by systemic antibiotic treatment. All patients underwent preoperative assessments and subsequent evaluations at 3, 6, 9, 12, 18, and 24 months post operation and at the most recent follow-up. Results: During the observation period, the survival rate after two-step septic revision was 90.7%. Although survival rates tended to be slightly lower for difficult-to-treat (DTT) microorganism, there was no difference between the pathogen groups (easy-to-treat (ETT) pathogens, methicillin-resistant staphylococci (MRS), and difficult-to-treat (DTT) pathogens). Furthermore, there were no differences between monomicrobial and polymicrobial infections. No difference in the survival rate was observed between patients with dual-antibiotic-loaded bone cement without an additional admixture (Copal® G+C and Copal® G+V) and patients with an additional admixture of antibiotics to proprietary cement. Conclusion: Employing multiple antibiotics within spacer cement, tailored to pathogen susceptibility, appears to provide reproducibly favorable success rates, even in instances of infections with DTT pathogens and polymicrobial infections. Full article
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17 pages, 2234 KiB  
Article
Daptomycin-Impregnated PMMA Cement against Vancomycin-Resistant Germs: Dosage, Handling, Elution, Mechanical Stability, and Effectiveness
by Martina Humez, Eugen Domann, Kai M. Thormann, Christian Fölsch, Rainer Strathausen, Sebastian Vogt, Volker Alt and Klaus-Dieter Kühn
Antibiotics 2023, 12(11), 1567; https://doi.org/10.3390/antibiotics12111567 - 26 Oct 2023
Cited by 7 | Viewed by 2087
Abstract
Background: The number of periprosthetic joint infections caused by vancomycin-resistant pathogens is increasing. Currently, no PMMA cement is commercially available to cover VRE. Daptomycin shows promising results in treating infection, offering a good safety profile and a reduced risk of developing resistance. The [...] Read more.
Background: The number of periprosthetic joint infections caused by vancomycin-resistant pathogens is increasing. Currently, no PMMA cement is commercially available to cover VRE. Daptomycin shows promising results in treating infection, offering a good safety profile and a reduced risk of developing resistance. The purpose of this in vitro study was to investigate the mechanical stability, handling properties, elution behavior, and antimicrobial effectiveness of PMMA cement loaded with three different daptomycin concentrations in comparison to commercially available antibiotic-loaded bone cement (ALBC). Methods: Mechanical properties and handling characteristics (ISO 5833, DIN 53435), HPLC elution, antimicrobial effectiveness with proliferation assay (DIN 17025), and inhibition zone testing were investigated. Results: All tested daptomycin concentrations met the ISO and DIN standards for mechanical strength. Loading of 40 g of PMMA cement with 0.5 g of daptomycin did not show any antimicrobial effectiveness, in contrast to 1.0 g and 1.5 g. PMMA cement with 1.5 g of daptomycin was the best in terms of elution and effectiveness, and it showed good ISO mechanical strength; ISO doughing was sticky for a little longer and setting was faster compared to the vancomycin-containing reference cement. Conclusion: PMMA cement containing 0.5 g of gentamicin and 1.5 g of daptomycin could be a good alternative to the already established COPAL® (Wehrheim, Germany) G+V for the treatment of PJIs caused by VRE. Full article
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