In-Vitro and In-Vivo Models for the Study of Prosthetic Joint Infections

2021 ◽  
pp. 41-47
Author(s):  
Nicholas Mannering ◽  
Raj Narulla ◽  
Benjamin Lenane
Keyword(s):  
In Vivo Models ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

Determining Optimal Current Intensity and Duration for Electrically Activated Silver-Based Prophylactic Hip Implant Prototype Design

2013 ◽  
Author(s):  
Zhuo Tan ◽  
Rohan A. Shirwaiker ◽  
Paul E. Orndoff
Keyword(s):  
Joint Infections ◽  
Main Challenge ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Optimal Current ◽  
Actual Design ◽  
Potential Benefits ◽  
The Cost

Infections associated with medical prostheses result in notable morbidity, and traditional osteomyelitis treatments are often accompanied by high risk and cost. The probability of prosthetic joint infections is 1–2.5 % for primary hip or knee replacements and 2.1–5.8 % for revision surgeries, and the cost of treating such an infection is estimated to be over $50,000 per episode. [1] While the potential benefits of silver surfaces stimulated by low intensity direct current (LIDC) have been discussed in literature, we have recently utilized that concept in the actual design of prophylactic indwelling residual hardware prostheses for the very first time. [2–4] A modular titanium hip stem coated with silver at the anode (and titanium as the cathode) and activated by a watch battery encapsulated within the two electrode modules (Figure 1) will result in oligodynamic iontophoresis (OI) in the soft tissue surrounding the implant which is prone to infections. Preliminary in vitro and in vivo results have demonstrated the potency of silver-based OI as an effective local antibacterial therapy in osteomyelitis treatment with advantages over various antibiotics. However, the main challenge here is achieving the antibacterial potency while minimizing any potential toxic effects on local tissues. [4]

scholarly journals Controlling Antibiotic Release from Polymethylmethacrylate Bone Cement

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 26
Author(s):  
Victoria Wall ◽  
Thi-Hiep Nguyen ◽  
Nghi Nguyen ◽  
Phong A. Tran
Keyword(s):  
Bone Cement ◽  
Joint Infections ◽  
Current State ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Bone Void

Bone cement is used as a mortar for securing bone implants, as bone void fillers or as spacers in orthopaedic surgery. Antibiotic-loaded bone cements (ALBCs) have been used to prevent and treat prosthetic joint infections by providing a high antibiotic concentration around the implanted prosthesis. High antibiotic concentrations are, on the other hand, often associated with tissue toxicity. Controlling antibiotic release from ALBCS is key to achieving effective infection control and promoting prosthesis integration with the surrounding bone tissue. However, current ALBCs still need significant improvement in regulating antibiotic release. In this review, we first provide a brief introduction to prosthetic joint infections, and the background concepts of therapeutic efficacy and toxicity in antibiotics. We then review the current state of ALBCs and their release characteristics before focusing on the research and development in controlling the antibiotic release and osteo-conductivity/inductivity. We then conclude by a discussion on the need for better in vitro experiment designs such that the release results can be extrapolated to predict better the local antibiotic concentrations in vivo.

scholarly journals Dalbavancin for the Treatment of Prosthetic Joint Infections: A Narrative Review

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 656
Author(s):  
Luis Buzón-Martín ◽  
I. Zollner-Schwetz ◽  
Selma Tobudic ◽  
Emilia Cercenado ◽  
Jaime Lora-Tamayo
Keyword(s):  
Joint Infection ◽  
Experimental Models ◽  
Narrative Review ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Wide Range ◽  
Prosthetic Joint Infections ◽  
Pharmacokinetic Properties

Dalbavancin (DAL) is a lipoglycopeptide with bactericidal activity against a very wide range of Gram-positive microorganisms. It also has unique pharmacokinetic properties, namely a prolonged half-life (around 181 h), which allows a convenient weekly dosing regimen, and good diffusion in bone tissue. These features have led to off-label use of dalbavancin in the setting of bone and joint infection, including prosthetic joint infections (PJI). In this narrative review, we go over the pharmacokinetic and pharmacodynamic characteristics of DAL, along with published in vitro and in vivo experimental models evaluating its activity against biofilm-embedded bacteria. We also examine published experience of osteoarticular infection with special attention to DAL and PJI.

scholarly journals Rifampin Combination Therapy for Nonmycobacterial Infections

2010 ◽  
Vol 23 (1) ◽  
pp. 14-34 ◽  
Author(s):  
Graeme N. Forrest ◽  
Kimberly Tamura
Keyword(s):  
Combination Therapy ◽  
Prosthetic Heart Valve ◽  
Case Series ◽  
Source Control ◽  
Retrospective Case ◽  
Coagulase Negative Staphylococci ◽  
Joint Infections ◽  
Prosthetic Joint Infections

SUMMARY The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.

scholarly journals Antimicrobial Activity of Dalbavancin and Comparator Agents Tested against Gram-Positive Clinical Isolates Causing Bone and Joint Infections in United States (US) Medical Centers (2011–2016)

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S373-S373
Author(s):  
Helio S Sader ◽  
Rodrigo E Mendes ◽  
Robert K Flamm ◽  
Michael A Pfaller
Keyword(s):  
Active Agent ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Joint Infections ◽  
Bone And Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Viridans Group Streptococci ◽  
Research Grant

Abstract Background Bone and joint infections (BJI) comprise a series of disorders, including septic arthritis, osteomyelitis, and prosthetic joint infections. We evaluated the activity of dalbavancin (DALBA) against pathogens isolated from BJI in US hospitals. Methods A total of 744 organisms collected from 55 hospitals in 2011–2016 were evaluated, including 463 S. aureus, 88 coagulase-negative staphylococci (CoNS), 104 β-haemolytic streptococci (BHS), 60 E. faecalis, and 29 viridans group streptococci (VGS). Bacteria were identified by standard algorithms and MALDI-TOF-MS. Susceptibility testing was performed by CLSI methods (M07-A10); interpretation of MIC results used CLSI (2017) and EUCAST (2017) criteria. Results S. aureus (62.2%) was the most common pathogen associated with BJI, followed by BHS (14.0%) and CoNS (11.8%). All S. aureus (41.5% methicillin-resistant [MRSA]) isolates were susceptible (S) to DALBA, linezolid (LNZ), teicoplanin (TEI) and vancomycin (VAN), while daptomycin (DAPTO) and clindamycin (CLI) showed susceptibility rates of 99.8% and 87.7% (CLSI), respectively. DALBA MIC results (MIC50/90, ≤0.03/0.06 μg/mL) were ≥8-fold lower compared with DAPTO (MIC50/90, 0.25/0.5 μg/mL) against all S. aureus. Among CoNS, (61.4% MRSA), DALBA (MIC50/90, ≤0.03/0.06 μg/mL) was the most potent agent, followed by DAPTO (MIC50/90, 0.25/0.5 μg/mL), LNZ (MIC50/90, 0.5/1 μg/mL), and VAN (MIC50/90, 1/2 μg/mL). DALBA inhibited all E. faecalis isolates at ≤0.25 μg/mL (FDA S breakpoint), except for 3 VAN-resistant (VanA) isolates. High susceptibility rates for ampicillin (98.3%; CLSI), DAPTO (100.0%), LNZ (100.0%), TEI (93.3%) and VAN (93.3%) were obtained against E. faecalis. DALBA, DAPTO, LNZ, ceftriaxone, penicillin, and VAN were active against all BHS (100.0%S), while DALBA (MIC50/90, ≤0.03/0.06 μg/mL; 100.0%S) was the most active agent against VGS, inhibiting all isolates at ≤0.06 μg/mL. Ceftriaxone, LNZ, DAPTO, and VAN were also active against VGS (93.1 – 100.0%S; CLSI), whereas CLI (82.8%S) had marginal activity. Conclusion DALBA demonstrated potent in vitro activity against common gram-positive isolates causing BJI (2011–2016) and appears to be a viable candidate for treating BJI/osteomyelitis caused by gram-positive cocci. Disclosures H. S. Sader, Allergan: Research Contractor, Research grant; R. E. Mendes, Allergan: Research Contractor, Research grant; R. K. Flamm, Allergan: Research Contractor, Research grant; M. A. Pfaller, Allergan: Research Contractor, Research grant

scholarly journals Vancomycin-Rifampin Combination Therapy Has Enhanced Efficacy against an Experimental Staphylococcus aureus Prosthetic Joint Infection

2013 ◽  
Vol 57 (10) ◽  
pp. 5080-5086 ◽  
Author(s):  
Jared A. Niska ◽  
Jonathan H. Shahbazian ◽  
Romela Irene Ramos ◽  
Kevin P. Francis ◽  
Nicholas M. Bernthal ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Combination Therapy ◽  
Mouse Model ◽  
Antibiotic Therapy ◽  
Joint Infection ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Implant Retention

ABSTRACTTreatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in whichStaphylococcus aureuswas inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention.In vivobioluminescence imaging,ex vivoCFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuablein vivopreclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects.

scholarly journals Effect of Sonication on the Elution of Antibiotics from Polymethyl Methacrylate (PMMA)

2017 ◽  
Vol 2 (4) ◽  
pp. 208-212 ◽  
Author(s):  
Anne Kummer ◽  
Ulrika Furustrand Tafin ◽  
Olivier Borens
Keyword(s):  
Polymethyl Methacrylate ◽  
Bacterial Growth ◽  
False Negative ◽  
Clinical Results ◽  
Two Stage ◽  
Negative Results ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

Abstract. Background: In the setting of prosthetic joint infections treated with a two-stage procedure, spacers can be sonicated after removal. We hypothesize that the sonication process may cause an increased elution of antibiotics from the spacer, leading to elevated concentrations of antibiotics in the sonication fluid inhibiting bacterial growth. We aimed to evaluate in vitro the influence of sonication on the elution of antibiotics from polymethyl methacrylate (PMMA) over time and to determine whether these concentrations are above the minimum inhibitory concentrations (MIC) for microorganisms relevant in prosthetic joint infections.Methods: PMMA blocks impregnated with vancomycin, fosfomycin, gentamicin or daptomycin were incubated in phosphate-buffered saline (PBS) at 37°C for up to 6 weeks. PBS was changed once a week. Concentrations were determined from samples of each antibiotic every week, and after 5 minutes of sonication at 2, 4 and 6 weeks.Results: With sonication there was a trend toward an increase of the elution of antibiotics. This increase was significant for vancomycin at 2 and 4 weeks (p=0.008 and 0.002 respectively) and for fosfomycin at 2 weeks (p=0.01).Conclusion: The effect of sonication could play a role in clinical results, especially for daptomycin and gentamicin for which the MIC is close to the concentration of antibiotics at 4 and 6 weeks.We conclude that elution of antibiotics from PMMA along with the effect of sonication could inhibit bacterial growth from spacers, resulting in false negative results in the setting of two-stage exchange procedures for prosthetic joint infections.

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