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 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.

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 In-Vitro Study of the Synergistic Effect of an Enzyme Cocktail and Antibiotics against Biofilms in a Prosthetic Joint Infection Model

2021 ◽  
Author(s):  
Hervé Poilvache ◽  
Albert Ruiz-Sorribas ◽  
Olivier Cornu ◽  
Françoise Van Bambeke
Keyword(s):  
Synergistic Effect ◽  
Joint Infection ◽  
In Vitro Study ◽  
Control Group ◽  
Infection Model ◽  
E Coli ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections

Prosthetic Joint Infections (PJI) are frequent complications of arthroplasties. Their treatment is made complex by the rapid formation of bacterial biofilms, limiting the effectiveness of antibiotic therapy. In this study, we explore the effect of a tri-enzymatic cocktail (TEC) consisting of an endo-1,4-β-d-glucanase, a β-1,6-hexosaminidase, and an RNA/DNA nonspecific endonuclease combined with antibiotics of different classes against biofilms of S. aureus, S. epidermidis, and E. coli grown on Ti6Al4V substrates. Biofilms were grown in TSB with 10g/L glucose and 20g/L NaCl (TGN). Mature biofilms were assigned to a control group or treated with the TEC for 30 min, then either analyzed or reincubated for 24h in TGN or TGN with antibiotics. The cytotoxicity of the TEC was assayed against MG-63 osteoblasts, primary murine fibroblasts, and J-774 macrophages using the LDH release test. The TEC dispersed 80.3 to 95.2% of the biofilms’ biomass after 30 min. The reincubation of the treated biofilms with antibiotics resulted in a synergistic reduction of the total culturable bacterial count (CFU) compared to biofilms treated with antibiotics alone in the three tested species (additional reduction from 2 to more than 3 log10 CFU). No toxicity of the TEC was observed against the tested cell lines after a 24 h of incubation. The combination of pretreatment with TEC followed by a 24 h of incubation with antibiotics had a synergistic effect against biofilms of S. aureus, S. epidermidis, and E. coli. Further studies should assess the potential of the TEC as an adjuvant therapy in in vivo models of PJI.

scholarly journals Antibiotics in Bone Cements Used for Prosthesis Fixation: An Efficient Way to Prevent Staphylococcus aureus and Staphylococcus epidermidis Prosthetic Joint Infection

2021 ◽  
Vol 7 ◽  
Author(s):  
Andréa Cara ◽  
Mathilde Ballet ◽  
Claire Hemery ◽  
Tristan Ferry ◽  
Frédéric Laurent ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Staphylococcus Epidermidis ◽  
Biofilm Formation ◽  
Joint Infection ◽  
Bone Cements ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Prosthesis Fixation

Prosthetic joint infections (PJIs) are one of the most frequent reasons for arthroplasty revision. These infections are mostly associated with the formation of biofilm, notably by staphylococci, such as Staphylococcus aureus and Staphylococcus epidermidis. To minimize the rates of PJIs following primary or revision total joint arthroplasty, antibiotic-loaded bone cements (ALBCs) can be used for prosthesis fixation. However, its use is still debated. Indeed, various studies reported opposite results. In this context, we aimed to compare the prophylactic anti-biofilm activity of ALBCs loaded with two antibiotics with ALBC loaded with only one antibiotic. We compared commercial ready-to-use cements containing gentamicin alone, gentamicin plus vancomycin, and gentamicin plus clindamycin to plain cement (no antibiotic), investigating staphylococcal biofilm formation for 10 strains of S. aureus and S. epidermidis with specific resistance to gentamicin, vancomycin, or clindamycin. Firstly, we performed disk diffusion assays with the elution solutions. We reported that only the cement containing gentamicin and clindamycin was able to inhibit bacterial growth at Day 9, whereas cements with gentamicin only or gentamicin and vancomycin lost their antibacterial activity at Day 3. Then, we observed that all the tested ALBCs can inhibit biofilm formation by methicillin-susceptible staphylococci without other antibiotic resistance ability. Similar results were observed when we tested vancomycin-resistant or clindamycin-resistant staphylococci, with some strain-dependent significant increase of efficacy for the two antibiotic ALBCs when compared with gentamicin-loaded cement. However, adding vancomycin or clindamycin to gentamicin allows a better inhibition of biofilm formation when gentamicin-resistant strains were used. Our in vitro results suggest that using commercially available bone cements loaded with gentamicin plus vancomycin or clindamycin for prosthesis fixation can help in preventing staphylococcal PJIs following primary arthroplasties, non-septic revisions or septic revisions, especially to prevent PJIs caused by gentamicin-resistant staphylococci.

scholarly journals A New Antibiotic-Loaded Sol-Gel Can Prevent Bacterial Prosthetic Joint Infection: From in vitro Studies to an in vivo Model

2020 ◽  
Vol 10 ◽  
Author(s):  
John Jairo Aguilera-Correa ◽  
Amaya Garcia-Casas ◽  
Aranzazu Mediero ◽  
David Romera ◽  
Francisca Mulero ◽  
...  
Keyword(s):  
Prosthetic Joint Infection ◽  
Joint Infection ◽  
Sol Gel ◽  
In Vitro Studies ◽  
In Vivo Model ◽  
Prosthetic Joint

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 Do Prosthetic Joint Infections Worsen the Functional Ambulatory Outcome of Patients with Joint Replacements? A Retrospective Matched Cohort Study

Antibiotics ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 872
Author(s):  
Isabel Mur ◽  
Marcos Jordán ◽  
Alba Rivera ◽  
Virginia Pomar ◽  
José Carlos González ◽  
...  
Keyword(s):  
Cohort Study ◽  
Joint Infection ◽  
Assistive Device ◽  
Matched Cohort ◽  
Knee Prostheses ◽  
Matched Cohort Study ◽  
Joint Infections ◽  
Prosthetic Joint ◽  
Prosthetic Joint Infections ◽  
Hip Arthroplasties

Objectives: To assess the effect on the functional ambulatory outcome of postoperative joint infection (PJI) cured at the first treatment attempt versus not developing PJI in patients with hip and knee prostheses. Methods: In a single-hospital retrospectively matched cohort study, each patient with PJI between 2007 and 2016 was matched on age, sex, type of prosthesis and year of implantation with two other patients with uninfected arthroplasties. The definition of a PJI cure included infection eradication, no further surgical procedures, no PJI-related mortality and no suppressive antibiotics. Functional ambulatory status evaluated one year after the last surgery was classified into four simple categories: able to walk without assistance, able to walk with one crutch, able to walk with two crutches, and unable to walk. Patients with total hip arthroplasties (THAs), total knee arthroplasties (TKAs) and partial hip arthroplasties (PHAs) were analysed separately. Results: A total of 109 PJI patients (38 TKA, 41 THA, 30 PHA) and 218 non-PJI patients were included. In a model adjusted for clinically relevant variables, PJI was associated with a higher risk of needing an assistive device for ambulation (vs. walking without aid) among THA (adjusted odds ratio (OR) 3.10, 95% confidence interval (95% CI) 1.26–7.57; p = 0.014) and TKA patients (OR 5.40, 95% CI 2.12–13.67; p < 0.001), and with requiring two crutches to walk or being unable to walk (vs. walking unaided or with one crutch) among PHA patients (OR 3.05, 95% CI 1.01–9.20; p = 0.047). Conclusions: Ambulatory outcome in patients with hip and knee prostheses with postoperative PJI is worse than in patients who do not have PJI.

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