CSA‐90 reduces periprosthetic joint infection in a novel rat model challenged with local and systemic Staphylococcus aureus

2020 ◽  
Vol 38 (9) ◽  
pp. 2065-2073 ◽  
Author(s):  
Rebecca J. Mills ◽  
Alexandra Boyling ◽  
Tegan L. Cheng ◽  
Lauren Peacock ◽  
Paul B. Savage ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Rat Model ◽  
Periprosthetic Joint Infection ◽  
Joint Infection

Phage Activity Against Planktonic and Biofilm Staphylococcus aureus Periprosthetic Joint Infection Isolates

2021 ◽  
Author(s):  
Katherine M. Caflisch ◽  
Robin Patel
Keyword(s):  
Staphylococcus Aureus ◽  
Successful Treatment ◽  
Periprosthetic Joint Infection ◽  
Joint Infection ◽  
Bacterial Isolates ◽  
Small Colony Variant ◽  
Small Colony ◽  
Planktonic State ◽  
Phage Activity

We recently reported the successful treatment of a case of periprosthetic joint infection (PJI) with phage. Phage activity against bacteria causing PJI has not been systematically evaluated. Here we examined the in vitro activity of seven lytic phages against 122 clinical isolates of Staphylococcus aureus recovered between April 1999 and February 2018 from subjects with PJI. Phages were assessed against planktonic and biofilm phenotypes. Activity of individual phages was demonstrated against up to 73% of bacterial isolates in the planktonic state and up to 100% of biofilms formed by isolates that were planktonically phage-susceptible. Susceptibility to phage was not correlated with small colony variant status. These results demonstrate that phages can infect S. aureus causing PJI in both planktonic and biofilm phenotypes, and thus are worthy of investigation as an alternative or addition to antibiotics in this setting.

scholarly journals Novel Use of Rifabutin and Rifapentine to Treat Methicillin-Resistant Staphylococcus aureus in a Rat Model of Foreign Body Osteomyelitis

2020 ◽  
Vol 222 (9) ◽  
pp. 1498-1504
Author(s):  
Melissa J Karau ◽  
Suzannah M Schmidt-Malan ◽  
Mariana Albano ◽  
Jayawant N Mandrekar ◽  
Christina G Rivera ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Foreign Body ◽  
Rat Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Kirschner Wire ◽  
Methicillin Resistant ◽  
Joint Infections ◽  
Single Animal ◽  
K Wires

Abstract Background Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. Methods Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. Results Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both P ≤ .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. Conclusions Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.

Periprosthetic joint infection following Staphylococcus aureus bacteremia

2011 ◽  
Vol 63 (1) ◽  
pp. 17-22 ◽  
Author(s):  
Parham Sendi ◽  
Florian Banderet ◽  
Peter Graber ◽  
Werner Zimmerli
Keyword(s):  
Staphylococcus Aureus ◽  
Periprosthetic Joint Infection ◽  
Joint Infection ◽  
Staphylococcus Aureus Bacteremia

scholarly journals 1255. In Vitro Activity of Vancapticin against Methicillin-Resistant Staphylococcus aureus from Periprosthetic Joint Infection

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S645-S645
Author(s):  
Hye-Kyung Cho ◽  
Melissa J Karau ◽  
Kerryl E Greenwood-Quaintance ◽  
Karl A Hansford ◽  
Matthew A Cooper ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Periprosthetic Joint Infection ◽  
Mayo Clinic ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Research Support ◽  
Material Support

Abstract Background The vancapticins are modified vancomycin derivatives developed by adding membrane targeting motifs to the C-terminus of vancomycin. We determined the in vitro activity of a lead vancapticin candidate against periprosthetic joint infection-associated methicillin-resistant Staphylococcus aureus (MRSA) in the planktonic and biofilm states, and the effect of adding 0.002% polysorbate 80 (P-80; Sigma-Aldrich) on vancapticin susceptibility testing. Methods Thirty-seven clinical isolates of MRSA collected at Mayo Clinic (Rochester, Minnesota) were studied. Vancapticin minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institutes guidelines. Minimum biofilm bactericidal concentrations (MBBCs) were determined using a pegged lid microtiter plate assay. Vancapticin MIC and MBBC values were assessed with and without P-80. Vancapticin, vancomycin, and dalbavancin biofilm time-kill assays were performed using biofilms formed by 10 MRSA isolates on Teflon coupons. Results Vancapticin MICs with and without P-80 ranged from 0.015 to 0.12 μg/mL and 0.25 to 1 μg/mL, respectively. Vancapticin MBBCs with and without P-80 ranged from 0.25 to 4 μg/mL and 1 to 8 μg/mL, respectively. Reductions of biofilm bacterial densities on Teflon coupons after 8 and 24 hours of incubation with vancapticin, vancapticin with P-80, vancomycin, or dalbavancin with P-80 were less than 3-log10 cfu/cm2 for all isolates tested. Conclusion Vancapticin has promising in vitro activity against planktonic MRSA and MRSA in a pegged lid biofilm assay, but was not bactericidal against biofilms on Teflon coupons. P-80 decreased vancapticin MICs and MBBCs. Disclosures Mark A. Blaskovich, PhD, MAB Consulting (Consultant)The University of Queensland (Employee, Grant/Research Support, Other Financial or Material Support, Inventor on patent) Robin Patel, MD, Accelerate Diagnostics (Grant/Research Support)CD Diagnostics (Grant/Research Support)Contrafect (Grant/Research Support)Curetis (Consultant)GenMark Diagnostics (Consultant)Heraeus Medical (Consultant)Hutchison Biofilm Medical Solutions (Grant/Research Support)Merck (Grant/Research Support)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Dr. Patel has a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, and a patent on an anti-biofilm substance issued.)Selux Dx (Consultant)Shionogi (Grant/Research Support)Specific Technologies (Consultant)

scholarly journals In Vitro Activity of Vancapticin MCC5145 against Methicillin-Resistant Staphylococcus aureus from Periprosthetic Joint Infection

2021 ◽  
Author(s):  
Hye-Kyung Cho ◽  
Melissa J. Karau ◽  
Kerryl E. Greenwood-Quaintance ◽  
Karl A. Hansford ◽  
Matthew A. Cooper ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Periprosthetic Joint Infection ◽  
Biofilm Formation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Joint Infection ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Methicillin Resistant

MRSA periprosthetic 1 joint infection (PJI) can be challenging to treat due to biofilm formation, alongside sometimes limited vancomycin activity (1-3).…

Intra-articular vancomycin for the prophylaxis of periprosthetic joint infection caused by methicillin-resistant S. aureus after total knee arthroplasty in a rat model: the dosage, efficacy, and safety

2021 ◽  
Author(s):  
Jian Wei ◽  
Kai Tong ◽  
Hui Wang ◽  
Yinxian Wen ◽  
Liaobin Chen
Keyword(s):  
Total Knee Arthroplasty ◽  
Knee Arthroplasty ◽  
Rat Model ◽  
Periprosthetic Joint Infection ◽  
Joint Infection ◽  
Efficacy And Safety ◽  
Methicillin Resistant ◽  
Tissue Inflammation ◽  
Vancomycin Powder ◽  
Total Knee

Although intra-articular vancomycin powder (VP) is sometimes applied before the closure of the incision to prevent periprosthetic joint infection (PJI) after joint replacement, the dosage, efficacy and safety remain controversial. This study aimed to explore the dosage, efficacy, and safety of intra-articular VP in the prophylaxis of infection after total knee arthroplasty (TKA) in a rat model. Sixty male rats were randomly divided into five groups after receiving TKA surgery: Control (no antibiotics); systemic vancomycin (SV) (intraperitoneal injection, 88 mg/kg, equal to 1g in a patient weighted 70kg); VP0.5, VP1.0 and VP2.0 (44 mg/kg, 88 mg/kg and 176 mg/kg respectively, intra-articular). All animals were inoculated in the knee with methicillin-resistant S. aureus (MRSA). General status, serum biomarkers, radiology, microbiological assay and histopathological tests were assessed within 14 days post-operatively. Compared with the Control and SV groups, bacterial counts, knee-width, tissue inflammation, and osteolysis were reduced in the VP0.5, VP1.0 and VP2.0 groups, without notable bodyweight loss and incision complications. Among all the VP groups, VP1.0 and VP2.0 groups presented superior outcomes in the knee-width and tissue inflammation than the VP0.5 group. Microbial culture indicated that no MRSA survived in the knee of VP1.0 and VP2.0 groups, while bacteria growth was observed in VP0.5 group. No obvious changes in the structure and functional biomarkers of liver and kidney were observed in both SV and VP groups. Therefore, intra-articular vancomycin powder at the dosage from 88 mg/kg to 176 mg/kg may be effective and safe in preventing PJI induced by methicillin-resistant S. aureus in the rat TKA model.

scholarly journals Large variations in clinical antibiotic activity against Staphylococcus aureus biofilms of periprosthetic joint infection isolates

2019 ◽  
Vol 37 (7) ◽  
pp. 1604-1609 ◽  
Author(s):  
Jonathan B. Mandell ◽  
Sara Orr ◽  
John Koch ◽  
Blake Nourie ◽  
Dongzhu Ma ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Periprosthetic Joint Infection ◽  
Joint Infection ◽  
Antibiotic Activity

scholarly journals Outcomes of Acute Hematogenous Periprosthetic Joint Infection in Total Ankle Arthroplasty Treated with Irrigation, Debridement, and Polyethylene Exchange

2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0007
Author(s):  
James Lachman ◽  
Jania A. Ramos ◽  
James Nunley ◽  
James DeOrio ◽  
Samuel Adams
Keyword(s):  
Staphylococcus Aureus ◽  
Failure Rate ◽  
Periprosthetic Joint Infection ◽  
Patient Reported Outcomes ◽  
Joint Infection ◽  
Total Ankle Arthroplasty ◽  
Ankle Arthroplasty ◽  
Primary Arthroplasty ◽  
Patient Reported

Category: Ankle Introduction/Purpose: Acute hematogenous periprosthetic joint infection(PJI) is defined in the literature as infection diagnosed and treated within two to four weeks from the onset of symptoms. In total hip and knee arthroplasty, irrigation, debridement(I&D) and polyethylene exchange with component retention is the treatment of choice. There is minimal literature evaluating this treatment method for PJI in total ankle arthroplasty (TAA), however, with four patients being the largest sample size. The purpose of this study was to evaluate both the clinical and patient reported outcomes and survivorship of treating PJI in TAA with I&D and polyethylene exchange in patients with acute hematogenous PJIs. Methods: A single center, retrospective chart review of prospectively collected data in patients with TAA PJI who subsequently underwent I&D and polyethylene exchange with retention of metal components was conducted. The primary outcome was failure rate of I&D and polyethylene exchange where failure was defined as subsequent removal of all components and two-stage revision or arthrodesis. Patient reported outcomes collected before primary arthroplasty, after primary arthroplasty and after polyethylene exchange were also analyzed. Results: We identified 11 patients with acute hematogenous PJI who underwent I&D/ polyethylene exchange with retention of metal components. The average time from onset of symptoms to I&D/ polyethylene exchange was 11.55 days +/-5.57. The mean follow-up after this surgery was 2.8 years +/-1.45. The long-term failure rate was 50%. The most common bacteria isolated in patients who failed was Methicillin Resistant Staphylococcus Aureus (MRSA). The most common bacteria isolated in patients who retained their implants was Methicillin Sensitive Staphylococcus Aureus(MSSA). Visual Analog Scale (VAS), Short Musculoskeletal Function Assessment (SMFA), Short Form-36 (SF36), and American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scale showed significant improvement when compared to preoperative scores in patients who retained their implants both after primary and after I&D and polyethylene exchange. Conclusion: I&D and polyethylene exchange with retention of metal components has comparable long-term survivorship to those reported in the Knee and Hip Arthroplasty literature. Patient reported outcomes after I&D and polyethylene exchange were comparable to those collected after primary arthroplasty in patients who ultimately retained their implants. Two variables which were independent predictors of failure of this surgery include duration of symptoms prior to I&D as well as organism isolated on culture. With a failure rate of 50%, the authors recommend thorough evaluation on a case by case basis prior to indicating a patient for single stage I&D with polyethylene exchange.

scholarly journals Intestinal methicillin-resistant Staphylococcus aureus causes prosthetic infection via ‘Trojan Horse’ mechanism: Evidence from a rat model

2020 ◽  
Vol 9 (4) ◽  
pp. 152-161
Author(s):  
Hongyi Zhu ◽  
Hanqiang Jin ◽  
Changqing Zhang ◽  
Ting Yuan
Keyword(s):  
Staphylococcus Aureus ◽  
Intravenous Injection ◽  
Rat Model ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Fluorescent Protein ◽  
Joint Infection ◽  
Trojan Horse ◽  
Methicillin Resistant ◽  
Prosthetic Joint ◽  
Green Fluorescent

Aims Methicillin-resistant Staphylococcus aureus (MRSA) can cause wound infections via a ‘Trojan Horse’ mechanism, in which neutrophils engulf intestinal MRSA and travel to the wound, releasing MRSA after apoptosis. The possible role of intestinal MRSA in prosthetic joint infection (PJI) is unknown. Methods Rats underwent intestinal colonization with green fluorescent protein (GFP)-tagged MRSA by gavage and an intra-articular wire was then surgically implanted. After ten days, the presence of PJI was determined by bacterial cultures of the distal femur, joint capsule, and implant. We excluded several other possibilities for PJI development. Intraoperative contamination was excluded by culturing the specimen obtained from surgical site. Extracellular bacteraemia-associated PJI was excluded by comparing with the infection rate after intravenous injection of MRSA or MRSA-carrying neutrophils. To further support this theory, we tested the efficacy of prophylactic membrane-permeable and non-membrane-permeable antibiotics in this model. Results After undergoing knee surgery eight or 72 hours after colonization, five out of 20 rats (25.0%) and two out of 20 rats (10.0%) developed PJI, respectively. Strikingly, 11 out of 20 rats (55.0%) developed PJI after intravenous injection of MRSA-carrying neutrophils that were isolated from rats with intestinal MRSA colonization. None of the rats receiving intravenous injections of MRSA developed PJI. These results suggest that intestinal MRSA carried by neutrophils could cause PJI in our rat model. Ten out of 20 (50.0%) rats treated with non-membrane-permeable gentamicin developed PJI, whereas only one out of 20 (5.0%) rats treated with membrane-permeable linezolid developed PJI. Conclusion Neutrophils as carriers of intestinal MRSA may play an important role in PJI development. Cite this article: Bone Joint Res. 2020;9(4):152–161.

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