Model of septic arthritis by intravenous inoculation of Staphylococcus aureus in Wistar rats

Batista, Flamarion dos Santos; Malafaia, Osvaldo; Filho, Jurandir Marcondes Ribas; Czeczko, Nicolau Gregory; Repka, João Carlos Domingues

doi:10.1590/s0102-86502004000700009

Cited by 4 publications

(3 citation statements)

References 8 publications

(7 reference statements)

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“…Therefore, the septic arthritis model selected to test the local release of the drug from the formulations in the presence of infection was appropriate since it is a localized infection. Although systemic bacterial inoculation represents an accurate way to simulate disease development, it takes roughly 21 days for the disease to develop in animal models [ 41 ]. In order to hasten the disease development, septic arthritis was induced by local inoculation of the bacteria into the joint space.…”

Section: Discussionmentioning

confidence: 99%

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Infection Responsive Smart Delivery of Antibiotics Using Recombinant Spider Silk Nanospheres

et al. 2021

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Frequent and inappropriate usage of antibiotics has changed the natural evolution of bacteria by reducing susceptibility and increasing resistance towards antibacterial agents. New resistance mechanisms evolved in the response to host defenses and pharmaceutical interventions are threatening our ability to treat common infections, resulting in increased mortality. In the face of this rising epidemic, antibiotic drug discovery, which has long been overlooked by big pharma, is reaching a critical low. Thus, the development of an infection-responsive drug delivery system, which may mitigate multidrug resistance and preserve the lifetime of our current antibiotic arsenal, has garnered the attention of both popular science and funding agencies. The present work describes the development of a thrombin-sensitive linker embedded into a recombinant spider silk copolymer to create a nanosphere drug delivery vehicle. Recent studies have suggested that there is an increase in thrombin-like activity during Staphylococcus aureus infection; thus, drug release from this new “smart” nanosphere can be triggered in the presence of infection. A thrombin sensitive peptide (TSP) was synthesized, and the thrombin cleavage sensitivity was determined by HPLC. The results showed no cleavage of the peptide when exposed to human serum whereas the peptide was cleaved when incubated with S. aureus exudate. Subsequently, the peptide was coupled with a silk copolymer via EDC-NHS chemistry and formulated into nanospheres encapsulating antibiotic vancomycin. These nanospheres were evaluated for in vitro infection-responsive drug release and antimicrobial activity. Finally, the drug responsive nanospheres were assessed for efficacy in an in vivo septic arthritis model. Our study provides evidence that the protein conjugate was enzyme responsive and can be used to formulate targeted drug release to combat infections against multidrug-resistant bacterial strains.

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Section: Discussionmentioning

confidence: 99%

“…An initial pilot study was done in a modified, induced septic arthritis rat model using a local inoculation of bacteria [ 40 , 41 , 42 ]. All studies were done under the supervision of the Institutional Animal Care and Use Committee (protocol A19068) at North Dakota State University.…”

Section: Methodsmentioning

confidence: 99%

Infection Responsive Smart Delivery of Antibiotics Using Recombinant Spider Silk Nanospheres

et al. 2021

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“…Many rodent models of septic arthritis are based on the injection of pathogens through the haematogenous route, 1,2,6–11 but these models have several obvious disadvantages. For instance, it is impossible to anticipate precisely which joint will become infected, even if the targeted joint is previously damaged to improve the success rate.…”

Section: Introductionmentioning

confidence: 99%

Development of an experimental model of septic knee arthritis in rats through intra-articular inoculation ofStaphylococcus aureus

et al. 2020

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Haematogenous models of septic arthritis have some inherent disadvantages, such as the manifestation of arthritis relies on chance, the size of the inoculum is unknown and the number of animals to be studied cannot be reduced because the animals cannot serve as their own controls. This study aimed to develop a rat model of knee septic arthritis by injecting a known inoculum of Staphylococcus aureus into the joint. The left knees of 27 Sprague Dawley rats were injected with four different inoculum concentrations of a sensitive strain of S. aureus (30,000 colony-forming units (CFUs), n = 3; 18,550 CFUs, n = 6; 15,500 CFUs, n = 9; and 7700 CFUs, n = 9); the right knees served as controls. Clinical, microbiological and histological variables were assessed two and seven days later. The main criterion for diagnosing septic arthritis was a positive culture of synovial fluid. The rate of microbiologically confirmed septic arthritis was high for all inoculum concentrations (3/3, 6/6, 8/9 and 7/9, respectively), and the rate of bacteraemia was also high. Animal welfare was better for the two lowest inoculum concentrations. No animal reached the pre-established humane end points. Overall, the third inoculum was considered the most suitable. Thus, acute septic arthritis can be caused in rats by inoculating 15,000 CFUs of an ATCC strain of S. aureus directly into the knee joint. Overall, the model seems to be useful for studying the effectiveness of drugs for the treatment of acute septic arthritis.

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Involvement of the phosphoryl transfer network on cardiac energetic metabolism during Staphylococcus aureus infection and its association to disease pathophysiology

Perin

Baldissera

Jaguezeski

et al. 2019

Microbial Pathogenesis

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Model of septic arthritis by intravenous inoculation of Staphylococcus aureus in Wistar rats

Abstract: An experimental model of septic arthritis by monobacterial inoculation of Staphylococcus aureus 10.9 in Wistar rats dorsal penis vein is describred.

Cited by 4 publications

References 8 publications

Infection Responsive Smart Delivery of Antibiotics Using Recombinant Spider Silk Nanospheres

Infection Responsive Smart Delivery of Antibiotics Using Recombinant Spider Silk Nanospheres

Development of an experimental model of septic knee arthritis in rats through intra-articular inoculation ofStaphylococcus aureus

Involvement of the phosphoryl transfer network on cardiac energetic metabolism during Staphylococcus aureus infection and its association to disease pathophysiology

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