Pharmacokinetics of cefazolin for prophylactic administration to dogs

Master of Science in Biomedical SciencesDepartment of Clinical SciencesWalter C. RenbergOBJECTIVE: The purpose of the study reported here was to evaluate pharmacokinetics of cefazolin in dogs receiving a single IV injection of cefazolin (22 mg/kg) and dogs receiving simultaneous IV and IM injections of cefazolin (total dose, 44 mg/kg). METHODS: Twelve purpose-bred Beagles (6/group) were assigned to receive a single injection of cefazolin (22 mg/kg, IV) or simultaneous injections (22 mg/kg, IV, and 22 mg/kg, IM). Interstitial fluid was collected over a 5-hour period using ultrafiltration probes for pharmacokinetic analysis. RESULTS: Mean cefazolin concentration in the interstitial fluid at 1, 1.5, 2, 3, 4, and 5 hours after injection was 39.6, 29.1, 21.1, 10.3, 6.4, and 2.7 μg/mL, respectively, for the IV group and 38.3, 53.3, 46.4, 31.7, 19.1, and 8.9 μg/mL, respectively, for the IV + IM group. The mean area under the concentration-time curve extrapolated to infinity, maximum concentration, half life and time to the maximum concentration was 74.99 and 154.16 h•μg/mL, 37.3 and 51.5 μg/mL, 0.96 and 1.11 hours, 1.28 and 1.65 hours, respectively, for the IV and IV + IM groups. CONCLUSIONS AND CLINICAL RELEVANCE: Cefazolin concentrations in interstitial fluid of dogs were maintained at > 4 μg/mL for 4 hours after a single IV injection and for 5 hours after simultaneous IV and IM injections. Based on these results, simultaneous administration of cefazolin IV + IM 30 to 60 minutes before surgery should provide interstitial fluid concentrations effective against the most common commensal organisms (Staphylococcus spp and Streptococcus spp) on the skin of dogs for surgical procedures lasting ≤ 4 hours

Ultraclean air systems and the claim that laminar airflow systems fail to prevent deep infections after total joint arthroplasty

The World Health Organization published guidelines in 2016 for preventing surgical site infections. The guidelines contained a conditional recommendation that laminar airflow (LAF) ventilation systems should not be used to reduce the risk of infection after total joint arthroplasty (TJA). This recommendation was largely based on a systematic review and meta-analysis of information from hospital infection surveillance registries. The recommendation contradicts information published in earlier major studies carried out by Charnley and the UK Medical Research Council (MRC). The first aim of this article is to revisit and explain the MRC study, and reply to criticisms of it. The second aim is to suggest reasons why some recent studies have failed to demonstrate that ultraclean air (UCA) systems reduce deep joint infection after TJA. It demonstrates that if a UCA system establishes average airborne concentrations of microbe-carrying particles (MCPs) <10/m , and preferably <1/m , then deep joint infection after TJA will be lower than in conventionally ventilated operating theatres

Operative Environment

Postoperative SSIs are believed to occur via bacterial inoculation at the time of surgery or as a result of bacterial contamination of the wound via open pathways to the deep tissue layers.1–3 The probability of SSI is reflected by interaction of parameters that can be categorized into three major groups.2 The first group consists of factors related to the ability of bacteria to cause infection and include initial inoculation load and genetically determined virulence factors that are required for adherence, reproduction, toxin production, and bypassing host defense mechanisms. The second group involves those factors related to the defense capacity of the host including local and systemic defense mechanisms. The last group contains environmental determinants of exposure such as size, time, and location of the surgical wound that can provide an opportunity for the bacteria to enter the surgical wound, overcome the local defense system, sustain their presence, and replicate and initiate local as well as systemic inflammatory reactions of the host. The use of iodine impregnated skin incise drapes shows decreased skin bacterial counts but no correlation has been established with SSI. However, no recommendations regarding the use of skin barriers can be made (see this Workgroup, Question 27)

Medical applications of space light-emitting diode technology-space station and beyond

Journal ArticleSpace light-emitting diode (LED) technology has provided medicine with a new tool capable of delivering light deep into tissues of the body, at wavelengths which are biologically optimal for cancer treatment and wound healing. This LED technology has already flown on Space Shuttle missions, and shows promise for wound healing applications of benefit to Space Station astronauts

Immune modulatory and antimicrobial properties of mesenchymal stromal cells delivered systemically

2020 Spring.Includes bibliographical references.To view the abstract, please see the full text of the document

Medicinal plants as therapeutic options for topical treatment in canine dermatology? A systematic review

BACKGROUND: Medicinal plants have been used traditionally since centuries for wound care and treatment of skin diseases both in human and animals. Skin diseases are one of the most common reasons for owners to take their dog to the veterinarian. The demands for treatment and prophylaxis of these diseases are broad. A wide range of bacteria including antibiotic-resistant bacteria can be involved, making the treatment challenging and bear an anthropo-zoonotic potential. The aim of this review is to systematically evaluate based on recent scientific literature, the potential of four medicinal plants to enrich the therapeutic options in pyoderma, canine atopic dermatitis, otitis externa, wounds and dermatophytosis in dogs. RESULTS: Based on four books and a survey among veterinarians specialized in phytotherapy, four medicinal plants were chosen as the subject of this systematic review: Calendula officinalis L. (Marigold), Hypericum perforatum L. agg. (St. John's Wort), Matricaria chamomilla L. (syn. Matricaria recutita L., Chamomile) and Salvia officinalis L. (Sage). According to the PRISMA statement through literature research on two online databases a total of 8295 publications was screened and narrowed down to a final 138 publications for which full-text documents were analyzed for its content resulting in a total of 145 references (21 clinical, 24 in vivo and 100 in vitro references). CONCLUSIONS: All four plants were proven to have antibacterial and antifungal effects of a rather broad spectrum including antibiotic-resistant bacteria. This makes them an interesting new option for the treatment of pyoderma, otitis externa, infected wounds and dermatophytosis. Marigold, St. John's Wort and Chamomile showed wound-healing properties and are thus promising candidates in line to fill the therapeutic gap in canine wound-healing agents. St. John's Wort and Chamomile also showed anti-inflammatory and other beneficial effects on healthy skin. Due to the wide range of beneficial effects of these medicinal plants, they should be taken into account for the treatment of dermatologic diseases in dogs at least in future clinical research

Implant-Related Osteomyelitis Models for the Assessment of Bacteriophage Therapeutics

Antibiotic resistant strains of bacteria continue to increase in prevalence, hindering the ability of clinicians to treat infection. One disease exacerbated by this trend is osteomyelitis, or bone infection. When osteomyelitis is induced by these antibiotic resistant strains, patients can experience prolonged hospital visits, greater economic burdens, amputation, and even death. Due to the limitations of antibiotics to clear these infections, we sought to identify new therapeutic options for osteomyelitis. Our aim was to first develop an in vivo implant-related model of osteomyelitis. We then wanted to explore the potential of novel CRISPR-Cas9 modified bacteriophage to treat infection. In vitro and in vivo investigations demonstrated that bacteriophage therapeutic may be a viable option for infection mitigation. Furthermore, our in vivo model of osteomyelitis proved to be reliable, consistent, and challenging. Future research will utilize this model as a platform for optimizing therapeutic regimen and delivery vehicle(s) for antimicrobial therapeutics

In vitro activity of gentamicin-loaded bioabsorbable beads against different microorganisms

Grâce à la prophylaxie antibiotique per-opératoire, à l'amélioration des techniques chirurgicales et au flux laminaire dans les blocs opératoires le taux d'infections postopératoires a pu être diminué dans les interventions chirurgicales orthopédiques. Il stagne néanmoins à environ 0,5- 2% dans les fractures fermées ainsi que dans les interventions orthopédiques électives, et peut monter jusqu'à 30% dans les fractures ouvertes stade III. L'ostéomyelite et la pseudarthrose infectée, qui peuvent en découler, sont responsables de séjours hospitaliers prolongés, engendrent des coûts de traitement élevés, et conduisent souvent à une morbidité substantielle. Le traitement de l'ostéomyelite combine le débridement chirurgical et l'administration d'antibiotiques. Cependant l'administration systémique d'antibiotiques à hautes doses est problématique en raison de leur toxicité systémique et de leur faible pénétration dans les tissus ischémiques et nécrotiques, souvent présents dans l'ostéomyelite. Pour ces raisons, le traitement standard actuel consiste, après débridement chirurgical, en la mise en place de billes de Polyrnéthylmétacrylate (PMMA) imprégnées d'antibiotique, qui fournissent des concentrations locales élevées mais systémiques basses. Malheureusement, ces billes doivent être enlevées une fois l'infection guérie, ce qui nécessite une nouvelle intervention chirurgicale. Des systèmes de libération antibiotique alternatifs devraient non seulement guérir l'infection osseuse, mais également encourager activement la consolidation osseuse et ne pas nécessiter de nouvelle chirurgie pour leur ablation. Nous avons investigué l'activité de billes résorbables chargées en gentamicine contre différents microorganismes (Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Enterococcus faecalis, Candida albicans), des germes communément responsables d'infections osseuses, par microcalorimétrie, une méthode novice basée sur la mesure de la chaleur produite par des microorganismes qui se répliquent dans une culture. Des billes composées essentiellement de sulfate de calcium et chargées en gentamicine ont été incubées dans des ampoules microcalorimétriques contenant différentes concentrations du germe correspondant. Les bouillons de culture avec chaque germe et billes non-chargées ont été utilisés comme contrôle positif, le bouillon de culture avec bille chargée mais sans germe comme contrôle négatif. La production de chaleur provenant de la croissance bactérienne à 37°C a été mesurée pendant 24 heures. Les cultures ne contenant pas de billes chargées en gentamicine ont. produit des pics de chaleur équivalents à la croissance exponentielle du microorganisme correspondant en milieu riche. Par contre, les germes susceptibles à la gentamicine incubés avec les billes chargées ont complètement supprimé leur production de chaleur pendant 24 heures, démontrant ainsi l'activité antibiotique des billes chargées en gentamicine contre ces germes. Les billes résorbables chargées en gentamicine inhibent donc de façon effective la croissance des germes susceptibles sous les conditions in vitro décrites. Des études sur animaux sont maintenant nécessaires pour déterminer la cinétique d'élution et l'effet antimicrobien de la gentamicine sous conditions in vivo. Finalement des études cliniques devront démontrer que l'utilisation de ces billes est effectivement une bonne option thérapeutique dans le traitement des infections osseuses

Translating focused ultrasound combined nanomedicines for treatment of bone infections and canine cancer patients

High-intensity focused ultrasound (HIFU) is a non-invasive and non-ionizing sonic energy-based therapeutic technology for inducing thermal and non-thermal effects in tissues. HIFU transducers are designed to focus high-energy pulses on a well-defined target region to minimize toxicities to healthy tissues. Depending on the parameters, HIFU can ablate tissue by heating them to >55 degrees C to induce denaturation and coagulative necrosis, improve radio- and chemo-sensitizations and local drug delivery from nanoparticles (NPs) at moderate hyperthermia (~ 41-43 degrees C), and mechanically fragment cells using acoustic cavitation (also known as histotripsy or HT). HIFU has already emerged as an attractive modality for treating human prostate cancer and neuromodulation. Based on this premise, the objective of this doctoral research was to investigate the feasibility of translating HIFU for the treatment of veterinary cancers and bone infections. Veterinary and human patients demonstrate anatomic and physiological similarities, and we hypothesize that HIFU will have a strong promise and translation basis for comparative oncology use. Veterinary research using HIFU can also inform on device innovations needed for human translation against various indications. In this project, we investigated several HIFU parameters to understand efficacy against a variety of veterinary cancers. We also determined immunopathological outcomes to provide the foundations for new treatment protocols. Unlike soft-tissue based tumors, the efficacy of HIFU in treating acoustically attenuating bone tissues that harbor metastasis or recalcitrant biofilm implant-associated osteomyelitis is still unclear. To address this question, a comprehensive assessment of HIFU against established implant-associated bone osteomyelitis was performed. Specifically, the ability of HIFU to induce bacterial killing and improve antibiotic treatments from NPs was determined. Our data from rodent and veterinary cancer studies provided important insights on the opportunities and challenges of HIFU technology, and we believe that the research studies can help jumpstart several clinical trials leading to greater use in patients