ABSTRACT
BACKGROUND: Candida auris (CA) is an organism that has spread globally over the last decade. We conducted a quality improvement project with the aim of decreasing or eliminating skin colonization of patients with CA through a modified bathing protocol. METHODS: An isotonic hypochlorite solution was added to routine bathing protocols for hospitalized patients colonized with CA. Weekly skin swabs from axillary and inguinal areas were tested for the presence of CA using polymerase chain reaction and culture. Multidisciplinary efforts, such as environmental terminal cleaning, dedicated equipment, education, and signage were reinforced among staff to improve patient outcomes. RESULTS: A total of 24 patients were included. After 4 weeks of a modified bathing protocol, 81.2% of the patients remained colonized with CA. Three patients were discharged safely to their homes and 3 were transferred to long-term care acute hospitals. Nine patients remained hospitalized after 60 days. Localized rash was reported in 3 patients, which resolved after discontinuation of the product. CONCLUSIONS: Modification of our bathing protocols by including an isotonic hypochlorite solution did not lead to skin decolonization of CA. Further studies are needed to identify effective measures to eradicate, eliminate or reduce colonization.
ABSTRACT
The administration of growth factors (GFs) for treatment of experimental spinal cord injury (SCI) has shown limited benefits. One reason may be the mode of delivery to the injury site. We have developed a minimally invasive and safe drug delivery system (DDS) consisting of a highly concentrated collagen solution that can be injected intrathecally at the site of injury providing localized delivery of GFs. Using the injectable DDS, epidermal growth factor (EGF) and basic fibroblast growth factor (FGF-2) were co-delivered in the subarachnoid space of Sprague-Dawley rats. The in vivo distribution of EGF and FGF-2 in both injured and uninjured animals was monitored by immunohistochemistry. Although significant differences in the distribution of EGF and FGF-2 in the spinal cord were evident, localized delivery of the GFs resulted in significantly less cavitation at the lesion epicenter and for at least 720 mum caudal to it compared to control animals without the DDS. There was also significantly more white matter sparing at the lesion epicenter in animals receiving the GFs compared to control animals. Moreover, at 14 days post-injection, delivery of the GFs resulted in significantly greater ependymal cell proliferation in the central canal immediately rostral and caudal to the lesion edge compared to controls. These results demonstrate that the injectable DDS provides a new paradigm for localized delivery of bioactive therapeutic agents to the injured spinal cord.
Subject(s)
Epidermal Growth Factor/administration & dosage , Fibroblast Growth Factor 2/administration & dosage , Spinal Cord Injuries/drug therapy , Spinal Cord/drug effects , Animals , Cell Proliferation/drug effects , Disease Models, Animal , Drug Administration Routes , Ependyma/drug effects , Ependyma/physiology , Epidermal Growth Factor/metabolism , Epidermal Growth Factor/pharmacokinetics , Female , Fibroblast Growth Factor 2/metabolism , Fibroblast Growth Factor 2/pharmacokinetics , Injections, Spinal/adverse effects , Injections, Spinal/instrumentation , Injections, Spinal/methods , Mice , Microinjections/adverse effects , Microinjections/instrumentation , Microinjections/methods , NIH 3T3 Cells , Nerve Degeneration/chemically induced , Nerve Degeneration/physiopathology , Nerve Regeneration/drug effects , Nerve Regeneration/physiology , Neural Pathways/drug effects , Neural Pathways/pathology , Neural Pathways/physiopathology , PC12 Cells , Rats , Rats, Sprague-Dawley , Recovery of Function/drug effects , Recovery of Function/physiology , Spinal Cord/pathology , Spinal Cord/physiopathology , Spinal Cord Injuries/metabolism , Spinal Cord Injuries/physiopathology , Subarachnoid Space/drug effects , Subarachnoid Space/physiology , Subarachnoid Space/surgery , Treatment OutcomeABSTRACT
A novel, localized method for potential delivery of therapeutic agents to the injured spinal cord was investigated. The strategy consists of a polymeric drug solution that gels after injection into the subarachnoid space (SAS). By dispersing therapeutic agents in the polymeric solution, a method is provided for localized delivery to the spinal cord. To determine whether intrathecal injection of this drug delivery system (DDS) would affect cerebrospinal fluid (CSF) flow, a spinal canal model was built using dimensional analysis. Blocking up to 52% of the modeled subarachnoid space of the spinal canal caused minimal pressure differences (9.22 +/- 1.45 Pa), suggesting that implantation of a DDS would not subject the spinal cord to increased pressure. The safety of the DDS was also assessed in vivo by injecting collagen into the SAS of Sprague Dawley rats. Controls received injections of artificial CSF (aCSF). Collagen or aCSF was injected at the T2-T3 spinal level of both uninjured rats and rats injured with a 20g compression clip. The injected collagen persisted in the SAS for at least 8 weeks post-implantation and did not elicit an inflammatory reaction in either uninjured or injured animals. Long-term functional behavior was evaluated with the Basso, Beattie, and Bresnahan (BBB) scale weekly for 8 weeks. Functional behavior was similar in the collagen and aCSF groups, also indicating that the DDS was safe. This minimally invasive DDS may provide an alternative, safe method to deliver therapeutic agents intrathecally.