-
Open Forum Infectious Diseases Jun 2024Osteoarticular infections (OAIs) are commonly treated with prolonged intravenous (IV) antimicrobials. The Oral versus Intravenous Antibiotics for Bone and Joint...
Variation in North American Infectious Disease Specialists' Practice Regarding Oral and Suppressive Antibiotics for Adult Osteoarticular Infections: Results of an Emerging Infections Network (EIN) Survey.
BACKGROUND
Osteoarticular infections (OAIs) are commonly treated with prolonged intravenous (IV) antimicrobials. The Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial demonstrated that oral (PO) antibiotics are noninferior to IV antibiotics in the treatment of OAIs. We surveyed infectious disease (ID) physicians about their use of PO antibiotics in the treatment of OAIs.
METHODS
An Emerging Infection Network survey with 9 questions regarding antibiotic prescribing for the treatment of OAIs was sent to 1475 North American ID physicians. The questions were mostly multiple choice and focused on the use of definitive oral antibiotic therapy (defined as oral switch within 2 weeks of starting antibiotics) and chronic suppressive antibiotic therapy (SAT).
RESULTS
Of the 413 physicians who reported treating OAIs, 91% used oral antibiotics at least sometimes and 31% used them as definitive therapy, most often for diabetic foot osteomyelitis and native joint septic arthritis. The oral antibiotics most frequently used for OAIs included trimethoprim-sulfamethoxazole, doxycycline/minocycline, and linezolid for , amoxicillin/cefadroxil/cephalexin for streptococci, and fluoroquinolones for gram-negative organisms. The most common rationales for not transitioning to oral antibiotics included nonsusceptible pathogens, comorbidities preventing therapeutic drug levels, and concerns about adherence. SAT use was variable but employed by a majority in most cases of periprosthetic joint infection managed with debridement and implant retention.
CONCLUSIONS
North American ID physicians utilize oral antibiotics and SAT for the management of OAIs, although significant practice variation exists. Respondents voiced a need for updated guidelines.
PubMed: 38868304
DOI: 10.1093/ofid/ofae280 -
ACS Applied Materials & Interfaces Jun 2024Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in...
Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in plaques and the main pro-inflammatory factor. Therefore, it is crucial to develop an effective therapeutic strategy that can simultaneously address the multiple pro-inflammatory factors removing cholesterol and inhibiting the overaccumulated ROS. In this study, we constructed macrophage membrane-encapsulated biomimetic nanoparticles (MM@DA-pCD@MTX), which not only alleviate cholesterol deposition at the plaque lesion reverse cholesterol transport but also scavenge the overaccumulated ROS. β-Cyclodextrin (β-CD) and the loaded methotrexate (MTX) act synergistically to induce cholesterol efflux for inhibiting the formation of foam cells. Among them, MTX up-regulated the expression of ABCA1, CYP27A1, and SR-B1. β-CD increased the solubility of cholesterol crystals. In addition, the ROS scavenging property of dopamine (DA) was perfectly preserved in MM@DA-pCD@MTX, which could scavenge the overaccumulated ROS to alleviate the oxidative stress at the plaque lesion. Last but not least, MM-functionalized "homing" targeting of atherosclerotic plaques not only enables the targeted drug delivery but also prolongs circulation time and drug half-life. In summary, MM@DA-pCD@MTX emerges as a potent, multifunctional therapeutic platform for AS treatment, offering a high degree of biosafety and efficacy in addressing the complex pathophysiology of atherosclerosis.
Topics: Dopamine; Nanoparticles; Atherosclerosis; Mice; Animals; Biomimetic Materials; Methotrexate; Cholesterol; Macrophages; Reactive Oxygen Species; Humans; Cyclodextrins; RAW 264.7 Cells; Oxidative Stress; Drug Carriers; beta-Cyclodextrins
PubMed: 38867426
DOI: 10.1021/acsami.4c04431 -
Otology & Neurotology : Official... Jul 2024To compare the rate of device failure for those cochlear implants (CIs) involved in the 2020 Food and Drug Administration (FDA) voluntary field corrective action (VFCA). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the rate of device failure for those cochlear implants (CIs) involved in the 2020 Food and Drug Administration (FDA) voluntary field corrective action (VFCA).
DATABASES REVIEWED
Medline, Embase, and Scopus.
METHODS
A systematic review was performed according to the PRISMA guidelines. Publications reporting institutional experiences with implants affected by the VFCA were included. Outcomes assessed included etiology of, rate of, and time to failure and pre-/post-device failure speech perception testing. All outcomes reported in at least two independent studies were included in a meta-analysis.
RESULTS
Six studies met criteria for analysis. The overall pooled failure rate was 23.7% (95% CI, 11.6-38.4%). The pooled device, inconclusive, and medical failure rates were 21.5%, 0.2%, and 0.7%, respectively. Pediatric failure rates were higher than those of adults (46.9% [95% CI, 11.2-84.5%] versus 32.6% [95% CI, 8.2-63.7%]). WRS declined with primary implant failure (55.1% [95% CI, 48.0-62.1%] to 34.1% [95% CI, 30.2-38.0%]) but improved after reimplantation (34.1% [95% CI, 30.2-38.0%] to 50.1% [95% CI, 45.2-55.1%]).
CONCLUSIONS
The rate of pooled reported failure for CIs falling under the 2020 VFCA in the literature thus far is 23.7%. The overwhelming majority of these failures were device related, the rates of which were higher in children. Speech perception improved significantly after reimplantation.
Topics: Humans; Cochlear Implants; United States; United States Food and Drug Administration; Prosthesis Failure; Cochlear Implantation; Speech Perception
PubMed: 38865719
DOI: 10.1097/MAO.0000000000004224 -
Materials Chemistry and Physics Feb 2024Titanium alloys are widely used as implant materials due to their biocompatibility and superior mechanical properties for high-load-bearing applications. However, one of...
Titanium alloys are widely used as implant materials due to their biocompatibility and superior mechanical properties for high-load-bearing applications. However, one of the major challenges is their inferior bioactivity and osseoconductivity. Hydroxyapatite is widely used as an alternative material for bone implants due to its compositional similarity to natural bone. In this study, hydroxyapatite is coated on Ti6Al4V discs to enhance its bioactivity. The coated discs are drop-casted with curcumin in the lower layer and vitamin C in the upper layer. This study aims to evaluate the effects of this dual drug delivery system on osteoblast cell proliferation, inhibition of osteoclastogenesis, chemo-preventive and infection control properties. The coating strength obtained is 22 ± 2 MPa. The release from the dual delivery system shows a 1.5-fold increase in osteoblast cell viability, a 1.5-fold reduction in osteoclast cell differentiation, a 2-fold decrease in osteosarcoma growth. The release of curcumin demonstrates a 94% antibacterial efficacy, while the release of vitamin C exhibits an efficacy of 98.6% aganist . This multifunctional system can be used as a potential implant for load-bearing applications.
PubMed: 38863477
DOI: 10.1016/j.matchemphys.2023.128622 -
Zhongguo Yi Liao Qi Xie Za Zhi =... May 2024The treatment of bone defects caused by fractures or bone tissue lesions has always been a difficult problem in the field of orthopedics. Implantation of...
The treatment of bone defects caused by fractures or bone tissue lesions has always been a difficult problem in the field of orthopedics. Implantation of high-performance titanium alloy prosthesis is an effective method to treat bone defects. 3D printing technology can produce low-modulus titanium alloy implants with porous structures, providing a better solution to the above problems. This technology is convenient to design and has a huge advantage in making orthopedic implants. The article used electron beam melting in 3D printing technology to create two samples of Ti-6Al-4V prosthesis, including solid structural pelvic prosthesis and porous structural pelvic prosthesis. The mechanical properties of the prosthesis showed that the yield and tensile strengths of the rod tensile specimen were 894 MPa and 956 MPa, respectively, and the compressive modulus and compressive strength of the porous pelvic prosthesis were 55 GPa and 65.2 MPa, respectively. The results of the L929 cytotoxicity assay and the MC3T3-E1 cell adhesion assay demonstrated good biocompatibility of the prosthetic samples. New Zealand white rabbits were used to prepare the femoral joint cavity defect models and two pelvic prostheses were implanted. A microscopic CT scan 4 weeks after implantation showed that the bone defect caused by the drill had healed and that the porous structure of the pelvic prosthesis formed a new trabecular structure within the hole. In conclusion, the 3D printed Ti-6Al-4V pelvic prosthesis has excellent mechanical properties, biocompatibility, and the ability to promote new bone growth.
Topics: Printing, Three-Dimensional; Titanium; Animals; Rabbits; Alloys; Biocompatible Materials; Materials Testing; Prostheses and Implants; Mice; Prosthesis Design; Porosity; Pelvic Bones; Pelvis
PubMed: 38863090
DOI: 10.12455/j.issn.1671-7104.230611 -
Scientific Reports Jun 2024In individuals with hearing loss, protection of residual hearing is essential following cochlear implantation to facilitate acoustic and electric hearing. Hearing...
In individuals with hearing loss, protection of residual hearing is essential following cochlear implantation to facilitate acoustic and electric hearing. Hearing preservation requires slow insertion, atraumatic electrode and delivery of the optimal quantity of a pharmacological agent. Several studies have reported variable hearing outcomes with osmotic pump-mediated steroid delivery. New drugs, such as sialyllactose (SL) which have anti-inflammatory effect in many body parts, can prevent tissue overgrowth. In the present study, the positive effects of the pharmacological agent SL against insults were evaluated in vitro using HEI-OC1 cells. An animal model to simulate the damage due to electrode insertion during cochlear implantation was used. SL was delivered using osmotic pumps to prevent loss of the residual hearing in this animal model. Hearing deterioration, tissue fibrosis and ossification were confirmed in this animal model. Increased gene expressions of inflammatory cytokines were identified in the cochleae following dummy electrode insertion. Following the administration of SL, insertion led to a decrease in hearing threshold shifts, tissue reactions, and inflammatory markers. These results emphasize the possible role of SL in hearing preservation and improve our understanding of the mechanism underlying hearing loss after cochlear implantation.
Topics: Cochlear Implantation; Animals; Lactose; Hearing Loss; Hearing; Cochlea; Mice; Disease Models, Animal; Cell Line; Cytokines; Male; Sialic Acids
PubMed: 38862572
DOI: 10.1038/s41598-024-62344-0 -
International Journal of Biological... Jun 2024Chronic bacterial infections, excessive inflammation, and oxidative stress significantly hinder diabetic wound healing by prolonging the inflammatory phase and...
Chronic bacterial infections, excessive inflammation, and oxidative stress significantly hinder diabetic wound healing by prolonging the inflammatory phase and complicating the healing process. In this study, phenylboronic acid functionalized dextran (PODP) was developed to encapsulate curcumin, referred to as PODP@Cur. Experimental results indicate that PODP significantly improves the water solubility of curcumin and exhibits synergistic biological activity both in vitro and in vivo. PODP@Cur is capable of accelerating drug release under the pathological microenvironment with ROS accumulation. Furthermore, phenylboronic acid (PBA) has demonstrated potential for targeted bacterial drug delivery, enhancing antibacterial efficacy and trapping free LPS/PGN from dead bacteria to reduce undesirable inflammation. In a diabetic mouse model, PODP@Cur exhibits an excellent antibacterial, anti-inflammatory and antioxidant activities to ultimately promote the efficient and safe wound healing. Due to the specific interaction between PBA and LPS, PODP@Cur could enhance antibacterial activity against bacteria, reduce toxic side effects on normal cells, and alleviate the LPS-mediated pro-inflammatory pathological microenvironment. Therefore, PODP@Cur is capable of being exploited as an efficient and safe candidate for promoting the bacteria-infected diabetic wound healing.
PubMed: 38862051
DOI: 10.1016/j.ijbiomac.2024.133062 -
ACS Applied Materials & Interfaces Jun 2024The ongoing global health has highlighted the critical issue of secondary infections, particularly antibiotic-resistant bacterial infections, which have been significant...
The ongoing global health has highlighted the critical issue of secondary infections, particularly antibiotic-resistant bacterial infections, which have been significant contributors to mortality rates. Orthopedic implants, while essential for trauma and orthopedic surgeries, are particularly susceptible to these infections, leading to severe complications and economic burdens. The traditional use of antibiotics in treating these infections poses further challenges including the risk of developing antibiotic-resistant bacteria. This study introduces a novel approach to combat this issue by developing nanostructured surfaces for orthopedic implants using target ion-induced plasma sputtering. Inspired by the natural design of dragonfly wings, these surfaces aim to prevent bacterial adhesion while promoting preosteoblast activity, offering a dual-function solution to the problems of bacterial infection and implant integration without relying on antibiotics. The in vitro results demonstrate the effectiveness of these bioinspired surfaces in eradicating bacteria and supporting cell proliferation and differentiation, presenting a promising alternative for the development of biomedical implants.
Topics: Anti-Bacterial Agents; Animals; Osseointegration; Nanostructures; Mice; Surface Properties; Staphylococcus aureus; Prostheses and Implants; Bacterial Adhesion; Osteoblasts; Cell Proliferation; Cell Line
PubMed: 38857475
DOI: 10.1021/acsami.4c06351 -
Nanoscale Jun 2024Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic...
Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O and GaPPIX upon US stimulation. The released O can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.
Topics: Animals; Fluorocarbons; Mice; Gallium; Protoporphyrins; Methicillin-Resistant Staphylococcus aureus; Biofilms; Oxygen; Ultrasonic Therapy; Staphylococcal Infections; Reactive Oxygen Species; Nanoparticles; Anti-Bacterial Agents; Mice, Inbred BALB C; Female; Pentanes
PubMed: 38855849
DOI: 10.1039/d4nr01244e -
Laryngoscope Investigative... Jun 2024To establish audiological and other outcomes following cochlear implantation in humans and animals with eluting electrodes. (Review)
Review
OBJECTIVES
To establish audiological and other outcomes following cochlear implantation in humans and animals with eluting electrodes.
METHODS
Systematic review and narrative synthesis. Databases searched (April 2023): MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov, and Web of Science. Studies reporting outcomes in either humans or animals following cochlear implantation with a drug-eluting electrode were included. No limits were placed on language or year of publication. Risk of bias assessment was performed on all included studies using either the Brazzelli or Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) assessment tools. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement.
RESULTS
Searches identified 146 abstracts and 108 full texts. Of these, 18 studies met the inclusion criteria, reporting outcomes in 523 animals (17 studies) and 24 humans (1 study). Eluting electrodes included dexamethasone (16 studies), aracytine (1 study), nicotinamide adenine dinucleotide (1 study), the growth factors insulin-like growth factor 1 (IGF1) and hepatocyte growth factor (HGF) (1 study), and neurotrophin-3 (1 study). All included studies compare outcomes following implantation with an eluting electrode with a control non-eluting electrode. In the majority of studies, audiological outcomes (e.g., auditory brainstem response threshold) were superior following implantation with an eluting electrode compared with a standard electrode. Most studies which investigated post-implantation impedance reported lower impedance following implantation with an eluting electrode. The influence of eluting electrodes on other reported outcomes (including post-implantation cochlear fibrosis and the survival of hair cells and spiral ganglion neurons) was more varied across the included studies.
CONCLUSIONS
Eluting electrodes have shown promise in animal studies in preserving residual hearing following cochlear implantation and in reducing impedance, though data from human studies remain lacking. Further in-human studies will be required to determine the clinical usefulness of drug-eluting cochlear implants as a future treatment for sensorineural hearing loss.
PubMed: 38855776
DOI: 10.1002/lio2.1263