Phage therapy is a promising antibacterial strategy, especially given that drug-resistant bacterial infections are escalating worldwide. Because phages are not active against all strains of a given species, phages being considered for therapeutic use would ideally be tested against bacterial isolates from individual patients prior to administration. Standardized, clinically validated phage susceptibility testing (PST) methods are needed for assessing phage activity.
View Article and Find Full Text PDFUnlabelled: Wound infections, exacerbated by the prevalence of antibiotic-resistant bacterial pathogens, necessitate innovative antimicrobial approaches. Polymicrobial infections, often involving and methicillin-resistant (MRSA), present challenges due to biofilm formation and antibiotic resistance. Hypochlorous acid (HOCl), a potent antimicrobial agent, holds promise as an alternative therapy.
View Article and Find Full Text PDFUnlabelled: Over 2.5 million prosthetic joint implantation surgeries occur annually in the United States. Periprosthetic joint infections (PJIs), though occurring in only 1-2% of patients receiving replacement joints, are challenging to diagnose and treat and are associated with significant morbidity.
View Article and Find Full Text PDFIntroduction: Implant sonication is useful for recovery of periprosthetic joint infection (PJI) pathogens in culture, but exact cutoff points for definition of clinically significant sonicate fluid culture results vary from study to study. The aim of this study was to define ideal sonicate fluid culture cutoff points for PJI diagnosis.
Methods: Sonicate fluid cultures from hip and knee prosthesis components removed between February 2007 and December 2020 were studied.
Staphylococcus epidermidis is part of the commensal microbiota of the skin and mucous membranes, though it can also act as a pathogen in certain scenarios, causing a range of infections, including periprosthetic joint infection (PJI). Transcriptomic profiling may provide insights into mechanisms by which S. epidermidis adapts while in a pathogenic compared to a commensal state.
View Article and Find Full Text PDFWound infections, exacerbated by the prevalence of antibiotic-resistant bacterial pathogens, necessitate innovative antimicrobial approaches. Polymicrobial infections, often involving and methicillin-resistant (MRSA), present formidable challenges due to biofilm formation and antibiotic resistance. Hypochlorous acid (HOCl), a potent antimicrobial agent produced naturally by the immune system, holds promise as an alternative therapy.
View Article and Find Full Text PDFOver 2.5 million prosthetic joint implantation surgeries occur annually in the United States. Periprosthetic joint infections (PJIs), though occurring in only 1-2% of patients receiving replacement joints, are challenging to diagnose and treat and are associated with significant morbidity.
View Article and Find Full Text PDFAntimicrob Agents Chemother
February 2024
The growing threat of antibiotic-resistant bacterial pathogens necessitates the development of alternative antimicrobial approaches. This is particularly true for chronic wound infections, which commonly harbor biofilm-dwelling bacteria. A novel electrochemical bandage (e-bandage) delivering low-levels of hypochlorous acid (HOCl) was evaluated against murine wound biofilms.
View Article and Find Full Text PDFStandardized approaches to phage susceptibility testing (PST) are essential to inform selection of phages for study in patients with bacterial infections. There is no reference standard for assessing bacterial susceptibility to phage. We compared agreement between PST performed at three centers: two centers using a liquid assay standardized between the sites with the third, a plaque assay.
View Article and Find Full Text PDFDeveloping and implementing the scientific agenda of the Antibacterial Resistance Leadership Group (ARLG) by soliciting input and proposals, transforming concepts into clinical trials, conducting those trials, and translating trial data analyses into actionable information for infectious disease clinical practice is the collective role of the Scientific Leadership Center, Clinical Operations Center, Statistical and Data Management Center, and Laboratory Center of the ARLG. These activities include shepherding concept proposal applications through peer review; identifying, qualifying, training, and overseeing clinical trials sites; recommending, developing, performing, and evaluating laboratory assays in support of clinical trials; and designing and performing data collection and statistical analyses. This article describes key components involved in realizing the ARLG scientific agenda through the activities of the ARLG centers.
View Article and Find Full Text PDFA novel electrochemical bandage (e-bandage) delivering low-level hypochlorous acid (HOCl) was evaluated against murine wound biofilms. 5 mm skin wounds were created on the dorsum of Swiss-Webster mice and infected with 10 colony forming units (CFU) of . Biofilms were formed over two days, after which e-bandages were placed on the wound beds and covered with Tegaderm™.
View Article and Find Full Text PDFRapid detection of carbapenemase (KPC) in the species is desirable. The MALDI Biotyper MBT Subtyping Module (Bruker Daltonics) uses an algorithm that detects a peak at ~11,109 m/z corresponding to a protein encoded by the gene to detect KPC simultaneously with organism identification by a matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-ToF MS). Here, the subtyping module was evaluated using 795 clinical isolates, with whole genome sequences used to assess for and .
View Article and Find Full Text PDFAims: As antimicrobial resistance is on the rise, treating chronic wound infections is becoming more complex. The presence of biofilms in wound beds contributes to this challenge. Here, the activity of a novel hypochlorous acid (HOCl) producing electrochemical bandage (e-bandage) against monospecies and dual-species bacterial biofilms formed by bacteria commonly found in wound infections was assessed.
View Article and Find Full Text PDFBiofilms formed by antibiotic-resistant bacteria in wound beds present unique challenges in terms of treating wound infections. In this work, the activity of a novel electrochemical bandage (e-bandage) composed of carbon fabric and controlled by a wearable potentiostat, designed to continuously deliver low amounts of hydrogen peroxide (HO) was evaluated against methicillin-resistant (MRSA), multidrug-resistant (MDR-PA) and mixed-species (MRSA and MDR-PA) wound infections. Wounds created on Swiss Webster mice were infected with the above-named bacteria and biofilms allowed to establish on wound beds for 3 days.
View Article and Find Full Text PDFSequencing is increasingly used for infective endocarditis (IE) diagnosis. Here, the performance of 16S rRNA gene PCR/sequencing of heart valves utilized in routine clinical practice was compared with conventional IE diagnostics. Subjects whose heart valves were sent to the clinical microbiology laboratory for 16S rRNA gene PCR/sequencing from August 2020 through February 2022 were studied.
View Article and Find Full Text PDFPurpose: This pilot study aimed to use proteomic profiling of sonicate fluid samples to compare host response during Staphylococcus aureus-associated periprosthetic joint infection (PJI) and non-infected arthroplasty failure (NIAF) and identify potential novel biomarkers differentiating the two.
Experimental Design: In this pilot study, eight sonicate fluid samples (four from NIAF and four from S. aureus PJI) were studied.
Chronic wound biofilm infections represent a major clinical challenge which results in a substantial burden to patients and healthcare systems. Treatment with topical antibiotics is oftentimes ineffective as a result of antibiotic-resistant microorganisms and biofilm-specific antibiotic tolerance. Use of biocides such as hypochlorous acid (HOCl) has gained increasing attention due to the lack of known resistance mechanisms.
View Article and Find Full Text PDFTrials
December 2022
Background: Bacteriophages (phages) are a promising anti-infective option for human disease. Major gaps remain in understanding their potential utility.
Methods: This is a randomized, placebo-controlled, double-blind study of a single dose of intravenous phage in approximately 72 clinically stable adult cystic fibrosis volunteers recruited from up to 20 US sites with Pseudomonas aeruginosa airway colonization.
Background: Although cellularity is traditionally assessed morphologically, deep sequencing approaches being used for microorganism detection may be able to provide information about cellularity. We hypothesized that cellularity predicted using CIBERSORTx (Stanford University), a transcriptomic-based cellular deconvolution tool, would differentiate between infectious and non-infectious arthroplasty failure.
Methods: CIBERSORTx-derived cellularity profiles of 93 sonicate fluid samples, including 53 from subjects who underwent failed arthroplasties due to periprosthetic joint infection (PJI) (abbreviated for the purpose of this study as PJIF) and 40 from subjects who had undergone non-infectious arthroplasty failure (abbreviated NIAF) that had been subjected to bulk RNA sequencing were evaluated.
The antibiofilm activity of a hypochlorous acid (HOCl)-producing electrochemical bandage (e-bandage) was assessed against 14 yeast isolates . The evaluated e-bandage was polarized at +1.5 V to allow continuous production of HOCl.
View Article and Find Full Text PDFJ Clin Microbiol
December 2022
The diagnosis of periprosthetic joint infection (PJI) is challenging, often requiring multiple clinical specimens and diagnostic techniques, some with prolonged result turnaround times. Here, the diagnostic performance of the Investigational Use Only (IUO) BioFire Joint Infection (JI) Panel was compared to 16S rRNA gene-based targeted metagenomic sequencing (tMGS) applied to synovial fluid for PJI diagnosis. Sixty synovial fluid samples from knee arthroplasty failure archived at -80°C were tested.
View Article and Find Full Text PDFPreoperative pathogen identification in patients with periprosthetic joint infection (PJI) is typically limited to synovial fluid culture. Whether sequencing-based approaches are of potential use in identification of pathogens in PJI, and if so which approach is ideal, is incompletely defined. The objective of the study was to analyze the accuracy of a 16S rRNA (rRNA) gene-based PCR followed by Sanger sequencing and/or targeted metagenomic sequencing approach (tMGS) performed on synovial fluid for PJI diagnosis.
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