Which allogeneic hematopoietic cell transplant recipients have an increased risk for delayed-onset clinically significant cytomegalovirus infection after letermovir prophylaxis?

Introduction: Cytomegalovirus (CMV) reactivation is one of the most common complications after allogeneic hematopoietic stem cell transplantation (HSCT). Letermovir is approved for CMV prophylaxis among high-risk recipients. However, delayed-onset post-prophylaxis clinically significant CMV infection (csCMVi) has been observed, suggesting the potential for extending letermovir prophylaxis beyond the first one hundred days post-HSCT.

Tiny but Nasty: A case report and a review of the literature on peritonitis.

, a member of the class, is a rare but significant pathogen in extragenital infections. This case report is the tenth known case of spp. peritonitis, occurring in a 36-year-old female post extensive surgery for metastatic sigmoid colon adenocarcinoma.

Risk Factors and Outcomes of Nocardiosis in Hematopoietic Stem Cell Transplantation Recipients.

Nocardiosis occurs in up to 1.7% of hematopoietic stem cell transplantation (HSCT) recipients. Risk factors for its development and subsequent outcomes have been incompletely studied.

Targeted Versus Shotgun Metagenomic Sequencing-based Detection of Microorganisms in Sonicate Fluid for Periprosthetic Joint Infection Diagnosis.

Background: Next-generation sequencing (NGS) is increasingly used for periprosthetic joint infection (PJI) diagnosis, but its clinical utility is poorly defined. Shotgun metagenomic sequencing (sNGS) has been reported to identify PJI pathogens undetected by culture in sonicate fluid. However, sNGS is complex and costly.

Metagenomic shotgun sequencing of blood to identify bacteria and viruses in leukemic febrile neutropenia.

Despite diagnostic advances in microbiology, the etiology of neutropenic fever remains elusive in most cases. In this study, we evaluated the utility of a metagenomic shotgun sequencing based assay for detection of bacteria and viruses in blood samples of patients with febrile neutropenia. We prospectively enrolled 20 acute leukemia patients and obtained blood from these patients at three time points: 1) anytime from onset of neutropenia until before development of neutropenic fever, 2) within 24 hours of onset of neutropenic fever, 3) 5-7 days after onset of neutropenic fever.

Detection of Pathogenic Bacteria From Septic Patients Using 16S Ribosomal RNA Gene-Targeted Metagenomic Sequencing.

Background: Conventional blood cultures were compared to plasma cell-free DNA-based 16S ribosomal RNA (rRNA) gene polymerase chain reaction (PCR)/next-generation sequencing (NGS) for detection and identification of potential pathogens in patients with sepsis.

Methods: Plasma was prospectively collected from 60 adult patients with sepsis presenting to the Mayo Clinic (Minnesota) Emergency Department from March through August 2019. Results of routine clinical blood cultures were compared to those of 16S rRNA gene NGS.

rhinosinusitis post chimeric antigen receptor T-cell therapy.

Chimeric antigen receptor T-cell (CAR-T) therapy is a novel treatment for various types of hematologic malignancy. We presented a case of refractory diffuse large B cell lymphoma patient who developed acute invasive fungal rhinosinusitis (AIFR) from species after CAR-T therapy. Our photos illustrated the classic clinical, endoscopic, and histopathologic findings of AIFR.

Targeted Metagenomics Offers Insights into Potential Tick-Borne Pathogens.

Tick-borne disease pathogen identification remains a diagnostic challenge due to the multiple tests necessary for diagnosis. Targeted metagenomic sequencing is an evolving method to detect multiple different pathogens with a single test. In this issue of the , L.

Comparison of Three Commercial Tools for Metagenomic Shotgun Sequencing Analysis.

Metagenomic shotgun sequencing for the identification of pathogens is being increasingly utilized as a diagnostic method. Interpretation of large and complicated data sets is a significant challenge, for which multiple commercial tools have been developed. Three commercial metagenomic shotgun sequencing tools, CosmosID, One Codex, and IDbyDNA, were compared to determine whether they result in similar interpretations of the same sequencing data.

Application of metagenomic shotgun sequencing to detect vector-borne pathogens in clinical blood samples.

Background: Vector-borne pathogens are a significant public health concern worldwide. Infections with these pathogens, some of which are emerging, are likely under-recognized due to the lack of widely-available laboratory tests. There is an urgent need for further advancement in diagnostic modalities to detect new and known vector-borne pathogens.

Evaluation of the CosmosID Bioinformatics Platform for Prosthetic Joint-Associated Sonicate Fluid Shotgun Metagenomic Data Analysis.

We previously demonstrated that shotgun metagenomic sequencing can detect bacteria in sonicate fluid, providing a diagnosis of prosthetic joint infection (PJI). A limitation of the approach that we used is that data analysis was time-consuming and specialized bioinformatics expertise was required, both of which are barriers to routine clinical use. Fortunately, automated commercial analytic platforms that can interpret shotgun metagenomic data are emerging.

Direct Detection and Identification of Prosthetic Joint Infection Pathogens in Synovial Fluid by Metagenomic Shotgun Sequencing.

Metagenomic shotgun sequencing has the potential to transform how serious infections are diagnosed by offering universal, culture-free pathogen detection. This may be especially advantageous for microbial diagnosis of prosthetic joint infection (PJI) by synovial fluid analysis since synovial fluid cultures are not universally positive and since synovial fluid is easily obtained preoperatively. We applied a metagenomics-based approach to synovial fluid in an attempt to detect microorganisms in 168 failed total knee arthroplasties.

Identification of Prosthetic Joint Infection Pathogens Using a Shotgun Metagenomics Approach.

Background: Metagenomic shotgun sequencing has the potential to change how many infections, particularly those caused by difficult-to-culture organisms, are diagnosed. Metagenomics was used to investigate prosthetic joint infections (PJIs), where pathogen detection can be challenging.

Methods: Four hundred eight sonicate fluid samples generated from resected hip and knee arthroplasties were tested, including 213 from subjects with infections and 195 from subjects without infection.

A Novel Prosthetic Joint Infection Pathogen, Mycoplasma salivarium, Identified by Metagenomic Shotgun Sequencing.

Defining the microbial etiology of culture-negative prosthetic joint infection (PJI) can be challenging. Metagenomic shotgun sequencing is a new tool to identify organisms undetected by conventional methods. We present a case where metagenomics was used to identify Mycoplasma salivarium as a novel PJI pathogen in a patient with hypogammaglobulinemia.

Impact of Contaminating DNA in Whole-Genome Amplification Kits Used for Metagenomic Shotgun Sequencing for Infection Diagnosis.

Whole-genome amplification (WGA) is a useful tool for amplification of very small quantities of DNA for many uses, including metagenomic shotgun sequencing for infection diagnosis. Depending on the application, background DNA from WGA kits can be problematic. Three WGA kits were tested for their utility in a metagenomics approach to identify the pathogens in sonicate fluid comprised of biofilms and other materials dislodged from the surfaces of explanted prosthetic joints using sonication.

Comparison of microbial DNA enrichment tools for metagenomic whole genome sequencing.

Metagenomic whole genome sequencing for detection of pathogens in clinical samples is an exciting new area for discovery and clinical testing. A major barrier to this approach is the overwhelming ratio of human to pathogen DNA in samples with low pathogen abundance, which is typical of most clinical specimens. Microbial DNA enrichment methods offer the potential to relieve this limitation by improving this ratio.

Random mutagenesis and topology analysis of the autoinducing peptide biosynthesis proteins in Staphylococcus aureus.

The Staphylococcus aureus accessory gene regulator (agr) is a peptide signalling system that regulates the production of secreted virulence factors required to cause infections. The signal controlling agr function is a 7-9 residue thiolactone-containing peptide called an autoinducing peptide (AIP) that is biosynthesized from the AgrD precursor by the membrane peptidase AgrB. To gain insight into AgrB and AgrD function, the agrBD genes were mutagenized and screened for deficiencies in AIP production.

Staphylococcus aureus regulates the expression and production of the staphylococcal superantigen-like secreted proteins in a Rot-dependent manner.

Staphylococcus aureus overproduces a subset of immunomodulatory proteins known as the staphylococcal superantigen-like proteins (Ssls) under conditions of pore-mediated membrane stress. In this study we demonstrate that overproduction of Ssls during membrane stress is due to the impaired activation of the two-component module of the quorum-sensing accessory gene regulator (Agr) system. Agr-dependent repression of ssl expression is indirect and mediated by the transcription factor repressor of toxins (Rot).

agr-Dependent interactions of Staphylococcus aureus USA300 with human polymorphonuclear neutrophils.

The emergence of serious infections due to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has fueled interest in the contributions of specific staphylococcal virulence factors to clinical disease. To assess the contributions of agr-dependent factors to the fate of organisms in polymorphonuclear neutrophils (PMN), we examined the consequences for organism and host cells of feeding PMN with wild-type CA-MRSA (LAC) or CA-MRSA (LAC agr KO) at different multiplicities of infection (MOIs). Phagocytosed organisms rapidly increased the transcription of RNAIII in a time- and MOI-dependent fashion; extracellular USA300 (LAC) did not increase RNAIII expression despite having the capacity to respond to autoinducing peptide-enriched culture medium.