From hit to vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation.

Vaccination can help prevent infection and can also be used to treat cancer, allergy, and potentially even drug overdose. Adjuvants enhance vaccine responses, but currently, the path to their advancement and development is incremental. We used a phenotypic small-molecule screen using THP-1 cells to identify nuclear factor-κB (NF-κB)-activating molecules followed by counterscreening lead target libraries with a quantitative tumor necrosis factor immunoassay using primary human peripheral blood mononuclear cells.

Species Delineation and Comparative Genomics within the Complex.

Campylobacter ureolyticus is an emerging pathogen increasingly appreciated as a common cause of gastroenteritis and extra-intestinal infections in humans. Outside the setting of gastroenteritis, little work has been done to describe the genomic content and relatedness of the species, especially regarding clinical isolates. We reviewed the epidemiology of clinical C.

Characteristics and calculations of paired vancomycin measurements for determination of 24-h area-under-curve (AUC).

Background: Current pharmacy practice guidelines recommend 24-h area-under-curve (AUC) targets for use of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA). AUC protocol-specific vancomycin orders were begun recently (2022) at our institution. We reviewed initial AUC protocol-associated data and calculations.

Estimated Impact of Low Isolate Numbers on the Reliability of Cumulative Antibiogram Data.

Antibiograms are cumulative reports of antimicrobial susceptibility results that are used to guide the selection of empirical antibiotic therapy. Although Clinical and Laboratory Standards Institute (CLSI) guidelines recommend including only organisms that have at least 30 isolates in an antibiogram, previous studies demonstrated that adherence to this recommendation is highly variable. This paper aims to model the impact of small sample sizes on expected levels of error in cumulative antibiograms by comparing percent susceptibility results for random samples to those of the larger, entire data set.

Outbreak of Burkholderia stabilis Infections Associated with Contaminated Nonsterile, Multiuse Ultrasound Gel - 10 States, May-September 2021.

In July 2021, the Virginia Department of Health notified CDC of a cluster of eight invasive infections with Burkholderia stabilis, a bacterium in the Burkholderia cepacia complex (BCC), among hospitalized patients at hospital A. Most patients had undergone ultrasound-guided procedures during their admission. Culture of MediChoice M500812 nonsterile ultrasound gel used in hospital A revealed contamination of unopened product with B.

Novel Assays for Molecular Detection of Severe Acute Respiratory Syndrome Coronavirus 2.

From the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/COVID-19 pandemic, there has been a major emphasis on molecular laboratory tests for the virus. Shortages in various testing supplies, the desire to increase testing capacity, and a push to make point-of-care or home-based testing available have fostered considerable innovation for SARS-CoV-2 molecular diagnostics, advancements likely to be applicable to other diagnostic uses. The authors attempt to cover some of the most compelling novel types of molecular assays or novel approaches in adapting established molecular methodologies for SARS-CoV-2 detection or characterization.

Clinical Microbiology in 2021: My Favorite Studies about Everything Except My Least Favorite Virus.

Maybe 2021 wasn't so bad after all! It was like 2020, but with COVID vaccines and better access to plastic pipette tips, and clearly, 2022 is getting off to a bad start. Even better, 2021 had some exciting papers in clinical microbiology, which is what is highlighted in this 2021 year in review. None of them are about COVID-19.

Bacille Calmette-Guérin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro.

Vaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology enables characterization of mechanisms of action, these tools have yet to be applied to infants, who are at high risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) and TB-unrelated infections via incompletely understood mechanisms.

Fever in a returning traveler: A case and literature review of melioidosis.

is an aerobic, motile, non-spore-forming gram-negative bacillus found in tropical endemic environments that causes the disease melioidosis. Melioidosis displays a diversity of clinical presentations ranging from septic shock to chronic latent infection, often with characteristic abscesses in multiple organs. Melioidosis is an opportunistic infection, with risk factors, including diabetes, alcohol use, chronic lung disease, and chronic renal disease, and these risk factors increase the severity of disease (Wiersinga et al.

Plasma Adenosine Deaminase (ADA)-1 and -2 Demonstrate Robust Ontogeny Across the First Four Months of Human Life.

Background: Human adenosine deaminases (ADAs) modulate the immune response: ADA1 metabolizing adenosine, a purine metabolite that inhibits pro-inflammatory and Th1 cytokine production, and the multi-functional ADA2, by enhancing T-cell proliferation and monocyte differentiation. Newborns are relatively deficient in ADA1 resulting in elevated plasma adenosine concentrations and a Th2/anti-inflammatory bias compared to adults. Despite the growing recognition of the role of ADAs in immune regulation, little is known about the ontogeny of ADA concentrations.

Modern Blood Culture: Management Decisions and Method Options.

The optimal care of septic patients depends on the successful recovery of clinically relevant microorganisms from blood cultures and the timely reporting of organism identification and antimicrobial susceptibility testing (AST) results. Many preanalytic factors play a critical role in culturing microorganisms, and advancements in blood culture instrument technology have reduced the time to positive results. Additionally, rapid organism identification and AST results directly from positive blood culture broth via new methods help to further shorten the time from empiric to targeted treatment.

Oral flora meningoencephalitis diagnosis by next-generation DNA sequencing.

Introduction: Standard culture methods may fail to detect the causative agents of bacterial infection for various reasons including specimen collection after antibiotic administration, or when standard techniques or environmental conditions are not appropriate for growth of the microorganisms. Conventional 16S rRNA gene sequencing is sometimes a useful alternative technique for identification of bacteria, but is confounded by polymicrobial infection. We present a case of a patient who developed a serious neurological infection for which causative oral flora organisms were observed by microscopy, failed to culture but were identified by next-generation DNA sequencing.

3-Dimensional Printed Alternative to the Standard Synthetic Flocked Nasopharyngeal Swabs Used for Coronavirus Disease 2019 Testing.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), can be detected in respiratory samples by real-time reverse transcriptase polymerase chain reaction (RT-PCR) or other molecular methods. Accessibility of diagnostic testing for COVID-19 has been limited by intermittent shortages of supplies required for testing, including flocked nasopharyngeal (FLNP) swabs.

Methods: We developed a 3-dimensional printed nasopharyngeal (3DP) swab as a replacement of the FLNP swab.

Can We Test Our Way Out of the COVID-19 Pandemic?

Frequent, low-cost, universal testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with quarantine of those with a positive result has been suggested as a strategy to address the coronavirus disease 2019 (COVID-19) pandemic in the United States. Specifically, home or community use of tests that use paper strip detection devices, which may have reduced sensitivity for SARS-CoV-2, has been advocated. There are several potential challenges or problems with this strategy, including the limited availability of such tests, consequences of incorrect test results, difficulties with adherence to testing, and the questionable accuracy of such tests for detection of infectious people.

Commercial Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Molecular Assays: Superior Analytical Sensitivity of cobas SARS-CoV-2 Relative to NxTAG CoV Extended Panel and ID NOW COVID-19 Test.

Context.—: We implemented multiple nucleic acid amplification test platforms because of the limited availability of test kits for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the early stages of the pandemic. Interpretation of results generated by different platforms and prioritization for testing algorithms required cross-comparison.

Hindsight Is 2019-the Year in Clinical Microbiology.

Much changed in clinical microbiology in 2019, and, like the organisms, we, as clinical microbiologists, are responsible to detect, characterize, and teach others about our discipline. Also, it is important for us to adapt to changes in the field. In this review, I highlight some of the papers, practices, and regulatory issues that defined 2019 for our field, from my perspective.

Cyclic AMP in human preterm infant blood is associated with increased TLR-mediated production of acute-phase and anti-inflammatory cytokines in vitro.

Background: Preterm infants are at high risk of infection and have distinct pathogen recognition responses. Suggested mechanisms include soluble mediators that enhance cellular levels of cAMP. The aim of this study was to assess the relationship between blood cAMP concentrations and TLR-mediated cytokine production in infants during the first month of life.

Probable Donor-Derived Human Adenovirus Type 34 Infection in 2 Kidney Transplant Recipients From the Same Donor.

Human adenovirus type 34 (HAdV-34) infection is a recognized cause of transplant-associated hemorrhagic cystitis and, in rare cases, tubulointerstitial nephritis. The source of such infections is often difficult to assess, that is, whether acquired as a primary infection, exposure to a pathogen in the transplanted organ, or reactivation of an endogenous latent infection. We present here 2 cases of likely transplant-acquired HAdV-34 infection from the same organ donor, manifesting as tubulointerstitial nephritis in 1.

Dynamic molecular changes during the first week of human life follow a robust developmental trajectory.

Systems biology can unravel complex biology but has not been extensively applied to human newborns, a group highly vulnerable to a wide range of diseases. We optimized methods to extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data from <1 ml of blood, a volume readily obtained from newborns. Indexing to baseline and applying innovative integrative computational methods reveals dramatic changes along a remarkably stable developmental trajectory over the first week of life.