Search

This study provides comprehensive information about the impact of the parent vessel's shape on the risk of cerebral aneurysm rupture. It focuses on internal carotid artery (ICA) aneurysms with varying parent vessel sizes, analyzing different aspects of blood flow dynamics. By comparing various hemodynamic factors such as wall shear stress (WSS), oscillatory shear index (OSI) and pressure distribution, the researchers aim to establish a meaningful relationship between the parent vessel's mean diameter and these significant hemodynamic parameters. [ABSTRACT FROM AUTHOR]

Abstract The influence of the aneurysm evolution on the hemodynamic characteristic of the blood flow inside the sac region is comprehensively investigated. By using the computational method, the blood flow through the vessel and aneurysm of the sac region is examined to find the role of aneurysm evolution on the wall shear stress, pressure, and risk of aneurysm rupture. Three different models of ICA aneurysms are chosen for the investigation of the aneurysm evolution at risk of rupture. Obtained data shows that the evolution of the aneurysm decreases the wall shear stress and pressure on the sac surface while an oscillatory index of blood increases on the aneurysm wall.

Background: Klebsiella pneumoniae is a common Gram-negative bacterium. Blood infection caused by K. pneumoniae is one of the most common causes of human sepsis, which seriously threatens the life of patients. The immune status of peripheral blood mononuclear cells (PBMCs) based on single-cell RNA sequencing (scRNA-seq) in acute stage and recovery stage of sepsis caused by K. pneumoniae bloodstream infection has not been studied. Methods: A total of 13 subjects were included in this study, 3 healthy controls, 7 patients with K. pneumoniae bloodstream infection in the acute stage (4 patients died), and 3 patients in the recovery stage. Peripheral blood of all patients was collected and PBMCs were isolated for scRNA-seq analysis. We studied the changes of PBMCs components, signaling pathways, differential genes, and cytokines in acute and recovery stages. Results: During K. pneumoniae acute infection we observed a decrease in the proportion of T cells, most probably due to apoptosis and the function of T cell subtypes was disorder. The proportion of monocytes increased in acute stage. Although genes related to their phagocytosis function were upregulated, their antigen presentation capacity-associated genes were downregulated. The expression of IL-1b, IL-18, IFNGR1 and IFNGR2 genes was also increased in monocytes. The proportion of DCs was depleted during the acute stage and did not recover during sepsis recovery. DCs antigen presentation was weakened during the acute stage but recovered fast during the recovery stage. pDCs response to MCP-1 chemokine was weakened, they recovered it quickly during the recovery stage. B cells showed apoptosis both in the acute stage and recovery stage. Their response to complement was weakened, but their antigen presentation function was enhanced. The proportion of NK cells stable during all disease's stages, and the expression of IFN-g gene was upregulated. Conclusion: The proportion of PBMCs and their immune functions undergo variations throughout the course of the disease, spanning from the acute stage to recovery. These findings provide new insights into the mechanism of PBMCs immune function during K. pneumoniae bloodstream infection sepsis and recovery and sets the basis for further understanding and treatment. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus bacteremia continues to be associated with significant morbidity and mortality, despite improvements in diagnostics and management. Persistent infections pose a major challenge to clinicians and have been consistently shown to increase the risk of mortality and other infectious complications. S. aureus, while typically not considered an intracellular pathogen, has been proven to utilize an intracellular niche, through several phenotypes including small colony variants, as a means for survival that has been linked to chronic, persistent, and recurrent infections. This intracellular persistence allows for protection from the host immune system and leads to reduced antibiotic efficacy through a variety of mechanisms. These include antimicrobial resistance, tolerance, and/or persistence in S. aureus that contribute to persistent bacteremia. This review will discuss the challenges associated with treating these complicated infections and the various methods that S. aureus uses to persist within the intracellular space. [ABSTRACT FROM AUTHOR]

The quantification of arsenic, mercury, cadmium and lead in the human bloodstream is routinely used today to assess exposure to these toxic metal(loid)s, but the interpretation of the obtained data in terms of their cumulative health relevance remains problematic. Seemingly unrelated to this, epidemiological studies strongly suggest that the simultaneous chronic exposure to these environmental pollutants is associated with the etiology of autism, type 2 diabetes, irritable bowel disease and other diseases. This from a public health point of view undesirable situation urgently requires research initiatives to establish functional connections between human exposure to multiple toxic metal(loid) species and adverse health effects. One way to establish causal exposure-response relationships is a molecular toxicology approach, which requires one to unravel the biomolecular mechanisms that unfold after individual toxic metal(loid)s enter the bloodstream/organ nexus as these interactions ultimately determine which metabolites impinge on target organs and thus provide mechanistic links to diseases of unknown etiology. In an attempt to underscore the importance of the toxicological chemistry of metal(loid)s in the bloodstream, this review summarizes recent progress into relevant bioinorganic processes that are implicated in the etiology of adverse organ-based health effects and possibly diseases. A better understanding of these bioinorganic processes will not only help to improve the regulatory framework to better protect humans from the adverse effects of toxic metal(loid) species, but also represents an important starting point for the development of treatments to ameliorate pollution-induced adverse health effects on human populations, including pregnant women, the fetus and children. [ABSTRACT FROM AUTHOR]

The influence of the aneurysm evolution on the hemodynamic characteristic of the blood flow inside the sac region is comprehensively investigated. By using the computational method, the blood flow through the vessel and aneurysm of the sac region is examined to find the role of aneurysm evolution on the wall shear stress, pressure, and risk of aneurysm rupture. Three different models of ICA aneurysms are chosen for the investigation of the aneurysm evolution at risk of rupture. Obtained data shows that the evolution of the aneurysm decreases the wall shear stress and pressure on the sac surface while an oscillatory index of blood increases on the aneurysm wall. [ABSTRACT FROM AUTHOR]

Abstract Background Healthcare-associated infections (HCAI) place a significant burden on healthcare systems globally. This systematic review and meta-analysis aimed to investigate the prevalence, risk factors, and aetiologic agents of endemic HCAI in Africa. Methods MEDLINE/PubMed, CINAHL, and Global Health databases (EBSCOhost interface) were searched for studies published in English and French describing HCAI in Africa from 2010 to 2022. We extracted data on prevalence of HCAI, risk factors, aetiologic agents, and associated antimicrobial resistance patterns. We used random-effects models to estimate parameter values with 95% confidence intervals for risk factors associated with HCAI. This study was registered in PROSPERO (CRD42022374559) and followed PRISMA 2020 guidelines. Results Of 2541 records screened, 92 were included, comprising data from 81,968 patients. Prevalence of HCAI varied between 1.6 and 90.2% with a median of 15% across studies. Heterogeneity (I 2 ) varied from 93 to 99%. Contaminated wound (OR: 1.75, 95% CI: 1.31–2.19), long hospital stay (OR: 1.39, 95% CI: 0.92–1.80), urinary catheter (OR: 1.57, 95% CI: 0.35–2.78), intubation and ventilation (OR: 1.53, 95% CI: 0.85–2.22), vascular catheters (OR: 1.49, 95% CI: 0.52–2.45) were among risk factors associated with HCAI. Bacteria reported from included studies comprised 6463 isolates, with E. coli (18.3%, n = 1182), S. aureus (17.3%, n = 1118), Klebsiella spp. (17.2%, n = 1115), Pseudomonas spp. (10.3%, n = 671), and Acinetobacter spp. (6.8%, n = 438) being most common. Resistance to multiple antibiotics was common; 70.3% (IQR: 50–100) of Enterobacterales were 3rd -generation cephalosporin resistant, 70.5% (IQR: 58.8–80.3) of S. aureus were methicillin resistant and 55% (IQR: 27.3–81.3) Pseudomonas spp. were resistant to all agents tested. Conclusions HCAI is a greater problem in Africa than other regions, however, there remains a paucity of data to guide local action. There is a clear need to develop and validate sustainable HCAI definitions in Africa to support the implementation of routine HCAI surveillance and inform implementation of context appropriate infection prevention and control strategies.

The geometrical aspects of the saccular aneurysm are an important factor for the rupture of aneurysm. In this paper, the effects of the sac centerline on the aneurysm rupture are fully investigated. Our attention is to disclose the important factors related to aneurysm rupture in different time instants. CFD method is applied for the analysis of WSS, OSI, pressure and velocity inside the saccular aneurysm with different sac centerlines. Our results also show that the coiling technique could sufficiently decrease the risk of rupture since decreasing the coil porosity (increasing the coil permeability) would increase the OSI and pressure and decrease WSS and blood velocity inside the aneurysm sac. [ABSTRACT FROM AUTHOR]

Background: Healthcare-associated infections (HCAI) place a significant burden on healthcare systems globally. This systematic review and meta-analysis aimed to investigate the prevalence, risk factors, and aetiologic agents of endemic HCAI in Africa. Methods: MEDLINE/PubMed, CINAHL, and Global Health databases (EBSCOhost interface) were searched for studies published in English and French describing HCAI in Africa from 2010 to 2022. We extracted data on prevalence of HCAI, risk factors, aetiologic agents, and associated antimicrobial resistance patterns. We used random-effects models to estimate parameter values with 95% confidence intervals for risk factors associated with HCAI. This study was registered in PROSPERO (CRD42022374559) and followed PRISMA 2020 guidelines. Results: Of 2541 records screened, 92 were included, comprising data from 81,968 patients. Prevalence of HCAI varied between 1.6 and 90.2% with a median of 15% across studies. Heterogeneity (I2) varied from 93 to 99%. Contaminated wound (OR: 1.75, 95% CI: 1.31–2.19), long hospital stay (OR: 1.39, 95% CI: 0.92–1.80), urinary catheter (OR: 1.57, 95% CI: 0.35–2.78), intubation and ventilation (OR: 1.53, 95% CI: 0.85–2.22), vascular catheters (OR: 1.49, 95% CI: 0.52–2.45) were among risk factors associated with HCAI. Bacteria reported from included studies comprised 6463 isolates, with E. coli (18.3%, n = 1182), S. aureus (17.3%, n = 1118), Klebsiella spp. (17.2%, n = 1115), Pseudomonas spp. (10.3%, n = 671), and Acinetobacter spp. (6.8%, n = 438) being most common. Resistance to multiple antibiotics was common; 70.3% (IQR: 50–100) of Enterobacterales were 3rd -generation cephalosporin resistant, 70.5% (IQR: 58.8–80.3) of S. aureus were methicillin resistant and 55% (IQR: 27.3–81.3) Pseudomonas spp. were resistant to all agents tested. Conclusions: HCAI is a greater problem in Africa than other regions, however, there remains a paucity of data to guide local action. There is a clear need to develop and validate sustainable HCAI definitions in Africa to support the implementation of routine HCAI surveillance and inform implementation of context appropriate infection prevention and control strategies. [ABSTRACT FROM AUTHOR]

We report a case of Spiroplasma bloodstream infection in a patient in China who developed pulmonary infection, acute respiratory distress syndrome, sepsis, and septic shock after emergency surgery for type A aortic dissection. One organism closely related to Spiroplasma eriocheiris was isolated from blood culture and identified by whole-genome sequencing.

Background: Bloodstream infections (BSI) in immunocompromised patients suffering from hematological malignancies continue to be an essential cause of morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA)-related BSI in patients with febrile neutropenia (FN) is a life-threatening bacterial infection and extremely challenging to treat. Methods: Blood samples were collected from febrile neutropenic patients. Conventional blood culture and direct PCR identification of 16S rRNA, mecA, femA, nuc, and lukS genes were performed for detection of MRSA. Antibiotic sensitivity profiles of the isolates were investigated using disc diffusion and minimum inhibitory concentration methods. Results: Among 24 positive blood cultures isolates, MRSA (12/24, 50%) was the predominant bacteria followed by coagulase negative staphylococci (CoNS) (6/24, 33.3%). All MRSA isolates were resistant to cefoxitin (MIC ≥ 8 μg/ml), and oxacillin (MIC ≥ 4 μg/ml) and harbored mecA gene. 10/12 MRSA isolates were vancomycin resistant (VRSA) (MIC ≥ 16 μg/ml). PCR for 16S rRNA and mecA genes yielded positive results in 14 negative blood culture samples. Conclusions: We cannot rely on blood culture as a reliable method for BSI diagnosis in patients with FN. 16S rRNA and characteristic MRSA genes PCR showed important role for diagnosis of culture-negative MRSA BSI particularly in patients with preceding prophylactic or empirical antibiotics.

Background: Bloodstream infections (BSI) in immunocompromised patients suffering from hematological malignancies continue to be an essential cause of morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA)-related BSI in patients with febrile neutropenia (FN) is a life-threatening bacterial infection and extremely challenging to treat. Methods: Blood samples were collected from febrile neutropenic patients. Conventional blood culture and direct PCR identification of 16S rRNA, mecA, femA, nuc, and lukS genes were performed for detection of MRSA. Antibiotic sensitivity profiles of the isolates were investigated using disc diffusion and minimum inhibitory concentration methods. Results: Among 24 positive blood cultures isolates, MRSA (12/24, 50%) was the predominant bacteria followed by coagulase negative staphylococci (CoNS) (6/24, 33.3%). All MRSA isolates were resistant to cefoxitin (MIC ≥ 8 μg/ml), and oxacillin (MIC ≥ 4 μg/ml) and harbored mecA gene. 10/12 MRSA isolates were vancomycin resistant (VRSA) (MIC ≥ 16 μg/ml). PCR for 16S rRNA and mecA genes yielded positive results in 14 negative blood culture samples. Conclusions: We cannot rely on blood culture as a reliable method for BSI diagnosis in patients with FN. 16S rRNA and characteristic MRSA genes PCR showed important role for diagnosis of culture-negative MRSA BSI particularly in patients with preceding prophylactic or empirical antibiotics. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus bacteremia continues to be associated with significant morbidity and mortality, despite improvements in diagnostics and management. Persistent infections pose a major challenge to clinicians and have been consistently shown to increase the risk of mortality and other infectious complications. S. aureus, while typically not considered an intracellular pathogen, has been proven to utilize an intracellular niche, through several phenotypes including small colony variants, as a means for survival that has been linked to chronic, persistent, and recurrent infections. This intracellular persistence allows for protection from the host immune system and leads to reduced antibiotic efficacy through a variety of mechanisms. These include antimicrobial resistance, tolerance, and/or persistence in S. aureus that contribute to persistent bacteremia. This review will discuss the challenges associated with treating these complicated infections and the various methods that S. aureus uses to persist within the intracellular space.

Cefiderocol is generally active against carbapenem-resistant Klebsiella spp. (CRK) with higher MICs against metallo-beta-lactamase producers. There is a variation in cefiderocol interpretive criteria determined by EUCAST and CLSI. Our objective was to test CRK isolates against cefiderocol and compare cefiderocol susceptibilities using EUCAST and CLSI interpretive criteria. A unique collection (n = 254) of mainly OXA-48-like- or NDM-producing CRK bloodstream isolates were tested against cefiderocol with disc diffusion (Mast Diagnostics, UK). Beta-lactam resistance genes and multilocus sequence types were identified using bioinformatics analyses on complete bacterial genomes. Median cefiderocol inhibition zone diameter was 24 mm (interquartile range [IQR] 24–26 mm) for all isolates and 18 mm (IQR 15–21 mm) for NDM producers. We observed significant variability between cefiderocol susceptibilities using EUCAST and CLSI breakpoints, such that 26% and 2% of all isolates, and 81% and 12% of the NDM producers were resistant to cefiderocol using EUCAST and CLSI interpretive criteria, respectively. Cefiderocol resistance rates among NDM producers are high using EUCAST criteria. Breakpoint variability may have significant implications on patient outcomes. Until more clinical outcome data are available, we suggest using EUCAST interpretive criteria for cefiderocol susceptibility testing. [ABSTRACT FROM AUTHOR]

Background and Objective: Recent reports describe the existence of a blood microbiome profile not associated with an infection state. Given the high impact that the dysbiotic human microbiome appears to have in chronic kidney disease and, in particular, in the outcome of kidney transplant recipients (KTRs), we aimed to explore the variations and correlations of the gut, oral, and blood microbiome of recipients, 3 months after kidney transplantation. Materials and Methods: We conducted a cross-sectional study where the microbiome of stool, saliva, and blood collected from recipients 3 months after kidney transplantation (N = 6) was analyzed by polymerase chain reaction (PCR) amplification and sequencing of the V3--V4 hypervariable regions of the 16S rRNA gene using MiSeq Illumina® technology. Results: Blood of KTRs harbors a distinct low-abundance microbiome dominated by Proteobacteria and Firmicutes. Gut and oral microbiome of KTRs also present distinct profiles. The existence of a proportion of shared operational taxonomic units among the different body sites is reported, mainly classified as Proteobacteria and Firmicutes. Conclusions: This study provides evidence of existence a blood microbiome in KTRs, different from the gut and the oral microbiome profiles, with a small number of operational taxonomic units representing a shared microbiome. The clinical relevance of this observation should be further explored in these patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Klebsiella oxytoca is an opportunistic pathogen causing serious nosocomial infections. Knowledge about the population structure and diversity of healthcare-associated K. oxytoca from a genomic standpoint remains limited. Here, we characterized the phylogenetic relationships and genomic characteristics of 20 K. oxytoca sensu stricto isolates recovered from bloodstream infections at the Dartmouth-Hitchcock Medical Center, New Hampshire, USA from 2017 to 2021. Results revealed a diverse population consisting of 15 sequence types (STs) that together harbored 10 variants of the intrinsic beta-lactamase gene bla OXY-2, conferring resistance to penicillins. Similar sets of antimicrobial resistance (AMR) determinants reside in multiple distinct lineages, with no one lineage dominating the local population. To place the New Hampshire K. oxytoca in a broader context, we compared them to 304 publicly available genomes of clinical isolates from 18 countries. This global clinical K. oxytoca sensu stricto population is represented by over 65 STs that together harbored resistance genes against 14 antimicrobial classes, including eight bla OXY-2 variants. Three dominant STs in the global population (ST2, ST176, ST199) circulate across multiple countries and were also present in the New Hampshire population. The global K. oxytoca population is genetically diverse, but there is evidence for broad dissemination of a few lineages carrying distinct set of AMR determinants. Our findings reveal the clinical diversity of K. oxytoca sensu stricto and its importance in surveillance efforts aimed at monitoring the evolution of this drug-resistant nosocomial pathogen. IMPORTANCE The opportunistic pathogen Klebsiella oxytoca has been increasingly implicated in patient morbidity and mortality worldwide, including several outbreaks in healthcare settings. The emergence and spread of antimicrobial resistant strains exacerbate the disease burden caused by this species. Our study showed that clinical K. oxytoca sensu stricto is phylogenetically diverse, harboring various antimicrobial resistance determinants and bla OXY-2 variants. Understanding the genomic and population structure of K. oxytoca is important for international initiatives and local epidemiological efforts for surveillance and control of drug-resistant K. oxytoca.

Although chronic low-level exposure to Hg2+ and Cd2+ causes human nephrotoxicity, the bioinorganic processes that deliver them to their target organs are poorly understood. Since the plasma protein human serum albumin (HSA) has distinct binding sites for these metal ions, we wanted to gain insight into these translocation processes and have employed size-exclusion chromatography coupled on-line to an inductively coupled plasma atomic emission spectrometer using phosphate-buffered saline mobile phases. When HSA 'labeled' with Hg2+ and Cd2+ (1:0.1:0.1) using 300 μM of L-methionine was analyzed, the co-elution of a single C, S, Cd, and Hg peak was observed, which implied the intact bis-metalated HSA complex. Since human plasma contains small molecular weight thiols and sulfur-containing metabolites, we analyzed the bis-metalated HSA complex with mobile phases containing 50–200 µM of L-cysteine (Cys), D,L-homocysteine (hCys), or glutathione (GSH), which provided insight into the comparative mobilization of each metal from their respective binding sites on HSA. Interestingly, 50 µM Cys, hCys, or GSH mobilized Hg2+ from its HSA binding site but only partially mobilized Cd2+ from its binding site. Since these findings were obtained at conditions simulating near-physiological conditions of plasma, they provide a feasible explanation for the higher 'mobility' of Hg2+ and its concomitant interaction with mammalian target organs compared to Cd2+. Furthermore, 50 µM Cys resulted in the co-elution of similar-sized Hg and Cd species, which provides a biomolecular explanation for the nephrotoxicity of Hg2+ and Cd2+. [ABSTRACT FROM AUTHOR]

Peripheral venous catheter (PVC) complications occur on average in approximately half of patients, necessitating premature PVC removal, suspending administration of ongoing therapies, and catheter replacement. To estimate the current incidence, complications, and costs of bloodstream infection (BSI) attributable to PVCs. Patients with PVC-related BSI (cases) were matched with patients without PVC-related BSI (controls). From January 1st, 2018 to March 31st, 2020, a total of 9833 out of 113,068 patients visiting the emergency department (9%) were hospitalized in a medical ward after insertion of a PVC. Among them, 581 (6%) had at least one positive blood culture. Twenty-five (4%) of these were judged as having a PVC-related BSI. Major complications were noted in nine patients. One patient presented severe sepsis requiring admission to intensive care unit for eleven days followed by thoracic (T4–T7) spondylodiscitis requiring prolonged antimicrobial therapy. Another patient developed mitral valve endocarditis also requiring prolonged antimicrobial therapy. One patient developed a pre-sacral abscess three months after initial PVC infection and required hospital readmission for 19 days for drainage. Median (interquartile range) hospital stay costs were €11,597 (8,479–23,759) for cases and €6,789 (4,019–10,764) for controls, leading to median additional costs of €5,587. Though the risk of developing PVC-related BSI in patients admitted to medical wards may seem low, complications of PVC-related BSI are severe, and associated mortality remains high. The financial resources used to treat these complications could be better spent on prevention, including the use of high-quality materials and technologies, and improved training of healthcare providers. [ABSTRACT FROM AUTHOR]

The exposure of humans to Cd exerts adverse human health effects at low chronic exposure doses, but the underlying biomolecular mechanisms are incompletely understood. To gain insight into the toxicologically relevant chemistry of Cd2+ in the bloodstream, we employed an anion-exchange HPLC coupled to a flame atomic absorption spectrometer (FAAS) using a mobile phase of 100 mM NaCl with 5 mM Tris-buffer (pH 7.4) to resemble protein-free blood plasma. The injection of Cd2+ onto this HPLC-FAAS system was associated with the elution of a Cd peak that corresponded to [CdCl3]−/[CdCl4]2− complexes. The addition of 0.1–10 mM L-cysteine (Cys) to the mobile phase significantly affected the retention behavior of Cd2+, which was rationalized by the on-column formation of mixed CdCysxCly complexes. From a toxicological point of view, the results obtained with 0.1 and 0.2 mM Cys were the most relevant because they resembled plasma concentrations. The corresponding Cd-containing (~30 μM) fractions were analyzed by X-ray absorption spectroscopy and revealed an increased sulfur coordination to Cd2+ when the Cys concentration was increased from 0.1 to 0.2 mM. The putative formation of these toxicologically relevant Cd species in blood plasma was implicated in the Cd uptake into target organs and underscores the notion that a better understanding of the metabolism of Cd in the bloodstream is critical to causally link human exposure with organ-based toxicological effects. [ABSTRACT FROM AUTHOR]

Creatine kinase (CK) is an enzyme that produces and uses phosphocreatine to transfer energy to maintain tissue and cellular energy homeostasis, being considered the main controller of cellular energy homeostasis. Its activity in plasma/serum has been commonly used to evaluate tissue damage, since CK is released into the bloodstream during damage. This review summarizes the current knowledge regarding the use of CK activity in fish, focusing on its potential as an indicator of the impairment of energetic homeostasis and tissue damage during stressful situations, such as exposure to contaminants (metals, pesticides, microplastic), hypoxia, thermal stress, and diseases (fungal, parasitic, and bacterial). Based on the data, we can conclude that tissue CK activity can be used as a suitable indicator of the impairment of energetic homeostasis in fish exposed to different aquaculture challenge conditions, while serum/plasma CK activity can be used as the first evidence of possible tissue damage, due to its release into the bloodstream. [ABSTRACT FROM AUTHOR]

The ability of bacterial pathogens to adapt to host niches is driven by the carriage and regulation of genes that benefit pathogenic lifestyles. Genes that encode virulence or fitness-enhancing factors must be regulated in response to changing host environments to allow rapid response to challenges presented by the host. Furthermore, this process can be controlled by preexisting transcription factors (TFs) that acquire new roles in tailoring regulatory networks, specifically in pathogens. However, the mechanisms underlying this process are poorly understood. The highly conserved Escherichia coli TF YhaJ exhibits distinct genome-binding dynamics and transcriptome control in pathotypes that occupy different host niches, such as uropathogenic E. coli (UPEC). Here, we report that this important regulator is required for UPEC systemic survival during murine bloodstream infection (BSI). This advantage is gained through the coordinated regulation of a small regulon comprised of both virulence and metabolic genes. YhaJ coordinates activation of both Type 1 and F1C fimbriae, as well as biosynthesis of the amino acid tryptophan, by both direct and indirect mechanisms. Deletion of yhaJ or the individual genes under its control leads to attenuated survival during BSI. Furthermore, all three systems are up-regulated in response to signals derived from serum or systemic host tissue, but not urine, suggesting a niche-specific regulatory trigger that enhances UPEC fitness via pleiotropic mechanisms. Collectively, our results identify YhaJ as a pathotype-specific regulatory aide, enhancing the expression of key genes that are collectively required for UPEC bloodstream pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract Background Dalbavancin is a semisynthetic antibiotic used as an alternative to vancomycin for skin infections and osteomyelitis. Its long half-life decreases length of hospitalizations. This study analyzes the effectiveness of Dalbavancin for bacteremia and infective endocarditis. Methods The authors performed a retrospective chart analysis on patients who received Dalbavancin due to being poor candidates for PICC placement, poor candidates for prolonged hospitalization, or who were leaving against medical advice. Their hospitalizations were analyzed and results were compiled using descriptive statistics. Results Our cohort had 22 patients treated with Dalbavancin for bacteremia and 1 for endocarditis. They were treated with IV antibiotics, typically a regimen of at least vancomycin and a cephalosporin, for a median of 6.5 days prior to receiving Dalbavancin. 20 received one dose, while three received two doses. 22 had confirmed culture clearance and one denied repeat culture. There were no reported side effects from the medication, no readmissions for worsened infection, and no deaths from the infection. 15 patients had follow-up visits within 90 days. Conclusions Overall, patients responded well. The lack of readmission to the hospital indicates possible outpatient treatment. This would help decrease cost and comorbidities of long-term hospital stays. These positive results are limited by small sample size and treatment of other antibiotics prior to receiving Dalbavancin. Further research is required to accurately estimate the efficacy of Dalbavancin on bloodstream infections and endocarditis, but these results are promising especially for patients who are not candidates for long term hospitalization or outpatient IV access.

Extraintestinal pathogenic Escherichia coli (ExPEC) is one of the leading causes of bloodstream infections in a broad spectrum of birds and mammals, thus poses a great threat to public health, while its underlying mechanism causing sepsis is not fully understood. Here we reported a high virulent ExPEC strain PU-1, which has a robust ability to colonize within host bloodstream, while induced a low level of leukocytic activation. Two serine protease autotransporters of Enterobacteriaceae (SPATEs), VatPU-1 and TshPU-1, were found to play critical roles for the urgent blood infection of strain PU-1. Although the Vat and Tsh homologues have been identified as virulence factors of ExPEC, their contributions to bloodstream infection are still unclear. In this study, VatPU-1 and TshPU-1 were verified to interact with the hemoglobin (a well-known mucin-like glycoprotein in red blood cell), degrade the mucins of host respiratory tract, and cleave the CD43 (a major cell surface component sharing similar O-glycosylated modifications with other glycoprotein expressed on leukocytes), suggesting that these two SPATEs have the common activity to cleave a broad array of mucin-like O-glycoproteins. These cleavages significantly impaired the chemotaxis and transmigration of leukocytes, and then inhibited the activation of diverse immune responses coordinately, especially downregulated the leukocytic and inflammatory activation during bloodstream infection, thus might mediate the evasion of ExPEC from immune clearance of blood leukocytes. Taken together, these two SPATEs play critical roles to cause a heavy bacterial load within bloodstream via immunomodulation of leukocytes, which provides a more comprehensive understanding how ExPEC colonize within host bloodstream and cause severe sepsis.

Objectives: Bloodstream infections (BSIs) acquired in the ICU represent a detrimental yet potentially preventable condition. We determined the prevalence of BSI acquired in the ICU (ICU-onset BSI), pathogen profile, and associated risk factors.Design: Retrospective cohort study.Data Sources: Eighty-five U.S. hospitals in the Cerner Healthfacts Database.Patient Selection: Adult hospitalizations between January 2009 and December 2015 including a (≥ 3 d) ICU stay.Data Extraction and Data Synthesis: Prevalence of ICU-onset BSI (between ICU Day 3 and ICU discharge) and associated pathogen and antibiotic resistance distributions were compared with BSI present on (ICU) admission (ICU-BSI POA ); and BSI present on ICU admission day or Day 2. Cox models identified risk factors for ICU-onset BSI among host, care setting, and treatment-related factors. Among 150,948 ICU patients, 5,600 (3.7%) had ICU-BSI POA and 1,306 (0.9%) had ICU-onset BSI. Of those with ICU-BSI POA , 4,359 (77.8%) were admitted to ICU at hospital admission day. Patients with ICU-onset BSI (vs ICU-BSI POA ) displayed higher crude mortality of 37.9% (vs 20.4%) ( p < 0.001) and longer median (interquartile range) length of stay of 13 days (8-23 d) (vs 5 d [3-8 d]) ( p < 0.001) (considering all ICU stay). Compared with ICU-BSI POA , ICU-onset BSI displayed more Pseudomonas , Acinetobacter , Enterococcus, Candida , and Coagulase-negative Staphylococcus species, and more methicillin-resistant staphylococci, vancomycin-resistant enterococci, ceftriaxone-resistant Enterobacter , and carbapenem-resistant Enterobacterales and Acinetobacter species, respectively. Being younger, male, Black, Hispanic, having greater comorbidity burden, sepsis, trauma, acute pulmonary or gastrointestinal presentations, and pre-ICU exposure to antibacterial and antifungal agents was associated with greater ICU-onset BSI risk after adjusted analysis. Mixed ICUs (vs medical or surgical ICUs) and urban and small/medium rural hospitals were also associated with greater ICU-onset BSI risk. The associated risk of acquiring ICU-onset BSI manifested with any duration of mechanical ventilation and 7 days after insertion of central venous or arterial catheters.Conclusions: ICU-onset BSI is a serious condition that displays a unique pathogen and resistance profile compared with ICU-BSI POA . Further scrutiny of modifiable risk factors for ICU-onset BSI may inform control strategies. [ABSTRACT FROM AUTHOR]

Bacterial flora has clinical significance for the host. The metabolic environment created by this flora influences immunotherapy in urothelial carcinoma. However, there are no reports on the clinical significance of bacterial flora in the host bloodstream. We aimed to clarify the correlation between extracellular vesicle (EV)-derived blood microflora information and tumor immunological status in urothelial carcinoma (UC) patients. Serum samples were collected from 20 healthy donors, 50 patients with localized UC, and 31 patients with metastatic UC (mUC) who had undergone pembrolizumab treatment. Bacterial DNA in EVs was extracted from each sample. Metagenomic sequencing was performed after amplification of the V1–V2 region of the bacterial 16S rRNA gene. Using the matched tumor tissue and serum samples, we revealed that the smaller amount of peripheral EVs carrying Firmicutes DNA was significantly correlated with the higher number of infiltrating T cells within tumor tissues (CD3; p = 0.015, CD4; p = 0.039, CD8; p = 0.0084) and the higher expression of activation markers on their surface (ICOS on both CD4; p = 0.0013 and CD8 T cells; p = 0.016 and 4-1BB on CD4 T cells; p = 0.016). In terms of circulating metabolic information, l-Ser and l-Pro levels, which play important roles in T cell expansion and proliferation, were significantly higher in the Firmicutes-low group (p = 0.010). All of the patients with higher Firmicutes abundance had disease progression without any clinical response (p = 0.026) and significantly inferior prognosis for pembrolizumab therapy (p = 0.035). This is the first study on the importance of peripheral bacterial EVs in cancer patients treated with cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Globally, an estimated 9 million deaths per year are caused by human exposure to environmental pollutants, including toxic metal(loid) species. Since pollution is underestimated in calculations of the global burden of disease, the actual number of pollution-related deaths per year is likely to be substantially greater. Conversely, anticancer metallodrugs are deliberately administered to cancer patients, but their often dose-limiting severe adverse side-effects necessitate the urgent development of more effective metallodrugs that offer fewer off-target effects. What these seemingly unrelated events have in common is our limited understanding of what happens when each of these toxic metal(loid) substances enter the human bloodstream. However, the bioinorganic chemistry that unfolds at the plasma/red blood cell interface is directly implicated in mediating organ/tumor damage and, therefore, is of immediate toxicological and pharmacological relevance. This perspective will provide a brief synopsis of the bioinorganic chemistry of AsIII, Cd2+, Hg2+, CH3Hg+ and the anticancer metallodrug cisplatin in the bloodstream. Probing these processes at near-physiological conditions and integrating the results with biochemical events within organs and/or tumors has the potential to causally link chronic human exposure to toxic metal(loid) species with disease etiology and to translate more novel anticancer metal complexes to clinical studies, which will significantly improve human health in the 21st century. [ABSTRACT FROM AUTHOR]

Although chronic low-level exposure to Hg2+ and Cd2+ causes human nephrotoxicity, the bioinorganic processes that deliver them to their target organs are poorly understood. Since the plasma protein human serum albumin (HSA) has distinct binding sites for these metal ions, we wanted to gain insight into these translocation processes and have employed size-exclusion chromatography coupled on-line to an inductively coupled plasma atomic emission spectrometer using phosphate-buffered saline mobile phases. When HSA ‘labeled’ with Hg2+ and Cd2+ (1:0.1:0.1) using 300 μM of L-methionine was analyzed, the co-elution of a single C, S, Cd, and Hg peak was observed, which implied the intact bis-metalated HSA complex. Since human plasma contains small molecular weight thiols and sulfur-containing metabolites, we analyzed the bis-metalated HSA complex with mobile phases containing 50–200 µM of L-cysteine (Cys), D,L-homocysteine (hCys), or glutathione (GSH), which provided insight into the comparative mobilization of each metal from their respective binding sites on HSA. Interestingly, 50 µM Cys, hCys, or GSH mobilized Hg2+ from its HSA binding site but only partially mobilized Cd2+ from its binding site. Since these findings were obtained at conditions simulating near-physiological conditions of plasma, they provide a feasible explanation for the higher ‘mobility’ of Hg2+ and its concomitant interaction with mammalian target organs compared to Cd2+. Furthermore, 50 µM Cys resulted in the co-elution of similar-sized Hg and Cd species, which provides a biomolecular explanation for the nephrotoxicity of Hg2+ and Cd2+.

Abstract Background Multiple organ dysfunction syndrome secondary to infection is the leading cause of death in burn patients. Bloodstream infection (BSI) and the prognosis of burn patients are negatively correlated. Metagenomic next-generation sequencing (mNGS) can detect many potential pathogens and may be more valuable for patients with severe burns. Methods We retrospectively explored the utility of mNGS in describing the clinical and microbial characteristics of severely burned patients with BSI. We compared mNGS with blood culture. Results Fourteen patients (127 blood samples) developed 71 episodes of BSIs with 102 unique causative pathogens. The median total body surface area was 93%. The overall 90-day mortality was 43%. In total, 17 (23.9%) episodes were polymicrobial, and 61 (86.1%) episodes originated from the wound. In total, 62/71 cases (87%) showed positive findings by mNGS, while 42/71 cases (59%) showed positive findings using blood culture. We found that mNGS outperformed culture, especially in terms of fungi (27% vs. 6%, p

Objectives: Bloodstream infection (BSI) causes significant morbidity and mortality in patients, especially in developing countries. Changes in the epidemiological pattern of microorganisms, as well as the growth of antibacterial resistance have become important health concerns in Iran. The aims of this study were to evaluate the spectrum of pathogens causing BSIs in hospitalized patients in Shiraz, Iran, and their corresponding antimicrobial resistance patterns. Materials and Methods: In this retrospective study, 1585 positive blood samples were analyzed from March 2013 to March 2014. Samples from all hospitals within Shiraz were transferred to Professor Alborzi Clinical Microbiology Center. Then, the isolates were identified according to standard methods such as the analytical profile index system, and antibiotic susceptibility patterns were established consistent with the recommendations of the Clinical and Laboratory Standards Institute. Results: Coagulase-negative staphylococci (39%), Staphylococcus aureus (15.3%), Escherichia coli (8.5%), Pseudomonas spp. (7.5%), Enterococcus spp. (7.3%), and Acinetobacter spp. (6.6%) were the most frequent bacteria isolated from blood cultures. Linezolid and vancomycin (VA) had the highest effectiveness against gram-positive bacteria and gram-negative bacteria had high sensitivity to polymyxin B and colistin. Totally, 56.2% of Enterococcus isolates were VA-resistant (VRE) and 55.2% (122) of S. aureus were methicillin-resistant (MRSA). Finally, 59.02% (72) of E. coli isolates, 33.3% (5) of Serratia spp., and 42.85% (33) of Klebsiella spp. were extended-spectrum β-lactamase (ESBL) positive. Conclusions: Considering the results, the emergence of resistant strains such as MRSA, VRE, and ESBL is an alarming threat that would be a severe clinical issue with critical restrictions on antibiotic therapy.

Purpose: This investigation endeavors to scrutinize the resistance profiles to antifungal agents, alongside the clinical distribution of Candida isolates that yielded positive results in blood cultures at Suining Central Hospital spanning the years 2015 to 2023. The objective is to provide crucial epidemiological insights that may aid in early clinical intervention and judicious deployment of antifungal therapies., Methods: This retrospective analysis analyses data on 182 different Candida strains with positive clinical blood cultures obtained from the Microbiology Laboratory of Suining Central Hospital over a period of nine consecutive years. The study involved identification of Candida species and assessment of resistance patterns to fungal drugs., Results: Our analysis revealed that the median age of patients diagnosed with Candidaemia from the 182 strains was 62 years, with a distribution of 63.7% females and 36.3% males. Within the cohort of 182 Candida strains, Candida albicans constituted 32.4%, while non-albicans Candida species comprised 67.6% of the cases. Specifically, Candida tropicalis represented 37.4%, Candida glabrata 12.1%, Candida parapsilosis 11.0%, Candida guilliermondii 3.8%, and both Candida krusei and Candida Dublin accounted for 1.6% each. These Candida species were predominantly identified in intensive care units (ICU), hematology, gastroenterology, neurology centers, and endocrine metabolism units., Conclusion: The findings of this investigation suggest a shift in the prevalence of non -Candida albicans species, notably C. tropicalis , as the predominant cause of Candidaemia at Suining Central Hospital, surpassing C. albicans . Although instances of antifungal resistance are infrequent, there has been a notable rise in resistance to azoles. This study provides important insights into the local epidemiology, which will be essential for informing the selection of empirical antifungal therapy and contributing to the global surveillance of antifungal resistance., Competing Interests: The authors hereby certify that there are no conflicts of interest, financial or otherwise, associated with this research work., (© 2024 Li et al.)

Pharmaceutical research is increasingly focusing on transdermal drug delivery due to its potential for improved compliance and bioavailability. However, it is challenging due to the tight intracellular junctions present in the skin. Researchers have developed noninvasive methods, like transfersomes, to overcome these challenges. Transfersomes are ultra-deformable vesicles utilized for improved transdermal applications. They are made up of a phospholipid-rich lipid bilayer, an edge activator, and an ethanol/aqueous core. After topical treatment, transfersomes can penetrate deeper skin regions, delivering larger concentrations of active compounds. A transfersomal patch is applied to the skin and left for an extended period of time to allow a large dose of medication to permeate into the bloodstream. The transfersomal patch offers an advantage over the transfersomal gel because it allows the transfersomes to be applied under occlusive conditions, resulting in greater permeability, a lower amount of active medication, and a steady supply rather than a massive dose. This review represents the preparation and evaluation of transfersomal patches, recent research approaches, and future aspects of transfersomal patches. This study suggests that drug-loaded transfersomal patches could be a unique option to avoid invasive therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Dalbavancin is a semisynthetic antibiotic used as an alternative to vancomycin for skin infections and osteomyelitis. Its long half-life decreases length of hospitalizations. This study analyzes the effectiveness of Dalbavancin for bacteremia and infective endocarditis. Methods: The authors performed a retrospective chart analysis on patients who received Dalbavancin due to being poor candidates for PICC placement, poor candidates for prolonged hospitalization, or who were leaving against medical advice. Their hospitalizations were analyzed and results were compiled using descriptive statistics. Results: Our cohort had 22 patients treated with Dalbavancin for bacteremia and 1 for endocarditis. They were treated with IV antibiotics, typically a regimen of at least vancomycin and a cephalosporin, for a median of 6.5 days prior to receiving Dalbavancin. 20 received one dose, while three received two doses. 22 had confirmed culture clearance and one denied repeat culture. There were no reported side effects from the medication, no readmissions for worsened infection, and no deaths from the infection. 15 patients had follow-up visits within 90 days. Conclusions: Overall, patients responded well. The lack of readmission to the hospital indicates possible outpatient treatment. This would help decrease cost and comorbidities of long-term hospital stays. These positive results are limited by small sample size and treatment of other antibiotics prior to receiving Dalbavancin. Further research is required to accurately estimate the efficacy of Dalbavancin on bloodstream infections and endocarditis, but these results are promising especially for patients who are not candidates for long term hospitalization or outpatient IV access. [ABSTRACT FROM AUTHOR]

Background: The Malawi-Liverpool Wellcome Trust Clinical Research Programme (MLW) has undertaken sentinel surveillance of bloodstream infection and meningitis at Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi for 20 years. Previously, three epidemics of Salmonella bloodstream infection have been identified. Here we provide updated surveillance data on invasive non-typhoidal Salmonella disease from 2011 – 2019. Methods: Surveillance data describing trends in invasive non-typhoidal Salmonella disease and associated antimicrobial susceptibility profiles are presented for the period January 2011 – December 2019. Results: Between January 2011-December 2019, 128,588 blood cultures and 40,769 cerebrospinal fluid cultures were processed at MLW. Overall, 1.00% of these were positive for S. Typhimurium, 0.10% for S. Enteritidis, and 0.05% positive for other Salmonella species. Estimated minimum incidence of invasive non-typhoidal Salmonella (iNTS) disease decreased from 21/100,000 per year in 2011 to 7/100,000 per year in 2019. Over this period, 26 confirmed cases of Salmonella meningitis were recorded (88.5% S. Typhimurium). Between 2011-2019 there was a substantial decrease in proportion of S. Typhimurium (78.5% to 27.7%) and S. Enteritidis (31.8% in 2011 to 0%) that were multidrug-resistant. Resistance to fluoroquinolones and third-generation generation cephalosporins (3GC) remained uncommon, however 3GC increased amongst Salmonella spp. and S. Typhimurium in the latter part of the period. Conclusions: The total number of iNTS bloodstream infections decreased between 2011-2019. Although the number multidrug resistance (MDR) S. Typhimurium and S. Enteritidis isolates has fallen, the number of MDR isolates of other Salmonella spp. has increased, including 3GC isolates.

The exposure of humans to Cd exerts adverse human health effects at low chronic exposure doses, but the underlying biomolecular mechanisms are incompletely understood. To gain insight into the toxicologically relevant chemistry of Cd2+ in the bloodstream, we employed an anion-exchange HPLC coupled to a flame atomic absorption spectrometer (FAAS) using a mobile phase of 100 mM NaCl with 5 mM Tris-buffer (pH 7.4) to resemble protein-free blood plasma. The injection of Cd2+ onto this HPLC-FAAS system was associated with the elution of a Cd peak that corresponded to [CdCl3]−/[CdCl4]2− complexes. The addition of 0.1–10 mM L-cysteine (Cys) to the mobile phase significantly affected the retention behavior of Cd2+, which was rationalized by the on-column formation of mixed CdCysxCly complexes. From a toxicological point of view, the results obtained with 0.1 and 0.2 mM Cys were the most relevant because they resembled plasma concentrations. The corresponding Cd-containing (~30 μM) fractions were analyzed by X-ray absorption spectroscopy and revealed an increased sulfur coordination to Cd2+ when the Cys concentration was increased from 0.1 to 0.2 mM. The putative formation of these toxicologically relevant Cd species in blood plasma was implicated in the Cd uptake into target organs and underscores the notion that a better understanding of the metabolism of Cd in the bloodstream is critical to causally link human exposure with organ-based toxicological effects.

Creatine kinase (CK) is an enzyme that produces and uses phosphocreatine to transfer energy to maintain tissue and cellular energy homeostasis, being considered the main controller of cellular energy homeostasis. Its activity in plasma/serum has been commonly used to evaluate tissue damage, since CK is released into the bloodstream during damage. This review summarizes the current knowledge regarding the use of CK activity in fish, focusing on its potential as an indicator of the impairment of energetic homeostasis and tissue damage during stressful situations, such as exposure to contaminants (metals, pesticides, microplastic), hypoxia, thermal stress, and diseases (fungal, parasitic, and bacterial). Based on the data, we can conclude that tissue CK activity can be used as a suitable indicator of the impairment of energetic homeostasis in fish exposed to different aquaculture challenge conditions, while serum/plasma CK activity can be used as the first evidence of possible tissue damage, due to its release into the bloodstream.

Background: Multiple organ dysfunction syndrome secondary to infection is the leading cause of death in burn patients. Bloodstream infection (BSI) and the prognosis of burn patients are negatively correlated. Metagenomic next-generation sequencing (mNGS) can detect many potential pathogens and may be more valuable for patients with severe burns.Methods: We retrospectively explored the utility of mNGS in describing the clinical and microbial characteristics of severely burned patients with BSI. We compared mNGS with blood culture.Results: Fourteen patients (127 blood samples) developed 71 episodes of BSIs with 102 unique causative pathogens. The median total body surface area was 93%. The overall 90-day mortality was 43%. In total, 17 (23.9%) episodes were polymicrobial, and 61 (86.1%) episodes originated from the wound. In total, 62/71 cases (87%) showed positive findings by mNGS, while 42/71 cases (59%) showed positive findings using blood culture. We found that mNGS outperformed culture, especially in terms of fungi (27% vs. 6%, p < 0.0001).Conclusions: The incidence of BSI and polymicrobial in patients with large-area severe burns is high. mNGS has potential value in the diagnosis of fungal infections and coinfections in such patients. In addition, mNGS may provide unique guidance for antibiotic therapy in complicated BSI. [ABSTRACT FROM AUTHOR]

Objectives: Bloodstream infection (BSI) causes significant morbidity and mortality in patients, especially in developing countries. Changes in the epidemiological pattern of microorganisms, as well as the growth of antibacterial resistance have become important health concerns in Iran. The aims of this study were to evaluate the spectrum of pathogens causing BSIs in hospitalized patients in Shiraz, Iran, and their corresponding antimicrobial resistance patterns. Materials and Methods: In this retrospective study, 1585 positive blood samples were analyzed from March 2013 to March 2014. Samples from all hospitals within Shiraz were transferred to Professor Alborzi Clinical Microbiology Center. Then, the isolates were identified according to standard methods such as the analytical profile index system, and antibiotic susceptibility patterns were established consistent with the recommendations of the Clinical and Laboratory Standards Institute. Results: Coagulase-negative staphylococci (39%), Staphylococcus aureus (15.3%), Escherichia coli (8.5%), Pseudomonas spp. (7.5%), Enterococcus spp. (7.3%), and Acinetobacter spp. (6.6%) were the most frequent bacteria isolated from blood cultures. Linezolid and vancomycin (VA) had the highest effectiveness against gram-positive bacteria and gram-negative bacteria had high sensitivity to polymyxin B and colistin. Totally, 56.2% of Enterococcus isolates were VA-resistant (VRE) and 55.2% (122) of S. aureus were methicillin-resistant (MRSA). Finally, 59.02% (72) of E. coli isolates, 33.3% (5) of Serratia spp., and 42.85% (33) of Klebsiella spp. were extended-spectrum β-lactamase (ESBL) positive. Conclusions: Considering the results, the emergence of resistant strains such as MRSA, VRE, and ESBL is an alarming threat that would be a severe clinical issue with critical restrictions on antibiotic therapy. [ABSTRACT FROM AUTHOR]

In modern clinical practice, the assessment of the state of blood microcirculation and the diagnosis of microcirculatory disorders are extremely relevant in a variety of diseases: in cardiology, diabetology, oncology, dermatology, dentistry, surgery and resuscitation. Microcirculatory disorders are very diverse both in their pathogenesis and in clinical manifestations. Therefore, in the pattern of various diseases and extreme conditions, as well as in the correction of microcirculatory disorders the methods are needed for both operative assessment of the state of blood flow at tissue level and for its long-term monitoring. The interest in the study of the microvascular bed of the circulatory system is sparked by the significant role of capillaries in the implementation of the basic processes of the body's vital activity, in the trophic support of organs and their direct participation in tissue and cellular respiration. The health and life expectancy of a person depend on the coordinated work of the heart, large blood lines, and microcirculation vessels. The authors have studied modern optical methods for diagnosing microcirculation. The feasibility of using the speckle imaging method for noninvasive rapid assessment of the state of the microvasculature of human surface biological tissues has been substantiated. To implement the speckle-visualization method, methodological and software have been developed. The processing parameters that are most optimal from the point of view of the ratio of spatiotemporal resolution and computation time have been experimentally substantiated. The purpose of this work is the experimental testing of the developed methodological and hardware speckle imaging for the diagnosis of microcirculation of human surface biological tissues. The authors have carried out the studies of the state of microcirculation in the superficial blood vessels of the skin during physiotherapeutic procedures and in the imitation of pathology. The results of the studies have proved the feasibility of using the developed software for a high-quality diagnosis of the state of microcirculation of human surface biological tissues: primary changes in microcirculation are revealed, further changes to occur during physiotherapeutic procedures are visualized.

Background: Klebsiella pneumoniae is a common Gram-negative bacterium. Blood infection caused by K. pneumoniae is one of the most common causes of human sepsis, which seriously threatens the life of patients. The immune status of peripheral blood mononuclear cells (PBMCs) based on single-cell RNA sequencing (scRNA-seq) in acute stage and recovery stage of sepsis caused by K. pneumoniae bloodstream infection has not been studied., Methods: A total of 13 subjects were included in this study, 3 healthy controls, 7 patients with K. pneumoniae bloodstream infection in the acute stage (4 patients died), and 3 patients in the recovery stage. Peripheral blood of all patients was collected and PBMCs were isolated for scRNA-seq analysis. We studied the changes of PBMCs components, signaling pathways, differential genes, and cytokines in acute and recovery stages., Results: During K. pneumoniae acute infection we observed a decrease in the proportion of T cells, most probably due to apoptosis and the function of T cell subtypes was disorder. The proportion of monocytes increased in acute stage. Although genes related to their phagocytosis function were upregulated, their antigen presentation capacity-associated genes were downregulated. The expression of IL-1β, IL-18, IFNGR1 and IFNGR2 genes was also increased in monocytes. The proportion of DCs was depleted during the acute stage and did not recover during sepsis recovery. DCs antigen presentation was weakened during the acute stage but recovered fast during the recovery stage. pDCs response to MCP-1 chemokine was weakened, they recovered it quickly during the recovery stage. B cells showed apoptosis both in the acute stage and recovery stage. Their response to complement was weakened, but their antigen presentation function was enhanced. The proportion of NK cells stable during all disease's stages, and the expression of IFN-γ gene was upregulated., Conclusion: The proportion of PBMCs and their immune functions undergo variations throughout the course of the disease, spanning from the acute stage to recovery. These findings provide new insights into the mechanism of PBMCs immune function during K. pneumoniae bloodstream infection sepsis and recovery and sets the basis for further understanding and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zhang, Han, Sun, Jiang, Huang, Kong, Li, Ren, Zhao, Jiang and Liu.)

Multidrug-resistant bacteremia 15 G-ve and 1 G+ve isolates were collected from inpatients and outpatients departments at Security Forces Hospital in Riyadh, Saudi Arabia. In studying the multidrug-resistance to antibiotics, it was recorded that the G-ve isolates of E. coli (11093623) & (11161644) were resistance to 19 out of 20 tested antibiotics except antibiotic(CN), while the G+ve isolate of MRSA was resistance to 9 out of 18 antibiotics, and it was sensitive to antibiotic (OX and CZ). The Gold Nanoparticles (AuNPs) was examined to discourage the growth of the multidrug-resistance isolates. Rod-AuNPs were the best to discourage the growth of tested bacteria, followed by the Spherical-AuNPs. Swabs were taken from inhibition zone resulting from the inhibitory effect of AuNPs, towards the tested bacteria and re-inoculated on the Nutrient Agar medium, to determine either the bacteriostatic/bactericidal effect for different NPs. The study proved that Rod-AuNPs gave bacteriostatic effect on Pseudomonas aeruginosa (11093627) & (11132667), Enterobacter cloacae (11159053) and Citrobacter freundii(11176991)&(11182565), and gave a bactericidal effect to the rest of the tested isolates. The Spherical-AuNPs gave a bacteriostatic impact of all tested isolates. Electromicroscopic studies disclosed the effect of AuNPs, either rods or spherical-shaped, on the external shape of some of the pathogenic tested bacteria e.g. E. coli, Klebsiella pneumoniae and P. aeruginosa of G-ve bacteria, MRSA of G+ve bacteria. From results obtained, it can be concluded that the nanostructures and morphologies of AuNPs may offer new possibilities for promising therapeutic applications of multidrug-resistance bacteremia. [ABSTRACT FROM AUTHOR]

Background: Multiple Randomized controlled trials (RCTs) have evaluated the efficacy of antimicrobial-impregnated catheters to prevent catheter-related bloodstream infections (CRBSI). However, the RCTs showed contradictory results, the studies were limited in sample size and methodology quality. Thus, we conducted a meta-analysis to overcome these RCT limitations.Methods: We designed a meta-analysis of RCTs comparing antimicrobial-impregnated and conventional catheters for the prevention of CRBSI. We conducted a detailed search of various databases for RCTs published before November 2019. We calculated mean differences (MDs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) using a random-effects model.Results: We included five RCTs with a total of 2,294 patients. The incidence of CRBSI between the two groups was 0.50 (95% CI, 0.19–1.27), with evidence of heterogeneity (I2 = 55%). The difference was not statistically significant (p = 0.15). On subgroup analysis based on the age of the sample, there was no difference in the rate of CRBSI in the neonatal population [0.42 (95% CI, 0.08–2.27 I2 = 61% p = 0.31] as well as pediatric population [0.45 (95% CI, 0.12–1.67 I2 = 39% p = 0.23]. The summary OR on the incidence of catheter colonization between antimicrobial-impregnated and conventional catheters was 0.64 (95% CI, 0.17–2.35), with no evidence of heterogeneity (I2 = 0%) and a non-significant difference (p = 0.50).Conclusions: To conclude, analysis of a limited number of heterogeneous studies mostly with a small sample indicates that the CRBSI and catheter colonization rates are similar between conventional and antimicrobial-impregnated catheters in the pediatric and neonatal population. There is an urgent need for large-scale RCTs focusing on different antimicrobial-impregnated catheters in these patients to further enhance current evidence.

Invasive candidiasis is known to be one of the most common healthcare-associated complications and is caused by several Candida species. First-line drugs, particularly echinocandins, are effective, but there are increasing reports of resistance to these molecules, though rarely related to C. albicans. Even though the rate of echinocandins resistance remains low (<3%), sporadic cases are emerging. Here, we present a case of bloodstream infection by a pan-echinocandin-resistant Candida albicans affecting a critically ill patient, who died in an intensive care unit following therapeutic failure and multiple organ dysfunction syndrome. This case highlights the need to suspect pan-echinocandin resistance in patients with prolonged echinocandin exposure, particularly in the presence of urinary tract colonization. Our study shows the importance of sequencing to predict therapeutic failure in patients treated with echinocandins and persistent candidemia. [ABSTRACT FROM AUTHOR]

Background: World is in grip of coronavirus disease-2019 (COVID-19) pandemic right now. Majority of studies center around its epidemiological and clinical characteristics. Information regarding secondary bacterial infections is limited. This retrospective observational study was done to determine the prevalence and characteristics of bloodstream infections in COVID-19 patients admitted in a tertiary care center in Jaipur. Materials and methods: All blood cultures received from COVID-19 positive patients admitted in designated COVID care ICUs and wards were included in the study. A predesigned pretested questionnaire was used to collect relevant data. Blood cultures were done using BD BACTEC™ FX40, and identification and antimicrobial susceptibility testing of isolates were done by VITEK® 2 COMPACT. Results: One thousand five hundred seventy-eight (1578) COVID-19 positive patients were admitted in center during 5-month study period from whom 158 blood cultures were received. Out of these, 15 (9.4%) were positive. Median age of patients with positive blood culture was 54 years and included 10 males and 5 females. Ten (67%) patients needed intensive care in ICU. Significant correlation of blood culture positivity was found with parameters like ICU admission, presence of an indwelling device, underlying comorbidity, raised biochemical markers, and adverse clinical outcome. Conclusions: Incidence of bloodstream infections is low for COVID-19 patients. Antibiotic prophylaxis needs to be used with caution, and prompt discontinuation should be done based on clinical judgment. [ABSTRACT FROM AUTHOR]

We report a case of Spiroplasma bloodstream infection in a patient in China who developed pulmonary infection, acute respiratory distress syndrome, sepsis, and septic shock after emergency surgery for type A aortic dissection. One organism closely related to Spiroplasma eriocheiris was isolated from blood culture and identified by whole-genome sequencing.