UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

Objective: To analyze the diagnostic value of cell-free plasma metagenomic next-generation sequencing (mNGS) pathogen identification for severe aplastic anemia (SAA) bloodstream infection. Methods: From February 2021 to February 2022, mNGS and conventional detection methods (blood culture, etc.) were used to detect 33 samples from 29 consecutive AA patients admitted to the Anemia Diagnosis and Treatment Center of the Hematology Hospital of the Chinese Academy of Medical Sciences to assess the diagnostic consistency of mNGS and conventional detection, as well as the impact on clinical treatment benefits and clinical accuracy. Results: ①Among the 33 samples evaluated by mNGS and conventional detection methods, 25 cases (75.76%) carried potential pathogenic microorganisms. A total of 72 pathogenic microorganisms were identified from all cases, of which 65 (90.28%) were detected only by mNGS. ②All 33 cases were evaluated for diagnostic consistency, of which 2 cases (6.06%) were Composite, 18 cases (54.55%) were mNGS only, 2 cases (6.06%) were Conventional method only, 1 case (3.03%) was both common compliances (mNGS/Conventional testing) , and 10 cases (30.3%) were completely non-conforming (None) . ③All 33 cases were evaluated for clinical treatment benefit. Among them, 8 cases (24.24%) received Initiation of targeted treatment, 1 case (3.03%) received Treatment de-escalation, 13 cases (39.39%) received Confirmation, and the remaining 11 cases (33.33%) received No clinical benefit. ④ The sensitivity of 80.77%, specificity of 70.00%, positive predictive value of 63.64%, negative predictive value of 84.85%, positive likelihood ratio of 2.692, and negative likelihood ratio of 0.275 distinguished mNGS from conventional detection methods (21/12 vs 5/28, P<0.001) . Conclusion: mNGS can not only contribute to accurately diagnosing bloodstream infection in patients with aplastic anemia, but can also help to guide accurate anti-infection treatment, and the clinical accuracy is high.
目的： 评估无细胞血浆宏基因组二代测序（mNGS）病原体识别对重型再生障碍性贫血（AA）血流感染的诊断意义。 方法： 应用mNGS与常规检测方法（血培养等）同步检测2021年2月至2022年2月中国医学科学院血液病医院贫血诊疗中心连续收治的29例AA患者共33例次送检样本，评估mNGS与常规检测的诊断一致性、对临床治疗获益的影响及临床准确度。 结果： ①33例次患者经mNGS和常规检测方法检测，其中25例次（75.76%）检出潜在病原微生物；共检出病原微生物72株，其中65株（90.28%）仅经mNGS检出。②诊断一致性评估：2例次（6.06%）组合符合（Composite），18例次（54.55%）mNGS唯一符合（mNGS only），2例次（6.06%）常规检测方法唯一符合（Conventional testing only），1例次（3.03%）共同符合（mNGS/Conventional testing），10例次（30.3%）完全不符合（None）。③临床治疗获益评估：8例次（24.24%）为启动靶向治疗（Initation of targeted treatment），1例次（3.03%）为降级治疗（Treatment de-escalation），13例次（39.39%）为确认治疗（Confirmation），11例次（33.33%）为无治疗获益（No clinical benefit）。④临床准确度：mNGS与常规检测方法差异有统计学意义（21/12对5/28，P<0.001），mNGS的敏感性80.77%，特异性70.00%，阳性预测值63.64%，阴性预测值84.85%，阳性似然比2.692，阴性似然比0.275。 结论： mNGS不仅有助于精准诊断AA患者的血流感染，而且有利于指导进行精准抗感染治疗，临床准确度高。.

Kosakonia radicincitans is a species within the new genus Kosakonia, which is typically a plant pathogen, with rare reports of human infection. The number of human infections may be underestimated because this new genus is under-represented among diagnostic tools. This report describes a case of bloodstream infection caused by K. radicincitans. The pathogen was identified by matrix-assisted laser desorption/ionization-TOF mass spectrometry and 16S rRNA gene sequencing. The hypervirulent human pathogenicity gene LON, which has not been described before, was detected in the bacterial genome by gene annotation. Thus, this discovery provides a new reference for studying the pathogenic mechanism of this rare pathogen.

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.

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.

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 (I 2 = 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 I 2 = 61% p = 0.31] as well as pediatric population [0.45 (95% CI, 0.12-1.67 I 2 = 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 (I 2 = 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.

Porcine extraintestinal pathogenic Escherichia coli (ExPEC) is occurring with increasing frequency in China, and leads to significant economic and welfare costs in the swine industry. The underlying mechanisms of porcine ExPEC in blood colonization during systematic infection is poorly understood. Here we measured the gene expression of porcine ExPEC in infected animal bloodstream in vivo and fresh swine blood in vitro. Using comparisons with P values of ≤ 0.01, we identified 354 and 313 genes as being significantly up- or down-regulated at least 2-fold change during bloodstream infection, respectively. Excepting for an array of iron acquisition systems, numerous genes involved in carbon central metabolism and anaerobic respiratory chains were upregulated here. These genes were categorized into several clusters including the TCA-cycle (frdABCD, citCEFXG), d-ribose transporter (rbsDACB), nickel transporter (nikABCDER), NiFe hydrogenase (hybOABCDEF, hycBCDEFG), Hyp-complex (hypABCDE), DMSO reductase (dmsABC and ynfEFGHI), format dehydrogenase (fdnGHI) and NADH dehydrogenase I (nuoA-N). The mutant with simultaneous inactivation of ribose and citrate imports showed significant reduced fitness in host blood, suggesting these two carbohydrates are utilized by central metabolism network as important carbon-source during bloodstream infection. Similar deficiency was also observed in the mutant double deleted NiFe hydrogenase 2 and 3 anaerobic respiratory chains. Further study found that FNR (a global regulator facilitating bacterial adaptation to anaerobic conditions) is an important regulator in response to bloodstream to activate center metabolism and anaerobic respiratory chains, thus contribute to the full-virulence of porcine ExPEC. These findings provide compelling evidence to support the notion that carbon central metabolism network and anaerobic respiratory chains play key roles for porcine ExPEC fitness within host bloodstream.

OBJECTIVE: This study aimed to analyze the clinical data and characteristics of an NDM-1 (New Delhi metallo-β-lactamase-1)-producing Klebsiella pneumoniae isolated from the bloodstream of a leukemia patient.
METHODS: A retrospective analysis was used for the clinical data of the patient. The modified Hodge test (MHT) and ethylenediaminetetraacetic acid (EDTA)-disk synergy test were used for detecting metallo-β-lactamase. Antibiotic resistance was determined using the agar dilution method. PCR was used to identify resistance genes. S1-PFGE (S1 nuclease/pulsed-field gel electrophoresis) and Southern blot hybridization were performed to determine the location of blaNDM-1. A conjugation experiment was used to confirm the transferable characteristics of the resistant genes. Multilocus sequence typing (MLST) was also performed.
RESULTS: The patient developed bloodstream infections caused by this NDM-1-producing strain and died due to worsening of the condition. The strain was highly resistant to β-lactam antibiotics and coharbored blaNDM-1, qnrB, and blaCTX-M-9 genes. Southern blot confirmed that blaNDM-1 was located on a plasmid of approximately 55 kb and could be transferred to Escherichia coli J53. MLST analysis showed that this strain belonged to an uncommon sequence type ST1224.
CONCLUSIONS: The coexistence of various resistant genes is the mechanism for resistance to most antibiotics. Additionally, infections caused by multi-drug resistant bacteria increase the mortality of patients with immunodeficiency, which alerts clinicians to establish a rational and effective combination drug therapy.

Streptococcus suis serotype 2 (SS2) is an important swine and human pathogen that causes global economic and public health problems. Virulent S. suis strains successfully maintain high bacterial concentrations in host blood and rapidly adapt to challenging environments within hosts. Successful survival in hosts is a major factor influencing the pathogenesis of SS2. We have previously identified that SS2 colonization in mouse brain is possibly affected by the ATPase, MsmK of carbohydrate ATP-binding cassette (ABC) transporters because of carbohydrate utilization. In this study, the chain length of the msmK deletion mutant was longer than that of the wild type, and the former was significantly more susceptible than the latter when theses strains were exposed to mouse blood both in vivo and in vitro. The hemolytic activity of the mutant strain was decreased. Although the adhesion of the mutant to HEp-2 cell lines was enhanced, the deletion of msmK impaired the abilities of SS2 to resist phagocytosis and survive severe stress conditions. MsmK contributed to the survival and adaptation of SS2 in host bloodstream. Therefore, MsmK was identified as a multifunctional component that not only contributed to carbohydrate utilization but also participated in SS2 pathogenesis.