Factor In Bacterial Infection Research Articles

Incidence and risk factors for bacterial infection in newly diagnosed multiple myeloma patients undergoing treatment with bortezomib, lenalidomide, and dexamethasone (RVD).

e20008 Background: Infection is an important cause of morbidity and mortality in newly diagnosed multiple myeloma (NDMM), but the risk of infection using novel treatment regimens is incompletely described in the literature. There are mixed trial results for antibacterial prophylaxis to reduce infection risk in newly diagnosed multiple myeloma and its use remains controversial. Methods: To evaluate the incidence of bacterial infection and early mortality in patients receiving bortezomib, lenalidomide, and dexamethasone (RVD) for NDMM, we performed a retrospective single-center cohort study of patients treated between 01/2014-01/2020. Demographic and clinical data were collected. Two cohorts were generated for those patients with or without bacterial infection during the follow-up period. A multivariate logistic regression was utilized to determine risk factors for bacterial infection. Variables with a P-value <0.2 on univariate analysis were considered for the model. For co-linear variables with a P-value <0.2 on univariate analysis, only one variable was included in the multivariable model. A receiver operating characteristic (ROC) curve was generated to assess the sensitivity and specificity of the model. Results: Of 144 patients, 21 patients (14.5%) experienced a bacterial infection of any grade. 11% of patients received pneumocystis prophylaxis, and 1 patient received levofloxacin prophylaxis. 11 (7.6%) patients experienced grade 3 (G3) or higher infection. One patient died in our cohort; there were no deaths from infection. G3 neutropenia occurred in 11% of patients with 2% experiencing any grade febrile neutropenia. Pneumonia and urinary tract infections were common, affecting 8(5.5%) and 6 (4.2%) patients, respectively. On multivariable analysis (Table), age, smoking history, history of diabetes, antibiotic use in the 60 days preceding 1st cycle of RVD, and high-risk cytogenetics (HR CG) were associated with a greater likelihood of experiencing a bacterial infection. The area under the ROC curve of the multivariable model was 0.829 (95% CI 0.729-0.934). Conclusions: The overall incidence of bacterial infection in NDMM patients receiving induction with RVD was low despite minimal use of antibacterial prophylaxis. Early mortality was uncommon and not attributable to infection. Clinical features may identify a subgroup of patients at greater risk of infection during induction therapy for MM and may impact clinical decisions to utilize antibacterial prophylaxis.[Table: see text]

Characteristics of and risk factors for biliary pathogen infection in patients with acute pancreatitis

BackgroundInfection in patients with acute pancreatitis, especially severe acute pancreatitis patients, is a common and important phenomenon, and the distributions and drug resistance profiles of bacteria causing biliary infection and related risk factors are dynamic. We conducted this study to explore the characteristics of and risk factors for bacterial infection in the biliary tract to understand antimicrobial susceptibility, promote the rational use of antibiotics, control multidrug-resistant bacterial infections and provide guidance for the treatment of acute pancreatitis caused by drug-resistant bacteria.MethodsThe distribution of 132 strains of biliary pathogenic bacteria in patients with acute pancreatitis from January 2016 to December 2020 were analyzed. We assessed drug resistance in the dominant Gram-negative bacteria and studied the drug resistance profiles of multidrug-resistant bacteria by classifying Enterobacteriaceae and nonfermentative bacteria. We then retrospectively analyzed the clinical data and risk factors associated with 72 strains of Gram-negative bacilli, which were divided into multidrug-resistant bacteria (50 cases) and non-multidrug-resistant bacteria (22 cases).ResultsThe main bacteria were Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli had a 66.67% detection rate. Acinetobacter baumannii had more than 50.00% drug resistance to carbapenems, ESBL-producing Klebsiella pneumoniae had 100.00% drug resistance, and Pseudomonas aeruginosa had 66.67% resistance to carbapenems. Multivariate logistic regression analysis suggested that the administration of third- or fourth-generation cephalosporins was an independent risk factor for Gram-negative multidrug-resistant biliary bacterial infection in acute pancreatitis patients.ConclusionDrug resistance among biliary pathogens in acute pancreatitis patients remains high; therefore, rational antimicrobial drug use and control measures should be carried out considering associated risk factors to improve diagnosis and treatment quality in acute pancreatitis patients.

The Pivotal Role of Signal Regulatory Protein α in Exacerbating Pulmonary Fibrosis Complicated with Bacterial Infection

The pathogenesis of pulmonary fibrosis remains unknown. However, bacterial infections in patients with idiopathic pulmonary fibrosis are a serious complication that exacerbate the disease. Serum levels of Surfactant Protein D (SPD) are known to be elevated in patients with pulmonary fibrosis, but the role of SPD in pulmonary fibrosis complicated with bacterial infection is unknown. Lipopolysaccharide upregulates Interleukin (IL)-12p40 expression and IL-12p40 promotes Interferon Gamma (IFNγ) production to induce the T helper cell 1 (Th1) immune response via Signal Transducers and Activators of Transcription 4 (STAT4) signaling. A lack of IFNγ shifts the immune response from Th1 to Th2. IL-4 is a profibrotic Th2 cytokine that activates fibroblasts. Granulocyte-macrophage colony-stimulating factor induced by IL-1 and TNFα during the Th1 immune response upregulates Signal Regulatory Protein α (SIRPα) expression. Interferon Regulatory Factor 1 (IRF1) functions as the promoter activator of IL-12p40 after stimulation with LPS. SPD is a ligand for SIRPα, and SPD/SIRPα ligation activates the Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Related Kinase (ERK) signal cascade; ERK downregulates Interferon Regulatory Factor 1 (IRF1) expression. Consequently, the SPD/SIRPα signaling pathway decreases IL-12p40 production in human macrophages after exposure to LPS. IL-12p40 is a key immunoregulatory factor in bacterial infection that promotes production of IFNγ by T lymphocytes. Pulmonary fibroblasts are activated by IL-4/IL-4R ligation. IFNγ induces IRF1 via STAT1 signaling, and IRF1 acts as the promoter repressor of IL-4 to attenuate its production. IFNγ also inhibits IL-4R expression. A reduction in IFNγ induced by IL-12p40 deficiency via the SPD/SIRPα signaling pathway enhances IL-4 and IL-4R expression to augment the activity of fibroblasts. This finding indicates that pulmonary fibrosis is exacerbated by SPD/SIRPα signaling during bacterial infection.

Molecular characterization of glutaminyl-peptide cyclotransferase(QPCT)in Scylla paramamosain and its role in Vibrio alginolyticus and white spot syndrome virus (WSSV) infection

Glutaminyl-peptide cyclotransferase (QPCT) catalyzes the posttranslational modification of an N-terminal glutamate of proteins to pyroglutamate. This renders the protein more resistant to protease degradation, more susceptible to hydrophobic interactions, aggregation, and neurotoxic. In this study, we evaluated the influence of QPCT in the crab Scylla paramamosain infected with white spot syndrome virus (WSSV) or with Vibrio alginolyticus. A cDNA clone, encompassing the entire 2445 bp of the S. paramamosain QPCT gene, containing a 1113 bp open reading frame (ORF) encoding a 370 amino acid protein was cloned from S. paramamosain. Real-time PCR indicated that QPCT was primarily expressed in the digestive tract of S. paramamosain, was up-regulated in hemocytes after infection with V. alginolyticus, and down-regulated in hemocytes after infection with WSSV. Knockdown of QPCT expression by double-stranded RNA (QPCT-dsRNA) resulted in down-regulation of prophenoloxidase (proPO) and crustin antimicrobial peptide, whereas myosin-II-essential-light-chain-like-protein was significantly up-regulated in hemocytes at 24 h post QPCT-dsRNA treatment. WSSV challenge in crabs treated with QPCT-dsRNA resulted in a reduction in viral burden and in the apoptotic rate of crab hemocytes, while the phagocytic activity of crab hemocytes and overall mortality rate were increased. This suggests that WSSV might take advantage of QPCT to benefit its replication. In contrast, V. alginolyticus infection in crabs treated with QPCT-dsRNA indicated that the apoptotic rate and phagocytic activity of hemocytes, and overall incidence of mortality, were increased compared to mock-treated animals, indicating that QPCT might be a resistance factor in bacterial infection. These results increase our understanding of the function of QPCT and its role in the innate immunity of S. paramamosain.

Comparison of the Eosinophil Count to C –reactive protein, Leukocyte Count, and Neutrophil Count for the detection of bacterial infection in ill-appearing children with fever admitted to the Emergency Department

Introduction. From late 19th century to the present day, several authors have investigated the value of low eosinophil count as a biomarker of bacterial infection. In this study, we examined the value of eosinopenia for diagnosing bacterial infection in ill-appearing children admitted to the pediatric emergency department.Methods. Retrospective review of the medical records of children age 1 month to 14 years who appeared ill on admission to the emergency department (ED). Data collected included; C-reactive protein (CRP) level leukocyte, neutrophil, eosinophil counts, results of microbiological tests, radiologic evaluation, and treatment given in the ED. Final outcome data were also collected. Results. In total, 878 met our case definition and inclusion criteria. 521 patients had confirmed or presumed bacterial infection and 355 patients had presumed or confirmed viral infection. Nineteen patients died; all had bacterial infections. Neutrophil, eosinophil counts and CRP level were independent risk factors for bacterial infection in the multivariate analysis (p 0.05). The sensitivities of the leukocyte, neutrophil, and eosinophil counts and CRP level were 57.5%, 62.9%, 61%, and 57.1%, respectively. The specificities of them were 59.1%, 63.3%, 67%, and 77.4%, respectively.Conclusion. In our study population, although the accuracies of eosinophil, neutrophil counts, and CRP level were not enough, they had similar in distinguishing viral from bacterial infection in ill appearing febrile children. By comparison the leukocyte count had limited predictive value.

Direct visualization of bacterial infection process in nematode hosts by an improved immunocytochemical method

Our previous work on Brevibacillus laterosporus G4 had demonstrated that an extracellular protease BLG4 played a key role as a pathogenic factor in bacterial infection of nematodes. In this study, we developed an improved method for the immunofluorescent localization of protease BLG4 to directly visualize the bacterial infection process in a nematode host and demonstrate the involvement of the protease in penetrating nematode cuticles in vivo. This work supplies a new basic knowledge that elucidates the microbial infection processes in nematodes.

Comparative functional genomic analysis of Pasteurellaceae adhesins using phage display

The Pasteurellaceae contain a number of important animal pathogens. Although related, the various members of this family cause a diversity of pathology in a wide variety of organ systems. Adhesion is an important virulence factor in bacterial infections. Surprisingly little is known about the adhesins of the Pasteurellaceae. To attempt to identify the genes coding for adhesins to some key components of the hosts extracellular matrix molecules, phage display libraries of fragmented genomic DNA from Haemophilus influenzae, Actinobacillus pleuropneumoniae, Pasteurella multocida and Aggregatibacter actinomycetemcomitans, were prepared in the phage display vector pG8SAET. The libraries were screened against human or porcine fibronectin, serum albumin or a commercial extracellular matrix containing type IV collagen, laminin and heparin sulphate. Four genes encoding putative adhesins were identified. These genes code for: (i) a 34 kDa human serum albumin binding protein from Haemophilus influenzae; (ii) a 12.8 kDa fibronectin-binding protein from Pasteurella multocida; (iii) a 13.7 kDa fibronectin-binding protein from A. actinomycetemcomitans; (iv) a 9.5 kDa serum albumin-binding protein from A. pleuropneumoniae. None of these genes have previously been proposed to code for adhesins. The applications of phage display with whole bacterial genomes to identify genes encoding novel adhesins in this family of bacteria are discussed.

Critical protective role of mast cell-derived tumour necrosis factor in bacterial infection

Critical protective role of mast cell-derived tumour necrosis factor in bacterial infection

Risk factors for bacterial infections in chronic haemodialysis adult patients: a multicentre prospective survey

All adult patients from 13 dialysis centres were prospectively followed up for 6 months in an attempt to appraise the current risk factors for bacterial infections in stable chronically haemodialysed patients. Parameters recorded as potential risk factors for BI were age, gender, cause of renal failure, time elapsed since the start of dialysis, history of transplantation, recent surgical procedure, previous bacterial infection, current immunosuppressive or erythropoietin therapy, type of angioaccess device, and serum ferritin level. Six hundred and seven patients (mean age 56.5 years, range 18-85) were enrolled in the study. Mean time elapsed since the start of dialysis was 4.7 years. One hundred and eighteen patients had developed at least one bacterial infection during the study period whereas 489 had remained free of bacterial infection at the end of the follow-up. In multivariate analysis three parameters were found to be significant and independent risk factors for bacterial infection: previous history of bacterial infection (at least one versus no previous episode), type of angioaccess device (catheter versus native fistula), and elevated serum ferritin level (greater versus lower than 500 micrograms/l). These results support the evidence that impaired host defences in chronic haemodialysis patients may be secondary to the dialysis procedure and suggest that the incidence of bacterial infection in these patients may be further reduced by appropriate supportive therapy.

Complement Deficiency and Neutrophil Dysfunction as Risk Factors for Bacterial Infection in Newborns and the Role of Granulocyte Transfusion in Therapy

The similarity in the susceptibility to bacterial infections of newborns and older patients with complement deficiencies, neutropenia, or neutrophil function defects has suggested that neutrophils and/or complement might also be defective in newborns. Although no individual element of the phagocytic host defense system is severely deficient, several partial deficiencies have been identified. These involve important amplification pathways of complement and neutrophil activation and may combine to cause significant decreases in phagocyte activity at sites of infection. Because of decreased specific antibody, initial activation of the classical complement pathway is decreased. Low levels of C3 and factor B decrease amplification by the alternative pathway and result in marked decreases in opsonization and generation of chemotactic activity from C5. There are also quantitative and qualitative neutrophil defects. The recent observations that newborns' neutrophils are relatively deficient in membrane expression of their major adherence protein/C3bi receptor help explain the decreased mobility and phagocytic activity of these cells. Thus, several partial deficiencies combine to cause severe impairments in delivery of neutrophils to sites of infection and contribute to the increased susceptibility of the newborn to infection.

Induction of histamine release from rat mast cells and human basophilic granulocytes by clinical Escherichia coli isolates and relation to hemolysin production and adhesin expression

We investigated the role of 27 disease-relevant Escherichia coli strains isolated from humans in the induction of histamine release from rat peritoneal mast cells and human basophilic granulocytes. Our data indicated that only the hemolysin-positive (HLY+) bacteria and the hemolysin-positive culture supernatants induced histamine release. For the latter, the hemolysin activity determined the degree of histamine secretion. Incubation of the target cells with washed HLY+ bacteria revealed a different secretory response. For the rat mast cells, histamine release paralleled expression of hemolysin activity, with the exception of strain S98 (O75:K5:H- HLY+), which induced less histamine, although its hemolysin activity was relatively high. No correlation between histamine secretion and hemolysin activity was observed when human basophils were stimulated with the HLY+ bacteria. Large amounts of histamine were still released, even when the hemolysin activity declined to zero. Our results support the potent role of the E. coli hemolysin as a pathogenicity factor in bacterial infection.