Bacteremia in patients with hematological malignancies and neutropenia

For hematological cancer patients, the risk of blood stream infection by bacterial pathogens is increased. Studies on pathogen panorama, efficacy of antimicrobial prophylaxis and antimicrobial resistance are important efforts to decrease morbidity, mortality and the risk of delays or reduction of intensity in cancer treatment. There is a need for continuous development of new techniques for diagnosing infections. In this research project we seek to expand the knowledge base to future improvements in clinical management of bacterial bloodstream infections during neutropenia, The studies focus on local bacterial distribution and antibiotic resistance patterns by applying new means for diagnostics with Next Generation Sequencing (NGS) and evaluates the effects of prophylactic antibiotic treatment. Study I: Totally, 142 episodes of fever from 124 neutropenic patients with different hematological malignancies were analyzed, and bacterial blood stream infections were found in 27% of the cases. In 58% of these Gram-positive bacteria could be isolated and Viridans streptococci, CoNS and E. coli were most common. A negative association between bacterial blood stream infection and non-Hodgkin´s lymphoma as underlying diagnosis were noted (p = 0.01). The bacterial distribution was coherent to contemporary reports from Scandinavia and antimicrobial resistance levels were lower compared to centers in Europe. No significant protective effect of antibiotic prophylaxis with ciprofloxacin could be detected in this heterogenous material, which led to a more comprehensive investigation in Study II: Aiming to further evaluate the effects of ciprofloxacin prophylaxis during the course of cancer treatment, 666 episodes (235 with and 431 without prophylactic ciprofloxacin treatment) of treatment-induced neutropenia in 245 Swedish adult Acute Myeloid Leukemia patients were compared. Ciprofloxacin seemed to have good prophylactic effect with reduced incidence of fever and bacteremia in this group and should be considered at least in the initial cycles of chemotherapy. In Study III, 130 blood samples from 33 hematological cancer patients with intensive chemotherapy were included prospectively. Samples from different time points during febrile neutropenia were collected and analyzed with 16S rRNA amplicon sequencing. For 62 samples, blood culture findings were compared with sequencing results. The high-throughput sequencing yielded reads with slight overweight to Gram negative bacteria (55.7%). In total, the reads detected were distributed over 55% Proteobacteria, 33% Firmicutes, 9% Actinobacteria. 0.4% Fusobacteria and 0.1% Bacteroidetes. A more diversified bacterial panorama than expected was revealed but, with low concordance between blood cultures and NGS, and, the results indicate that bacterial translocation is important as etiological factor in febrile neutropenia. Study IV: In this study Shotgun metagenomics were applied for 27 blood samples collected during febrile neutropenia in nine acute leukemia patients. Even though the applied method needs development on several points, the study indicates the techniques applicability for diagnostics in bloodstream infections and reveals pathogenic dynamics during fever episodes that may become of value for more targeted antimicrobial strategies for this patient group

Excluded volume effects on the structure of a linear polymer under shear flow

The effect of excluded volume interactions on the structure of a polymer in shear flow is investigated by Brownian Dynamics simulations for chains with size $30\leq N\leq 300$. The main results concern the structure factor $S({\bf q})$ of chains of N=300 Kuhn segments, observed at a reduced shear rate $\beta=\dot{\gamma}\tau=3.2$, where $\dot{\gamma}$ is the bare shear rate and $\tau$ is the longest relaxation time of the chain. At low q, where anisotropic global deformation is probed, the chain form factor is shown to match the form factor of the continuous Rouse model under shear at the same reduced shear rate, computed here for the first time in a wide range of wave vectors. At high q, the chain structure factor evolves towards the isotropic equilibrium power law $q^{-1/\nu}$ typical of self-avoiding walk statistics. The matching between excluded volume and ideal chains at small q, and the excluded volume power law behavior at large q are observed for ${\bf q}$ orthogonal to the main elongation axis but not yet for ${\bf q}$ along the elongation direction itself, as a result of interferences with finite extensibility effects. Our simulations support the existence of anisotropic shear blobs for polymers in good solvent under shear flow for $\beta>1$ provided chains are sufficiently long.Comment: 36 pages, 11 figures, submitted to J. Chem. Phy

The Procedural Index for Mortality Risk (PIMR): an index calculated using administrative data to quantify the independent influence of procedures on risk of hospital death

<p>Abstract</p> <p>Background</p> <p>Surgeries and other procedures can influence the risk of death in hospital. All published scales that predict post-operative death risk require clinical data and cannot be measured using administrative data alone. This study derived and internally validated an index that can be calculated using administrative data to quantify the independent risk of hospital death after a procedure.</p> <p>Methods</p> <p>For all patients admitted to a single academic centre between 2004 and 2009, we estimated the risk of all-cause death using the Kaiser Permanente Inpatient Risk Adjustment Methodology (KP-IRAM). We determined whether each patient underwent one of 503 commonly performed therapeutic procedures using Canadian Classification of Interventions codes and whether each procedure was emergent or elective. Multivariate logistic regression modeling was used to measure the association of each procedure-urgency combination with death in hospital independent of the KP-IRAM risk of death. The final model was modified into a scoring system to quantify the independent influence each procedure had on the risk of death in hospital.</p> <p>Results</p> <p>275 460 hospitalizations were included (137,730 derivation, 137,730 validation). In the derivation group, the median expected risk of death was 0.1% (IQR 0.01%-1.4%) with 4013 (2.9%) dying during the hospitalization. 56 distinct procedure-urgency combinations entered our final model resulting in a Procedural Index for Mortality Rating (PIMR) score values ranging from -7 to +11. In the validation group, the PIMR score significantly predicted the risk of death by itself (c-statistic 67.3%, 95% CI 66.6-68.0%) and when added to the KP-IRAM model (c-index improved significantly from 0.929 to 0.938).</p> <p>Conclusions</p> <p>We derived and internally validated an index that uses administrative data to quantify the independent association of a broad range of therapeutic procedures with risk of death in hospital. This scale will improve risk adjustment when administrative data are used for analyses.</p

Mannose-Binding Lectin 2 Polymorphisms Do Not Influence Frequency or Type of Infection in Adults with Chemotherapy Induced Neutropaenia

BACKGROUND: Mannose-binding Lectin protein (MBL) has been suggested to be relevant in the defence against infections in immunosuppressed individuals. In a Swedish adult cohort immunosuppressed from both the underlying disease and from iatrogenic treatments for their underlying disease we investigated the role of MBL in susceptibility to infection. METHODS: In this cross sectional, prospective study, blood samples obtained from 96 neutropaenic febrile episodes, representing 82 individuals were analysed for single nucleotide polymorphism (SNP) in the MBL2 gene. Concurrent measurement of plasma MBL protein concentrations was also performed for observation of acute response during febrile episodes. FINDINGS: No association was observed between MBL2 genotype or plasma MBL concentrations, and the type or frequency of infection. Adding to the literature, we found no evidence that viral infections or co-infections with virus and bacteria would be predisposed by MBL deficiency. We further saw no correlation between MBL2 genotype and the risk of fever. However, fever duration in febrile neutropaenic episodes was negatively associated with MBL2 SNP mutations (p<0.05). Patients with MBL2 SNP mutations presented a median febrile duration of 1.8 days compared with 3 days amongst patients with wildtype MBL2 genotype. INTERPRETATION: We found no clear association between infection, or infection type to MBL2 genotypes or plasma MBL concentration, and add to the reports casting doubts on the benefit of recombinant MBL replacement therapy use during iatrogenic neutropaenia

Viral Findings in Adult Hematological Patients with Neutropenia

BACKGROUND: Until recently, viral infections in patients with hematological malignancies were concerns primarily in allogeneic hematopoietic stem cell transplant (HSCT) recipients. During the last years, changed treatment regimens for non-transplanted patients with hematological malignancies have had potential to increase the incidence of viral infections in this group. In this study, we have prospectively investigated the prevalence of a broad range of respiratory viruses in nasopharyngeal aspirate (NPA) as well as viruses that commonly reactivate after allogeneic HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Patients with hematological malignancies and therapy induced neutropenia (n = 159) were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22%) and NPA (18%) with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL) (p<0.01) and patients with fever (p<0.001) were overrepresented in the virus-positive group. Furthermore, viral findings in NPA were associated with upper respiratory symptoms (URTS) (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Both respiratory viral infections and low titers of viruses in blood from patients with neutropenia were common. Patients with CLL and patients with fever were independently associated to these infections, and viral findings in NPA were associated to URTS indicating active infection. These findings motivate further studies on viruses' impact on this patient category and their potential role as causative agents of fever during neutropenia

ECOLOGICAL ENGINEERING

www elsev~er com/locate/ecoleng Spatial and temporal patterns of carbon storage and species richness in three South Carolina coastal plain riparian forest

Bacterial Landscape of Bloodstream Infections in Neutropenic Patients via High Throughput Sequencing

<div><p>Background</p><p>Bloodstream infection (BSI) is a common and potentially life-threatening complication in patients with hematological malignancies and therapy-induced neutropenia. Administration of broad spectrum antibiotics has substantially decreased the mortality rate in febrile neutropenia, but bacterial infection is documented in only one-third or fewer of the cases. BSI is typically diagnosed by blood culture; however, this method can detect only culturable pathogens.</p><p>Methods</p><p>In the present study, a total of 130 blood samples from hematological patients receiving dose-intensive antitumoural treatment were subjected to 16S rRNA PCR and 62 of them were cultured. PCR positive samples were processed to high throughput sequencing by amplifying the V1-V3 regions of the 16S rRNA gene to obtain a full spectrum of bacteria present in BSI.</p><p>Results</p><p>Five phyla and 30 genera were identified with sequencing compared to 2 phyla and 4 genera with culture. The largest proportion of bacteria detected by sequencing belonged to Proteobacteria (55.2%), Firmicutes (33.4%) and Actinobacteria (8.6%), while Fusobacteria (0.4%) and Bacteroidetes (0.1%) were also detected. Ninety-eight percent of the bacteria identified by sequencing were opportunistic human pathogens and 65% belonged to the normal human microbiota.</p><p>Conclusions</p><p>The present study indicates that BSIs in neutropenic hosts contain a much broader diversity of bacteria, likely with host origin, than previously realized. The elevated ratio of Proteobacteria in BSI corroborates the results found in other systemic inflammatory diseases, such as inflammatory bowel disease or mucosal infections. This knowledge may become of value for tailoring antimicrobial drug administration.</p></div

MBL concentrations and microbiological findings of febrile and afebrile neutropaenic episodes.

1<p>Comparison of MBL concentrations from episodes of A/A individuals with fever and without fever.</p>2<p>Comparison of MBL concentrations from episodes of A/O and O/O individuals with fever and without fever.</p><p>N.D. Bacteria investigations were not performed as a routine.</p