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Multisite external validation of a risk prediction model for the diagnosis of blood stream infections in febrile pediatric oncology patients without severe neutropenia.
Esbenshade AJ, Zhao Z, Aftandilian C, Saab R, Wattier RL, Beauchemin M, Miller TP, Wilkes JJ, Kelly MJ, Fernbach A, Jeng M, Schwartz CL, Dvorak CC, Shyr Y, Moons KGM, Sulis ML, Friedman DL
(2017) Cancer 123: 3781-3790
MeSH Terms: Bacteremia, Child, Child, Preschool, Datasets as Topic, Febrile Neutropenia, Gram-Negative Bacterial Infections, Humans, Immunocompromised Host, Models, Statistical, Neoplasms, Predictive Value of Tests, Retrospective Studies, Risk, Staphylococcal Infections, Staphylococcus aureus, Uncertainty
Show Abstract · Added April 3, 2018
BACKGROUND - Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness.
METHODS - A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding 2 less clinically reliable variables also was created using the initial EsVan model derivative cohort, and was validated using all 5 external validation cohorts. One data set was used only in sensitivity analyses due to missing some variables.
RESULTS - From the 5 primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C statistic for predicting bacteremia was 0.695, with a calibration slope of 0.50 for the original model and a calibration slope of 1.0 when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (gram-negative or Staphylococcus aureus infection) versus BSI alone, with a C statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across data sets with a C statistic of 0.733 for predicting BSI and a C statistic of 0.841 for high-risk BSI.
CONCLUSIONS - The results of this external validation demonstrated that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and, once validated and implemented prospectively, could assist in decision making in clinical practice. Cancer 2017;123:3781-3790. © 2017 American Cancer Society.
© 2017 American Cancer Society.
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How bacterial pathogens use type III and type IV secretion systems to facilitate their transmission.
Byndloss MX, Rivera-Chávez F, Tsolis RM, Bäumler AJ
(2017) Curr Opin Microbiol 35: 1-7
MeSH Terms: Animals, Brucella, Brucellosis, Gram-Negative Bacteria, Gram-Negative Bacterial Infections, Host-Pathogen Interactions, Humans, Protein Transport, Salmonella, Salmonella Infections, Type III Secretion Systems, Type IV Secretion Systems, Virulence Factors
Show Abstract · Added March 30, 2020
Work on type III or type IV secretion systems (T3SSs or T4SSs) is often focused on elucidating how these sophisticated bacterial virulence factors manipulate host cell physiology to cause disease. But to fully understand their role in pathogen biology, it is important to consider whether the morbidity or mortality they trigger is somehow linked to enhancing communicability of the microbe. Recent work on Salmonella enterica and Brucella abortus provide captivating examples of how manipulation of host cells with T3SSs or T4SSs instigates distant downstream consequences that promote spread of the pathogen. It is clear from these examples that T3SSs and T4SSs are ultimately transmission factors placed under selection by an incredibly complex series of events unfolding during host pathogen interaction.
Copyright © 2016 Elsevier Ltd. All rights reserved.
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Pharmacokinetics and pharmacodynamics of imipenem and meropenem in critically ill patients treated with continuous venovenous hemodialysis.
Afshartous D, Bauer SR, Connor MJ, Aduroja OA, Amde M, Salem C, Groszek JJ, Fissell WH
(2014) Am J Kidney Dis 63: 170-1
MeSH Terms: Anti-Bacterial Agents, Critical Illness, Drug Dosage Calculations, Female, Gram-Negative Bacterial Infections, Humans, Imipenem, Male, Medication Errors, Meropenem, Metabolic Clearance Rate, Middle Aged, Renal Dialysis, Thienamycins
Added February 25, 2014
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14 MeSH Terms
The tripartite associations between bacteriophage, Wolbachia, and arthropods.
Bordenstein SR, Marshall ML, Fry AJ, Kim U, Wernegreen JJ
(2006) PLoS Pathog 2: e43
MeSH Terms: Animals, Bacteriophages, Female, Gene Dosage, Gram-Negative Bacterial Infections, Male, Penetrance, Spermatids, Symbiosis, Wasps, Wolbachia
Show Abstract · Added March 28, 2016
By manipulating arthropod reproduction worldwide, the heritable endosymbiont Wolbachia has spread to pandemic levels. Little is known about the microbial basis of cytoplasmic incompatibility (CI) except that bacterial densities and percentages of infected sperm cysts associate with incompatibility strength. The recent discovery of a temperate bacteriophage (WO-B) of Wolbachia containing ankyrin-encoding genes and virulence factors has led to intensifying debate that bacteriophage WO-B induces CI. However, current hypotheses have not considered the separate roles that lytic and lysogenic phage might have on bacterial fitness and phenotype. Here we describe a set of quantitative approaches to characterize phage densities and its associations with bacterial densities and CI. We enumerated genome copy number of phage WO-B and Wolbachia and CI penetrance in supergroup A- and B-infected males of the parasitoid wasp Nasonia vitripennis. We report several findings: (1) variability in CI strength for A-infected males is positively associated with bacterial densities, as expected under the bacterial density model of CI, (2) phage and bacterial densities have a significant inverse association, as expected for an active lytic infection, and (3) CI strength and phage densities are inversely related in A-infected males; similarly, males expressing incomplete CI have significantly higher phage densities than males expressing complete CI. Ultrastructural analyses indicate that approximately 12% of the A Wolbachia have phage particles, and aggregations of these particles can putatively occur outside the Wolbachia cell. Physical interactions were observed between approximately 16% of the Wolbachia cells and spermatid tails. The results support a low to moderate frequency of lytic development in Wolbachia and an overall negative density relationship between bacteriophage and Wolbachia. The findings motivate a novel phage density model of CI in which lytic phage repress Wolbachia densities and therefore reproductive parasitism. We conclude that phage, Wolbachia, and arthropods form a tripartite symbiotic association in which all three are integral to understanding the biology of this widespread endosymbiosis. Clarifying the roles of lytic and lysogenic phage development in Wolbachia biology will effectively structure inquiries into this research topic.
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11 MeSH Terms
Epidemiology of bloodstream infections in the first year after pediatric lung transplantation.
Danziger-Isakov LA, Sweet S, Delamorena M, Huddleston CB, Mendeloff E, Debaun MR
(2005) Pediatr Infect Dis J 24: 324-30
MeSH Terms: Adolescent, Bacteremia, Blood, Candida, Candidiasis, Child, Child, Preschool, Culture Media, Female, Fungemia, Gram-Negative Bacteria, Gram-Negative Bacterial Infections, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, Humans, Infant, Infant, Newborn, Lung Transplantation, Male
Show Abstract · Added November 27, 2013
BACKGROUND - Substantial morbidity and mortality rates are associated with infections in the first year after pediatric lung transplantation. To understand better the clinical significance of bloodstream infections (BSIs), we evaluated systematically the epidemiologic features of BSIs in the first year after transplantation.
METHODS - A retrospective case-cohort study of pediatric primary lung transplant recipients was performed. The frequency of BSIs and the organisms isolated were determined through medical and laboratory record review. We assessed variations in causative organisms and rates of BSIs in 3 time periods after transplantation, ie, early (0-30 days), intermediate (31-90 days) and late (91-365 days).
RESULTS - Between July 1990 and November 2000, 190 pediatric patients received primary lung transplants. Twenty-six percent (49 of 190) of recipients had at least 1 BSI. The most commonly isolated organisms were coagulase-negative Staphylococcus (n = 25, 28.4%), Pseudomonas aeruginosa (n = 14, 16.0%) and Candida spp. (n = 9, 10.2%). The overall rate of BSIs was 2.1 episodes per 1000 catheter-days. The highest rate of BSIs occurred in the early period, compared with the intermediate and late periods (5.5, 1.3 and 1.6 episodes per 1000 catheter-days, respectively; P = 0.21). Early BSIs were associated with death in the first year after transplantation (relative risk, 3.9; 95% confidence interval, 1.6-9.4; P = 0.002).
CONCLUSIONS - BSIs occur frequently after primary pediatric lung transplantation, with the highest rate being in the first 30 days after transplantation. Early BSIs are associated with death in the first year after transplantation.
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19 MeSH Terms
Bioartificial kidney ameliorates gram-negative bacteria-induced septic shock in uremic animals.
Fissell WH, Lou L, Abrishami S, Buffington DA, Humes HD
(2003) J Am Soc Nephrol 14: 454-61
MeSH Terms: Animals, Bioartificial Organs, Cardiovascular System, Cytokines, Dogs, Gram-Negative Bacterial Infections, Kidneys, Artificial, Shock, Septic, Uremia
Show Abstract · Added August 21, 2013
The bioartificial kidney (BAK) consists of a conventional hemofiltration cartridge in series with a renal tubule assist device (RAD) containing 10(9) porcine renal proximal tubule cells. BAK replaces filtration, transport, and metabolic and endocrinologic activities of a kidney. Previous work in an acutely uremic dog model demonstrated that BAK ameliorated endotoxin (lipopolysaccharide [LPS])-induced hypotension and altered plasma cytokine levels. To further assess the role of BAK in sepsis in acute renal failure, dogs were nephrectomized and 48 h later administered intraperitoneally with 30 x 10(10) bacteria/kg of E. coli. One hour after bacterial administration, animals were placed in a continuous venovenous hemofiltration circuit with either a sham RAD without cells (n = 6) or a RAD with cells (n = 6). BP, cardiac output, heart rate, pulmonary capillary wedge pressure, and systemic vascular resistance were measured throughout the study. All animals tested were in renal failure, with blood urea nitrogen and serum creatinine concentrations greater than 60 and 6 mg/dl, respectively. RAD treatment maintained significantly better cardiovascular performance, as determined by arterial BP (P < 0.05) and cardiac output (P < 0.02), for longer periods than sham RAD therapy. Consistently, all sham RAD-treated animals, except one, expired within 2 to 9 h after bacterial administration, whereas all RAD-treated animals survived more than 10 h. Plasma levels of TNF-alpha, IL-10, and C-reactive protein (CRP) were measured during cell RAD and sham RAD treatment. IL-10 levels were significantly higher (P < 0.01) during the entire treatment interval in the RAD animals compared with sham controls. These data demonstrated in a pilot large animal experiment that the BAK with RAD altered plasma cytokine levels in acutely uremic animals with septic shock. This change was associated with improved cardiovascular performance and increased survival time. These results demonstrate that the addition of cell therapy to hemofiltration in an acutely uremic animal model with septic shock ameliorates cardiovascular dysfunction, alters systemic cytokine balance, and improves survival time.
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9 MeSH Terms
Recurrent Achromobacter xylosoxidans bacteremia associated with persistent lymph node infection in a patient with hyper-immunoglobulin M syndrome.
Weitkamp JH, Tang YW, Haas DW, Midha NK, Crowe JE
(2000) Clin Infect Dis 31: 1183-7
MeSH Terms: Alcaligenes, Bacteremia, Child, Follow-Up Studies, Gram-Negative Bacterial Infections, Humans, Hypergammaglobulinemia, Infant, Infant, Newborn, Lymph Nodes, Male, Recurrence, Syndrome
Show Abstract · Added February 27, 2014
Achromobacter xylosoxidans (formerly Alcaligenes xylosoxidans) is a rare but important cause of bacteremia in immunocompromised patients, and strains are usually multiply resistant to antimicrobial therapy. We report an immunocompromised patient with hyper-immunoglobulin M syndrome who suffered from 14 documented episodes of A. xylosoxidans bacteremia. Each episode was treated and resulted in rapid clinical improvement, with blood cultures testing negative for bacteria. Between episodes, A. xylosoxidans was isolated from an excised right axillary lymph node, whereas the culture of the central venous catheter, removed at the same time, was negative. Multiple cultures from sputum, stool, and urine samples, as well as from gastrointestinal biopsies or environmental sources, were negative. Results from antibiotic sensitivity testing and pulsed-field gel electrophoresis suggested that a single strain of A. xylosoxidans caused the recurrent bacteremias in this patient; this strain originated from persistently infected lymph nodes. Lymphoid hyperplasia is a prominent characteristic of hyper-IgM syndrome and may serve as a source of bacteremia with low-pathogenicity organisms.
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13 MeSH Terms
Outcomes of single organism peritonitis in peritoneal dialysis: gram negatives versus gram positives in the Network 9 Peritonitis Study.
Bunke CM, Brier ME, Golper TA
(1997) Kidney Int 52: 524-9
MeSH Terms: Aged, Female, Gram-Negative Bacterial Infections, Gram-Positive Bacterial Infections, Humans, Male, Middle Aged, Outcome Assessment, Health Care, Peritoneal Dialysis, Peritonitis, Quality of Health Care
Show Abstract · Added August 7, 2015
The use of the "peritonitis rate" in the management of patients undergoing peritoneal dialysis is assuming importance in comparing the prowess of facilities, care givers and new innovations. For this to be a meaningful outcome measure, the type of infection (causative pathogen) must have less clinical significance than the number of infections during a time interval. The natural history of Staphylococcus aureus, pseudomonas, and fungal peritonitis would not support that the outcome of an episode of peritonitis is independent of the causative pathogen. Could this concern be extended to other more frequently occurring pathogens? To address this, the Network 9 Peritonitis Study identified 530 episodes of single organism peritonitis caused by a gram positive organism and 136 episodes caused by a single non-pseudomonal gram negative (NPGN) pathogen. Coincidental soft tissue infections (exit site or tunnel) occurred equally in both groups. Outcomes of peritonitis were analyzed by organism classification and by presence or absence of a soft tissue infection. NPGN peritonitis was associated with significantly more frequent catheter loss, hospitalization, and technique failure and was less likely to resolve regardless of the presence or absence of a soft tissue infection. Hospitalization and death tended to occur more frequently with enterococcal peritonitis than with other gram positive peritonitis. The outcomes in the NPGN peritonitis group were significantly worse (resolution, catheter loss, hospitalization, technique failure) compared to coagulase negative staphylococcal or S. aureus peritonitis, regardless of the presence or absence of a coincidental soft tissue infection. Furthermore, for the first time, the poor outcomes of gram negative peritonitis are shown to be independent of pseudomonas or polymicrobial involvement or soft tissue infections. The gram negative organism appears to be the important factor. In addition, the outcome of peritonitis caused by S. aureus is worse than that of other staphylococci. Thus, it is clear that all peritonitis episodes cannot be considered equivalent in terms of outcome. The concept of peritonitis rate is only meaningful when specific organisms are considered.
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11 MeSH Terms
Veillonella parvula bacteremia without an underlying source.
Fisher RG, Denison MR
(1996) J Clin Microbiol 34: 3235-6
MeSH Terms: Bacteremia, Child, Preschool, Gram-Negative Bacterial Infections, Humans, Male, Neuroblastoma, Opportunistic Infections, Veillonella
Show Abstract · Added February 19, 2015
Veillonella parvula is an anaerobic gram-negative coccus that is part of the normal human flora. It has rarely been identified as a pathogen in humans, and the most frequently reported infection caused by V. parvula is osteomyelitis. We report a case of bacteremia unrelated to a central venous catheter and without an underlying source of infection.
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8 MeSH Terms
Meningitis caused by mixed anaerobic species complicating tethered cord syndrome.
Borowsky AD, Stein SM, Tulipan NB, Dermody TS
(1995) Clin Infect Dis 21: 706-7
MeSH Terms: Actinomycetales Infections, Bifidobacterium, Female, Gram-Negative Bacterial Infections, Humans, Infant, Magnetic Resonance Imaging, Meningitis, Bacterial, Spina Bifida Occulta, Veillonella
Added December 10, 2013
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10 MeSH Terms