scholarly journals Results from a 13-Year Prospective Cohort Study Show Increased Mortality Associated with Bloodstream Infections Caused by Pseudomonas aeruginosa Compared to Other Bacteria

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Joshua T. Thaden ◽  
Lawrence P. Park ◽  
Stacey A. Maskarinec ◽  
Felicia Ruffin ◽  
Vance G. Fowler ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Cox Regression ◽  
Medical Center ◽  
Bacterial Species ◽  
Bloodstream Infections ◽  
Source Control ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
The Impact

ABSTRACT The impact of bacterial species on outcome in bloodstream infections (BSI) is incompletely understood. We evaluated the impact of bacterial species on BSI mortality, with adjustment for patient, bacterial, and treatment factors. From 2002 to 2015, all adult inpatients with monomicrobial BSI caused by Staphylococcus aureus or Gram-negative bacteria at Duke University Medical Center were prospectively enrolled. Kaplan-Meier curves and multivariable Cox regression with propensity score models were used to examine species-specific bacterial BSI mortality. Of the 2,659 enrolled patients, 999 (38%) were infected with S. aureus, and 1,660 (62%) were infected with Gram-negative bacteria. Among patients with Gram-negative BSI, Enterobacteriaceae (81% [1,343/1,660]) were most commonly isolated, followed by non-lactose-fermenting Gram-negative bacteria (16% [262/1,660]). Of the 999 S. aureus BSI isolates, 507 (51%) were methicillin resistant. Of the 1,660 Gram-negative BSI isolates, 500 (30%) were multidrug resistant. The unadjusted time-to-mortality among patients with Gram-negative BSI was shorter than that of patients with S. aureus BSI (P = 0.003), due to increased mortality in patients with non-lactose-fermenting Gram-negative BSI generally (P < 0.0001) and Pseudomonas aeruginosa BSI (n = 158) in particular (P < 0.0001). After adjustment for patient demographics, medical comorbidities, bacterial antibiotic resistance, timing of appropriate antibiotic therapy, and source control in patients with line-associated BSI, P. aeruginosa BSI remained significantly associated with increased mortality (hazard ratio = 1.435; 95% confidence interval = 1.043 to 1.933; P = 0.02). P. aeruginosa BSI was associated with increased mortality relative to S. aureus or other Gram-negative BSI. This effect persisted after adjustment for patient, bacterial, and treatment factors.

Diversity profiling of xenic cultures of Dientamoeba fragilis following systematic antibiotic treatment and prospects for genome sequencing

Parasitology ◽  
2019 ◽  
Vol 147 (1) ◽  
pp. 29-38
Author(s):  
Rory Gough ◽  
Joel Barratt ◽  
Damien Stark ◽  
John Ellis
Keyword(s):  
Antibiotic Treatment ◽  
Genome Sequencing ◽  
Ribosomal Dna ◽  
Bacterial Species ◽  
Nutritional Requirement ◽  
Gram Negative Bacteria ◽  
Gram Positive ◽  
Gram Negative ◽  
Dientamoeba Fragilis ◽  
The Impact

AbstractThe presence of bacterial DNA in Dientamoeba fragilis DNA extracts from culture poses a substantial challenge to sequencing the D. fragilis genome. However, elimination of bacteria from D. fragilis cultures has proven difficult in the past, presumably due to its dependence on some unknown prokaryote/s. This study explored options for removal of bacteria from D. fragilis cultures and for the generation of genome sequence data from D. fragilis. DNA was extracted from human faecal samples and xenic D. fragilis cultures. Extracts were subjected to 16S ribosomal DNA bacterial diversity profiling. Xenic D. fragilis cultures were then subject to antibiotic treatment regimens that systematically removed bacterial species depending on their membrane structure (Gram-positive or Gram-negative) and aerobic requirements. The impact of these treatments on cultures was assessed by 16S amplicon sequencing. Prior to antibiotic treatment, the cultures were dominated by Gram-negative bacteria. Addition of meropenem to cultures eliminated anaerobic Gram-negative bacteria, but it also led to protozoan death after 5 days incubation. The seeding of meropenem resistant Klebsiella pneumoniae strain KPC-2 into cultures before treatment by meropenem prevented death of D. fragilis cells beyond this 5 day period, suggesting that one or more species of Gram-negative bacteria may be an essential nutritional requirement for D. fragilis. Gram-positive cells were completely eliminated using vancomycin without affecting trophozoite growth. Finally, this study shows that genome sequencing of D. fragilis is feasible following bacterial elimination from cultures as the result of the major advances occurring in bioinformatics. We provide evidence on this fact by successfully sequencing the D. fragilis 28S large ribosomal DNA subunit gene using culture-derived DNA.

scholarly journals Predictors of Mortality in Bloodstream Infections Caused by Pseudomonas aeruginosa and Impact of Antimicrobial Resistance and Bacterial Virulence

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Raúl Recio ◽  
Mikel Mancheño ◽  
Esther Viedma ◽  
Jennifer Villa ◽  
María Ángeles Orellana ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Multivariate Logistic Regression Analysis ◽  
Empirical Therapy ◽  
Bloodstream Infections ◽  
Multivariate Logistic Regression ◽  
Related Factors ◽  
Content Type ◽  
Crude Mortality ◽  
The Impact

ABSTRACT Whether multidrug resistance (MDR) is associated with mortality in patients with Pseudomonas aeruginosa bloodstream infections (BSI) remains controversial. Here, we explored the prognostic factors of P. aeruginosa BSI with emphasis on antimicrobial resistance and virulence. All P. aeruginosa BSI episodes in a 5-year period were retrospectively analyzed. The impact in early (5-day) and late (30-day) crude mortality of host, antibiotic treatment, and pathogen factors was assessed by multivariate logistic regression analysis. Of 243 episodes, 93 (38.3%) were caused by MDR-PA. Crude 5-day (20%) and 30-day (33%) mortality was more frequent in patients with MDR-PA (34.4% versus 11.3%, P < 0.001 and 52.7% versus 21.3%, P < 0.001, respectively). Early mortality was associated with neutropenia (adjusted odds ratio [aOR], 9.21; 95% confidence interval [CI], 3.40 to 24.9; P < 0.001), increased Pitt score (aOR, 2.42; 95% CI, 1.34 to 4.36; P = 0.003), respiratory source (aOR, 3.23; 95% CI,2.01 to 5.16; P < 0.001), inadequate empirical therapy (aOR, 4.57; 95% CI, 1.59 to 13.1; P = 0.005), shorter time to positivity of blood culture (aOR, 0.88; 95% CI, 0.80 to 0.97; P = 0.010), an exoU-positive genotype (aOR, 3.58; 95% CI, 1.31 to 9.79; P = 0.013), and the O11 serotype (aOR, 3.64; 95% CI, 1.20 to 11.1; P = 0.022). These risk factors were similarly identified for late mortality, along with an MDR phenotype (aOR, 2.18; 95% CI, 1.04 to 4.58; P = 0.040). Moreover, the O11 serotype (15.2%, 37/243) was common among MDR (78.4%, 29/37) and exoU-positive (89.2%, 33/37) strains. Besides relevant clinical variables and inadequate empirical therapy, pathogen-related factors such as an MDR phenotype, an exoU-positive genotype, and the O11 serotype adversely affect the outcome of P. aeruginosa BSI.

scholarly journals Construction of a Broad-Host-Range Tn7-Based Vector for Single-Copy PBAD-Controlled Gene Expression in Gram-Negative Bacteria

2012 ◽  
Vol 79 (2) ◽  
pp. 718-721 ◽  
Author(s):  
F. Heath Damron ◽  
Elizabeth S. McKenney ◽  
Herbert P. Schweizer ◽  
Joanna B. Goldberg
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Host Range ◽  
Single Copy ◽  
Broad Host Range ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Delivery Vector ◽  
Inducible Gene

ABSTRACTWe describe a mini-Tn7-based broad-host-range expression cassette for arabinose-inducible gene expression from the PBADpromoter. This delivery vector, pTJ1, can integrate a single copy of a gene into the chromosome of Gram-negative bacteria for diverse genetic applications, of which several are discussed, usingPseudomonas aeruginosaas the model host.

scholarly journals National Surveillance of Antimicrobial Susceptibility of Bacteremic Gram-Negative Bacteria with Emphasis on Community-Acquired Resistant Isolates: Report from the 2019 Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART)

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Po-Yu Liu ◽  
Yu-Lin Lee ◽  
Min-Chi Lu ◽  
Pei-Lan Shao ◽  
Po-Liang Lu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Klebsiella Pneumoniae ◽  
Gram Negative Bacteria ◽  
National Surveillance ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Carbapenem Resistant

ABSTRACT A multicenter collection of bacteremic isolates of Escherichia coli (n = 423), Klebsiella pneumoniae (n = 372), Pseudomonas aeruginosa (n = 300), and Acinetobacter baumannii complex (n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-resistant isolates. Nineteen (67.8%) carbapenem-resistant K. pneumoniae (n = 28) and one (20%) carbapenem-resistant E. coli (n = 5) isolate harbored blaKPC (n = 17), blaOXA-48 (n = 2), and blaVIM (n = 1) genes.

scholarly journals Susceptibility of Multiresistant Gram-Negative Bacteria to Fosfomycin and Performance of Different Susceptibility Testing Methods

2013 ◽  
Vol 58 (3) ◽  
pp. 1763-1767 ◽  
Author(s):  
L. V. Perdigão-Neto ◽  
M. S. Oliveira ◽  
C. F. Rizek ◽  
C. M. D. M. Carrilho ◽  
S. F. Costa ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Susceptibility Testing ◽  
Gram Negative Bacteria ◽  
Testing Methods ◽  
Gram Negative ◽  
Content Type ◽  
Agar Dilution ◽  
And Performance ◽  
Systemic Infections

ABSTRACTFosfomycin may be a treatment option for multiresistant Gram-negative bacteria. This study compared susceptibility methods using 94 multiresistant clinical isolates. With agar dilution (AD), susceptibilities were 81%, 7%, 96%, and 100% (CLSI) and 0%, 0%, 96%, and 30% (EUCAST), respectively, forAcinetobacter baumannii,Pseudomonas aeruginosa,Klebsiella pneumoniae, andEnterobacterspp. Categorical agreement between Etest and AD forEnterobacteriaceaeandA. baumanniiwas ≥80%. Disk diffusion was adequate only forEnterobacter. CLSI criteria for urine may be adequate for systemic infections.

scholarly journals Pseudomonas aeruginosa Contact-Dependent Growth Inhibition Plays Dual Role in Host-Pathogen Interactions

mSphere ◽  
2017 ◽  
Vol 2 (6) ◽  
Author(s):  
Jeffrey A. Melvin ◽  
Jordan R. Gaston ◽  
Shawn N. Phillips ◽  
Michael J. Springer ◽  
Christopher W. Marshall ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acute Infection ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Microbial Pathogenesis ◽  
Host Pathogen Interactions ◽  
Gram Negative ◽  
Content Type ◽  
Disease Outcomes ◽  
Host Pathogen

ABSTRACT How bacteria compete and communicate with each other is an increasingly recognized aspect of microbial pathogenesis with a major impact on disease outcomes. Gram-negative bacteria have recently been shown to employ a contact-dependent toxin-antitoxin system to achieve both competition and regulation of their physiology. Here, we show that this system is vital for virulence in acute infection as well as for establishment of chronic infection in the multidrug-resistant pathogen Pseudomonas aeruginosa. Greater understanding of the mechanisms underlying bacterial virulence and infection is important for the development of effective therapeutics in the era of increasing antimicrobial resistance. Microorganisms exist in a diverse ecosystem and have evolved many different mechanisms for sensing and influencing the polymicrobial environment around them, utilizing both diffusible and contact-dependent signals. Contact-dependent growth inhibition (CDI) is one such communication system employed by Gram-negative bacteria. In addition to CDI mediation of growth inhibition, recent studies have demonstrated CDI-mediated control of communal behaviors such as biofilm formation. We postulated that CDI may therefore play an active role in host-pathogen interactions, allowing invading strains to establish themselves at polymicrobial mucosal interfaces through competitive interactions while simultaneously facilitating pathogenic capabilities via CDI-mediated signaling. Here, we show that Pseudomonas aeruginosa produces two CDI systems capable of mediating competition under conditions of growth on a surface or in liquid. Furthermore, we demonstrated a novel role for these systems in contributing to virulence in acute infection models, likely via posttranscriptional regulation of beneficial behaviors. While we did not observe any role for the P. aeruginosa CDI systems in biofilm biogenesis, we did identify for the first time robust CDI-mediated competition during interaction with a mammalian host using a model of chronic respiratory tract infection, as well as evidence that CDI expression is maintained in chronic lung infections. These findings reveal a previously unappreciated role for CDI in host-pathogen interactions and emphasize their importance during infection. IMPORTANCE How bacteria compete and communicate with each other is an increasingly recognized aspect of microbial pathogenesis with a major impact on disease outcomes. Gram-negative bacteria have recently been shown to employ a contact-dependent toxin-antitoxin system to achieve both competition and regulation of their physiology. Here, we show that this system is vital for virulence in acute infection as well as for establishment of chronic infection in the multidrug-resistant pathogen Pseudomonas aeruginosa. Greater understanding of the mechanisms underlying bacterial virulence and infection is important for the development of effective therapeutics in the era of increasing antimicrobial resistance.

scholarly journals Exposure to the Gram-Negative Bacteria Pseudomonas aeruginosa Influences the Lung Dendritic Cell Population Signature by Interfering With CD103 Expression

2021 ◽  
Vol 11 ◽  
Author(s):  
Julyanne Brassard ◽  
Joanny Roy ◽  
Anne-Marie Lemay ◽  
Marie-Josée Beaulieu ◽  
Emilie Bernatchez ◽  
...  
Keyword(s):  
Immune Response ◽  
Pseudomonas Aeruginosa ◽  
Intracellular Localization ◽  
Receptor Internalization ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Gm Csf ◽  
Dendritic Cell Population ◽  
The Impact

Lung dendritic cells (DCs) are divided into two major populations, which include CD103+XCR1+ cDC1s and CD11b+Sirpα+ cDC2s. The maintenance of their relative proportions is dynamic and lung inflammation, such as caused by exposure to lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, can have a significant impact on the local cDC signature. Alterations in the lung cDC signature could modify the capacity of the immune system to respond to various pathogens. We consequently aimed to assess the impact of the Gram-negative bacteria Pseudomonas aeruginosa on lung cDC1 and cDC2 populations, and to identify the mechanisms leading to alterations in cDC populations. We observed that exposure to P. aeruginosa decreased the proportions of CD103+XCR1+ cDC1s, while increasing that of CD11b+ DCs. We identified two potential mechanisms involved in this modulation of lung cDC populations. First, we observed an increase in bone marrow pre-DC IRF4 expression suggesting a higher propensity of pre-DCs to differentiate towards the cDC2 lineage. This observation was combined with a reduced capacity of lung XCR1+ DC1s to express CD103. In vitro, we demonstrated that GM-CSF-induced CD103 expression on cDCs depends on GM-CSF receptor internalization and RUNX1 activity. Furthermore, we observed that cDCs stimulation with LPS or P. aeruginosa reduced the proportions of intracellular GM-CSF receptor and decreased RUNX1 mRNA expression. Altogether, these results suggest that alterations in GM-CSF receptor intracellular localization and RUNX1 signaling could be involved in the reduced CD103 expression on cDC1 in response to P. aeruginosa. To verify whether the capacity of cDCs to express CD103 following P. aeruginosa exposure impacts the immune response, WT and Cd103-/- mice were exposed to P. aeruginosa. Lack of CD103 expression led to an increase in the number of neutrophils in the airways, suggesting that lack of CD103 expression on cDC1s could favor the innate immune response to this bacterium.

scholarly journals Pathogenicity Genomic Island-Associated CrpP-Like Fluoroquinolone-Modifying Enzymes among Pseudomonas aeruginosa Clinical Isolates in Europe

2020 ◽  
Vol 64 (7) ◽  
Author(s):  
José Manuel Ortiz de la Rosa ◽  
Patrice Nordmann ◽  
Laurent Poirel
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Genomic Island ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Genomic Islands ◽  
Clinical Isolates ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Content Type ◽  
Genes Encoding

ABSTRACT Many transferable quinolone resistance mechanisms have been identified in Gram-negative bacteria. The plasmid-encoded 65-amino-acid-long ciprofloxacin-modifying enzyme CrpP was recently identified in Pseudomonas aeruginosa isolates. We analyzed a collection of 100 clonally unrelated and multidrug-resistant P. aeruginosa clinical isolates, among which 46 were positive for crpP-like genes, encoding five CrpP variants conferring variable levels of reduced susceptibility to fluoroquinolones. These crpP-like genes were chromosomally located as part of pathogenicity genomic islands.

scholarly journals Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 632 ◽  
Author(s):  
Matteo Bassetti ◽  
Antonio Vena ◽  
Chiara Sepulcri ◽  
Daniele Roberto Giacobbe ◽  
Maddalena Peghin
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibiotic Resistance ◽  
Treatment Options ◽  
Bloodstream Infections ◽  
Gram Negative Bacteria ◽  
Beta Lactamase ◽  
Gram Negative ◽  
Extended Spectrum Beta Lactamase ◽  
Carbapenem Resistant ◽  
Rising Incidence

The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii.

scholarly journals Identification of OprF as a Complement Component C3 Binding Acceptor Molecule on the Surface of Pseudomonas aeruginosa

2015 ◽  
Vol 83 (8) ◽  
pp. 3006-3014 ◽  
Author(s):  
Meenu Mishra ◽  
Adam Ressler ◽  
Larry S. Schlesinger ◽  
Daniel J. Wozniak
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Opportunistic Pathogen ◽  
Gram Negative Bacteria ◽  
Acceptor Molecule ◽  
Wild Type ◽  
Gram Negative ◽  
Content Type ◽  
Persistent Infections ◽  
Structural Identity ◽  
Complement Component C3

Pseudomonas aeruginosais a versatile opportunistic pathogen that can cause devastating persistent infections. Complement is a highly conserved pathway of the innate immune system, and its role in the first line of defense against pathogens is widely appreciated. One of the earliest events in the complement cascade is the conversion of C3 to C3a and C3b, the latter typically binds to one or more acceptor molecules on the pathogen surface. We previously demonstrated that complement C3b binding acceptors exist on theP. aeruginosasurface. In the current study, we utilized either C3 polyclonal or C3b monoclonal antibodies in a far-Western technique followed by mass spectroscopy to identify the C3b acceptor molecule(s) on theP. aeruginosasurface. Our data provide evidence that OprF (an outer membrane porin, highly conserved in thePseudomonadaceae) binds C3b. AnoprF-deficientP. aeruginosastrain exhibits reduced C3 deposition compared to the wild type. We observed reduced internalization ofoprF-deficient bacteria by neutrophils after opsonization compared with wild-typeP. aeruginosa. Heterologous expression of OprF significantly enhanced C3b binding and increased serum-mediated bactericidal effects in complement-susceptibleEscherichia coli. Furthermore, the predicted secondary structure of the C-terminal, surface-exposed region of OprF has high structural identity to the OmpA domain of several other Gram-negative bacteria, one of which is known to bind C3b. Therefore, these findings provide new insights into the biology of complement interactions withP. aeruginosaand other Gram-negative bacteria.

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