scholarly journals Saturability of Granulocyte Kill of Pseudomonas aeruginosa in a Murine Model of Pneumonia

2011 ◽  
Vol 55 (6) ◽  
pp. 2693-2695 ◽  
Author(s):  
G. L. Drusano ◽  
B. VanScoy ◽  
W. Liu ◽  
S. Fikes ◽  
D. Brown ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Immune System ◽  
Murine Model ◽  
Antimicrobial Chemotherapy ◽  
Ventilator Associated Pneumonia ◽  
Bacterial Burden ◽  
Content Type ◽  
The Impact ◽  
Over Time

ABSTRACTOutcomes for patients with dense bacterial burdens, such as ventilator-associated pneumonia (VAP) patients, are often critically influenced by the adequacy of antimicrobial chemotherapy and by the response of the immune system, particularly the granulocytes. Little information is available about the quantitation of kill of organisms over time by granulocytes. In this investigation, we examined the impact of the baseline bacterial burden on the ability of granulocytes alone (without chemotherapy) to keep the number of organisms in check or to kill them over a 24-h period.Pseudomonas aeruginosaATCC 27853 was the study organism, and we employed a murine pneumonia model (granulocyte replete) for the study. We found that the ability of the immune system to killP. aeruginosawas saturable. The burden at which the system was half saturated was 2.15 × 106± 2.66 × 106CFU/g. Burdens greater than 107CFU/g demonstrated net growth over 24 h. These findings suggest the need for aggressive chemotherapy early in the treatment of VAP to keep the burden from saturating the granulocytes. This should optimize the outcome for these seriously infected patients.

scholarly journals Bioengineered Lysozyme Reduces Bacterial Burden and Inflammation in a Murine Model of Mucoid Pseudomonas aeruginosa Lung Infection

2013 ◽  
Vol 57 (11) ◽  
pp. 5559-5564 ◽  
Author(s):  
Charlotte C. Teneback ◽  
Thomas C. Scanlon ◽  
Matthew J. Wargo ◽  
Jenna L. Bement ◽  
Karl E. Griswold ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Murine Model ◽  
Repeated Administration ◽  
Bacterial Burden ◽  
Human Lysozyme ◽  
Content Type ◽  
Markers Of Inflammation ◽  
Lung Infections ◽  
A Charge

ABSTRACTThe spread of drug-resistant bacterial pathogens is a growing global concern and has prompted an effort to explore potential adjuvant and alternative therapies derived from nature's repertoire of bactericidal proteins and peptides. In humans, the airway surface liquid layer is a rich source of antibiotics, and lysozyme represents one of the most abundant and effective antimicrobial components of airway secretions. Human lysozyme is active against both Gram-positive and Gram-negative bacteria, acting through several mechanisms, including catalytic degradation of cell wall peptidoglycan and subsequent bacterial lysis. In the infected lung, however, lysozyme's dense cationic character can result in sequestration and inhibition by polyanions associated with airway inflammation. As a result, the efficacy of the native enzyme may be compromised in the infected and inflamed lung. To address this limitation, we previously constructed a charge-engineered variant of human lysozyme that was less prone to electrostatic-mediated inhibitionin vitro. Here, we employ a murine model to show that this engineered enzyme is superior to wild-type human lysozyme as a treatment for mucoidPseudomonas aeruginosalung infections. The engineered enzyme effectively decreases the bacterial burden and reduces markers of inflammation and lung injury. Importantly, we found no evidence of acute toxicity or allergic hypersensitivity upon repeated administration of the engineered biotherapeutic. Thus, the charge-engineered lysozyme represents an interesting therapeutic candidate forP. aeruginosalung infections.

scholarly journals The Impact of Intervention-Related Risk Factors on the Risk of Ventilator-Associated Pneumonia Is High in a Neurosurgical Intensive Care Unit

2020 ◽  
Vol 41 (S1) ◽  
pp. s407-s409
Author(s):  
Ksenia Ershova ◽  
Oleg Khomenko ◽  
Olga Ershova ◽  
Ivan Savin ◽  
Natalia Kurdumova ◽  
...  
Keyword(s):  
Risk Factors ◽  
Mechanical Ventilation ◽  
Negative Slope ◽  
Infection Prevention And Control ◽  
Ventilator Associated Pneumonia ◽  
Related Factors ◽  
Icu Patients ◽  
The Impact ◽  
Adf Test ◽  
Over Time

Background: Ventilator-associated pneumonia (VAP) represents the highest burden among all healthcare-associated infections (HAIs), with a particularly high rate in patients in neurosurgical ICUs. Numerous VAP risk factors have been identified to provide a basis for preventive measures. However, the impact of individual factors on the risk of VAP is unclear. The goal of this study was to evaluate the dynamics of various VAP risk factors given the continuously declining prevalence of VAP in our neurosurgical ICU. Methods: This prospective cohort unit-based study included neurosurgical patients who stayed in the ICU >48 consecutive hours in 2011 through 2018. The infection prevention and control (IPC) program was implemented in 2010 and underwent changes to adopt best practices over time. We used a 2008 CDC definition for VAP. The dynamics of VAP risk factors was considered a time series and was checked for stationarity using theAugmented Dickey-Fuller test (ADF) test. The data were censored when a risk factor was present during and after VAP episodes. Results: In total, 2,957 ICU patients were included in the study, 476 of whom had VAP. Average annual prevalence of VAP decreased from 15.8 per 100 ICU patients in 2011 to 9.5 per 100 ICU patients in 2018 (Welch t test P value = 7.7e-16). The fitted linear model showed negative slope (Fig. 1). During a study period we observed substantial changes in some risk factors and no changes in others. Namely, we detected a decrease in the use of anxiolytics and antibiotics, decreased days on mechanical ventilation, and a lower rate of intestinal dysfunction, all of which were nonstationary processes with a declining trend (ADF testP > .05) (Fig. 2). However, there were no changes over time in such factors as average age, comorbidity index, level of consciousness, gender, and proportion of patients with brain trauma (Fig. 2). Conclusions: Our evidence-based IPC program was effective in lowering the prevalence of VAP and demonstrated which individual measures contributed to this improvement. By following the dynamics of known VAP risk factors over time, we found that their association with declining VAP prevalence varies significantly. Intervention-related factors (ie, use of antibiotics, anxiolytics and mechanical ventilation, and a rate of intestinal dysfunction) demonstrated significant reduction, and patient-related factors (ie, age, sex, comorbidity, etc) remained unchanged. Thus, according to the discriminative model, the intervention-related factors contributed more to the overall risk of VAP than did patient-related factors, and their reduction was associated with a decrease in VAP prevalence in our neurosurgical ICU.Funding: NoneDisclosures: None

scholarly journals Exogenous Alginate Protects Staphylococcus aureus from Killing by Pseudomonas aeruginosa

2019 ◽  
Vol 202 (8) ◽  
Author(s):  
Courtney E. Price ◽  
Dustin G. Brown ◽  
Dominique H. Limoli ◽  
Vanessa V. Phelan ◽  
George A. O’Toole
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Physical Space ◽  
Late Time ◽  
Protective Effects ◽  
Content Type ◽  
Alginate Production ◽  
The Impact

ABSTRACT Cystic fibrosis (CF) patients chronically infected with both Pseudomonas aeruginosa and Staphylococcus aureus have worse health outcomes than patients who are monoinfected with either P. aeruginosa or S. aureus. We showed previously that mucoid strains of P. aeruginosa can coexist with S. aureus in vitro due to the transcriptional downregulation of several toxic exoproducts typically produced by P. aeruginosa, including siderophores, rhamnolipids, and HQNO (2-heptyl-4-hydroxyquinoline N-oxide). Here, we demonstrate that exogenous alginate protects S. aureus from P. aeruginosa in both planktonic and biofilm coculture models under a variety of nutritional conditions. S. aureus protection in the presence of exogenous alginate is due to the transcriptional downregulation of pvdA, a gene required for the production of the iron-scavenging siderophore pyoverdine as well as the downregulation of the PQS (Pseudomonas quinolone signal) (2-heptyl-3,4-dihydroxyquinoline) quorum sensing system. The impact of exogenous alginate is independent of endogenous alginate production. We further demonstrate that coculture of mucoid P. aeruginosa with nonmucoid P. aeruginosa strains can mitigate the killing of S. aureus by the nonmucoid strain of P. aeruginosa, indicating that the mechanism that we describe here may function in vivo in the context of mixed infections. Finally, we investigated a panel of mucoid clinical isolates that retain the ability to kill S. aureus at late time points and show that each strain has a unique expression profile, indicating that mucoid isolates can overcome the S. aureus-protective effects of mucoidy in a strain-specific manner. IMPORTANCE CF patients are chronically infected by polymicrobial communities. The two dominant bacterial pathogens that infect the lungs of CF patients are P. aeruginosa and S. aureus, with ∼30% of patients coinfected by both species. Such coinfected individuals have worse outcomes than monoinfected patients, and both species persist within the same physical space. A variety of host and environmental factors have been demonstrated to promote P. aeruginosa-S. aureus coexistence, despite evidence that P. aeruginosa kills S. aureus when these organisms are cocultured in vitro. Thus, a better understanding of P. aeruginosa-S. aureus interactions, particularly mechanisms by which these microorganisms are able to coexist in proximal physical space, will lead to better-informed treatments for chronic polymicrobial infections.

scholarly journals Changes in the Use of Broad-Spectrum Antibiotics after Cefepime Shortage: a Time Series Analysis

2011 ◽  
Vol 56 (2) ◽  
pp. 989-994 ◽  
Author(s):  
C. Plüss-Suard ◽  
A. Pannatier ◽  
C. Ruffieux ◽  
A. Kronenberg ◽  
K. Mühlemann ◽  
...  
Keyword(s):  
Time Series ◽  
Pseudomonas Aeruginosa ◽  
Broad Spectrum ◽  
Interrupted Time Series ◽  
Antibiotic Policy ◽  
Content Type ◽  
Broad Spectrum Antibiotics ◽  
Before And After ◽  
Alternative Antibiotic ◽  
The Impact

ABSTRACTThe original cefepime product was withdrawn from the Swiss market in January 2007 and replaced by a generic 10 months later. The goals of the study were to assess the impact of this cefepime shortage on the use and costs of alternative broad-spectrum antibiotics, on antibiotic policy, and on resistance ofPseudomonas aeruginosatoward carbapenems, ceftazidime, and piperacillin-tazobactam. A generalized regression-based interrupted time series model assessed how much the shortage changed the monthly use and costs of cefepime and of selected alternative broad-spectrum antibiotics (ceftazidime, imipenem-cilastatin, meropenem, piperacillin-tazobactam) in 15 Swiss acute care hospitals from January 2005 to December 2008. Resistance ofP. aeruginosawas compared before and after the cefepime shortage. There was a statistically significant increase in the consumption of piperacillin-tazobactam in hospitals with definitive interruption of cefepime supply and of meropenem in hospitals with transient interruption of cefepime supply. Consumption of each alternative antibiotic tended to increase during the cefepime shortage and to decrease when the cefepime generic was released. These shifts were associated with significantly higher overall costs. There was no significant change in hospitals with uninterrupted cefepime supply. The alternative antibiotics for which an increase in consumption showed the strongest association with a progression of resistance were the carbapenems. The use of alternative antibiotics after cefepime withdrawal was associated with a significant increase in piperacillin-tazobactam and meropenem use and in overall costs and with a decrease in susceptibility ofP. aeruginosain hospitals. This warrants caution with regard to shortages and withdrawals of antibiotics.

scholarly journals Activity of Ceftazidime-Avibactam against Fluoroquinolone-Resistant Enterobacteriaceae and Pseudomonas aeruginosa

2015 ◽  
Vol 59 (6) ◽  
pp. 3059-3065 ◽  
Author(s):  
C. Pitart ◽  
F. Marco ◽  
T. A. Keating ◽  
W. W. Nichols ◽  
J. Vila
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistant Mutant ◽  
Fluoroquinolone Resistance ◽  
Cross Resistance ◽  
Content Type ◽  
E Coli ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
The Impact

ABSTRACTCeftazidime-avibactam and comparator antibiotics were tested by the broth microdilution method against 200Enterobacteriaceaeand 25Pseudomonas aeruginosastrains resistant to fluoroquinolones (including strains with the extended-spectrum β-lactamase [ESBL] phenotype and ceftazidime-resistant strains) collected from our institution. The MICs and mechanisms of resistance to fluoroquinolone were also studied. Ninety-nine percent of fluoroquinolone-resistantEnterobacteriaceaestrains were inhibited at a ceftazidime-avibactam MIC of ≤4 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference). Ceftazidime-avibactam was very active against ESBLEscherichia coli(MIC90of 0.25 mg/liter), ESBLKlebsiella pneumoniae(MIC90of 0.5 mg/liter), ceftazidime-resistant AmpC-producing species (MIC90of 1 mg/liter), non-ESBLE. coli(MIC90of ≤0.125 mg/liter), non-ESBLK. pneumoniae(MIC90of 0.25 mg/liter), and ceftazidime-nonresistant AmpC-producing species (MIC90of ≤0.5 mg/liter). Ninety-six percent of fluoroquinolone-resistantP. aeruginosastrains were inhibited at a ceftazidime-avibactam MIC of ≤8 mg/liter (using the susceptible CLSI breakpoint for ceftazidime alone as a reference), with a MIC90of 8 mg/liter. Additionally, fluoroquinolone-resistant mutants from each species tested were obtainedin vitrofrom two strains, one susceptible to ceftazidime and the other a β-lactamase producer with a high MIC against ceftazidime but susceptible to ceftazidime-avibactam. Thereby, the impact of fluoroquinolone resistance on the activity of ceftazidime-avibactam could be assessed. The MIC90values of ceftazidime-avibactam for the fluoroquinolone-resistant mutant strains ofEnterobacteriaceaeandP. aeruginosawere ≤4 mg/liter and ≤8 mg/liter, respectively. We conclude that the presence of fluoroquinolone resistance does not affectEnterobacteriaceaeandP. aeruginosasusceptibility to ceftazidime-avibactam; that is, there is no cross-resistance.

scholarly journals Firm’s strategic choices and network knowledge dynamics: how do they affect innovation?

2018 ◽  
Vol 22 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Jose Antonio Belso-Martinez ◽  
Isabel Diez-Vial
Keyword(s):  
Absorptive Capacity ◽  
Knowledge Networks ◽  
Knowledge Network ◽  
Strategic Choices ◽  
Network Growth ◽  
Content Type ◽  
Endogenous Factors ◽  
The Impact ◽  
Innovative Capacity ◽  
Over Time

Purpose This paper aims to explain how the evolution of knowledge networks and firms’ strategic choices affect innovation. Endogenous factors associated with a path-dependent evolution of the knowledge network are jointly considered with a firm’s development of international relationships and increasing internal absorptive capacity over time. Design/methodology/approach In a biotech cluster, the authors gathered data on the firms’ characteristics and network relationships by asking about the technological knowledge they received in the cluster in 2007 and 2012 – “roster-recall” method. Estimation results were obtained using moderated regression analysis. Findings Firms that increase their involvement in knowledge networks over time also tend to increase their innovative capacity. However, efforts devoted to building international links or absorptive capacity negatively moderate the impact of network growth on innovation. Practical implications Practitioners have two alternative ways of increasing innovation inside knowledge networks: they can increase their centrality by developing their knowledge network interactions or invest in developing their internal absorptive capacity and new international sources of knowledge. Investing in both of these simultaneously does not seem to improve a firm’s innovative capacity. Originality/value Coupling firms’ strategic options with knowledge network dynamics provide a more complete way of explaining how firms can improve their innovative capacity.

The dynamics of regional and global expansion

2015 ◽  
Vol 23 (4) ◽  
pp. 306-327 ◽  
Author(s):  
Christian Geisler Asmussen ◽  
Bo Bernhard Nielsen ◽  
Tom Osegowitsch ◽  
Andre Sammartino
Keyword(s):  
Design Methodology ◽  
Global Market ◽  
Market Penetration ◽  
Content Type ◽  
Global Expansion ◽  
Rates Of Change ◽  
Global Space ◽  
The Impact ◽  
The Relationship ◽  
Over Time

Purpose – The purpose of this paper is to model and test the dynamics of home-regional and global penetration by multi-national enterprises (MNEs). Design/methodology/approach – Drawing on international business (IB) theory, the authors model MNEs adjusting their home-regional and global market presence over time. The authors test the resulting hypotheses using sales data from a sample of 220 of the world’s largest MNEs over the period 1995-2005. The authors focus specifically on the relationship between levels of market penetration inside and outside the home region and rates of change in each domain. Findings – The authors demonstrate that MNEs do penetrate both home-regional and global markets, often simultaneously, and that penetration levels often oscillate within an MNE over time. The authors show firms’ rates of regional and global expansion to be affected by their existing regional and global penetration, as well as their interplay. Finally, the authors identify differences in the steady states at which firms stabilize their penetration levels in the home-regional and the global space. The findings broadly confirm the MNE as an interdependent portfolio with important regional demarcations. Originality/value – The authors identify complex interdependencies between home-regional and global penetration and growth, paving the way for further studies of the impact of regions on MNE expansion.

Three stages of entrepreneurial orientation: the founder’s role

2019 ◽  
Vol 26 (2) ◽  
pp. 285-306 ◽  
Author(s):  
Torbjörn Ljungkvist ◽  
Börje Boers ◽  
Joachim Samuelsson
Keyword(s):  
Entrepreneurial Orientation ◽  
Single Case ◽  
Annual Reports ◽  
Structured Interviews ◽  
Theoretical Understanding ◽  
Content Type ◽  
Five Dimensions ◽  
The Impact ◽  
Over Time

Purpose The purpose of this paper is to understand the development of the five dimensions of entrepreneurial orientation (EO) over time by taking a founder’s perspective. Design/methodology/approach The paper draws on an in-depth single-case study. It combines semi-structured interviews in the company with archival data, such as annual reports, press clips and interviews in business magazines. Findings The results indicate that the EO dimensions change from being personalized and directly solution-oriented to being intangible value-creation-oriented. Originality/value By suggesting ownership-based EO configurations, this study contributes insights into how different ownership forms propel EO. These configurations – that is, personal, administrative based and intangible focused – show the impact of the EO dimensions and provide a systematic and theoretical understanding of EO change over time.

Brand awareness: revisiting an old metric for a new world

2017 ◽  
Vol 26 (5) ◽  
pp. 469-476 ◽  
Author(s):  
Jenni Romaniuk ◽  
Samuel Wight ◽  
Margaret Faulkner
Keyword(s):  
Market Share ◽  
Brand Management ◽  
Brand Awareness ◽  
Underlying Structure ◽  
Cross Sectional ◽  
Content Type ◽  
Country Level ◽  
Global Brand ◽  
The Impact ◽  
Over Time

Purpose Brand awareness is a pivotal, but often neglected, aspect of consumer-based brand equity. This paper revisits brand awareness measures in the context of global brand management. Design/methodology/approach Drawing on the method of Laurent et al. (1995), this cross-sectional longitudinal study examines changes in brand awareness over time, with sample sizes of approximately 300 whisky consumers per wave in three countries: United Kingdom, Taiwan and Greece. Findings There is consistency in the underlying structure of awareness scores across countries, and over time, extending the work of Laurent et al. (1995). Results show that a relevant operationalisation of brand awareness needs to account for the history of the brand. Furthermore, the nature of the variation of brand awareness over time interacts with a brand’s market share. Research limitations/implications When modelling the impact of brand awareness researchers need to consider two factors – the brand’s market share and whether a more stable or volatile measure is sought. This avoids mis-specifying the country-level contribution of brand awareness. Practical implications Global brand managers should be wary of adopting a “one size fits all” approach. The choice of brand awareness measure depends on the brand’s market share, and the desire for higher sensitivity or stability. Originality/value The paper provides one of the few multi-country investigations into brand awareness that can help inform global brand management.

Rebuilding Nepal: traditional and modern approaches, building or diminishing resilience?

2018 ◽  
Vol 9 (3) ◽  
pp. 218-229 ◽  
Author(s):  
Catherine Forbes
Keyword(s):  
Building Materials ◽  
Local Community ◽  
Vernacular Architecture ◽  
Research Approach ◽  
Content Type ◽  
Knowledge And Skills ◽  
Masonry Construction ◽  
Action Research Approach ◽  
The Impact ◽  
Over Time

Purpose The purpose of this paper is to highlight the importance of vernacular architecture and traditional knowledge to building resilience in Nepal and the impact of modernisation on that resilience and architectural diversity. Design/methodology/approach Using an action research approach, including field observations and discussions with local community members, artisans, architects, engineers and other international experts, the study examines the resilience of traditional building typologies to natural hazards in Nepal, including earthquake; the changes that have occurred over time leading to the failure and/or rejection of traditional construction; and a review of post-earthquake reconstruction options, both traditional and modern. Findings Although traditional approaches have been cyclically tested over time, this study found that changes in building materials, technologies, knowledge and skills, access to resources, maintenance practices, urban environments and societal aspirations have all contributed to the popular rejection of vernacular architecture following the earthquakes. Research limitations/implications The research is limited to traditional timber and masonry construction in the Kathmandu Valley and surrounding mountain areas. Practical implications To improve resilience the study identifies the need for capacity building in both traditional and modern construction technologies; adoption of approaches that use local materials, knowledge and skills, whilst addressing local timber shortages and access issues; a transparent construction certification system; good drainage; and regular maintenance. Originality/value The study critically evaluates the impact of technological, environmental, social and economic changes over time on the resilience of vernacular housing in Nepal.

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