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 ◽  
...  

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.

2017 ◽  
Vol 61 (6) ◽  
Author(s):  
Joshua T. Thaden ◽  
Lawrence P. Park ◽  
Stacey A. Maskarinec ◽  
Felicia Ruffin ◽  
Vance G. Fowler ◽  
...  

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.


2012 ◽  
Vol 56 (7) ◽  
pp. 3936-3942 ◽  
Author(s):  
Teena Chopra ◽  
Dror Marchaim ◽  
Jennifer Veltman ◽  
Paul Johnson ◽  
Jing J. Zhao ◽  
...  

ABSTRACTExtended-spectrum-β-lactamase (ESBL)-producing pathogens are associated with extensive morbidity and mortality and rising health care costs. Scant data exist on the impact of antimicrobial therapy on clinical outcomes in patients with ESBL bloodstream infections (BSI), and no large studies have examined the impact of cefepime therapy. A retrospective 3-year study was performed at the Detroit Medical Center on adult patients with BSI due to ESBL-producingKlebsiella pneumoniaeorEscherichia coli. Data were collected from the medical records of study patients at five hospitals between January 2005 and December 2007. Multivariate analysis was performed using logistic regression. One hundred forty-five patients with BSI due to ESBL-producing pathogens, includingK. pneumoniae(83%) andE. coli(16.5%), were studied. The mean age of the patients was 66 years. Fifty-one percent of the patients were female, and 79.3% were African-American. Fifty-three patients (37%) died in the hospital, and 92 survived to discharge. In bivariate analysis, the variables associated with mortality (P< 0.05) were presence of a rapidly fatal condition at the time of admission, use of gentamicin as a consolidative therapeutic agent, and presence of one or more of the following prior to culture date: mechanical ventilation, stay in the intensive care unit (ICU), and presence of a central venous catheter. In multivariate analysis, the predictors of in-hospital mortality included stay in the intensive care unit (odds ratio [OR], 2.17; 95% confidence interval [CI], 0.98 to 4.78), presence of a central-line catheter prior to positive culture (OR, 2.33; 95% CI, 0.77 to 7.03), presence of a rapidly fatal condition at the time of admission (OR, 5.13; 95% CI, 2.13 to 12.39), and recent prior hospitalization (OR, 1.92; 95% CI, 0.83 to 4.09). When carbapenems were added as empirical therapy to the predictor model, there was a trend between empirical carbapenem therapy and decreased mortality (OR, 0.61; 95% CI, 0.26 to 1.50). When added to the model, receipt of empirical cefepime alone (n= 43) was associated with increased mortality, although this association did not reach statistical significance (OR, 1.66; 95% CI, 0.71 to 3.87). The median length of hospital stay was shorter for patients receiving empirical cefepime than for those receiving empirical or consolidated carbapenem therapy. In multivariate analysis, empirical therapy with cefepime for BSI due to an ESBL-producing pathogen was associated with a trend toward an increased mortality risk and empirical carbapenem therapy was associated with a trend toward decreased mortality risk.


2016 ◽  
Vol 60 (3) ◽  
pp. 1767-1778 ◽  
Author(s):  
Gabriel Cabot ◽  
Laura Zamorano ◽  
Bartolomé Moyà ◽  
Carlos Juan ◽  
Alfonso Navas ◽  
...  

Pseudomonas aeruginosa, a major cause of nosocomial and chronic infections, is considered a paradigm of antimicrobial resistance development. However, the evolutionary trajectories of antimicrobial resistance and the impact of mutator phenotypes remain mostly unexplored. Therefore, whole-genome sequencing (WGS) was performed in lineages of wild-type and mutator (ΔmutS) strains exposed to increasing concentrations of relevant antipseudomonal agents. WGS provided a privileged perspective of the dramatic effect of mutator phenotypes on the accumulation of random mutations, most of which were transitions, as expected. Moreover, a frameshift mutagenic signature, consistent with error-prone DNA polymerase activity as a consequence of SOS system induction, was also seen. This effect was evidenced for all antibiotics tested, but it was higher for fluoroquinolones than for cephalosporins or carbapenems. Analysis of genotype versus phenotype confirmed expected resistance evolution trajectories but also revealed new pathways. Classical mechanisms included multiple mutations leading to AmpC overexpression (ceftazidime), quinolone resistance-determining region (QRDR) mutations (ciprofloxacin),oprDinactivation (meropenem), and efflux pump overexpression (ciprofloxacin and meropenem). Groundbreaking findings included gain-of-function mutations leading to the structural modification of AmpC (ceftazidime), novel DNA gyrase (GyrA) modification (ciprofloxacin), and the alteration of the β-lactam binding site of penicillin-binding protein 3 (PBP3) (meropenem). A further striking finding was seen in the evolution of meropenem resistance, selecting for specific extremely large (>250 kb) genomic deletions providing a growth advantage in the presence of the antibiotic. Finally, fitness and virulence varied within and across evolved antibiotic-resistant populations, but mutator lineages showed a lower biological cost for some antibiotics.


2013 ◽  
Vol 57 (12) ◽  
pp. 5811-5819 ◽  
Author(s):  
T. W. Felton ◽  
J. Goodwin ◽  
L. O'Connor ◽  
A. Sharp ◽  
L. Gregson ◽  
...  

ABSTRACTManagement of nosocomial pneumonia is frequently complicated by bacterial resistance. Extended infusions of beta-lactams are increasingly being used to improve clinical outcomes. However, the impact of this strategy on the emergence of antimicrobial resistance is not known. A hollow-fiber infection model withPseudomonas aeruginosa(PAO1) was used. Pharmacokinetic (PK) profiles of piperacillin-tazobactam similar to those in humans were simulated over 5 days. Three dosages of piperacillin-tazobactam were administered over 0.5 h or 4 h, with redosing every 8 h. Two initial bacterial densities were investigated (∼104CFU/ml and ∼107CFU/ml). The time courses of the total bacterial population and the resistant subpopulation were determined. All data were described using a mathematical model, which was then used to define the relationship between drug concentrations, bacterial killing, and emergence of piperacillin resistance. There was logarithmic growth in controls in the initial 24 h, reaching a plateau of ∼9 log10CFU/ml. Bacterial killing following administration of piperacillin via bolus dosing and that after extended infusions were similar. For the lower initial bacterial density, trough total plasma piperacillin concentration/MIC ratios of 3.4 and 10.4 for bolus and extended-infusion regimens, respectively, were able to suppress the emergence of piperacillin resistance. For the higher initial bacterial density, all regimens were associated with progressive growth of a resistant subpopulation. A stratified approach, according to bacterial density, is required to treat patients with nosocomial pneumonia. Antimicrobial monotherapy may be sufficient for some patients. However, for patients with a high bacterial burden, alternative therapeutic strategies are required to maximize bacterial killing and prevent antimicrobial resistance.


2019 ◽  
Vol 202 (8) ◽  
Author(s):  
Courtney E. Price ◽  
Dustin G. Brown ◽  
Dominique H. Limoli ◽  
Vanessa V. Phelan ◽  
George A. O’Toole

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.


2011 ◽  
Vol 56 (2) ◽  
pp. 989-994 ◽  
Author(s):  
C. Plüss-Suard ◽  
A. Pannatier ◽  
C. Ruffieux ◽  
A. Kronenberg ◽  
K. Mühlemann ◽  
...  

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.


2015 ◽  
Vol 59 (6) ◽  
pp. 3059-3065 ◽  
Author(s):  
C. Pitart ◽  
F. Marco ◽  
T. A. Keating ◽  
W. W. Nichols ◽  
J. Vila

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.


2021 ◽  
Vol 11 (2) ◽  
pp. 350-368
Author(s):  
Tirivavi Moyo ◽  
Gerrit Crafford ◽  
Fidelis Emuze

PurposeWhile operational factors reduce construction workers' productivity in Zimbabwe, the impact of the people-centred management aspects has not been empirically interrogated as a remedy. This article reports on a study that sought to determine significant people-centred management aspects that lead to improved labour productivity and assesses the existence of statistically significant differences due to the demographic variables of respondents. Demographic-specific strategies that enhance construction “workers” productivity were revealed.Design/methodology/approachThe survey research design using a self-administered questionnaire was deployed to collect the primary data. The design followed a positivist paradigm to evaluate objectively how people-centred management affects construction workers' productivity. The statistical data were descriptively and inferentially analysed.FindingsPeople-centred management was determined to be significant in improving construction workers' productivity, with the most significant aspect being the building of employee confidence in related approaches. Designations and educational levels mostly indicated a statistically significant difference in several aspects that included the adoption of a functional reward culture for workers and training on people-centred principles. Training on-site management and construction workers in people-centred management and its application are crucial to improving construction workers' productivity.Research limitations/implicationsConstruction companies should drastically improve their concern for people while they sustain a high concern for production within their construction sites. Although several factors affect construction workers' productivity, this study determined that management-related factors and people-centred management were significant towards influencing low productivity in Zimbabwe.Originality/valueThe study determined people-centred management and demographic-specific interventions as being able to improve construction workers' productivity in Zimbabwe.


2014 ◽  
Vol 80 (12) ◽  
pp. 3656-3666 ◽  
Author(s):  
Basanta Kumar Biswal ◽  
Ramzi Khairallah ◽  
Kareem Bibi ◽  
Alberto Mazza ◽  
Ronald Gehr ◽  
...  

ABSTRACTWastewater discharges may increase the populations of pathogens, includingEscherichia coli, and of antimicrobial-resistant strains in receiving waters. This study investigated the impact of UV and peracetic acid (PAA) disinfection on the prevalence of virulence and antimicrobial resistance genes in uropathogenicEscherichia coli(UPEC), the most abundantE. colipathotype in municipal wastewaters. Laboratory disinfection experiments were conducted on wastewater treated by physicochemical, activated sludge, or biofiltration processes; 1,766E. coliisolates were obtained for the evaluation. The target disinfection level was 200 CFU/100 ml, resulting in UV and PAA doses of 7 to 30 mJ/cm2and 0.9 to 2.0 mg/liter, respectively. The proportions of UPECs were reduced in all samples after disinfection, with an average reduction by UV of 55% (range, 22% to 80%) and by PAA of 52% (range, 11% to 100%). Analysis of urovirulence genes revealed that the decline in the UPEC populations was not associated with any particular virulence factor. A positive association was found between the occurrence of urovirulence and antimicrobial resistance genes (ARGs). However, the changes in the prevalence of ARGs in potential UPECs were different following disinfection, i.e., UV appears to have had no effect, while PAA significantly reduced the ARG levels. Thus, this study showed that both UV and PAA disinfections reduced the proportion of UPECs and that PAA disinfection also reduced the proportion of antimicrobial resistance gene-carrying UPEC pathotypes in municipal wastewaters.


2018 ◽  
Vol 11 (3) ◽  
pp. 708-733 ◽  
Author(s):  
Martin Morgan Tuuli

Purpose The purpose of this paper is to explore the impact of project settings on empowerment experiences of individuals and teams by examining the effects of specific project characteristics on facets of the empowerment concept (i.e. the structural and psychological perspectives). Design/methodology/approach A parallel questionnaire survey of client, consultant and contractor organisations was conducted in Hong Kong to test hypotheses relating three facets of the empowerment concept and five project-level antecedents. Hierarchical linear modelling and ordinary least square regression were employed to test the hypotheses. Findings The analyses show that dynamic project environments, high project team integration and high interdependence of project tasks lead to high individual psychological empowerment, while public-client projects (compared with private-client projects), a hostile project environment and high client integration lead to a low individual psychological empowerment. Uncertainty in project technology also leads to high team psychological empowerment, while hostile project environments lead to low team psychological empowerment. Further, dynamic project environments lead to more empowering work climate, while hostile project environments lead to less empowering work climate. However, project team integration, project complexity, project lifecycle and quasi-public-client projects (compared with private-client projects) have no significant association with the empowerment of individuals and teams. Originality/value This study examined task-related factors (i.e. project in this case) which traditionally have not been the focus of studies examining the antecedents of empowerment. Further, project-level antecedents and their link to an integrated perspective of empowerment comprising a sociostructural perspective, a psychological perspective and a team-based perspective are examined, which is a significant departure from the unitary perspective of empowerment taken in most previous studies.


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