Bacterial and Clinical Characteristics of Health Care- and Community-Acquired Bloodstream Infections Due to Pseudomonas aeruginosa

The Veterans Affairs Western New York Healthcare System, Western New York, Buffalo, NY.
Antimicrobial Agents and Chemotherapy (Impact Factor: 4.45). 08/2013; 57(8). DOI: 10.1128/AAC.02467-12

ABSTRACT Health care-associated infections, including Pseudomonas aeruginosa bloodstream infection, have been linked to delays in appropriate antibiotic therapy and an increased mortality rate. The objective of this study was to evaluate intrinsic virulence, bacterial resistance, and clinical outcomes of health care-associated bloodstream infections (HCABSIs) in comparison with those of community-acquired bloodstream infections (CABSIs) caused by P. aeruginosa. We conducted a retrospective multicenter study of consecutive P. aeruginosa bacteremia patients at two university-affiliated hospitals. Demographic, clinical, and treatment data were collected. Microbiologic analyses included in vitro susceptibility profiles and type III secretory (TTS) phenotypes. Sixty CABSI and 90 HCABSI episodes were analyzed. Patients with HCABSIs had more organ dysfunction at the time of bacteremia (P = 0.05) and were more likely to have been exposed to antimicrobial therapy (P < 0.001) than those with CABSIs. Ninety-two percent of the carbapenem-resistant P. aeruginosa infections were characterized as HCABSIs. The 30-day mortality rate for CABSIs was 26% versus 36% for HCABSIs (P = 0.38). The sequential organ failure assessment score at the time of bacteremia (hazard ratio [HR], 1.2; 95% confidence interval [CI], 1.1 to 1.3) and the TTS phenotype (HR 2.1; 95% CI, 1.1 to 3.9) were found to be independent predictors of the 30-day mortality rate. No mortality rate difference was observed between CABSIs and HCABSIs caused by P. aeruginosa. Severity of illness and expression of TTS proteins were the strongest predictors of the 30-day mortality rate due to P. aeruginosa bacteremia. Future P. aeruginosa bacteremia trials designed to neutralize TTS proteins are warranted.

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    ABSTRACT: Pseudomonas aeruginosa is the most common gram-negative pathogen causing pneumonia in immunocompromised patients. Acute lung injury induced by bacterial exoproducts is associated with a poor outcome in P. aeruginosa pneumonia. The major pathogenic toxins among the exoproducts of P. aeruginosa and the mechanism by which they cause acute lung injury have been investigated: exoenzyme S and co-regulated toxins were found to contribute to acute lung injury. P. aeruginosa secretes these toxins through the recently defined type III secretion system (TTSS), by which gram-negative bacteria directly translocate toxins into the cytosol of target eukaryotic cells. TTSS comprises the secretion apparatus (termed the injectisome), translocators, secreted toxins, and regulatory components. In the P. aeruginosa genome, a pathogenic gene cluster, the exoenzyme S regulon, encodes genes underlying the regulation, secretion, and translocation of TTSS. Four type III secretory toxins, namely ExoS, ExoT, ExoU, and ExoY, have been identified in P. aeruginosa. ExoS is a 49-kDa form of exoenzyme S, a bifunctional toxin that exerts ADP-ribosyltransferase and GTPase-activating protein (GAP) activity to disrupt endocytosis, the actin cytoskeleton, and cell proliferation. ExoT, a 53-kDa form of exoenzyme S with 75% sequence homology to ExoS, also exerts GAP activity to interfere with cell morphology and motility. ExoY is a nucleotidal cyclase that increases the intracellular levels of cyclic adenosine and guanosine monophosphates, resulting in edema formation. ExoU, which exhibits phospholipase A2 activity activated by host cell ubiquitination after translocation, is a major pathogenic cytotoxin that causes alveolar epithelial injury and macrophage necrosis. Approximately 20% of clinical isolates also secrete ExoU, a gene encoded within an insertional pathogenic gene cluster named P. aeruginosa pathogenicity island-2. The ExoU secretory phenotype is associated with a poor clinical outcome in P. aeruginosa pneumonia. Blockade of translocation by TTSS or inhibition of the enzymatic activity of translocated toxins has the potential to decrease acute lung injury and improve clinical outcome.
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    ABSTRACT: Some previous studies have identified bacteria in semen as being a potential factor in male infertility. However, only few types of bacteria were taken into consideration while using PCR-based or culturing methods. Here we present an analysis approach using next-generation sequencing technology and bioinformatics analysis to investigate the associations between bacterial communities and semen quality. Ninety-six semen samples collected were examined for bacterial communities, measuring seven clinical criteria for semen quality (semen volume, sperm concentration, motility, Kruger's strict morphology, antisperm antibody (IgA), Atypical, and leukocytes). Computer-assisted semen analysis (CASA) was also performed. Results showed that the most abundant genera among all samples were Lactobacillus (19.9%), Pseudomonas (9.85%), Prevotella (8.51%) and Gardnerella (4.21%). The proportion of Lactobacillus and Gardnerella was significantly higher in the normal samples, while that of Prevotella was significantly higher in the low quality samples. Unsupervised clustering analysis demonstrated that the seminal bacterial communities were clustered into three main groups: Lactobacillus, Pseudomonas, and Prevotella predominant group. Remarkably, most normal samples (80.6%) were clustered in Lactobacillus predominant group. The analysis results showed seminal bacteria community types were highly associated with semen health. Lactobacillus might not only be a potential probiotic for semen quality maintenance, but also might be helpful in countering the negative influence of Prevotella and Pseudomonas. In this study, we investigated whole seminal bacterial communities and provided the most comprehensive analysis of the association between bacterial community and semen quality. The study significantly contributes to the current understanding of the etiology of male fertility.
    PLoS ONE 10/2014; 9(10):e110152. DOI:10.1371/journal.pone.0110152 · 3.53 Impact Factor
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    ABSTRACT: Background Antibiotic resistance is increasing in many community settings. The purpose of this study was to determine the proportion of antibiotic resistant community-associated bloodstream infections (CA-BSIs) present on hospital admissions to identify risk factors for acquiring resistant versus susceptible CA-BSIs and to describe the incidence of concurrent infections with CA-BSIs. Methods We conducted a retrospective cohort study of patients discharged from one community, one pediatric, and two tertiary/quaternary care hospitals within an academically affiliated network in the borough of Manhattan in New York, NY, from 2006 to 2008. The CA-BSIs present at hospital admission were defined as BSIs occurring within the first 48 h of hospitalization. Infections and patient characteristics were identified using data available from patients’ electronic medical records and discharge records. Results In total, 1677 CA-BSIs were identified. Staphylococcus aureus had the largest proportion of resistance (41.2%), followed by enterococcal species (24.3%), Pseudomonas aeruginosa (20.2%), Streptococcus pneumoniae (16.6%), Acinetobacter baumannii (10.0%), and Klebsiella pneumoniae (9.9%). Significant predictors of resistance were prior residence in a skilled nursing facility (OR, 2.55; 95% CI, 1.39–4.70), advanced age (1.01; 1.002–1.02), presence of malignancy (0.58; 0.37–0.91), prior hospitalization (1.62; 1.17–2.23), a weighted Charlson score (1.09; 1.02–1.17) for S. aureus, presence of malignancy (1.82; 1.004–3.30), prior hospitalizations (2.03; 1.12–3.38) for enterococcal species, and younger age for S. pneumoniae (p = 0.02). Urinary tract infections were the most common concurrent infection (n = 45/87, 51.7%). Conclusion Over 27% of the CA-BSIs present on admission were antibiotic resistant. Understanding the prevalence and risk factors for CA-BSIs may help improve empiric antibiotic therapy and outcomes for patients with community-onset infections.
    Journal of Infection and Public Health 05/2014; DOI:10.1016/j.jiph.2014.01.001

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