Bacterial and clinical characteristics of health care- and community-acquired bloodstream infections due to Pseudomonas aeruginosa.

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.

Clinical outcomes of type III Pseudomonas aeruginosa bacteremia.

BACKGROUND: Pseudomonas aeruginosa bacteremia is a serious and life-threatening infection associated with high mortality. Among the multitude of virulence determinants possessed by P. aeruginosa, the type 3 secretion system has been implicated with more acute and invasive infection in respiratory diseases. However, the relationship between the type 3 secretion system and clinical outcomes in P. aeruginosa bacteremia has not been investigated. OBJECTIVES: To determine the association between the type 3 secretion system virulence factor in P. aeruginosa bloodstream infection and 30-day mortality. DESIGN: Retrospective analysis of 85 cases of P. aeruginosa bacteremia. SETTING: Tertiary care hospital. INTERVENTIONS: Bacterial isolates were assayed in vitro for secretion of type 3 exotoxins (ExoU, ExoT, and ExoS). Strain relatedness was analyzed using randomly amplified polymorphic DNA polymerase chain reaction genotyping. Antimicrobial susceptibilities were determined by means of the Kirby-Bauer disk-diffusion test. MEASUREMENTS AND MAIN RESULTS: At least one of the type 3 secretion system proteins was detected in 37 out of the 85 isolates (44%). Septic shock was identified in 43% of bacteremic patients with type 3 secretion system+ isolates compared to 23% of patients with type 3 secretion system- isolates (p = .12). A high frequency of resistance in the type 3 secretion system+ isolates was observed to ciprofloxacin (59%), cefepime (35%), and gentamicin (38%). There was a significant difference in the 30-day cumulative probability of death after bacteremia between secretors and nonsecretors (p = .02). None of the type 3 secretion system+ patients who survived the first 30 days had a P. aeruginosa isolate which exhibited ExoU phenotype. CONCLUSIONS: The expression of type 3 secretion system exotoxins in bacteremic isolates of P. aeruginosa confers poor clinical outcomes independent of antibiotic susceptibility profile.

Does linezolid modulate lung innate immunity in a murine model of methicillin-resistant Staphylococcus aureus pneumonia?

OBJECTIVES: Methicillin-resistant Staphylococcus aureus is an important cause of mortality among nosocomial infections. Recent investigations suggest that linezolid is superior to vancomycin in achieving clinical cure in patients with nosocomial pneumonia. We hypothesized that linezolid may exhibit anti-inflammatory properties in vivo model of pneumonia. DESIGN: Prospective interventional study. SETTING: University affiliated laboratory. SUBJECTS: BALB/c mice. INTERVENTIONS: Three groups of BALB/c mice were inoculated with methicillin-resistant S. aureus American Type Culture Collection 33,591 to induce pneumonia. Each group (n = 6) underwent bronchoalveolar lavage at 24 hrs, 48 hrs, and 72 hrs after inoculation after treatment with vancomycin, linezolid, or no antibiotic. Bronchoalveolar lavage fluid levels of monocyte chemotactic protein-5 and interleukin-6 were quantified using cytometric bead array. Metalloproteinase-9 was detected by enzyme-linked immunosorbent assay and gelatin zymography. Neutrophil apoptosis in bronchoalveolar lavage was assessed by annexin V and 7-aminoactinomycin D staining. Neutrophil activity was determined by myeloperoxidase enzyme activity. Phagocytosis of apoptotic neutrophils by linezolid- vs. vancomycin treated-alveolar macrophages was examined in vitro. MEASUREMENTS AND MAIN RESULTS: Infected mice had a significant reduction in lung bacterial titers compared with controls (p < .05) after treatment with linezolid or vancomycin. There was no difference in bronchoalveolar lavage levels of monocyte chemotactic protein-5 or interleukin-6 between vancomycin- and linezolid-treated groups. Both antimicrobials were comparable in modulating the expression of matrix metalloproteinase-9 in bronchoalveolar lavage. Neutrophil apoptosis was comparable in both vancomycin- and linezolid-treated groups at all three time points. Vancomycin showed lower myeloperoxidase activity compared with linezolid in the first 24 hrs after inoculation (p = .03), but the difference was undetectable at 48 hrs and 72 hrs. Neither compound had an impact on the process of removal of apoptotic neutrophils by alveolar macrophages. CONCLUSIONS: Linezolid did not display an advantage over vancomycin in modulating pulmonary innate immune response in a murine model of methicillin-resistant S. aureus pneumonia.

Naïve and memory B cells in the rhesus macaque can be differentiated by surface expression of CD27 and have differential responses to CD40 ligation.

The rhesus macaque (RM) model has the potential to be an invaluable tool for studying B cell populations during pathogenic infections, however, to date, there has been no definitive delineation of naïve and memory B cell populations in the RM. This has precluded a rigorous analysis of the generation, persistence and resolution of a pathogen-specific memory B cell response. The present study utilized multiple analyses to demonstrate that CD27 expression on B cells is consistent with a memory phenotype. Compared to CD20+CD27- B cells, CD20+CD27+ B cells were larger in size, and preferentially accumulated at effector sites. Direct sequence analysis revealed that CD20+CD27+ B cells had an increased frequency of point mutations that were consistent with somatic hypermutation and at a functional level, CD40 ligation improved CD20+CD27- but not CD20+CD27+ B cell survival in vitro. These data provide definitive evidence that the naïve and memory B cell populations of the RM can be differentiated using surface expression of CD27.