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 III secretion system (TTSS) has been implicated with more acute and invasive infection in respiratory diseases. However, the relationship between TTSS and clinical outcomes in P. aeruginosa bacteremia has not been investigated. Objectives To determine the association between the TTSS virulence factor in P. aeruginosa blood stream 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 III exotoxins (ExoU, ExoT, and ExoS). Strain-relatedness was analyzed using randomly amplified polymorphic DNA PCR genotyping. Antimicrobial susceptibilities were determined by means of the Kirby-Bauer disk-diffusion test. Measurements and Main results At least one of the TTSS proteins was detected in 37 out of the 85 isolates (44%). Septic shock was identified in 43% of bacteremic patients with TTSS+ isolates compared to 23% of patients with TTSS− isolates (p=0.12). A high frequency of resistance in the TTSS+ isolates was observed to ciprofloxacin (59%), cefipime (35%), and gentamycin (38%). There was a significant difference in the 30-day cumulative probability of death after bacteremia between secretors and nonsecretors (p=0.02). None of the TTSS+ patients who survived the first 30 days had a P. aeruginosa isolate which exhibited ExoU phenotype. Conclusions The expression of TTSS exotoxins in bacteremic isolates of P. aeruginosa confers poor clinical outcomes independent of antibiotic susceptibility profile.

f 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. Bloodstream infections (BSIs) are serious clinical events with life-threatening consequences. The total number of deaths resulting from nosocomial BSIs is difficult to estimate and varies greatly, depending on the etiology. However, the attributable mortality rate may be as high as 80% among patients in intensive care units (1). Pseudomonas aeruginosa accounts for 3 to 7% of all BSIs and 23 to 26% of Gram-negative bacteremias (2, 3). Pneumonia, pancreaticobiliary tract infection, indwelling catheters, and urinary tract infection have all been implicated as potential sources of infection (1, 4). Despite recent advances in critical-care management, mortality rates due to P. aeruginosa BSI remain high, ranging between 27 and 48% (1, 5).Poor outcomes of P. aeruginosa BSIs have been associated with both microbial and host factors. Neutropenia, a respiratory source of bacteremia, shock, renal failure, and metastatic foci of infection are among the host factors implicated in increased mortality rates (4, 6). Bacterial attributes include a high degree of intrinsic virulence (7, 8) and widespread antibiotic resistance. P. aeruginosa is intrinsically resistant to many structurally unrelated antimicrobial agents (9) because of the low permeability of its outer membrane, the constitutiv...

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.

Linezolid did not display an advantage over vancomycin in modulating pulmonary innate immune response in a murine model of methicillin-resistant S. aureus pneumonia.