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.

Pseudomonas aeruginosa is an important cause of nosocomial pneumonia associated with a high morbidity and mortality rate. This bacterium expresses a variety of factors that confer resistance to a broad array of antimicrobial agents. Empirical antibiotic therapy is often inadequate because cultures from initial specimens grow strains that are resistant to initial antibiotics. Surveillance data, hospital antibiogram and individualization of regimens based on prior antibiotic use may reduce the risk of inadequate therapy. The use of combination therapies for P. aeruginosa pneumonia has been a long-advocated practice, but the potential increased value of combination therapy over monotherapy remains controversial. Doripenem and biapenem are new carbapenems that have excellent activity against P. aeruginosa; however, they lack activity against strains that express resistance to the currently available carbapenems. The polymyxins remain the most consistently effective agents against multidrug-resistant P. aeruginosa. Strains that are panantibiotic-resistant are rare, but their incidence is increasing. Antibiotic combinations that yield some degree of susceptibility in vitro are the recourse, although the efficacy of these regimens has yet to be established in clinical studies. Experimental polypeptides may provide a new therapeutic approach. Among these, the anti-PcrV immunoglobulin G antibody that blocks the type III secretion system-mediated virulence of P. aeruginosa has recently entered Phase I/II clinical trials.