Archive for August 19, 2008

Persistent Infection with Pseudomonas aeruginosa in Ventilator-associated Pneumonia

American Journal of Respiratory and Critical Care Medicine 1 September 2008  V.178 N.5  p.513-519

Ali A. El Solh1, Morohunfolu E. Akinnusi1, Jeanine P. Wiener-Kronish2, Susan V. Lynch2, Lilibeth A. Pineda1 and Kristie Szarpa1

1 Western New York Respiratory Research Center, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York and 2 Department of Anesthesia and Perioperative Care, Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California

Rationale: Pseudomonas aeruginosa is one of the leading causes of gram-negative ventilator-associated pneumonia (VAP) associated with a mortality rate of 34 to 68%. Recent evidence suggests that P. aeruginosa in patients with VAP may persist in the alveolar space despite adequate antimicrobial therapy. We hypothesized that failure to eradicate P. aeruginosa from the lung is linked to type III secretory system (TTSS) isolates.

Objectives: To determine the mechanism by which infection with P. aeruginosa in patients with VAP may evade the host immune response.

Methods: Thirty-four patients with P. aeruginosa VAP underwent noninvasive bronchoalveolar lavage (BAL) at the onset of VAP and on Day 8 after initiation of antibiotic therapy. Isolated pathogens were analyzed for secretion of type III cytotoxins. Neutrophil apoptosis in BAL fluid was quantified by assessment of nuclear morphology on Giemsa-stained cytocentrifuge preparations. Neutrophil elastase was assessed by immunoenzymatic assay.

Measurements and Main Results: Twenty-five out of the 34 patients with VAP secreted at least one of type III proteins. There was a significant difference in apoptotic rate of neutrophils at VAP onset between those strains that secreted cytotoxins and those that did not. Neutrophil elastase levels were positively correlated with the rate of apoptosis (r = 0.43, P < 0.01). Despite adequate antimicrobial therapy, 13 out of 25 TTSS+ isolates were recovered at Day 8 post-VAP, whereas eradication was achieved in all patients who had undetectable levels of type III secretion proteins.

Conclusions: The increased apoptosis in neutrophils by the TTSS+ isolates may explain the delay in eradication of Pseudomonas strains in patients with VAP. Short-course antimicrobial therapy may not be adequate in clearing the infection with a TTSS secretory phenotype.


August 19, 2008 at 6:27 pm Leave a comment

Mortality Reduction with Influenza Vaccine in Patients with Pneumonia Outside “Flu” Season

American Journal of Respiratory and Critical Care Medicine 1 September 2008  V.178 N.5  p.527-533

Pleiotropic Benefits or Residual Confounding?

Dean T. Eurich1, Thomas J. Marrie2, Jennie Johnstone2 and Sumit R. Majumdar1,2

1 Department of Public Health Sciences, School of Public Health, and the 2 Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada

Rationale: Observational studies suggest a 50% mortality reduction for older patients receiving influenza vaccination; some deem this magnitude of benefit implausible and invoke confounding by the “healthy user effect” as an alternate explanation.

Objectives: To evaluate unrecognized confounding by hypothesizing the presence of a 50% mortality reduction with vaccination for patients with pneumonia outside of influenza season.

Methods: Clinical, laboratory, and functional data were prospectively collected on 1,813 adults with community-acquired pneumonia admitted to six hospitals outside of influenza season in the Capital Health region (AB, Canada). Vaccination status was ascertained by interview and chart review. Outcome was in-hospital mortality. Influenza-vaccinated patients were matched to a nonvaccinated control using propensity scores, and then multivariable regression was used to determine the independent association between vaccination and mortality.

Measurements and Main Results: The cohort consisted of 352 vaccine recipients and 352 matched control subjects. Most (85%) patients were 65 years or older, 29% had severe pneumonia, and 12% died. Influenza vaccination was associated with a 51% mortality reduction (28 of 352 [8%] died vs. 53 of 352 [15%] control subjects; unadjusted odds ratio [OR], 0.49; 95% confidence interval [CI], 0.30–0.79; P = 0.004) outside influenza season. Adjustment for age, sex, and comorbidities did not alter these findings (adjusted OR, 0.45; 95% CI, 0.27–0.76). More complete adjustment for confounding (e.g., functional and socioeconomic status) markedly attenuated these benefits and their statistical significance (adjusted OR, 0.81; 95% CI, 0.35–1.85; P = 0.61).

Conclusions: The 51% reduction in mortality with vaccination initially observed in patients with pneumonia who did not have influenza was most likely a result of confounding. Previous observational studies may have overestimated mortality benefits of influenza vaccination.


August 19, 2008 at 6:22 pm Leave a comment


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