Published ahead of print on May 8, 2008, doi:10.1164/rccm.200802-239OC
© 2008 American Thoracic Society doi: 10.1164/rccm.200802-239OC
Persistent Infection with Pseudomonas aeruginosa in Ventilator-associated Pneumonia1 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 Correspondence and requests for reprints should be addressed to Ali A. El Solh, M.D., M.P.H., Division of Pulmonary, Critical Care, and Sleep Medicine, Erie County Medical Center, 462 Grider Street, Buffalo, NY 14215. E-mail: solh{at}buffalo.edu 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.
Key Words: ventilator-associated pneumonia • Pseudomonas aeruginosa • antimicrobial therapy • outcome
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