Published ahead of print on May 8, 2008, doi:10.1164/rccm.200802-239OC Am. J. Respir. Crit. Care Med., Volume 178, Number 5, September 2008, 513-519 A more recent version of this article appeared on September 1, 2008
Submitted on February 8, 2008 Persistent Infection with Pseudomonas Aeruginosa in Ventilator Associated PneumoniaAli A El Solh1*,1 Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Western New York Respiratory Research Center, State University of New York at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, NY, USA, 2 Department of Anesthesia and Perioperative Care, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA * To whom correspondence should be addressed. 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. Methods: Thirty four patients with Pseudomonas aeruginosa VAP underwent non-invasive 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 (NE) was assessed by immunoenzymatic assay. Results: Twenty five out of the 34 VAP patients 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 who did not. NE 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 while 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 TTSS secretory phenotype. Key words: Ventilator-associated pneumonia, Pseudomonas aeruginosa, antimicrobial therapy, outcome
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