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Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia.

Abstract：

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.

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

El Solh AA,Akinnusi ME,Wiener-Kronish JP,Lynch SV,Pineda LA,Szarpa K

doi

10.1164/rccm.200802-239OC

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

513-9

issue

eissn

1073-449X

issn

1535-4970

pii

200802-239OC

journal_volume

178

pub_type

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Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia.