ABSTRACT
OBJECTIVE: To investigate the frequency and outcomes of ventilated patients with newly acquired large burdens of Pseudomonas aeruginosa and to test the hypothesis that large quantities of bacteria are associated with adverse patient outcomes. DESIGN: A prospective, single-center, observational, cohort study. SETTING: Medical-surgical intensive care units in a tertiary care university hospital. PATIENTS: All adult patients requiring > or = 48 hrs of mechanical ventilation and identified as having newly acquired P. aeruginosa in their lower respiratory tracts between October 2002 and April 2006. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily surveillance cultures of endotracheal aspirates were performed on patients intubated > or = 48 hrs; 69 patients with newly acquired P. aeruginosa were enrolled. Daily P. aeruginosa quantification of endotracheal aspirates was performed; clinical signs of infection were noted. Of 45 patients with high P. aeruginosa burdens (> or = 1,000,000 colony-forming units/mL in endotracheal aspirates; > or = 10,000 colony-forming units/mL in bronchoalveolar-lavage), 17 (37.8%) patients did not meet clinical criteria for ventilator-associated pneumonia and had a statistically significant higher risk of death (adjusted hazard ratio, 37.53; 95% confidence interval, 3.79-371.96; p = 0.002) when compared with the patients who had P. aeruginosa ventilator-associated pneumonia. When excluding the ten patients who had ventilator-associated pneumonia attributed to bacteria other than P. aeruginosa or attributed to multiple bacteria including P. aeruginosa, the risk of death remained statistically significant (adjusted hazard ratio, 23.98; 95% confidence interval: 2.49-230.53; p = 0.006). Furthermore, more patients with high P. aeruginosa burdens secreted the type III secretion facilitator protein, PcrV (p = 0.01). CONCLUSIONS: A group of patients with large burdens of P. aeruginosa who did not meet clinical criteria for ventilator-associated pneumonia had an increased risk of death when compared with patients who had high P. aeruginosa burdens and met ventilator-associated pneumonia criteria. Patients with high P. aeruginosa burden seemed to possess more virulent strains.
Subject(s)
Pneumonia, Ventilator-Associated/diagnosis , Pneumonia, Ventilator-Associated/mortality , Pseudomonas aeruginosa/isolation & purification , Respiration, Artificial , Trachea/microbiology , Aged , Anti-Bacterial Agents/therapeutic use , Colony Count, Microbial , Diagnosis, Differential , Female , Hospitals, University , Humans , Male , Middle Aged , Pneumonia, Ventilator-Associated/drug therapy , Prospective Studies , Risk Factors , Time Factors , Treatment OutcomeABSTRACT
Deletion of integrin alphav beta6 has been associated with significant protection in experiments where lung injury was induced by bleomycin, lipophilic polysaccharides, and high tidal volume ventilation. This has led to the suggestion that antibody blockade of this integrin is a novel therapy for acute lung injury. We questioned whether beta6 gene deletion would also protect against Pseudomonas aeruginosa-induced acute lung injury. Wild-type and littermate beta6-null mice, as well as recombinant soluble TGF-beta receptor type II-Fc (rsTGF-betaRII-Fc) and anti-alphav beta6 treated wild-type mice, were instilled with live P. aeruginosa. Four or 8 h after bacterial instillation, the mice were euthanized, and either bronchoalveolar lavage fluid or lung homogenates were obtained. Deletion of the beta6 gene resulted in an overall increase in inflammatory cells in the lungs. Bacterial numbers from the lung homogenates of infected beta6-null mice were significantly decreased compared to the numbers in the wild-type mice (1.6 x 10(6) CFU versus 4.2 x 10(6) CFU [P < 0.01]). There were no significant differences in P. aeruginosa-mediated increases in lung endothelial permeability between wild-type and beta6-null mice. Similarly, pretreatment with the alphav beta6 antibody or with rsTGF-betaRII-Fc did not significantly affect the P. aeruginosa-induced lung injury or rate of survival compared to pretreatment with control immunoglobulin G. We conclude that deletion or inhibition of the integrin alphav beta6 did not protect animals from P. aeruginosa-induced lung injury. However, these therapies also did not increase the lung injury, suggesting that host defense was not compromised by this promising new therapy.
