title: Saturability of granulocyte kill of Pseudomonas aeruginosa in a murine model of pneumonia.
abstract: Outcomes for patients with dense bacterial burdens, such as ventilator-associated pneumonia (VAP) patients, are often critically influenced by the adequacy of antimicrobial chemotherapy and by the response of the immune system, particularly the granulocytes. Little information is available about the quantitation of kill of organisms over time by granulocytes. In this investigation, we examined the impact of the baseline bacterial burden on the ability of granulocytes alone (without chemotherapy) to keep the number of organisms in check or to kill them over a 24-h period. Pseudomonas aeruginosa ATCC 27853 was the study organism, and we employed a murine pneumonia model (granulocyte replete) for the study. We found that the ability of the immune system to kill P. aeruginosa was saturable. The burden at which the system was half saturated was 2.15 × 10⁶ ± 2.66 × 10⁶ CFU/g. Burdens greater than 10⁷ CFU/g demonstrated net growth over 24 h. These findings suggest the need for aggressive chemotherapy early in the treatment of VAP to keep the burden from saturating the granulocytes. This should optimize the outcome for these seriously infected patients.
authors.affiliation: Ordway Research Institute, 150 New Scotland Ave., Albany, NY 12208, USA. gdrusano@ordwayresearch.org
authors.forename: G L
authors.initials: GL
authors.lastname: Drusano
authors.forename: B
authors.initials: B
authors.lastname: Vanscoy
authors.forename: W
authors.initials: W
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Fikes
authors.forename: D
authors.initials: D
authors.lastname: Brown
authors.forename: A
authors.initials: A
authors.lastname: Louie
mesh_terms: D000818:Animals; D001770:Blood Bactericidal Activity; D004195:Disease Models, Animal; D005260:Female; D006098:Granulocytes / Q000276:immunology*; D051379:Mice; D018410:Pneumonia, Bacterial / Q000276:immunology*; D053717:Pneumonia, Ventilator-Associated / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000276:immunology*