TY - JOUR

T1 - Augmented effect of early antibiotic treatment in mice with experimental lung infections due to sequentially adapted mucoid strains of Pseudomonas aeruginosa

AU - van Gennip, Maria

AU - Moser, Claus

AU - Christensen, Louise D

AU - Bjarnsholt, Thomas

AU - Calum, Henrik

AU - Jensen, Peter Østrup

AU - Christophersen, Lars

AU - Hougen, Hans Petter

AU - Ciofu, Oana

AU - Molin, Søren

AU - Givskov, Michael

AU - Høiby, Niels

N1 - Keywords: Animals; Anti-Bacterial Agents; Chemokine CXCL2; Colony Count, Microbial; Cystic Fibrosis; Disease Models, Animal; Female; Granulocyte Colony-Stimulating Factor; Humans; Lung; Mice; Mice, Inbred BALB C; Pneumonia, Bacterial; Pseudomonas Infections; Pseudomonas aeruginosa; Severity of Illness Index; Time Factors; Tobramycin

PY - 2009/12/1

Y1 - 2009/12/1

N2 - BACKGROUND: Effects of treatment with tobramycin initiated 1 or 24 h post-infection were investigated in a new version of a pulmonary infection model in mice. The model reflects the differentiated behaviour of Pseudomonas aeruginosa mucoid strains isolated from the lungs of one chronically infected cystic fibrosis (CF) patient at different time periods during chronic lung infection. METHODS: BALB/c mice were challenged with alginate-embedded mucoid clinical isolates isolated in 1988, 1997 or 2003. Mice were euthanized on day 1, 2 or 3 post-infection for estimation of quantitative bacteriology, histopathology, and measurement of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein 2 (MIP-2). RESULTS: There was a significant reduction of bacteria when comparing treatment initiated 1 h post-infection with treatment initiated after 24 h for isolates 1997 and 2003. Treatment initiated 1 h post-infection also resulted in a reduction of the pulmonary cytokines G-CSF, for all three isolates, and MIP-2, for isolates 1997 and 2003. Histological evaluation showed a shift from the acute-type inflammatory immune response to a chronic-type in mice infected with isolate 2003. CONCLUSIONS: A significant reduction in the number of bacteria was observed when initiating treatment 1 h post-infection compared with initiating treatment after 24 h, although the latest isolate avoided complete clearance. Early antibiotic treatment directed at the mucoid phenotype in mice also reduced the inflammation and, thereby, the lung tissue damage.

AB - BACKGROUND: Effects of treatment with tobramycin initiated 1 or 24 h post-infection were investigated in a new version of a pulmonary infection model in mice. The model reflects the differentiated behaviour of Pseudomonas aeruginosa mucoid strains isolated from the lungs of one chronically infected cystic fibrosis (CF) patient at different time periods during chronic lung infection. METHODS: BALB/c mice were challenged with alginate-embedded mucoid clinical isolates isolated in 1988, 1997 or 2003. Mice were euthanized on day 1, 2 or 3 post-infection for estimation of quantitative bacteriology, histopathology, and measurement of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein 2 (MIP-2). RESULTS: There was a significant reduction of bacteria when comparing treatment initiated 1 h post-infection with treatment initiated after 24 h for isolates 1997 and 2003. Treatment initiated 1 h post-infection also resulted in a reduction of the pulmonary cytokines G-CSF, for all three isolates, and MIP-2, for isolates 1997 and 2003. Histological evaluation showed a shift from the acute-type inflammatory immune response to a chronic-type in mice infected with isolate 2003. CONCLUSIONS: A significant reduction in the number of bacteria was observed when initiating treatment 1 h post-infection compared with initiating treatment after 24 h, although the latest isolate avoided complete clearance. Early antibiotic treatment directed at the mucoid phenotype in mice also reduced the inflammation and, thereby, the lung tissue damage.

U2 - 10.1093/jac/dkp352

DO - 10.1093/jac/dkp352

M3 - Journal article

C2 - 19815632

VL - 64

SP - 1241

EP - 1250

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 6

ER -