Prevention of descending pneumonia in rts with perflubron-delivered tobramycin.
OBJECTIVE
Patients undergoing emergent endotracheal intubation are at increased risk for developing pneumonia. Although numerous strategies have been investigated to reduce ventilator-associated pneumonia (VAP), the incidence of VAP and its associated mortality remains high. This investigation tested the hypothesis that LiquiVent (Alliance Pharmaceutical, San Diego, CA-LV) delivered antibiotics (via spray-dried microspheres-SDM) would improve survival in a rat model of descending gram-negative pneumonia.


METHODS
Wistar rats (n = 49) were randomized to receive prophylaxis with 1). nothing (controls); 2). intramuscular (IM) tobramycin, 3). intratracheal LV plus SDM shells (vehicle), 4). intratracheal LV plus SDM shells plus IM tobramycin, or 5). intratracheal LV plus SDM containing 1 mg/kg of tobramycin. All interventions were given 24 hours before a bacterial challenge with 10(8) colony-forming units of intratracheal Klebsiella pneumoniae. Mortality at ten days was the sole outcome measure. Survival in individual groups was compared with controls by Fisher's exact test with Bonferroni correction for multiple comparisons.


RESULTS
All animals in the control group died of pneumonia within ten days of bacterial inoculation (0% survival). Prophylaxis with either IM tobramycin or SDM vehicle plus IM tobramycin provided no protection (0% survival). This is in sharp contrast to the cohort receiving pretreatment with tobramycin-containing SDM delivered via LV, in which 60% of the animals survived to study completion (p < 0.05).


CONCLUSIONS
Prophylaxis with SDM containing antibiotics delivered in low-dose LV provided significant protection in a rat model of descending gram-negative pneumonia. These data support the hypothesis that perfluorocarbon-delivered intratracheal antimicrobials may be useful in the prevention of VAP.
Dickson
Eric W
EW
Department of Emergency Medicine, University of Massachusetts Medical School, Worcester MA, USA. ericdickson@uiowa.edu
Doern
Gary V
GV
Trevino
Leo
L
Mazzoni
Michelle
M
Heard
Stephen O
SO
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D004195:Disease Models, Animal; D007440:Intubation / Q000009:adverse effects; D007710:Klebsiella Infections / Q000517:prevention & control*; D007711:Klebsiella pneumoniae / Q000187:drug effects; D018410:Pneumonia, Bacterial / Q000209:etiology* / Q000517:prevention & control*; D011446:Prospective Studies; D051381:Rats; D017208:Rats, Wistar; D014031:Tobramycin / Q000627:therapeutic use*; D012122:Ventilators, Mechanical / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D014031:Tobramycin