Prevention of Descending Pneumonia in Rats with Perflubron-delivered Tobramycin

Authors

  • Eric W. Dickson MD,

    Corresponding author
    1. Departments of Emergency Medicine (EWD), Physiology (EWD)
    2. Anesthesiology (EWD, SOH) and Surgery (SOH), University of Massachusetts Medical School, Worcester MA; the Departments of Emergency Medicine
    3. Pathology (GVD), University of Iowa, Iowa City, IA; and Alliance Pharmaceutical Corp. (LT, MM), San Diego, CA.
      Director of Emergency Medicine, Roy J. and Lucille A. Carver College of Medicine, Room 1193 Carver Pavilion, 200 Hawkins Drive, Iowa City, IA 52242-1009. Fax: 319-384-9184; e-mail: eric-dickson@uiowa.edu.
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  • Gary V. Doern PhD,

    1. Pathology (GVD), University of Iowa, Iowa City, IA; and Alliance Pharmaceutical Corp. (LT, MM), San Diego, CA.
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  • Leo Trevino PhD,

    1. Pathology (GVD), University of Iowa, Iowa City, IA; and Alliance Pharmaceutical Corp. (LT, MM), San Diego, CA.
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  • Michelle Mazzoni PhD,

    1. Pathology (GVD), University of Iowa, Iowa City, IA; and Alliance Pharmaceutical Corp. (LT, MM), San Diego, CA.
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  • Stephen O. Heard MD

    1. Anesthesiology (EWD, SOH) and Surgery (SOH), University of Massachusetts Medical School, Worcester MA; the Departments of Emergency Medicine
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Director of Emergency Medicine, Roy J. and Lucille A. Carver College of Medicine, Room 1193 Carver Pavilion, 200 Hawkins Drive, Iowa City, IA 52242-1009. Fax: 319-384-9184; e-mail: eric-dickson@uiowa.edu.

Abstract

Objectives: 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 108 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.

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