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Research ArticleOriginal Research

Aerosolized Antibiotics for Treatment of Pneumonia in Mechanically Ventilated Subjects

Fatima J Wong, Tina Dudney and Rajiv Dhand
Respiratory Care August 2019, 64 (8) 962-979; DOI: https://doi.org/10.4187/respcare.07024
Fatima J Wong
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Graduate School of Medicine, University of Tennessee Health Sciences Center Knoxville, Knoxville, Tennessee.
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Tina Dudney
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Graduate School of Medicine, University of Tennessee Health Sciences Center Knoxville, Knoxville, Tennessee.
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Rajiv Dhand
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Graduate School of Medicine, University of Tennessee Health Sciences Center Knoxville, Knoxville, Tennessee.
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    Fig. 1.

    Amikacin levels in epithelial lining fluid (ELF) at day 3. The dotted line corresponds to 128 μg/mL, which is 10 times the critical 90% minimum inhibitory concentration for Pseudomonas aeruginosa. T-bars represent the 10th and 90th percentiles, and the horizontal line in the box is the median; the lower and upper limits of the box represent the 25th and 75th percentiles, respectively. Circles represent outliers. From Reference 12, with permission.

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    Fig. 2.

    The concentration of ciprofloxacin in lung sputum, bronchial secretions (mean concentration), and serum following inhaled (Pulm), oral, or intravenous (IV) administration. The oral and IV formulations contained unencapsulated (free) ciprofloxacin, while the inhaled formulations contained liposomal ciprofloxacin or combinations of free and liposomal ciprofloxacin. The oral dose, even at twice the maximum labeled dose of 750 mg, leads to a maximum drug concentration in the sputum lower than the MIC for P. aeruginosa in the biofilm of 4 μg/mL, represented by the dotted line. In contrast, the maximum drug concentration in the sputum by inhalation exceeds the MIC by more than 50-fold, and the mean concentration over the 24-h dosing period exceeds the MIC by 20-fold. However, the peak serum drug concentration following inhalation is only a fraction (3–5%) of that for oral dosing, thus reducing the potential for systemic side effects. MIC = minimum inhibitory concentration. From Reference 60, with permission.

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    Fig. 3.

    Amikacin concentrations in tracheal aspirate after day 1 and day 3 in all treated subjects. Values are for all treated subjects with tracheal aspirate amikacin concentrations at the relevant time point. q12h = every 12 h; q24h = every 24 h. From Reference 13, with permission.

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    Fig. 4.

    Levels of colistin in ELF (A) at 1, 4, and 8 h after administration of 80 mg nebulized colistemethate sodium. Serum colistin concentrations (B) at 0.16, 0.5, 1, 2, 4, and 8 h after administration of 80 mg nebulized colistemethate sodium. Median levels and interquartile ranges are shown. Dashed lines represent minimum inhibitory concentration (MIC) for A. baumannii, K. pneumoniae, according to EUCAST susceptibility. Adapted from Reference 14, with permission.

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Respiratory Care: 64 (8)
Respiratory Care
Vol. 64, Issue 8
1 Aug 2019
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Aerosolized Antibiotics for Treatment of Pneumonia in Mechanically Ventilated Subjects
Fatima J Wong, Tina Dudney, Rajiv Dhand
Respiratory Care Aug 2019, 64 (8) 962-979; DOI: 10.4187/respcare.07024

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Aerosolized Antibiotics for Treatment of Pneumonia in Mechanically Ventilated Subjects
Fatima J Wong, Tina Dudney, Rajiv Dhand
Respiratory Care Aug 2019, 64 (8) 962-979; DOI: 10.4187/respcare.07024
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  • Article
    • Abstract
    • Introduction
    • Ventilator-Associated Infections
    • Aerosolized Agents
    • Clinical Application of Aerosolized Antibiotics for Treatment of VAP
    • Limitations and Barriers to Use of Aerosolized Antibiotics
    • The Future for Aerosolized Antibiotics
    • Conclusions
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Keywords

  • Multidrug-resistant infections
  • artificial respiration
  • ventilator-associated pneumonia
  • ICU infection
  • inhalation therapy
  • nebulizers

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